Silybin supplementation during HCV therapy with pegylated interferon-α plus ribavirin reduces depression and anxiety and increases work ability.

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Malaguarnera, Giulia; Bertino, Gaetano; Chisari, Giuseppe; Motta, Massimo; Vecchio, Michele; Vacante, Marco; Caraci, Filippo; Greco, Carmela; Drago, Filippo; Nunnari, Giuseppe; Malaguarnera, Michele

2016-11-15

Hepatitis C virus infection and interferon treatment are often associated with anxiety, depressive symptoms and poor health-related quality of life. To evaluate the Silybin-vitamin E-phospholipids complex effect on work ability and whether health related factors (anxiety and depression) were associated with work ability in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b (Peg-IFN) and Ribavirin (RBV). Thirty-one patients (Group A) with chronic hepatitis and other 31 subjects in Group B were recruited in a randomized, prospective, placebo controlled, double blind clinical trial. Group A received 1.5 mg/kg per week of Peg-IFN plus RBV and placebo, while Group B received the same dosage of Peg-IFN plus RBV plus association of Silybin 94 mg + vitamin E 30 mg + phospholipids 194 mg in pills for 12 months. All subjects underwent to laboratory exams and questionnaires to evaluate depression (Beck Depression Inventory - BDI), anxiety (State-trait anxiety inventory - STAI) and work ability (Work ability Index - WAI). The comparison between group A and group B showed significant differences after 6 months in ALT (P work ability and reduced depression and anxiety in patients treated with Peg-IFN and RBV. NCT01957319 , First received: September 25, 2013. Last updated: September 30, 2013 (retrospectively registered).

[Cost-effectiveness analysis of sofosbuvir, peginterferon and ribavirin in patients with chronic hepatitis C: Early treatment in the initial stage of fibrosis vs. delayed treatment in advanced fibrosis].

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Buti, María; Domínguez-Hernández, Raquel; Oyagüez, Itziar; Casado, Miguel Ángel

2016-01-01

Cost-effectiveness analysis of sofosbuvir combined with peginterferon alpha-2a and ribavirin (SOF/Peg-IFN/RBV) in early versus advanced fibrosis in previously untreated patients with chronic hepatitis C genotype 1 (CHC-GT1), from the perspective of the Spanish National Health System (NHS). A Markov model was developed to compare lifetime costs and outcomes (life years gained [LYGs] and quality-adjusted life years [QALYs]) of 2 treatment strategies: SOF/Peg-IFN/RBV administered during early fibrosis (mild-moderate fibrosis; F2-F3) or advanced fibrosis (cirrhosis; F4). Efficacy (sustained virologic response), annual transition probabilities, disease management costs and utilities were obtained from the literature. Costs and outcomes were discounted annually at 3%. Direct costs were considered, expressed in Euros (€, 2014). Probabilistic sensitivity analysis (PSA) was also performed. SOF/Peg-IFN/RBV therapy at F2-F3 was more effective (19.12 LYGs and 14.14 QALYs) compared to F4. In a cohort of 1,000 patients, SOF/Peg-IFN/RBV prevented 66 cases of decompensated cirrhosis, 60 hepatocellular carcinomas and 4 liver transplantations compared with therapy in advanced fibrosis. The total lifetime cost of early therapy (€43,263) was less than the cost of treatment in the advanced stage (€49,018). Early therapy was a dominant strategy, more effective and less costly in all simulations. In the PSA analysis, administration of SOF/PEG-IFN/RBV at F2-F3 was dominant in all simulations. Starting SOF/Peg-IFN/RBV therapy at F2-F3, compared with therapy at F4, reduced the incidence of liver disease complications and was associated with cost savings for the Spanish NHS in CHC-GT1 patients. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

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Nathália Delvaux

2015-08-01

Full Text Available Inosine triphosphatase (ITPA single nucleotide polymorphisms (SNPs are strongly associated with protection against ribavirin (RBV-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354 frequency in healthy and hepatitis C virus (HCV-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101 and CC genotypes (rs1127354, respectively. Men with AA (rs7270101 showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475. In women, there was no influence of genotype (p = 0.5295. For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.

Patient-reported outcomes assessment in chronic hepatitis C treated with sofosbuvir and ribavirin: the VALENCE study

NARCIS (Netherlands)

Younossi, Zobair M.; Stepanova, Maria; Zeuzem, Stefan; Dusheiko, Geoffrey; Esteban, Rafael; Hezode, Christophe; Reesink, Hendrik W.; Weiland, Ola; Nader, Fatema; Hunt, Sharon L.

2014-01-01

Interferon (IFN) negatively impacts patients' well-being and patient-reported outcomes (PROs). Our aim was to assess PROs during treatment with an IFN-free regimen [sofosbuvir (SOF)+ribavirin (RBV)]. Four PRO questionnaires [Short Form-36 (SF-36), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV),

Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

Science.gov (United States)

Santagostino, E; Pol, S; Olveira, A; Reesink, H W; van Erpecum, K; Bogomolov, P; Xu, D; Critelli, L; Srinivasan, S; Cooney, E

2016-09-01

This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC. © 2016 John Wiley & Sons Ltd.

Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

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Balk JM

2015-08-01

Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil.

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Artico, Simara; Amaral, Karine Medeiros; Gonçalves, Candice Beatriz Treter; Picon, Paulo Dornelles

2012-12-27

More than 50% of patients infected with chronic hepatitis C virus (HCV) do not respond to treatment with conventional interferon (IFN) combined with ribavirin (RBV). The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b) concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR). From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg) per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR). Virological Response (VR) within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031). As predictive factors that contribute to improve SVR, were identified the age (p = 0.005), to be relapsers to previous treatment (p = 0.023) and present liver biopsy examination Metavir F0-F2 (p = 0.004). In assessing the safety profile, 51 patients (23.6%) discontinued treatment prematurely. This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.

The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil

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Artico Simara

2012-12-01

Full Text Available Abstract Background More than 50% of patients infected with chronic hepatitis C virus (HCV do not respond to treatment with conventional interferon (IFN combined with ribavirin (RBV. The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR. Methods From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR. Virological Response (VR within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. Results The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031. As predictive factors that contribute to improve SVR, were identified the age (p = 0.005, to be relapsers to previous treatment (p = 0.023 and present liver biopsy examination Metavir F0-F2 (p = 0.004. In assessing the safety profile, 51 patients (23.6% discontinued treatment prematurely. Conclusions This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.

The safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in the treatment of orthotopic liver transplant recipients with recurrent hepatitis C: real-world data.

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Pyrsopoulos, Nikolaos; Trilianos, Panagiotis; Lingiah, Vivek A; Fung, Phoenix; Punnoose, Merlin

2018-07-01

Recurrent hepatitis C (RHC) in orthotopic liver transplantation (OLT) population is associated with accelerated rates of fibrosis, low efficacy and decreased tolerability with traditional therapies. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir (LED/SOF) with or without ribavirin (RBV) in OLT patients with RHC. Patients at least 3 months post-OLT and with documented RHC were treated with LED/SOF with or without RBV for either 12 or 24 weeks. End-of-treatment and sustained virological response 12 weeks after the completion of treatment were documented. Patients were closely monitored for treatment-related adverse effects and the potential need for adjustment in their immunosuppression. Seventy-one patients were included in the study. Median age was 62 years. Median time from OLT was 55 months. Twenty-six (36.6%) patients were treatment-naive and 45 (63.4%) had previously failed interferon-based therapies. The majority of patients (57.7%) had stage F0-F2 fibrosis. Sixty-seven (94.3%) patients completed 12 weeks of LED/SOF with RBV, three patients completed 12 or 24 weeks of LED/SOF without RBV, and one patient completed only 8 weeks of LED/SOF without RBV owing to severe allograft dysfunction. Sustained virological response was near universal in our cohort (98.5%) regardless of genotype, fibrosis stage, and regimen or treatment duration. Most commonly reported side effects were malaise and gastrointestinal upset. No patient required adjustment in immunosuppression and no episodes of rejection were documented during treatment. The combination of LED/SOF with RBV for 12 weeks or LED/SOF for 24 weeks is very effective and safe in treating OLT recipients with RHC.

Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

DEFF Research Database (Denmark)

Waldenström, Jesper; Westin, Johan; Nyström, Kristina

2016-01-01

In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (......In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard......, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes....

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

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Tsai, Pei-Chien; Liu, Ta-Wei; Tsai, Yi-Shan; Ko, Yu-Min; Chen, Kuan-Yu; Lin, Ching-Chih; Huang, Ching-I; Liang, Po-Cheng; Lin, Yi-Hung; Hsieh, Ming-Yen; Hou, Nai-Jen; Huang, Chung-Feng; Yeh, Ming-Lun; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Chuang, Wan-Long; Huang, Jee-Fu; Yu, Ming-Lung

2017-06-01

For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

Protein pathway activation associated with sustained virologic response in patients with chronic hepatitis C treated with pegylated interferon (PEG-IFN) and ribavirin (RBV).

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Younossi, Zobair M; Limongi, Dolores; Stepanova, Maria; Pierobon, Mariaelena; Afendy, Arian; Mehta, Rohini; Baranova, Ancha; Liotta, Lance; Petricoin, Emanuel

2011-02-04

Only half of chronic hepatitis C (CH-C) patients treated with pegylated interferon and ribavirin (PEG-IFN+RBV) achieve sustained virologic response) SVR. In addition to known factors, we postulated that activation of key protein signaling networks in the peripheral blood mononuclear cells (PBMCs) may contribute to SVR due to inherent patient-specific basal immune cell signaling architecture. In this study, we included 92 patients with CH-C. PBMCs were collected while patients were not receiving treatment and used for phosphoprotein-based network profiling. Patients received a full course of PEG-IFN+RBV with overall SVR of 55%. From PBMC, protein lysates were extracted and then used for Reverse Phase Protein Microarray (RPMA) analysis, which quantitatively measured the levels of cytokines and activation levels of 25 key protein signaling molecules involved in immune cell regulation and interferon alpha signaling. Regression models for predicting SVR were generated by stepwise bidirectional selection. Both clinical-laboratory and RPMA parameters were used as predictor variables. Model accuracies were estimated using 10-fold cross-validation. Our results show that by comparing patients who achieved SVR to those who did not, phosphorylation levels of 6 proteins [AKT(T308), JAK1(Y1022/1023), p70 S6 Kinase (S371), PKC zeta/lambda(T410/403), TYK2(Y1054/1055), ZAP-70(Y319)/Syk(Y352)] and overall levels of 6 unmodified proteins [IL2, IL10, IL4, IL5, TNF-alpha, CD5L] were significantly different (P < 0.05). For SVR, the model based on a combination of clinical and proteome parameters was developed, with an AUC = 0.914, sensitivity of 92.16%, and specificity of 85.0%. This model included the following parameters: viral genotype, previous treatment status, BMI, phosphorylated states of STAT2, AKT, LCK, and TYK2 kinases as well as steady state levels of IL4, IL5, and TNF-alpha. In conclusion, SVR could be predicted by a combination of clinical, cytokine, and protein signaling

Antiviral Effect of Ribavirin against HCV Associated with Increased Frequency of G-to-A and C-to-U Transitions in Infectious Cell Culture Model

DEFF Research Database (Denmark)

Galli, Andrea; Mens, Helene; Gottwein, Judith M

2018-01-01

-polymerase gene was amplified, cloned, and sequenced to estimate genetic distances. We confirm that the antiviral effect of all three RBV-drug forms on HCV relies on induction of specific transitions (G-to-A and C-to-U). These mutations lead to generation of non-infectious virions, reflected by decreased spread......Ribavirin (RBV) is a broad-spectrum antiviral active against a wide range of RNA viruses. Despite having been used for decades in the treatment of chronic hepatitis C virus (HCV) infection, the precise mechanism of action of RBV is unknown. In other viruses, it inhibits propagation by increasing...... the rate of G-to-A and C-to-U transitions. Here, we utilized the J6/JFH1 HCV cell-culture system to investigate whether RBV inhibits HCV through the same mechanism. Infected Huh7.5 cells were treated with increasing concentrations of RBV or its phosphorylated forms. A fragment of the HCV NS5B...

Impact of weight-based ribavirin with peginterferon alfa-2b in African Americans with hepatitis C virus genotype 1.

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Jacobson, Ira M; Brown, Robert S; McCone, Jonathan; Black, Martin; Albert, Clive; Dragutsky, Michael S; Siddiqui, Firdous A; Hargrave, Thomas; Kwo, Paul Y; Lambiase, Louis; Galler, Greg W; Araya, Victor; Freilich, Bradley; Harvey, Joann; Griffel, Louis H; Brass, Clifford A

2007-10-01

WIN-R (Weight-based dosing of pegINterferon alfa-2b and Ribavirin) was a multicenter, randomized, open-label, investigator-initiated trial involving 236 community and academic sites in the United States, comparing response to pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in treatment-naive patients with chronic hepatitis C and compensated liver disease. Patients were randomized to receive PEG-IFN alfa-2b at 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based-dose RBV (800 mg/day for weight 85-105 kg, or 1400 mg/day for >105- or =65 kg was the primary end point. Low SVR rates have been reported among African American individuals, in whom there is a preponderance of HCV genotype 1. This subanalysis of WIN-R was conducted to evaluate the efficacy of weight-based dosing among African American individuals with genotype 1 infection enrolled in the trial. Of 362 African American patients in the primary efficacy analysis, 188 received RBV flat dosing and 174 received weight-based dosing. SVR rates were higher (21% versus 10%; P = 0.0006) and relapse rates were lower (22% versus 30%) in the weight-based-dose group than in the flat-dose group. Safety and rates of drug discontinuation were similar between the 2 groups. Weight-based dosing of RBV is more effective than flat dosing in combination with PEG-IFN alfa-2b in African American individuals with HCV genotype 1. Even with weight-based dosing, response rates in African American individuals are lower than reported in other ethnic groups.

Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial.

Science.gov (United States)

Jacobson, Ira M; Brown, Robert S; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul Y; Santoro, John; Becker, Scott; Wakil, Adil E; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauly, Mary Pat; Mukhopadhyay, Pabak; Griffel, Louis H; Brass, Clifford A

2007-10-01

This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

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Antonio Rivero-Juárez

Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

A randomized, controlled study of peginterferon lambda-1a/ribavirin ± daclatasvir for hepatitis C virus genotype 2 or 3.

Science.gov (United States)

Foster, Graham R; Chayama, Kazuaki; Chuang, Wan-Long; Fainboim, Hugo; Farkkila, Martti; Gadano, Adrian; Gaeta, Giovanni B; Hézode, Christophe; Inada, Yukiko; Heo, Jeong; Kumada, Hiromitsu; Lu, Sheng-Nan; Marcellin, Patrick; Moreno, Christophe; Roberts, Stuart K; Strasser, Simone I; Thompson, Alexander J; Toyota, Joji; Paik, Seung Woon; Vierling, John M; Zignego, Anna L; Cohen, David; McPhee, Fiona; Wind-Rotolo, Megan; Srinivasan, Subasree; Hruska, Matthew; Myler, Heather; Portsmouth, Simon D

2016-01-01

Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection. In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV. The primary outcome measure was sustained virologic response at post-treatment Week 12 (SVR12). Overall, 874 patients were treated: Lambda/RBV, n = 353; Lambda/RBV + DCV, n = 349; alfa/RBV, n = 172. Patients were 65 % white and 33 % Asian, 57 % male, with a mean age of 47 years; 52 % were infected with genotype 2 (6 % cirrhotic) and 48 % with genotype 3 (9 % cirrhotic). In the Lambda/RBV + DCV group, 83 % (95 % confidence interval [CI] 78.5, 86.5) achieved SVR12 (90 % genotype 2, 75 % genotype 3) whereas SVR12 was achieved by 68 % (95 % CI 63.1, 72.9) with Lambda/RBV (72 % genotype 2, 64 % genotype 3) and 73 % (95 % CI 66.6, 79.9) with peginterferon alfa/RBV (74 % genotype 2, 73 % genotype 3). Lambda/RBV + DCV was associated with lower incidences of flu-like symptoms, hematological abnormalities, and discontinuations due to adverse events compared with alfa/RBV. The 12-week regimen of Lambda/RBV + DCV was superior to peginterferon alfa/RBV in the combined population of treatment-naive patients with genotype 2 or 3 infection, with an improved tolerability and safety profile compared with alfa/RBV.

Antiviral therapy in chronic hepatitis C (G1 in Russia: cost and effectiveness

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2015-01-01

Full Text Available Genotype 1 HCV treatment in Russia assume as bitherapy (pegylated interferon – PG plus ribavirin – RBV as three therapy based on HCV protease inhibitor such as telaprevir (TLV, boceprevir (BCV or simeprevir (SMV plus PG/RBV. Medical technologies characterize neither clinical effectiveness, safety profile nor cost-effectiveness so it’s crucial to assess different costs related antiviral regimens. Three therapy costs for naïve patients including TLV, BCV, SMV are higher bitherapy 2,6; 2,5; 3,1 times accordingly. Similar TLV and BCV effectiveness for naïve patients defines TLV or BCV as the preferable 1-st line regimen, depending on regional features of pricing. SMV and TLV efficacy is similar among naïve patients and ralapsers but SMV is affordable for partially responders and non-responders after previous bitherapy. SMV cost is 1,4 times higher vs TLV but SMV has improved tolerability, less drug-drug interactions and shorter course. Insufficient bitherapy effectiveness for G1 HCV (SVR 24 – 39%-55% is required repeated course of three therapy for half of patient population. The first line regimen based on innovation will improve clinical outcomes for more patients and provide cost saving vs previous bitherapy based on PG/RBV. 

Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

Science.gov (United States)

Ranganathan, Raghini; Janarthanan, Krishnaveni; Rajasekaran, Senthilkumar

2012-01-01

A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection. She attained rapid virological response. She presented with diabetic ketoacidosis after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL, and the treatment course was completed. This case underlines the importance of periodic plasma glucose monitoring in patients during and after PEG-IFN and ribavirin therapy. PMID:25755410

Bell's palsy and choreiform movements during peginterferon α and ribavirin therapy

Institute of Scientific and Technical Information of China (English)

Sener Barut; Hatice Karaer; Erol Oksuz; Asl Gündodu Eken; Ayse Nazl Basak

2009-01-01

Neuropsychiatric side effects of long-term recombinant interferon-α therapy consist of a large spectrum of symptoms. In the literature, cranial neuropathy, especially Bell's palsy, and movement disorders, have been reported much less often than other neurotoxic effects. We report a case of Bell's palsy in a patient with chronic hepatitis C during peginterferon-α and ribavirin therapy. The patient subsequently developed clinically inapparent facial nerve involvement on the contralateral side and showed an increase in choreic movements related to Huntington's disease during treatment.

Association of ITPA gene variation and serum ribavirin concentration with a decline in blood cell concentrations during pegylated interferon-alpha plus ribavirin therapy for chronic hepatitis C.

Science.gov (United States)

Nakagawa, Mina; Sakamoto, Naoya; Watanabe, Takako; Nishimura-Sakurai, Yuki; Onozuka, Izumi; Azuma, Seishin; Kakinuma, Sei; Nitta, Sayuri; Kiyohashi, Kei; Kusano-Kitazume, Akiko; Murakawa, Miyako; Yoshino, Kohei; Itsui, Yasuhiro; Tanaka, Yasuhito; Mizokami, Masashi; Watanabe, Mamoru

2013-03-01

Genetic variation leading to inosine triphosphatase (ITPA) deficiency protects chronic hepatitis C patients receiving ribavirin against hemolytic anemia. The relationship between ITPA gene variation and serum ribavirin concentration was analyzed in association with a reduction in blood cells and dose reduction of pegylated interferon (PEG-IFN) or ribavirin. A total of 300 hepatitis C patients treated with PEG-IFN plus ribavirin were analyzed. Genetic polymorphisms were determined in ITPA and the quantitative reduction in blood cells from the baseline was analyzed every 4 weeks for the duration of treatment and after the end of therapy. The decline in hemoglobin (Hb) or platelet (PLT) level at week 4 compared to baseline was also assessed according to ribavirin concentrations. Patients with the ITPA-CA/AA genotypes showed a lower degree of Hb reduction throughout therapy than those with the ITPA-CC genotype and a marked difference in mean Hb reduction was found at week 4 (CA/AA -1.0 vs. CC -2.8, p < 0.001). The ITPA-CC genotype had significantly less reduction in the mean platelet count than the ITPA-CA/AA genotypes early during treatment (p < 0.001 for weeks 4 and 8). Patients with the ITPA-CA/AA genotypes were less likely to develop anemia, regardless of the concentration of ribavirin. Patients with baseline PLT counts below 130 × 10(3)/μl had a significantly lower tendency to achieve sustained virological response (SVR), especially those with the ITPA-CA/AA genotypes. ITPA gene variation was not extracted by multivariable analysis as an important predictor of SVR. Despite the fact that ITPA variants were less likely to develop anemia, patients with low baseline PLT counts were difficult to treat, especially those with the ITPA-CA/AA genotype. These results may give a valuable pharmacogenetic diagnostic tool for the tailoring of dosing to minimize drug-induced adverse events.

Role of ribavirin in HCV treatment response: now and in the future.

Science.gov (United States)

Jain, Mamta K; Zoellner, Cindy

2010-03-01

Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation. Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted. To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials. Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.

Therapy of chronic hepatitis C: Virologic response monitoring

Directory of Open Access Journals (Sweden)

Kuljić-Kapulica Nada

2010-01-01

Full Text Available Background/Aim. Virological testing is considered to be essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, and, most importantly, as a quide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR and various factors associated with response rates in chronic hepatitis C infected patients treated with pegiinterferon alpha (PEGINF and ribavirin (RBV combination therapy. Methods. A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR as relapse of HCV-RNA during the post-treatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. Results. At the end of post-treatment follow-up 19 (55.8% patients demonstrated a SVR. The majority of the patients were genotype 1 (27, and the other were genotype 3 (5 patients and genotype 4 (2 patients. There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. Conclusion. We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.

The RBV metadata catalog

Science.gov (United States)

Andre, Francois; Fleury, Laurence; Gaillardet, Jerome; Nord, Guillaume

2015-04-01

RBV (Réseau des Bassins Versants) is a French initiative to consolidate the national efforts made by more than 15 elementary observatories funded by various research institutions (CNRS, INRA, IRD, IRSTEA, Universities) that study river and drainage basins. The RBV Metadata Catalogue aims at giving an unified vision of the work produced by every observatory to both the members of the RBV network and any external person interested by this domain of research. Another goal is to share this information with other existing metadata portals. Metadata management is heterogeneous among observatories ranging from absence to mature harvestable catalogues. Here, we would like to explain the strategy used to design a state of the art catalogue facing this situation. Main features are as follows : - Multiple input methods: Metadata records in the catalog can either be entered with the graphical user interface, harvested from an existing catalogue or imported from information system through simplified web services. - Hierarchical levels: Metadata records may describe either an observatory, one of its experimental site or a single dataset produced by one instrument. - Multilingualism: Metadata can be easily entered in several configurable languages. - Compliance to standards : the backoffice part of the catalogue is based on a CSW metadata server (Geosource) which ensures ISO19115 compatibility and the ability of being harvested (globally or partially). On going tasks focus on the use of SKOS thesaurus and SensorML description of the sensors. - Ergonomy : The user interface is built with the GWT Framework to offer a rich client application with a fully ajaxified navigation. - Source code sharing : The work has led to the development of reusable components which can be used to quickly create new metadata forms in other GWT applications You can visit the catalogue (http://portailrbv.sedoo.fr/) or contact us by email rbv@sedoo.fr.

Frequency of thyroid disorders during interferon and ribavirin therapy in chronic hepatitis C infection

International Nuclear Information System (INIS)

Masood, N.; Memon, A.; Memon, S.; Jaffri, M.

2008-01-01

The objective of this study was to assess the frequency of thyroid dysfunction in response to combination of interferon and ribavirin therapy in chronic hepatitis C (CHC) patients and HCV outcome. One hundred cases of CHC, proven by anti-HCV and HCV RNA-positive with baseline TSH, FT4 and FT3 within the normal reference range, who were treated with interferon alpha-2b (3 million unit subcutaneously three times per week) and oral ribavirin (1000-1200 mg per day) were included in this study. All patients were assessed for TSH, FT4, FT3 levels at 12 weeks and 24 weeks during therapy. Among the 100 patients, overt thyroid disease developed in 13 (13%) and sub-clinical thyroid disease in 5 (5%). Out of 13 patients of overt thyroid disorders, 11 (84.6%) had hypothyroidism and 02 (15.3%) hyperthyroidism. Four (80%) patients were of sub-clinical hypothyroidism and 01 (20%) patient was of sub-clinical hyperthyroidism. Overall, thyroid disorders developed in 18 (18%) both as overt and sub-clinical thyroid disorders. Ninety one (91%) patients became negative by HCV RNA. Treatment of HCV with IFN-alpha and ribavirin can be safely continued in patients with over and sub clinical hypothyroidism because thyroid disease responds well to treatment. (author)

Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

Science.gov (United States)

Fernández-Rodríguez, Conrado M; Morillas, Rosa María; Masnou, Helena; Navarro, José María; Bárcena, Rafael; González, José Manuel; Martín-Martín, Leticia; Poyato, Antonio; Miquel-Planas, Mireia; Jorquera, Francisco; Casanovas, Teresa; Salmerón, Javier; Calleja, José Luis; Solà, Ricard; Alonso, Sonia; Planas, Ramón; Romero-Gomez, Manuel

2014-01-01

Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13). RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (Clin Trials Gov NCT00830609). Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

Science.gov (United States)

Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

2016-01-01

A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary

Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C

DEFF Research Database (Denmark)

Manns, Michael P; Gane, Edward; Rodriguez-Torres, Maribel

2012-01-01

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV......). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 μg/week) and RBV (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600...... in viral load, with HCV RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%; P

Ribavirin plus interferon versus interferon for chronic hepatitis C

DEFF Research Database (Denmark)

Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

2010-01-01

Hepatitis C is a major cause of liver-related morbidity and mortality. Standard therapy is ribavirin plus pegylated interferon to achieve undetectable level of virus in the blood, but the effect on clinical outcomes is controversial.......Hepatitis C is a major cause of liver-related morbidity and mortality. Standard therapy is ribavirin plus pegylated interferon to achieve undetectable level of virus in the blood, but the effect on clinical outcomes is controversial....

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy

Directory of Open Access Journals (Sweden)

Soon Jae Lee

2016-09-01

Full Text Available Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

Should ribavirin be used to treat hepatitis C in dialysis patients?

Science.gov (United States)

Carrion, Andres F; Fabrizi, Fabrizio; Martin, Paul

2011-01-01

Hepatitis C virus infection adversely affects outcomes in patients with chronic kidney disease undergoing maintenance dialysis. Pegylated interferon and ribavirin, the standard-of-care treatment in patients with intact renal function, is associated with severe side effects, toxicity, and high dropout rates in this population. Ribavirin has an important role in maintaining antiviral response following completion of therapy and increases sustained viral response (SVR) rates. However, the use of ribavirin in dialysis patients has been limited by the high frequency of severe hemolytic anemia and is currently reserved for study protocols and highly selected candidates treated at experienced centers. Encouraging data from small trials have shown a significant increase in SVR rates with the use of different dosing regimens of ribavirin in addition to interferon-based therapy and aggressive erythroid-stimulating agent support in dialysis patients. Use of ribavirin in selected dialysis patients, particularly renal transplant candidates, by experienced clinicians is appropriate. © 2011 Wiley Periodicals, Inc.

The Next Step in the Evolution of the RBV

DEFF Research Database (Denmark)

Foss, Kirsten; Foss, Nicolai Juul

2004-01-01

This essay addresses the role of transaction cost economics (TCE) inadvancing the resource-based view. In particular, it is argued that TCE hasthe potential to remedy a number of weak spots in the RBV, such as theabsence of attention in the RBV to the interaction between value creation andvalue...

Response to standard interferon A2b and ribavirin combination therapy in chronic hepatitis C treatment naive patients

International Nuclear Information System (INIS)

Jadoon, S.M.K.; Muhammad, I.

2010-01-01

Background: Treatment of Chronic Hepatitis C is now well established with conventional interferon or pegylated interferon in combination with ribavirin. Peginterferon Alfa and Ribavirin for 6 to 12 months is currently approved initial therapy, which is expensive. Response of our patients to standard Interferon-alpha-2b and ribavirin for 24 weeks have been studied. The objective of this study was to asses Sustained Viral Response (SVR) with standard Interferon A2b and Ribavirin combination treatment in chronic Hepatitis C patients. Methods: This quasi-experimental study was conducted at Combined Military Hospital, Quetta from Jan 2006 to Jun 2007. One hundred and three patients, with 20-60 years of age suffering from chronic Hepatitis C were selected on the basis of raised ALT, positive anti-HCV antibodies, evidence of viraemia by quantitative PCR for HCV RNA and liver biopsy. All patients were started on same brand of Interferon alpha-2b, 3 MIU subcutaneously, thrice weekly and oral Ribavirin (1,000-1,200 mg/day) for 24 weeks. End treatment response (ETR) after completion of treatment and SVR six months after ETR were recorded. Results: The 103 patients, 85 males and 18 females with mean age of 21-48 years completed the treatment for 24 weeks. Mean ALT was 96.17 (SD +- 49.98). End treatment response (ETR) was 89.3% (p=0.032). Sustained Viral Response after 6 months of treatment was 86.4% (p=0.034). Conclusion: Standard Interferon and Ribavirin had excellent SVR. It is effective as well as economical treatment in Chronic Hepatitis C patients. (author)

Hepatitis C treatment outcomes using interferon- and ribavirin-based therapy in Kigali, Rwanda.

Science.gov (United States)

Riedel, David J; Taylor, Simone; Simango, Raulina; Kiromera, Athanase; Sebeza, Jackson; Baribwira, Cyprien; Musabeyezu, Emmanuel

2016-08-01

Hepatitis C virus (HCV) treatment data in sub-Saharan Africa are limited. This study was to determine HCV sustained virologic response(SVR) at 24 weeks in patients undergoing HCV therapy in Kigali, Rwanda. The paper presents data for all patients treated for HCV with ribavirin/interferon at King Faisal Hospital in Kigali, Rwanda, from 1 January 2007 to 31 December 2014. There were 69 evaluable patients. HCV genotype 4(61%, 42/69) predominated. 24-week SVR was 70%(26/37) by per-protocol and 32%(26/69) by intention-to-treat analysis. HCV treatment in Rwanda is feasible. SVR with interferon/ribavirin was acceptable in the per-protocol analysis. Transition to newer direct acting antivirals is urgently needed in Rwanda and sub-Saharan Africa more generally to improve treatment outcomes. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

Science.gov (United States)

Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

Pegylated interferon alpha-2a and ribavirin combination therapy in HCV liver transplant recipients. Experience of 7 cases.

Science.gov (United States)

Iacob, Speranta; Gheorghe, Liana; Hrehoret, Doina; Becheanu, Gabriel; Herlea, Vlad; Popescu, Irinel

2008-06-01

Hepatitis C virus (HCV) related cirrhosis represents the leading indication for liver transplantation (LT) worldwide and HCV reinfection is the rule among transplant recipients. Combination therapy with interferon and ribavirin is the treatment of choice for established recurrent hepatitis C. To evaluate the efficacy and safety of the combination of pegylated interferon alpha-2a and ribavirin in LT recipients with histological recurrence of hepatitis C. Seven LT recipients with chronic hepatitis C recurrence were treated with peginterferon alpha-2a with an initial intended dose of 180 microg/week and an intended dose of ribavirin 800-1000 mg/day for at least 12 months and followed-up for at least 24 weeks. Early virological response rate was 57.1%. Three patients (42.8%) had end of treatment virological response and all had also sustained viral response (SVR). Five patients had end of treatment biological response, out of which 4 had also sustained biochemical response. Three patients had both SVR and sustained biochemical response. Four patients had end of treatment histological response, out of which 3 patients had also SVR. Cytopenia was the most common adverse event: anemia (57.1%), leucopenia/neutropenia (71.4%), thrombocytopenia (42.8%). Combination of pegylated interferon and ribavirin can be safely and successfully used in liver transplant recipients.

Interferon alfa and ribavirin induced hair changes

International Nuclear Information System (INIS)

Amir, S.; Taj, A.; Muhamud, T.H.; Iqbal, Z.; Yaqub, F.

2007-01-01

Combination therapy of Interferon alfa and ribavirin in chronic hepatitis C has well documented cutaneous adverse effects. Most interesting of these has been reported on hair physiology. This study was conducted to determine the frequency and pattern of adverse effects involving hair in patients receiving combination of interferon alfa 2a and ribavirin for chronic hepatitis C. The study was conducted in Department of Dermatology, Division of Medicine Shaikh Zayed Hospital. Thirty Eight patients who completed treatment with interferon alfa (3 MIU subcutaneously thrice weekly) and 1200 mg ribavirin daily for 24 weeks were enrolled in this single-center study. The patient's response and examination finding particularly regarding involvement of hair was noted on a Proforma. Thirty Two out of thirty eight (84%) patients noted adverse effects involving hair. The most frequent was diffuse hair loss and occurred in 27 patients (71%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 18 (47%) and 16 (42%) patients respectively. Graying of hair was noted in 4 patients (11%), while discoloration of moustache hair was seen in 2 patients (5%). Epilation at the site of subcutaneous injection was noted in 10 patients (26%). Alopecia areata was reported in 2 patients (5%). It is concluded that adverse effects involving hair are frequent and varied (hair loss to excess hair growth) during combination therapy with Interferon alfa-2a and Ribavirin for chronic hepatitis C. (author)

Effect of Sofosbuvir plus Ribavirin therapy on hepatitis C patients in Pakistan: a retrospective study

Directory of Open Access Journals (Sweden)

Zubia Jamil

2018-05-01

Full Text Available Background The annual global deaths from viral hepatitis is 1.4 million. Pakistan has the second highest burden of hepatitis C in the world. There is dire need to evaluate the response of new direct acting antivirals for the treatment of hepatitis C patients in Pakistan. World Health Organization has developed a strategy to treat 80% of HCV patients by 2030. In Pakistan, HCV treatment rate is 1%. The aim of the study was to analyze the effect of Sofosbuvir plus Ribavirin therapy on HCV patients in Pakistan. Methods An observational study was conducted at Fauji Foundation Hospital Rawalpindi from November-2016 to July-2017. All the drugs were administered according to the guidelines of Asia Pacific Association for the Study of Liver (APASL for the treatment of HCV patients. A total 327 chronic HCV patients were enrolled in the study and 304 completed the treatment. Patients belonged to three different groups including treatment: Naïve patients (n = 107, Non-Responder patients (n = 126 and patients who relapsed to Interferon therapy (n = 71. All the patients were given Sofosbuvir plus Ribavirin therapy for 24 weeks and the early virological response (EVR and end treatment response (ETR was calculated. Different parameters including patient age, viral load, viral genotype, blood picture, ultrasound findings and liver function tests were also studied. Results Out of 304 patients, 301 (99% achieved EVR and 300 achieved ETR (98.7%. End treatment response was 95.6% in HCV genotype 1 and 98.9% in HCV genotype 3 patients. ETR was 99.06% in treatment Naïve, 99.20% in non-responders and 97.18% in previously relapsed patients. We did not find the association of any host and viral factor in the determination of EVR and ETR. Conclusion The Sofosbuvir plus Ribavirin treatment is highly effective, safe and cost-effective for the treatment of hepatitis C patients in Pakistan.

Development and validation of a dried blood spot assay for the quantification of ribavirin using liquid chromatography coupled to mass spectrometry

Science.gov (United States)

Jimmerson, Leah C.; Zheng, Jia-Hua; Bushman, Lane R.; MacBrayne, Christine E.; Anderson, Peter L.; Kiser, Jennifer J.

2014-01-01

Efficient, inexpensive and sensitive assays for the measurement of drugs are of interest for pharmacokinetic and pharmacodynamics (PK-PD) analysis. Dried blood spots (DBS) are a unique bioanaltyical matrix with the potential to fulfill this interest for the measurement of numerous analytes. Here we describe the development and validation of a reversed-phase high performance liquid chromatographic (LC), tandem mass spectrometry (MS/MS) assay for the determination of ribavirin (RBV) in DBS. A 3mm punch from spotted and dried whole blood was extracted in methanol utilizing isotopically labeled internal standard for LC-MS/MS analysis. Validation was performed over a range of 0.05 μg/mL to 10.0 μg/mL and the method was shown to be precise (coefficient of variation ≤ 15%) and accurate (within ±15% of control). These acceptance criteria were met for hematocrit ranges of 20-54%, for center versus edge punches and for spot volumes from 10-60 μL. RBV was stable for up to 140 days at room temperature and −20°C as well as for three freeze/thaw cycles. Correlation of RBV in DBS versus in plasma yielded r2 ≥ 0.98 demonstrating that DBS can be used as an alternative to plasma for PK-PD studies in human subjects. PMID:24291608

Response of interferon alone and with ribavirin inpatients of chronic hepatitis C

International Nuclear Information System (INIS)

Niaz, A.

2003-01-01

Objective: The aim of the study was to compare the response of interferon alone and interferon plus ribavirin in patients of chronic hepatitis C. Results: At completion of treatment HCV-RNA levels in serum were not detectable in 15 of 20 (75%) patients who received interferon alpha and ribavirin combination therapy as compared to 10 of 20 (50%) patients who received interferon alpha alone. Only 1 patient became HCV RNA negative in the control group. Normalization of ALT concentration and histologic response was proportionate to the virological response. Conclusion: Combination therapy of interferon and ribavirin is more effective than treatment with interferon alone for minimizing viral load, improving ALT levels and histology. (author)

Hepatitis C Prevalence and Responses to Pegylated Interferon + Ribavirin Treatment Among Prisoners

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Hasan Selçuk ÖZGER

2017-12-01

Full Text Available Objective: The aim of our study was to identify the hepatitis C prevalence in prisoners and to share experiences of pegylated interferon (peg-IFN + ribavirin (RBV treatment. Materials and Methods: The study was conducted by assessing the records of prisoners between January 2014 and 2016, retrospectively. Patients in whom planned treatments were applied in a given time were determined and, virologic responses at the end of treatment and 6 months after treatment were evaluated. Chi-square test was used and a p value of less than 0.05 was considered statistically significant. Results: Among prisoners, the anti-hepatitis C virus (HCV positivity rate was 7.82% and HCV-RNA positivity rate was 5.72%. The most common genotype was genotype 3a (66 of 99 patients. End-of-treatment and 6th month sustained virologic response rates were 84.6% and 80.5%, respectively. In genotype 3a group, end-of-treatment and 6th month sustained virologic response rates were found to be higher than other genotypes but not statistically significant. Conclusion: In our study, which assessed prisoners, the rate of HCV positivity was higher than hepatitis C in the general population in Turkey. In accordance with the literature, genotype 3 was the most common genotype among prisoners. Sustained virologic response rates obtained with peg-IFN+RBV treatment suggested that peg-IFN treatment should be used with current treatment combinations in prisoners infected with HCV genotype 3.

Effects of adding ribavirin to interferon to treat chronic hepatitis C infection

DEFF Research Database (Denmark)

Brok, Jesper; Gluud, Lise L; Gluud, Christian

2005-01-01

Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon...... vs interferon alone for treatment of patients with chronic hepatitis C infection. Randomized trials were included irrespective of blinding, language, or publication status. Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Library, MEDLINE....... In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events....

Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

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Abbate, I; Cappiello, G; Lo Iacono, O; Longo, R; Ferraro, D; Antonucci, G; Di Marco, V; Di Stefano, R; Craxì, A; Solmone, M C; Spanò, A; Ippolito, G; Capobianchi, M R

2003-01-01

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

Institute of Scientific and Technical Information of China (English)

Chiaki Okuse; Hiroshi Yotsuyanagi; Yoshihiko Nagase; Yuhtaro Kobayashi; Kiyomi Yasuda; Kazuhiko Koike; Shiro Iino; Michihiro Suzuki; Fumio Itoh

2006-01-01

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.

Factors Associated with Quality of Life in Chronic Hepatitis C Patients Who Received Interferon Plus Ribavirin Therapy

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Shu-Chuan Chang

2008-06-01

Conclusion: The study found that patients with chronic hepatitis C who received interferon plus ribavirin therapy had poor quality of life during the treatment period. There was significant difference among patients with different financial stress, and a negative relationship between tangible support and hepatitis quality of life. Financial stress and tangible support are predictors of quality of life for all subjects. The results of this study might assist healthcare personnel to comprehend the quality of life and its related factors in patients with chronic hepatitis C treated with antiviral therapy.

In vitro and in vivo activity of ribavirin against Andes virus infection.

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David Safronetz

Full Text Available Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS. The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV, an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 µg ml(-1. In hamsters, treatment with as little as 5 mg kg(-1 day(-1 was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day 1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1 day(-1. Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against

Variability of hepatitis C virus hypervariable region 1 (HVR-1) during the early phase of pegylated interferon and ribavirin therapy.

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Caraballo Cortés, K; Laskus, T; Bukowska-Ośko, I; Pawełczyk, A; Berak, H; Horban, A; Fic, M; Radkowski, M

2012-01-01

Genetic variability of hepatitis C virus (HCV) is considered to be an important factor defining viral pathogenesis, persistence and resistance to treatment. The aim of the present study was to characterize HCV genetic heterogeneity within a hypervariable region 1 (HVR-1) before and during the early period of pegylated interferon alfa (PEG-IFN-α) and ribavirin treatment in correlation with treatment outcome. The study involved 24 patients treated with PEG-IFN-α and ribavirin whose sera were collected before (baseline) and at 7, 14, 21 28 and 56 day of treatment. HCV HVR-1 region was amplified by nested RT- PCR and subjected to SSCP (single strand conformational polymorphism) analysis. SSCP changes of HCV HVR-1 over time in each patient were compared to treatment outcome results. In 2/11 (18%) SVR+ and 8/13 (62%) SVR- treated patients, HVR-1 genetic changes manifested by new SSCP bands (new genetic variants) and were significantly more frequent in nonresponders (P HVR-1 variability during the early phase of PEG-IFN-α and ribavirin therapy may be predictive of treatment outcome.

Outsourcing from the perspectives of TCE and RBV: a multiple case study

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Lincoln Wolf de Almeida Neves

2014-09-01

Full Text Available The theories of transaction cost economics (TCE and the resource-based view (RBV have been applied in studies of outsourcing. The research presented in this study was conducted to gain an understanding of why firms outsource their value chain activities, using a combined TCE and RBV perspective. The research assesses how six instant coffee firms in Brazil perceive the rationale for their outsourcing processes. The authors conclude that the two theories should be used together to determine a firm's frontiers, and they offer a mechanism for combining them. The results, relevant to both academics and practitioners, reveal that outsourcing should be defined at two stages: an initial strategic stage in which the activities that should be performed internally are identified, based on RBV, and a second stage in which the activities that can be performed externally are examined and those that should be outsourced are identified on the basis of both TCE and RBV. Insights relevant to practitioners include the importance of the executive leadership role in defining a firm's outsourcing strategy and the need for constant vigilance to prevent opportunism in relationships with trading partners.

Impact of Pentoxifylline and Vitamin E on Ribavirin-Induced Haemolytic Anaemia in Chronic Hepatitis C Patients: An Egyptian Survey

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M. Assem

2011-01-01

Full Text Available Background/Aim. We evaluate the impact of combined pentoxifylline and high-dose vitamins E to standard antiviral treatment on RBV-induced haemolytic anaemia. Patients and Methods. Selected 200 naïve chronic HCV patients, were randomized to receive either the standard antiviral therapy (peginterferon α-2b and RBV plus pentoxifylline (800 mg and high-dose vitamin E (1000 iu daily (combined group or received standard antiviral therapy plus placebo only (control group. They were followed up during treatment course and for 6 months posttreatment to assess the occurrence of anaemia and virological response, respectively. Results. RBV dose modification due to anaemia were significantly less in combined group (8.5 versus 21.5%. P<.05.Withdrawal, secondary to sever anemia (Hb<8.5 gm%, was recorded only in 6 (28.6% patients of the control group. Both (ETR and (SVR were significantly higher in combined group than control group by both intention-to-treat analysis (71 versus 56%, P<.05 and 66 versus 49%, P<.05 and per-protocol analysis (85.5 versus 70.9%, P<.05 and 79.5 versus 62%, P<.05. Conclusion. Pentoxifylline and vitamin E can ameliorate RBV-associated haemolysis; improve compliance and virologic clearance when combined with the standard antiviral therapy in patients with chronic hepatitis C.

Viral hepatitis C gets personal--the value of human genomics to public health.

Science.gov (United States)

Zhang, L; Gwinn, M; Hu, D J

2013-01-01

About 180 million people worldwide are chronically infected with hepatitis C virus (HCV), with 3-4 million newly infected each year. Only 15-25% of acute HCV infections clear spontaneously, and the remainder persists as chronic HCV infection. More than 350,000 people die every year from hepatitis C-related liver failure and cancer. There is currently no vaccine and the standard-of-care therapies--peg-interferon alpha (pegIFN) plus ribavirin (RBV)--are expensive and have serious side effects. Also, they may be effective in only 40-50% of patients infected with HCV genotype 1, the most common HCV genotype in the US. Interleukin 28B (IL28B) genotype was recently and convincingly associated with response to pegIFN and RBV therapy. It has emerged as a robust pretreatment predictor of sustained virological response (SVR, i.e. virologic clearance) to pegIFN and RBV as well as to new triple therapy regimens that include a direct-acting antiviral agent with pegIFN and RBV and increase SVR rates as much as 75% in patients infected with HCV genotype 1. Testing for IL28B genotype may contribute to clinical decision-making and could inform clinical guidelines and public health policies. © 2013 S. Karger AG, Basel.

Direct-acting antiviral-based triple therapy on alpha-fetoprotein level in chronic hepatitis C patients.

Science.gov (United States)

Takayama, Koji; Furusyo, Norihiro; Ogawa, Eiichi; Ikezaki, Hiroaki; Shimizu, Motohiro; Murata, Masayuki; Hayashi, Jun

2015-04-21

To investigate the impact of telaprevir-based triple therapy on the serum alpha-fetoprotein (AFP) level of chronic hepatitis C patients. A total of 210 patients with chronic hepatitis C genotype 1 of high viral load (baseline serum hepatitis C virus RNA > 5.0 log10 IU/mL) were divided into two groups by type of treatment: triple therapy with telaprevir, pegylated-interferon-α (PEG-IFNα), and ribavirin (RBV) for 24 wk (n = 88), or dual therapy with PEG-IFNα and RBV for 48 wk (n = 122). The relationship between virological response and the change in the serum AFP level from baseline to 24 wk after the end of treatment was examined. No significant difference in mean baseline AFP level was found between the triple and dual therapy groups (8.8 ng/mL vs 7.8 ng/mL). Triple therapy produced significant declines in the AFP level in sustained virological response (SVR) and non-SVR patients (7.8 ng/mL at baseline to 3.5 ng/mL at 24 wk after the end of treatment, P < 0.001 and 14.3 ng/mL to 9.5 ng/mL, P = 0.004, respectively). In contrast, dual therapy resulted in a significant decline in AFP level only in SVR patients (4.7 ng/mL to 2.8 ng/mL, P < 0.001), but not in non-SVR patients (10.2 ng/mL to 10.1 ng/mL). Among patients with a high-baseline AFP level (≥ 10 ng/mL), the decline in the AFP level was significantly higher in the triple therapy than in the dual therapy group (15.9 ng/mL vs 1.6 ng/mL, P = 0.037). Regardless of virological response, telaprevir-based triple therapy reduced the serum AFP level.

Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV–HCV co-infected patients: final results of the Spanish BOC HIV–HCV Study

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M. Laguno

2016-12-01

Conclusions: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC + PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

The presence of non-organ-specific autoantibodies is associated with a negative response to combination therapy with interferon and ribavirin for chronic hepatitis C

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Matern Siegfried

2004-02-01

Full Text Available Abstract Background Non-organ-specific autoantibodies are found in a considerable number of anti-HCV positive patients. Previous studies investigated the clinical relevance of these antibodies in patients treated with interferon monotherapy, but not combination therapies. Methods Anti-nuclear, anti-smooth muscle, anti-mitochondrial, anti-neutrophil-cytoplasmatic and anti-liver/kidney microsomal antibodies were determined in 78 consecutive anti-HCV positive patients by indirect immunofluorescence. The presence of these antibodies was related to demographic variables and to the outcome of antiviral combination therapy with interferon-α and ribavirin in 65 patients. Results In our study, positivity for autoantibodies was associated with higher alanine aminotransferase levels and higher mean values for HCV-RNA (p Conclusions The absence of non-organ-specific autoantibodies might indicate a significantly higher chance for viral clearance in response to combination therapy for chronic hepatitis C infection. Therefore, despite of an overall higher treatment response, the addition of the immunomodulatory drug ribavirin could accentuate immunological differences that affect treatment outcome and might have been less obvious in earlier studies analysing interferon monotherapy.

The Source of Competitive Advantage and Entrepreneurial Judgment in the RBV

DEFF Research Database (Denmark)

Ishikawa, Ibuki

The purpose of this paper is to identify the source of competitive advantage in the resource based view of strategic management literature. In particular, it is argued that the source of competitive advantage is rooted in entrepreneur judgment. In this argument, this paper consists largely of three...... on Lachmann (1947,1956), Mises (1946) and Knight (1921) to improve the RBV framework; thirdly, to apply the Austrian perspective to the RBV and demonstrate that the source of competitive advantage is derived from entrepreneurial judgment per se, not the resource per se, and to discuss some possible future...... the source of competitive advantage.Jel Code: B25, D21, D81, M13...

Ribavirin monotherapy for chronic hepatitis C infection

DEFF Research Database (Denmark)

Brok, Jesper; Gluud, Lise L; Gluud, Christian

2006-01-01

Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C....

Ribavirin monotherapy for chronic hepatitis C

DEFF Research Database (Denmark)

Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

2009-01-01

BACKGROUND: Hepatitis C is a major cause of liver-related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients....... OBJECTIVES: To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C. SEARCH STRATEGY: We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009....... SELECTION CRITERIA: We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C. DATA COLLECTION AND ANALYSIS: The primary outcome measures were serum sustained virological response...

Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse

DEFF Research Database (Denmark)

Lagging, Martin; Rembeck, Karolina; Rauning Buhl, Mads

2013-01-01

Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy.......Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy....

Ribavirin and boceprevir are able to reduce Canine distemper virus growth in vitro.

Science.gov (United States)

Lanave, Gianvito; Cavalli, Alessandra; Martella, Vito; Fontana, Tommaso; Losappio, Ruggero; Tempesta, Maria; Decaro, Nicola; Buonavoglia, Domenico; Camero, Michele

2017-10-01

Canine distemper virus (CDV) is a major infectious disease of dogs. Although vaccines were successful to control CDV spread in canine population, the disease is still common and may pose a threat to unvaccinated dogs. In the attempt to develop specific anti-viral therapeutic tools, the efficacy of several molecules against CDV has been investigated in vitro. In this study the antiviral efficacy in vitro against CDV of ribavirin and boceprevir alone or in combination was evaluated. CDV growth in VERO cells was inhibited by ribavirin, by boceprevir and by a combination of the two molecules at non-cytotoxic concentrations, as evaluated by end-point viral titration in cell monolayers and by quantification of viral RNA using quantitative RT-PCR. By end-point titration, a statistically significant reduction in CDV replication was observed only using ribavirin and boceprevir in combination. By quantitative RT-PCR, a significant reduction of viral growth was observed either in cells treated with ribavirin or boceprevir or with both the two molecules. The association of ribavirin or boceprevir was able to decrease CDV growth by up to 3.4458 logs with respect to untreated infected cells, chiefly at the highest virus dilutions. The results obtained in this study may constitute an important basis for the development of CDV therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

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Chien, Cheng-Hung; Lin, Chih-Lang; Hu, Ching-Chih; Chang, Jia-Jang; Chien, Rong-Nan

2015-12-01

Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

IFN-λ: A New Class of Interferon with Distinct Functions-Implications for Hepatitis C Virus Research

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Bing Liu

2015-01-01

Full Text Available Pegylated interferon-α and ribavirin (PEG-IFN/RBV is widely used to treat chronic hepatitis C virus infection with notorious adverse reactions since the broad expression of IFN-α receptors on all nucleated cells. Accordingly, a Type III IFN with restricted receptors distribution is much safer as an alternative for HCV therapy. In addition, single nucleotide polymorphisms (SNPs near the human IFN-λ3 gene, IL-28B, correlate strongly with the ability to achieve a sustained virological response (SVR to therapy with pegylated IFN-α plus ribavirin in patients infected with chronic hepatitis C. Furthermore, we also discuss the most recent findings: IFN-λ4 predicts treatment outcomes of HCV infection. In consideration of the apparent limitations of current HCV therapy, especially high failure rate and universal side effects, prediction of treatment outcomes prior to the initiation of treatment and developing new alternative drugs are two important goals in HCV research.

Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed.

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Yoshida, Kanako; Hai, Hoang; Tamori, Akihiro; Teranishi, Yuga; Kozuka, Ritsuzo; Motoyama, Hiroyuki; Kawamura, Etsushi; Hagihara, Atsushi; Uchida-Kobayashi, Sawako; Morikawa, Hiroyasu; Enomoto, Masaru; Murakami, Yoshiki; Kawada, Norifumi

2017-05-03

We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients. During the median follow-up period of 64 weeks, the RAS at D168 became less dominant in 9 of 16 patients. Among 25 DCV/ASV failures, RASs at D168, L31, and Y93 were found in 57.1%, 72.2%, and 76.9%, respectively. NS5A deletions were detected in 3 of 10 patients treated previously with SMV/PEG-IFN/RBV. The number of RASs in the breakthrough patients exceeded that in relapsers (mean 3.9 vs. 2.7, p < 0.05). RAS at D168 in NS3/4A became less dominant in 6 of 15 patients within 80 weeks. Y93H emerged at the time of relapse, then decreased gradually by 99% at 130 weeks post-treatment. Emerged RASs were associated with the clinical course of treatment and could not be detected during longer follow-up.

[Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C].

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Pizarro, Carolina; Venegas, Mauricio; Hola, Karen; Smok, Gladys; Brahm, Javier

2011-06-01

The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. To report our experience in the treatment of chronic hepatitis C. Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg/day. Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. Twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that influenced the response to treatment. Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.

Concurrent autoimmune hepatitis and grave's disease in hepatitis C during pegylated interferon α-2a and ribavirin therapy.

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Trikudanathan, Guru V; Ahmad, Imad; Israel, Jonathan L

2011-01-01

Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, and liver biopsy findings. It was confirmed by positive response to steroid challenge and was assessed according to the international AIH scoring system. Based on the previous case reports, we review the existing literature. Clinicians should be aware of the possibility of multiple autoimmune disorders during interferon-based therapy for chronic hepatitis.

Ribavirin: recent insights into antiviral mechanisms of action.

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Reyes, G R

2001-09-01

Ribavirin, a nucleoside analog, used in combination with interferon-alpha (IFN alpha) results in a substantial improvement in the sustained virologic response in chronic hepatitis C. Identified antiviral mechanisms of action for ribavirin include: (i) inhibition of viral encoded polymerases; (ii) inhibition of genomic RNA capping; and (iii) inhibition of cellular encoded enzymes that control de novo synthesis of purine nucleosides. More recently, ribavirin has been shown to engender a bias toward helper T-cell (CD4+) type 1 (Th1) cytokine responses in models of immunity. Recent detailed analysis has also shown that ribavirin can be utilized and incorporated by the polio viral polymerase into genomic and antigenomic transcripts, and is capable of base pairing with either UMP (uridine monophosphate) or CMP (cytidine monophosphate). This results in ribavirin-mediated mutagenesis of the viral genome and has the potential to push the virus beyond tolerable set points in its mutation rate, leading to an overall reduced fitness of the viral population. Of the many mechanisms of action demonstrated for ribavirin, the current clinical trials of selective inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors and immunomodulating agents in hepatitis may facilitate our understanding of what activity (if any) predominates when ribavirin is used in combination with IFN alpha.

Comparative therapeutic response to pegylated interferon plus ribavirin versus interferon alpha-2b in chronic hepatitis C patients

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Ali, S.; Nazir, G.; Khan, S.A.; Fatima, F.; Iram, S.

2010-01-01

Background: Hepatitis C is an epidemic worldwide since discovery in 1989. Conventional interferon alpha-2b plus Ribavirin therapy was started in 1998 but over all sustained viral response (SVR) rates are much below the desired rates to eradicate the diseases and stopping its epidemic. This study was conducted to access the therapeutic and cost-effectiveness of long acting pegylated interferon alpha-2b plus Ribavirin therapy verses conventional interferon alpha-2b plus Ribavirin. Methods: This comparative study was done at PAF Hospital Shorkot Cantt from July 2005 to July 2008. One hundred anti-HCV positive patients were selected randomly for the study according to willingness due to cost afford ability of the patients for conventional interferon. Group-A was labelled as pegylated interferon alpha-2b plus Ribavirin group, and Group-B interferon alpha-2b plus Ribavirin group. Both groups were given treatment for 24 weeks. Early virological response (EVR) was accessed at 12 weeks of the treatment. Sustained virological response (SVR) in both the groups was done at 24 week during the treatment and 6 monthly after treatment for 2 years. Initially non-responders and relapsed patients within 2 years of treatment were re-treated for 24 weeks with the same treatment. In both groups non-responders and relapsed patients were labelled as resistant patients. Both groups were followed with same protocol for 2 years. Results: Out of 100 patients included in the study, 34% were females and 66% were males. Group-A patients over all showed 94% SVR as compare to 80% in Group-B in 2 year follow-up. Group-A showed 6% resistant patients as compare to Group-B (20%). Conventional interferons were better tolerated. Higher incidence of side-effects was seen in Group-A. Conclusion: Pegylated interferon plus Ribavirin showed 94% SVR in 2 years. Pegylated interferon plus Ribavirin is the treatment of choice.

[Autoimmunity in children with chronic hepatitis C treated with interferon alpha and ribavirin].

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Gora-Gebka, Magdalena; Liberek, Anna; Bako, Wanda; Raczkowska-Kozak, Janina; Sikorska-Wisniewska, Grazyna; Korzon, Maria

2004-01-01

The role of interferon alpha or the virus itself in the pathogenesis and the risk of autoimmunological disorders in patients infected with HCV, still remain unknown, especially in children. The aim of the study was to evaluate the incidence of autoantibodies and the risk of autoimmunological disorders in children with chronic hepatitis C, treated with interferon alpha and ribavirin in the Department of Paediatrics, Paediatric Gastroenterology and Oncology in Gdansk. In the studied group of 12 patients, in 4 cases autoantibodies were present in low titers prior to the treatment and they had no prognostic value for the response to the therapy or the risk of autoimmunological disorders. Positive response for the treatment was achieved in 4 cases; in 3 cases indications for discontinuation of the therapy were established. During the therapy with interferon alpha and ribavirin, in 2 children elevation of serum titers of antibodies to liver-kidney microsome type 1 (anti-LKM1) (> 1:640) with normal gammaglobulin levels was noted. In none of the children autoimmunological disorders were observed.

Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

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Ružić Maja

2010-01-01

Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

Ribavirin monotherapy for chronic hepatitis C

DEFF Research Database (Denmark)

Brok, J; Gluud, L L; Gluud, C

2005-01-01

Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients.......Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients....

Hepatocellular Carcinoma after Sustained Viral Response to Interferon and Ribavirin Therapy in Cirrhosis Secondary to Chronic Hepatitis C

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Khokhar, N.; Qureshi, M.U.; Niazi, T.K.

2013-01-01

Objective: To determine the frequency of development of hepatocellular carcinoma in patients with chronic liver disease secondary to hepatitis C who had achieved sustained virological response with Interferon and Ribavirin therapy. Study Design: Retrospective descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012. Methodology: Hepatitis C related chronic liver disease patients who were treated with interferon and ribavirin, after they achieved sustained virological response, they were followed for a mean of 42 A+- 17 months. During this time, development of hepatocellular carcinoma was ascertained. All underwent surveillance with alpha-feto-protein and ultrasonography every 6 months. Results: Out of the 58 patients who had achieved sustained virological response, 3 developed hepatocellular carcinoma after a mean follow-up of 38 A+- 14 months. It was multifocal in 2 cases and was single lesion in the 3rd. Two patients ultimately died, one with upper GI bleeding and the other with hepatic encephalopathy, while 3rd patient with single lesion is still surviving. Conclusion: Three out of 58 patients of hepatitis C related chronic liver disease developed hepatocellular carcinoma during follow-up in patients who had achieved sustained virological response. These patients need closer follow-up, for development of complications, even if they have achieved sustained viral response. (author)

Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin.

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Cuevas, José Manuel; Torres-Puente, Manuela; Jiménez-Hernández, Nuria; Bracho, María Alma; García-Robles, Inmaculada; Wrobel, Boris; Carnicer, Fernando; del Olmo, Juan; Ortega, Enrique; Moya, Andrés; González-Candelas, Fernando

2008-08-26

We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective pressures.

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results.

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Bichoupan, Kian; Tandon, Neeta; Crismale, James F; Hartman, Joshua; Del Bello, David; Patel, Neal; Chekuri, Sweta; Harty, Alyson; Ng, Michel; Sigel, Keith M; Bansal, Meena B; Grewal, Priya; Chang, Charissa Y; Leong, Jennifer; Im, Gene Y; Liu, Lawrence U; Odin, Joseph A; Bach, Nancy; Friedman, Scott L; Schiano, Thomas D; Perumalswami, Ponni V; Dieterich, Douglas T; Branch, Andrea D

2017-11-12

To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response - the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response (SVR) 12] - were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression. SVR12 rates were as follows: 86% (95%CI: 80%-91%) among 178 patients on SMV/SOF ± RBV; 62% (95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78% (95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR12 were $174442 (standard deviation: ± $18588) for SMV/SOF ± RBV; $223003 (± $77946) for SOF/RBV; and $126496 (± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio (OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin (OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR12 (OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. SVR12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype

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Motomura Takashi

2012-11-01

Full Text Available Abstract Background IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined. Methods Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group and 90 who did not (non-Spx group were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15 and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen. Results Sustained virological response (SVR rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3% and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P 3/μl vs 168.7 × 103/μl, P Conclusions IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.

Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin.

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José Manuel Cuevas

2008-08-01

Full Text Available We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective pressures.

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges

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Ali, Muhammad; Afzal, Samia; Zia, Asad; Hassan, Ahmed; Khalil, Ali Talha; Ovais, Muhammad; Shinwari, Zabta Khan; Idrees, Muhammad

2016-01-01

Abstract Background: The estimated hepatitis C virus (HCV) carriers are approximately 10 million in Pakistan which usually progresses to chronic hepatitis, with rare cases of spontaneous viral eradication. The present article reviews the treatment status of HCV infection in Pakistani population and various factors associated with the treatment response rates. Methods: Literature on anti-HCV therapy was searched in PubMed, Google Scholar and PakMediNet. Thirty three different studies representing different geographic regions of Pakistan published from 2002 to 2016 were included in the present review. Weighted mean, standard error estimates (SE) and standard deviation (SD) were determined for each population group. Results: Mean value for sustained virological response (SVR) for standard IFN plus ribavirin (RBV) combination therapy was 68.38% ± 14.13% (range 33.8%–87.10%; SE 3.08) and pegylated-IFN plus RBV combination therapy 64.38% ± 8.68% (range 55.0%–76.00%; SE 3.88). The lowest value for SVR has been reported to be 24.3% (for genotype 1; administering INF-α 2b 3MU 3 times/week and RBV 1000–1200 mg/day for 48 weeks) while highest of 87.5% (genotype 3a; INF-α 2a 3MU 3 times/week and RBV 1000–1200 mg/day for 24 weeks). The mean value for rapid virological response (RVR) was found to be 48.18% ± 29.20% (SE 9.73). As PEG-interferon and direct acting antivirals (DAAs) are relatively expensive, interferon-alfa (IFN-α) and RBV combination therapy have been used widely to treat HCV infected patients in Pakistan for the last one and half decade. On average, 2.45% of the patients discontinued treatment due to severe side effects. Conclusion: We encourage further studies on understanding host and viral factors associated with specific focus on harder to treat viral variants (relapsers and nonresponders). These variants are currently rising in the country. PMID:27977575

The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.

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Czarny, Piotr; Merecz-Sadowska, Anna; Majchrzak, Kinga; Jabłkowski, Maciej; Szemraj, Janusz; Śliwiński, Tomasz; Karwowski, Bolesław

2017-07-01

Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.

Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response.

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Bichoupan, Kian; Martel-Laferriere, Valerie; Sachs, David; Ng, Michel; Schonfeld, Emily A; Pappas, Alexis; Crismale, James; Stivala, Alicia; Khaitova, Viktoriya; Gardenier, Donald; Linderman, Michael; Perumalswami, Ponni V; Schiano, Thomas D; Odin, Joseph A; Liu, Lawrence; Moskowitz, Alan J; Dieterich, Douglas T; Branch, Andrea D

2014-10-01

In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR. © 2014 by the American Association for the Study of Liver Diseases.

The role of pharmacogenetics in the treatment of chronic hepatitis C infection.

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Kawaguchi-Suzuki, Marina; Frye, Reginald F

2014-02-01

Hepatitis C virus (HCV) chronically infects 170 million people worldwide. Until recently, combination therapy with peginterferon-α (pegIFN) and ribavirin (RBV) has been the standard of care. However, for many patients, especially those infected with the most common HCV genotype 1 (HCV-1), this treatment has resulted in unsatisfactory treatment response rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. Genetic variation in the interleukin 28B (IL28B) gene is the major determinant of treatment response, a finding that has been replicated in multiple independent cohorts. This review focuses on the association between pharmacogenetics and conventional pegIFN/RBV therapy in patients infected with HCV non-genotype 1; patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. We also review the pharmacogenetic data for boceprevir and telaprevir triple therapy in patients with HCV-1 infection, as well as viral genomic polymorphisms and genetic variants that may protect against anemia. Pharmacogenetic information offers a personalized medicine approach to help clinicians and patients make better informed decisions to maximize response and minimize toxicity for the treatment of chronic HCV infection. © 2013 Pharmacotherapy Publications, Inc.

Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis.

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Zhifang Jia

Full Text Available Many studies have been published on the association between single nucleotide polymorphisms (SNP near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN and ribavirin (RBV in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method.Association studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software.Thirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80 compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28 or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90. However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV.Polymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult-to-treat genotype 1 or 4 HCV.

Interferon-Free Hepatitis C Treatment before and after Liver Transplantation: The Role of HCV Drug Resistance

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Bruno Roche

2015-09-01

Full Text Available Hepatitis C virus (HCV infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection progressing to cirrhosis within five years in 20% to 30% of them. Obtaining a sustained virological response (SVR greatly improves overall and graft survival. Until 2011, standard antiviral therapy using PEGylated interferon (PEG-IFN and ribavirin (RBV was the only effective therapy, with an SVR rate around 30% in this setting. For patients infected with genotype 1, first generation NS3/4A protease inhibitors (PIs, boceprevir (BOC or telaprevir (TVR, associated with PEG-IFN and RBV for 48 weeks have increased the SVR rates to 60% in non-transplant patients. However, tolerability and drug-drug interactions with calcineurin inhibitors (CNI are both limiting factors of their use in the liver transplant setting. Over recent years, the efficacy of antiviral C therapy has improved dramatically using new direct-acting antiviral (DAA agents without PEG-IFN and/or RBV, leading to SVR rates over 90% in non-transplant patients. Results available for transplant patients showed a better efficacy and tolerability and less drug-drug interactions than with first wave PIs. However, some infrequent cases of viral resistance have been reported using PIs or NS5A inhibitors pre- or post-LT that can lead to difficulties in the management of these patients.

Simultaneous determination of ribavirin and ribavirin base in monkey plasma by high performance liquid chromatography with tandem mass spectrometry.

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Li, Wenkui; Luo, Suyi; Li, Shaoyong; Athill, Lawrence; Wu, Amy; Ray, Tapan; Zhou, Wei; Ke, June; Smith, Harold T; Tse, Francis L S

2007-02-01

For the first time, a liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the simultaneous determination of ribavirin and rabavirin base was developed and validated over the concentration range of 10-5,000 ng/ml, respectively, using a 0.025 ml monkey plasma sample. Ribavirin, ribavirin base, and the internal standards were extracted from monkey plasma via protein precipitation. After evaporation of the supernatant, the extract was reconstituted with 5% methanol (containing 0.1% formic acid) and injected onto the LC-MS/MS system. Optimum chromatographic separation was achieved on a Waters Atlantis dc18 (150 mm x 2.1mm, 5 microm) column with mobile phase run in gradient with 100% water containing 0.5% formic acid (A) and 90% acetonitrile (containing 0.5% formic acid (B). The flow rate was 0.4-0.6 ml/min with total cycle time of approximately 7.0 min. Post-column addition of acetonitrile (containing 0.1% formic acid) at 0.3 ml/min was used to increase the ionization efficiency in the MS source. The method was validated for sensitivity, linearity, reproducibility, stability and recovery. Lack of adverse matrix effect and carry-over was also demonstrated. The intra-day and inter-day precision and accuracy of the quality control (QC) samples were <9.0% relative standard deviation (R.S.D.) and 10.8% bias for ribavirin, and 10.3% R.S.D. and 11.3% bias for ribavirin base. The current specific, accurate and precise assay is useful in support of the toxicokinetic and pharmacokinetic studies of these compounds.

Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis

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G Gail

2010-07-01

Full Text Available Abstract Background Crimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common. Methods We carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method. Results 21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33. Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence; but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence. Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported. Conclusions No clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality

The effectiveness of different antiviral treatment regimens in patients with chronic hepatitis C infected with genotype 3 virus

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E.V. Riabokon

2018-02-01

Full Text Available Background. Chronic hepatitis C (CHC remains one of the most urgent problems of modern infectology. In recent years, the principles of antiviral therapy have substantially changed due to the emergence of new drugs with a direct mechanism of action and the development of non-interferon treatment regimens. Two regimens included HCV NS5B polymerase inhibitors were available in Ukraine for treating CHC patients infected with genotype 3 virus. Objective: to analyze the effectiveness of different schemes of antiviral treatment in patients with chronic hepatitis C infected with genotype 3 virus. Materials and methods. The study included 66 patients with CHC infected with genotype 3 virus. All patients underwent study of liver fibrosis degree by the method of fibrotest; in the dynamics, we have tested viral load, liver tests, indicators of complete blood count, functional kidney tests. Antiviral treatment and analysis of its effectiveness were carried out in accordance with the Unified Protocol of the Ministry of Health of Ukraine. Results. According to the results of treating CHC patients infected with genotype 3 virus, high efficacy of both applied schemes of antiviral therapy in clinical practice is shown. A rapid virologic response occurred in 93.5 % of CHC patients treated with peginterferon (peg-IFN α2a + sofosbuvir (SOF + ribavirin (RBV regimen, and in 82.9 % of patients receiving non-interferon therapy with SOF + RBV. The immediate response to treatment was achieved according to treatment regimens in 90.3 and 94.3 % of patients. Sustained virological response at week 24 after antiviral treatment was noted in 87.5 and 91.4 % of patients, respectively. The frequency of virological response to antiviral treatment in CHC patients infected with genotype 3 virus did not depend on the stage of liver fibrosis, either in the use of non-interferon treatment by SOF + RBV scheme, or in the treatment with interferon-containing scheme included the drug with

Pegylated vs. standard interferon in combination with ribavirin for genotype 2 and 3 in chronic hepatitis C: 10 years experience in local population

International Nuclear Information System (INIS)

Sarwar, S.; Khan, A.A.

2011-01-01

To compare the response in patients of chronic hepatitis C of genotype 2 and 3 to standard interferon (IFN) plus ribavirin vs. Pegylated interferon plus ribavirin. Type of Study: Cohort type of case series. Setting: Study was based on 10 years data of patients of hepatitis C treated at Garden Clinic Lahore. Patients and Methods: Patients of chronic hepatitis C of genotype 2 and 3 were included and treated with either standard IFN plus ribavirin or peg IFN plus ribavirin for 6 months. Response to therapy was evaluated with qualitative PCR for end of treatment response(ETR) and sustained viral response (SVR). Both groups of patients were compared using chi square test. Results: Total of 609 patients with mean age 39.8 (+- 9.37) and male to female ratio 1.67 / 1 (381 / 228) were included. Genotype 3 was seen in 587 (96.4%) patients and genotype 2 in 22 (3.6%). Peg IFN plus ribavirin was given to 51 (8.4%) while 558 (91.6%) patients were treated with standard IFN and ribavirin. Biochemical response was noted in 462 (75.9%) while ETR was seen in 514(84.4%) patients. Relapse was noted in 99 (16.3%) patients, while PCR was negative both at end of treatment and 6 months later in 415 (68.7%) of them. Of patients with positive PCR at end of treatment, 38 had negative PCR 6 months later, while 57 still had positive PCR result. Overall sustained viral response (SVR) was 74.4% (453 / 609). SVR in patients receiving peg IFN was 90.19% (46 / 51) which was significantly better (p value 0.007) than 72.93% (407 / 558), for standard IFN and ribavirin. Conclusion: Pegylated IFN plus ribavirin had better response in patients of chronic hepatitis C with genotype 2 and 3 as compared to standard IFN plus ribavirin. (author)

Influence of psychiatric diagnosis on treatment uptake and interferon side effects in patients with hepatitis C.

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Wu, Jing Yuan J; Shadbolt, Bruce; Teoh, Narci; Blunn, Anne; To, Caroline; Rodriguez-Morales, Ilys; Chitturi, Shivakumar; Kaye, Graham; Rodrigo, Kalyana; Farrell, Geoff

2014-06-01

Pegylated-interferon-α/ribavirin (PEG-IFN/RBV) treatment can cure hepatitis C virus (HCV) infection but has frequent neuropsychiatric side-effects. Patients with pre-existing psychiatric illness may not be offered therapy. We established prevalence of self-reported psychiatric comorbidity among HCV-infected patients in a hospital-liver clinic, and determined the impact of such diagnoses on uptake and tolerance to PEG-IFN/RBV. All HCV cases referred for assessment in Australian Capital Territory/surrounding regions April 2004-March 2012 were entered into a clinical database. We conducted univariate and multivariate analyses of variables correlating with uptake of antiviral therapy and frequency of treatment-related side-effects. Of 773 referred patients, 235 (30%) described pre-existing psychiatric illness. Among these, 26% received antiviral therapy, compared with 30% of 538 without psychiatric comorbidity. History of depression (usually validated by liaison psychiatry) was associated with higher incidence of treatment-related neuropsychiatric side-effects (odds ratio 2.79 [1.35-5.70], P schizophrenia: three (11%) received antiviral therapy, compared with 30% admitting depression and 20% with bipolar affective disorder (all assessed by psychiatrist). In most schizophrenia cases, the reason for not offering antiviral treatment was psychological illness, yet none of five treated (these three plus two others in a psychiatric rehabilitation facility) experienced worsening psychiatric symptoms. A history of depression is common with hepatitis C but does not affect initiation of antiviral treatment, despite substantially increased risk of psychiatric side-effects. In contrast, pre-existing schizophrenia appears to influence treatment decisions, despite little evidence that PEG-IFN/RBV exacerbates the psychiatric condition, and well-supervised antiviral therapy can have good outcomes.

Impact of obesity on the bioavailability of peginterferon-α2a and ribavirin and treatment outcome for chronic hepatitis C genotype 2 or 3.

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Åsa Alsiö

Full Text Available BACKGROUND AND AIMS: Having a body mass index above or equal to 30 kg/m(2 in conjunction with chronic hepatitis C virus infection is associated with non-responsiveness to treatment with interferon and ribavirin, but details regarding the mechanisms whereby obesity reduces the efficacy of therapy remain unclear. METHODS: This study evaluated impact of obesity on outcome as well as interferon and ribavirin concentrations following standard-of-care fixed dosing with peginterferon-α2a 180 µg once weekly and ribavirin 800 mg daily among 303 HCV genotype 2/3-infected patients enrolled in the per-protocol analysis of a recently completed phase III trial (NORDynamIC. RESULTS: Patients with BMI ≥30 kg/m(2 showed poorer outcome following 24 weeks of therapy (SVR 62% vs. 89% for BMI ≥30 vs. <30; P = 0.006 along with significantly higher steatosis grade (P = 0.002, HOMA-IR (P<0.0001, triglyceride levels (P = 0.0002, and baseline viral load (P = 0.028. Obesity was also significantly associated with lower plasma interferon concentrations on days 3, 7, and 29 (P = 0.02, P = 0.0017, and P<0.0001, respectively and lower plasma ribavirin concentrations day 29 (P = 0.025, and lower concentration of interferon in turn was associated with a poorer first phase reduction in HCV RNA (P<0.0001. In multivariate analysis, ribavirin concentrations week 12, interferon concentrations day 29, and baseline HCV RNA levels were independent predictors of achieving SVR among patients treated for 24 weeks (n = 140. CONCLUSIONS: Reduced bioavailability of interferon and ribavirin along with higher baseline viral load are dominant risk factors for treatment failure in obese patients with chronic hepatitis C.

Comparative effectiveness and adverse effects of interferon alpha-2b plus ribavirin therapy in hepatitis 'C' for 26 weeks

International Nuclear Information System (INIS)

Ali, S.

2009-01-01

Hepatitis C is major emerging challenge for pathologists and treating physicians all over the world. Already 10 million Pakistani population has become anti-HCV positive. It is not only affecting hepatobiliary system but with passage of time research is revealing that Hepatitis C is going to involve almost every organ of the body. With timely diagnosis and treatment, millions of patients can be saved from morbidity and mortality. The nation has to sacrifice initial economic allocations to avoid later millions of mortalities and greater economic losses on affected patients and to support their families. The objective of this study was to evaluate effectiveness of combine therapy of Hepatitis C in local population of Pakistan. This case series study was done at CMH Okara, Kohat, Abbottabad, and PAF Hospital, Shorkot from August 2000 to August 2009. All 1,000 patients from 10 to 60 years of age, confirmed anti-HCV Positive by ELISA and PCR Positive for HCV RNA, were subjected to Interferon alpha-2b and Ribavirin therapy for similar period of time. Response and adverse affects were observed by clinical examination, blood complete picture including platelet count and ALT fortnightly. PCR for HCV RNA and ultrasound abdomen (hepatobiliary system) was done quarterly during treatment and 6 monthly for 2 years after treatment to review the sustained response and relapse. Over all cure rate after 2 years was 855 (85.5%) excluding the 50 (5%) of initial resistant to one year treatment and 95 (9.5%) re-treated relapse cases. One hundred and forty-five (14.5%) patients were found to be resistant to treatment. Hepatitis C must be treated timely after proper diagnosis. Interferon and Ribavirin combination have shown high 'cure' rate in Hepatitis C. In spite of high cure rate of 85.5% with timely and proper treatment, low socio-economic status is a major problem for poor individuals to get treatment. Preventive aspect must be strictly followed and implemented. (author)

Comparative effectiveness and adverse effects of interferon alpha-2b plus ribavirin therapy in hepatitis 'C' for 26 weeks.

Science.gov (United States)

Ali, Shafqut; Iram, Samia

2009-01-01

Hepatitis C is major emerging challenge for pathologists and treating physicians all over the world. Already 10 million Pakistani population has become anti-HCV positive. It is not only affecting hepatobiliary system but with passage of time research is revealing that Hepatitis C is going to involve almost every organ of the body. With timely diagnosis and treatment, millions of patients can be saved from morbidity and mortality. The nation has to sacrifice initial economic allocations to avoid later millions of mortalities and greater economic losses on affected patients and to support their families. The objective of this study was to evaluate effectiveness of combine therapy of Hepatitis C in local population of Pakistan. This case series study was done at CMH Okara, Kohat, Abbottabad, and PAF Hospital, Shorkot from August 2000 to August 2009. All 1,000 patients from 10 to 60 years of age, confirmed anti-HCV Positive by ELISA and PCR Positive for HCV RNA, were subjected to Interferon alpha-2b and Ribavirin therapy for similar period of time. Response and adverse affects were observed by clinical examination, blood complete picture including platelet count and ALT fortnightly. PCR for HCV RNA and ultrasound abdomen (hepatobilliary system) was done quarterly during treatment and 6 monthly for 2 years after treatment to review the sustained response and relapse. Over all cure rate after 2 years was 855 (85.5%) excluding the 50 (5%) of initial resistant to one year treatment and 95 (9.5%) re-treated relapse cases. One hundred and forty-five (14.5%) patients were found to be resistant to treatment. Hepatitis C must be treated timely after proper diagnosis. Interferon and Ribavirin combination have shown high 'cure' rate in Hepatitis C. In spite of high cure rate of 85.5% with timely and proper treatment, low socio-economic status is a major problem for poor individuals to get treatment. Preventive aspect must be strictly followed and implemented.

Interferon alfa with or without ribavirin for chronic hepatitis C

DEFF Research Database (Denmark)

Kjaergard, L L; Krogsgaard, K; Gluud, C

2001-01-01

To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C.......To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C....

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

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Vogel M

2010-03-01

Full Text Available Abstract Objective This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. Methods Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day for 24 - 48 weeks in one of four treatment arms: HIV-negative (A, HIV-positive without HAART (B and HIV-positive on HAART (C. Patients within arm C were randomized to receive open label either a nucleoside containing (C1 or a nucleoside free HAART (C2. Results 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000. Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708. Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209. Conclusions Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.

A Multicenter Study To Evaluate The Safety And Efficacy Of Heber On (Interferon Alfa-2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Iran

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H. Mirmomen

2005-05-01

Full Text Available Combination therapy with interferon and ribavirin is the most effective treatment for chronic hepatitis C today. The aim of this study was to evaluate the efficacy and safety of thrice-weekly Heberon (interferon alfa-2b in combination with ribavirin as first -line treatment of chronic hepatitis C. Methods: A total of97 treatment-naive patients received Heberon three million units thrice-weekly subcutaneously in combination with ribavirin for 12 months. Serum HCV RNA levels were measured before and during therapy and 6 months after the end of therapy. End-of-treatment and sustained virological responses was defmed as an undetectable HCV-RNA level at the end of treatment, and 6 months after treatment was completed (end of follow-up, respectively. Results: In an intent-to-treat analysis, HCV-RNA was undetectable at the end of treatment in 49.5% of patients. At the end of follow-up, sustained virological response was 36.1 %. Combination treatment was generally well tolerated. Six patients stopped therapy because of side effects: severe cytopenia (n=4, depression (n=1, and hyperthyroidism (n= 1 . Common side effects of therapy include: Flu-like syndrome (85.6%, generalized alopecia (41.2% , injection site inflammation (37.1% , mood changes (36% , anorexia (34% and weight loss (32% . Conclusion: Heberon as an IFN product in combination with ribavirin for treat-ment of patients with chronic hepatitis Cis relatively safe, feasible, and potentially efficacious. It has comparable results in achieving end-of-treatment and sustained virological responses in chronic hepatitis C.

Revisiting policy on chronic HCV treatment under the Thai Universal Health Coverage: An economic evaluation and budget impact analysis.

Science.gov (United States)

Rattanavipapong, Waranya; Anothaisintawee, Thunyarat; Teerawattananon, Yot

2018-01-01

Thailand is encountering challenges to introduce the high-cost sofosbuvir for chronic hepatitis C treatment as part of the Universal Health Care's benefit package. This study was conducted in respond to policy demand from the Thai government to assess the value for money and budget impact of introducing sofosbuvir-based regimens in the tax-based health insurance scheme. The Markov model was constructed to assess costs and benefits of the four treatment options that include: (i) current practice-peginterferon alfa (PEG) and ribavirin (RBV) for 24 weeks in genotype 3 and 48 weeks for other genotypes; (ii) Sofosbuvir plus peginterferon alfa and ribavirin (SOF+PEG-RBV) for 12 weeks; (iii) Sofosbuvir and daclatasvir (SOF+DCV) for 12 weeks; (iv) Sofosbuvir and ledipasvir (SOF+LDV) for 12 weeks for non-3 genotypes and SOF+PEG-RBV for 12 weeks for genotype 3 infection. Given that policy options (ii) and (iii) are for pan-genotypic infection, the cost of genotype testing was applied only for policy options (i) and (iv). Results reveal that all sofosbuvir-based regimens had greater quality adjusted life years (QALY) gains compared with the current treatment, therefore associated with lower lifetime costs and more favourable health outcomes. Additionally, among the three regimens of sofosbuvir, SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype are the most cost-effective treatment option with the threshold of 160,000 THB per QALY gained. The results of this study had been used in policy discussion which resulted in the recent inclusion of SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype in the Thailand's benefit package.

[Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

Science.gov (United States)

Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

2006-02-01

A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

Dynamic contrast-enhanced micro-CT on mice with mammary carcinoma for the assessment of antiangiogenic therapy response

Energy Technology Data Exchange (ETDEWEB)

Eisa, Fabian [University of Erlangen-Nuremberg, Institute of Medical Physics, Erlangen (Germany); University of Erlangen-Nuremberg, Graduate School in Advanced Optical Technologies (SAOT), Erlangen (Germany); Brauweiler, Robert; Hupfer, Martin; Nowak, Tristan; Kalender, Willi A. [University of Erlangen-Nuremberg, Institute of Medical Physics, Erlangen (Germany); Lotz, Laura; Hoffmann, Inge; Dittrich, Ralf; Beckmann, Matthias W. [University of Erlangen-Nuremberg, OB/GYN, University Hospital Erlangen, Erlangen (Germany); Wachter, David [University Hospital Erlangen, Institute of Pathology, Erlangen (Germany); Jost, Gregor; Pietsch, Hubertus [Bayer Pharma AG, Berlin (Germany)

2012-04-15

To evaluate the potential of in vivo dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma. 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined. The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P{sub per}{sup K} = 0.032, P{sub per}{sup rBV} = 0.029), but not for the total and central tumour VOIs (P{sub total}{sup K} = 0.108, P{sub central}{sup K} = 0.246, P{sub total}{sup rBV} = 0.093, P{sub central}{sup rBV} = 0.136). Mean tumour volume was significantly smaller in therapy (P{sub in} {sub vivo} = 0.001, P{sub ex} {sub vivo} = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy. This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response. (orig.)

Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

International Nuclear Information System (INIS)

Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

1981-01-01

Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

Rapid emergence of hepatitis C virus protease inhibitor resistance is expected

Energy Technology Data Exchange (ETDEWEB)

Rong, Libin [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory

2009-01-01

Approximately 170 million people worldwide are infected with hepatitis C virus (HCV). Current therapy, consisting of pegylated interferon (PEG-IFN) and ribavirin (RBV), leads to sustained viral elimination in only about 45% of patients treated. Telaprevir (VX-950), a novel HCV NS3-4A serine protease inhibitor, has demonstrated substantial antiviral activity in patients with chronic hepatitis C genotype 1 infection. However, some patients experience viral breakthrough during dosing, with drug resistant variants being 5%-20% of the virus population as early as day 2 after treatment initiation. Why viral variants appear such a short time after the start of dosing is unclear, especially since this has not been seen with monotherapy for either human immunodeficiency virus or hepatitis B virus. Here, using a viral dynamic model, we explain why such rapid emergence of drug resistant variants is expected when potent HCV protease inhibitors are used as monotherapy. Surprisingly, our model also shows that such rapid emergence need not be the case with some potent HCV NS5B polymerase inhibitors. Examining the case of telaprevir therapy in detail, we show the model fits observed dynamics of both wild-type and drug-resistant variants during treatment, and supports combination therapy of direct antiviral drugs with PEG-IFN and/or RBV for hepatitis C.

Superiority of Interferon-Free Regimens for Chronic Hepatitis C: The Effect on Health-Related Quality of Life and Work Productivity.

Science.gov (United States)

Younossi, Zobair M; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

2017-02-01

Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients.Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy-Fatigue, Chronic Liver Disease Questionnaire- HCV, Work Productivity and Activity-Specific Health Problem) before, during, and after treatment.A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to -24.4% by treatment week 12, up to -8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to -7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs.IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores.

Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

DEFF Research Database (Denmark)

Smit, Colette; Arends, Joop; Peters, Lars

2015-01-01

BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in H...

Combined therapy of interferon plus ribavirin promotes multiple adaptive solutions in hepatitis C virus.

Science.gov (United States)

Cuevas, José M; Torres-Puente, Manuela; Jiménez-Hernández, Nuria; Bracho, María A; García-Robles, Inmaculada; Carnicer, Fernando; Olmo, Juan Del; Ortega, Enrique; González-Candelas, Fernando; Moya, Andrés

2009-04-01

Hepatitis C virus (HCV) presents several regions involved potentially in evading antiviral treatment and host immune system. Two regions, known as PKR-BD and V3 domains, have been proposed to be involved in resistance to interferon. Additionally, hypervariable regions in the envelope E2 glycoprotein are also good candidates to participate in evasion from the immune system. In this study, we have used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples obtained just before initiation of therapy and after 6 or/and 12 months of treatment were available. A range of 25-100 clones per patient, genome region and time sample were obtained. The predominant amino acid sequences for each time sample and patient were determined. Next, the sequences of the PKR-BD and V3 domains and the hypervariable regions from different time samples were compared for each patient. The highest levels of variability were detected at the three hypervariable regions of the E2 protein and, to a lower extent, at the V3 domain of the NS5A protein. However, no clear patterns of adaptation to the host immune system or to antiviral treatment were detected. In summary, although high levels of variability are correlated to viral adaptive response, antiviral treatment does not seem to promote convergent adaptive changes. Consequently, other regions must be involved in evasion strategies likely based on a combination of multiple mechanisms, in which pools of changes along the HCV genome could confer viruses the ability to overcome strong selective pressures. (c) 2009 Wiley-Liss, Inc.

Predominance of hepatitis C virus Q80K among NS3 baseline-resistance-associated amino acid variants in direct-antiviral-agent-naïve patients with chronic hepatitis: single-centre experience.

Science.gov (United States)

Ruggiero, Tina; Proietti, Alex; Boglione, Lucio; Milia, Maria Grazia; Allice, Tiziano; Burdino, Elisa; Orofino, Giancarlo; Bonora, Stefano; Di Perri, Giovanni; Ghisetti, Valeria

2015-11-01

In the era of direct-acting antiviral agents (DAAs), hepatitis C virus (HCV) genotyping tests at baseline are controversial. The HCV NS3-Q80K polymorphism is associated with resistance to the recently approved NS3 inhibitor simeprevir (SMV) when combined with PEG-interferon and ribavirin (PEG-IFN/RBV) and alternative therapy should be considered for patients with baseline Q80K. The aim of this study was to provide an estimate of Q80K prevalence at baseline in a study group of 205 DAA-naïve patients (21% of them with HIV coinfection) using NS3 full-population direct sequencing to detect resistance-associated amino acid variants (RAVs). NS3 RAVs were identified in 56 patients (27.3%). Q80K was the most frequently reported one (41%), in both HIV/HCV-coinfected and HCV-monoinfected patients, but it was only detectable in cases of HCV-subtype 1a infection. Therefore, in clinical practice, an NS3-Q80K genotyping test prior to simeprevir plus PEG-IFN/RBV treatment is highly recommended.

Construindo a interação entre o gerenciamento de projetos e a resource-based view-rbv

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Francisco Carlos Cobaito

2014-08-01

Full Text Available Pode-se considerar que a abordagem da teoria do RBV (Resource-based View, e o ponto de vista da teoria de Gerenciamento de projetos apresentam pressupostos distintos. Enquanto a primeira se volta para o modo como os recursos se comportam para a criação e sustentação de vantagem competitiva, a segunda se dirige aos recursos e competências necessários para maximizar a probabilidade de sucesso de um empreendimento. Ambas, contudo, apoiam-se em pressupostos teóricos que identificam capacidades distintivas e competências essenciais nas organizações. Como objetivo exploram-se os elos entre estas duas teorias. Baseado em um estudo de caso foi possível identificar quais são e como os recursos de valor, sob a ótica da RBV, atuam simultânea e sinergicamente no Gerenciamento de projetos.

Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C

NARCIS (Netherlands)

de Knegt, R. J.; Bezemer, G.; van Gool, A. R.; Drenth, J. P. H.; Hansen, B. E.; Droogleever Fortuyn, H. A.; Weegink, C. J.; Hengeveld, M. W.; Janssen, H. L. A.

2011-01-01

Background Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. Aim To assess the efficacy of prophylactic escitalopram to prevent psychiatric side-effects during peginterferon and

Interleukin28B and inosine triphosphatase help to personalize hepatitis C treatment.

Science.gov (United States)

Tanaka, Yasuhito

2011-01-01

In the therapy using a combination of pegylated interferon-α and ribavirin (PEG-IFN/RBV) for chronic hepatitis C (CHC), approximately 50% of CHC patients infected with high viremia of HCV genotype 1 reached sustained viral response. The recent discovery revealed by a genome-wide association study technology provides the unexpected role of IL28B and inosine triphosphatase (ITPA) in HCV infection. The former single nucleotide polymorphisms (SNPs) around the IL28B gene could improve the diagnostics on the prediction of spontaneous clearance and the response to anti-HCV treatment, suggesting that these findings could be strong evidence to enhance the development of a novel therapeutic strategy and the basic study of IFN-λs. Interestingly, the discovered IL28B SNPs revealed the enigma that the viral clearance rate was dependent on ethnicity. The latter functional SNP in ITPA locus was the most significant SNP associated with RBV-induced anemia as well as IFN-induced thrombocytopenia. Note that severe Hb decline, which is mainly found in ITPA-CC patients, was inversely correlated with platelet reduction, contributing to an association between severe anemia and relative reactive increase in platelet count. These data may provide a valuable pharmacogenetic diagnostic tool for tailoring PEG-IFN/RBV dosing to minimize drug-induced adverse events and for further optimization of clinical anti-HCV chemotherapeutics. Copyright © 2011 S. Karger AG, Basel.

Long-term effect of interferon plus ribavirin on hepatitis B surface antigen seroclearance in patients dually infected with hepatitis B and C viruses.

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Ming-Lun Yeh

Full Text Available BACKGROUND: Interferon-α/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV, but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-α/ribavirin combination therapy in HBV/HCV dually-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Eighty-one patients who received interferon-α/ribavirin combination therapy for 24 weeks with a follow-up period of >24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-of-treatment, respectively. Fifteen (18.5% patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5-5.1 years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR, 95% confidence intervals (CI of 16.6, 1.8-153 and 9.2, 1.4-62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5-745. Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss. CONCLUSIONS: We demonstrated that interferon-α/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCV-infected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were

Peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus

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Gluud, Lise Lotte; Marchesini, Emanuela; Iorio, Alfonso

2009-01-01

OBJECTIVES: The aim of this study was to assess the effects of peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus (HIV). METHODS: Trials were identified through manual and electronic searches. Randomized trials comparing peginterferon plus ribavirin...... with other antiviral treatments for patients with chronic hepatitis C and HIV were included. The primary outcome measure was virological response at the end of treatment and after > or =6 months (sustained). Intention-to-treat meta-analyses including data on all patients who were randomized were carried out....... RESULTS: Seven randomized trials were eligible for inclusion. The patients included had chronic hepatitis C and stable HIV and were not previously treated with interferon or ribavirin (treatment naive). The mean dosages were 180 or 1.5 microg/kg once weekly for peginterferon and 800 mg daily for ribavirin...

Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients.

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D'Avolio, Antonio; De Nicolò, Amedeo; Cusato, Jessica; Ciancio, Alessia; Boglione, Lucio; Strona, Silvia; Cariti, Giuseppe; Troshina, Giulia; Caviglia, Gian Paolo; Smedile, Antonina; Rizzetto, Mario; Di Perri, Giovanni

2013-10-01

Functional variants rs7270101 and rs1127354 of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of no functional rs6051702 polymorphism. Since a simultaneous evaluation of the three ITPA SNPs for hemolytic anemia has not yet been investigated, we aimed to understand the contribution of each SNPs and its potential clinical use to predict anemia in HCV treated patients. A retrospective analysis included 379 HCV treated patients. The ITPA variants rs6051702, rs7270101 and rs1127354 were genotyped and tested for association with achieving anemia at week 4. We also investigated, using multivariate logistic regression, the impact of each single and paired associated polymorphism on anemia onset. All SNPs were associated with Hb decrease. The carrier of at least one variant allele in the functional ITPA SNPs was associated with a lower decrement of Hb, as compared to patients without a variant allele. In multivariate logistic regression analyses the carrier of a variant allele in the rs6051702/rs1127354 association (OR=0.11, p=1.75×10(-5)) and Hb at baseline (OR=1.51, p=1.21×10(-4)) were independently associated with protection against clinically significant anemia at week 4. All ITPA polymorphisms considered were shown to be significantly associated with anemia onset. A multivariate regression model based on ITPA genetic polymorphisms was developed for predicting the risk of anemia. Considering the characterization of pre-therapy anemia predictors, rs6051702 SNP in association to rs1127354 is more informative in order to avoid this relevant adverse event. Copyright © 2013 Elsevier B.V. All rights reserved.

NS5A resistance leading to failure of 24-week therapy with sofosbuvir/ledipasvir and ribavirin for the treatment of hepatitis C genotype 1a infection in a HIV-1 co-infected patient.

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Sevastianova, Ksenia; Dean, Jonathan; Bannan, Ciaran; Coghlan, Miriam; Farrell, Gillian; Murray, Catherine; De Gascun, Cillian F; Bergin, Colm

2016-09-01

Herein we report a previously undescribed case of treatment-emergent non-structural protein 5A (NS5A) resistance mutations, Q30H and Y93C, leading to a failure of 24-week course of sofosbuvir/ledipasvir+ribavirin therapy for the treatment of hepatitis C virus (HCV) genotype 1a in interferon-experienced, human immunodeficiency virus type 1 (HIV-1) co-infected patient with cirrhosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

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Luis Jesuino de Oliveira Andrade

Full Text Available OBJECTIVE: To investigate the frequency of thyroid disorders (TD in patients with chronic hepatitis C before and during interferon-alpha (IFN-α and ribavirin (RIB treatment. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab were systematically tested at entry (m0, week 12 (m3 and week 24 (m6 of treatment. RESULTS: Mean age of the 65 patients (38 females and 27 males was 49.61 ± 11.83 years. Seven (10.76% patients presented baseline thyroid disorders (m0, three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92% patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3. A total of 18 patients (27.69% developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6. The relative risk of developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6, hyperthyroidism 1.2 (95% CI: 1.1 to 1.4, and TPO-Ab positivity 7.6 (95% CI: 3.9 to 14.5. The study showed a significant association between female sex and thyroid disease (p = 0.009. CONCLUSION: Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey

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Orhan Yıldız

2015-09-01

Full Text Available Background: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV for the retreatment of chronic hepatitis C virus (HCV infection without a sustained virological response (SVR prior to PegIFN/RBV treatment has resulted in low success rates. Aims: To investigate the efficacy and safety of telaprevir (TVR in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. Study Design: Multi-center, retrospective, cross-sectional study. Methods: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR, early virological response (EVR, extended rapid virological response (eRVR, and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. Results: The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002. EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001. eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001. The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%; it was 56% in prior null responders and 66.7% in prior partial

Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C

NARCIS (Netherlands)

Knegt, R.J. de; Bezemer, G.; Gool, A.R. van; Drenth, J.P.H.; Hansen, B.E.; Droogleever Fortuyn, H.A.; Weegink, C.J.; Hengeveld, M.W.; Janssen, H.L.

2011-01-01

Aliment Pharmacol Ther 2011; 34: 1306-1317 SUMMARY: Background Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. Aim To assess the efficacy of prophylactic escitalopram to prevent

Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

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Iva Bozic

2015-01-01

Full Text Available Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.

Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

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Bozic, Iva; Savic, Danijela; Jovanovic, Marija; Bjelobaba, Ivana; Laketa, Danijela; Nedeljkovic, Nadezda; Stojiljkovic, Mirjana; Pekovic, Sanja; Lavrnja, Irena

2015-01-01

Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation. PMID:26413464

Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

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Aline Gonzalez Vigani

Full Text Available BACKGROUND: Pegylated interferon (Peg-IFN and standard interferon (IFN play a significant role in the treatment of hepatitis C virus (HCV infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR rates following treatment with biosimilar standard IFN plus ribavirin (RBV versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7% patients with HCV genotype 2 infections. One hundred fourteen (66.3% were treated with biosimilar standard IFN plus RBV, whist 58 (33.7% patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172 patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58 had SVR compared to 49.1% (56/114 among those treated with biosimilar standard IFN plus RBV (p = 0.0001. CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.

Ribavirin: an effective treatment of crimean-congo hemorrhagic fever

International Nuclear Information System (INIS)

Sheikh, A.S.

2004-01-01

Objective: To determine the efficiency of Ribavirin, an anti-viral drug, in patients diagnosed to have CCHF. Patients and Methods: A total of 94 cases were included in the study on high index of suspicion of CCHF. The major criteria of admission were a short history of high-grade fever associated with bleeding from more than one site, i.e., haematemesis, epistaxis etc. the mean age was 34.71 plus minus 12.81 years. All the suspected cases were kept in isolation unit of the hospital and barrier nursing was advised. Results: All the 94 cases were sent to CDC, Atlanta, USA for confirmation and 39 (41.4%) were confirmed to have CCHF. Symptomatic treatment like platelet concentration transfusions, fresh-blood transfusions and antipyretics were given to all cases. Oral Ribavirin was given only to the confirmed cases. It was started in a dose of 2 gm initially, followed by 1 gm 6 hourly for 4 days and then 500 mg 8 hours for 6 days. After a mean period of 2.30 plus minus 0.69 days to treatment with Ribavirin, the clinical as well as the laboratory parameters started improving and returned to normal level after 10 -day course of treatment. Mild anemia and thrombocytosis were seen as adverse effects in some of the patients. Conclusion: For treatment of this fatal disease, we recommended use of oral Ribavirin in all patients diagnosed to have CCHF in the above-mentioned doses, on the basis of our study results.(author)

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

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Debora Lucia Seguro Danilovic

2011-01-01

Full Text Available OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels, which occur despite stable free T4 and TSH levels. A thyroid

The value of some genetic factors for prediction of chronic hepatitis C antiviral treatment effectiveness

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V. M. Mitsura

2014-01-01

Full Text Available Aim: To determine the value of gene polymorphisms of interleukin-28B (IL28B, RNase L, HLA DRB1*1101 and HLADQB1*03 alleles as predictors of antiviral treatment efficacy in patients with chronic hepatitis C (CHC.Material and methods. A total of 156 in-patients with chronic hepatitis C (65.4% men, 62.4% had genotype 1 hepatitis C virus – HCV were studied. The results of treatment with interferon (IFN and ribavirin (RBV were analyzed in 74 patients. Polymerase chain reaction identified single nucleotide polymorphisms (SNP of the gene IL28B 39743165T>G (rs8099917, SNP 39738787C> T (rs12979860, RNase L gene (1385G>A, HLA DRB1*1101 and HLA-DQB1*03 alleles.Results. In patients with HCV genotype 1 mutant alleles were more common in SNP 39743165T>G (p=0.001 and 39738787C>T (p=0.0002 than in patients with other genotypes. Response to therapy IFN/RBV was higher in those with “favorable” TT variant (SNP 39743165T>G and CC (SNP 39738787C>T, in those with their combination virologic response ffect were found according to genes IL28B and RNase L SNP variants, DRB1*1101 and HLA-DQB1*03 alleles.Conclusion. Testing for SNP 39738787C>T of IL28B gene is recommended before starting therapy IFN / RBV for all patients with genotype 1 HCV as a predictor of treatment response. Testing SNP 1385G>A gene RNase L and DRB1*1101, HLA-DQB1*03 alleles has no apparent prognostic value for patients with CHC antiviral therapy.

Environmental exposure of primary care personnel to ribavirin aerosol when supervising treatment of infants with respiratory syncytial virus infections.

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Rodriguez, W J; Bui, R H; Connor, J D; Kim, H W; Brandt, C D; Parrott, R H; Burch, B; Mace, J

1987-01-01

The potential exposure to ribavirin aerosol in the environment was assessed in nurses caring for infants and children with severe lower respiratory tract infections due to respiratory syncytial virus. Ribavirin aerosol was administered via a ventilator, oxygen tent, or oxygen hood. Participants worked directly with infants receiving ribavirin for 20.0 to 35.0 h over a 3-day period. No toxic or adverse effects of ribavirin aerosol were observed in any of the 19 nurses studied, and ribavirin was not detected in erythrocytes, plasma, or urine collected after the potential exposure period. PMID:3662474

Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV.

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Nigel J Stevenson

Full Text Available The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV.

Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis

International Nuclear Information System (INIS)

Airaksinen, Antero; Pariente, Nonia; Menendez-Arias, Luis; Domingo, Esteban

2003-01-01

BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) can be cured of virus by treatment with the antiviral nucleoside analogue ribavirin. To study whether the process involved an increase in the number of mutations in the mutant spectrum of the viral population, viral genomes were cloned from persistently infected cells treated or untreated with ribavirin. An increase of up to 10-fold in mutation frequencies associated with ribavirin treatment was observed in the viral genomes from the treated cultures as compared with parallel, untreated cultures. To address the possible mechanisms of enhanced mutagenesis, we investigated the mutagenic effects of ribavirin together with guanosine, and mycophenolic acid in the presence or absence of guanosine. Changes in the intracellular nucleotide concentrations were determined for all treatments. The results suggest that the increased mutation frequencies were not dependent on nucleotide pool imbalances or due to selection of preexisting genomes but they were produced by a mutagenic action of ribavirin

Ribavirin Treatment of Toga-, Arena- and Bunyavirus Infections in Subhuman Primates and Other Laboratory Animal Species

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1979-09-01

trernd reversed. After 1 hour, only 15 -percent of the la - beled ribavirin was retained by BW-JII cells and only I1 percent at 24 hours. Glial and...days after the cessation of treatment. E. Studies in Subhuman Primates (Intramuscular Administracion of Ribavirin) Rhesus monkeys inoculated with FVF...guinea pigs) ~4AC + + (guinea pigs)+ LAS + + (guinea pigs) + Bunva- RVF +’ + + (mice) + SFS + No model No model MIyxo- Influenza + (mice) + Ribavirin

HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

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Amador-Cañizares, Yalena; Martínez-Donato, Gillian; Álvarez-Lajonchere, Liz; Vasallo, Claudia; Dausá, Mariacarla; Aguilar-Noriega, Daylen; Valenzuela, Carmen; Raíces, Ivette; Dubuisson, Jean; Wychowski, Czeslaw; Cinza-Estévez, Zurina; Castellanos, Marlén; Núñez, Magdalys; Armas, Anny; González, Yaimé; Revé, Ismariley; Guerra, Ivis; Pérez Aguiar, Ángel; Dueñas-Carrera, Santiago

2014-01-01

AIM: To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230. METHODS: CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided. RESULTS: From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response. CONCLUSION: CIGB-230, combined with IFN

IL-10 and IL-28B gene variants as predictors of sustained response to peginterferon and ribavirin therapy in chronic HCV infection.

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Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi

2017-04-05

Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features. Study subjects comprised 120 patients infected with HCV-1b, and treated with Peg-IFN/RBV. Genotyping of six IL-10 promoter variants in the intron region (rs1878672, rs1554286, rs1518111) and promotor region (rs1800872, rs1800871, rs1800896) were done by real-time PCR. Compared to G/G, carriage of IL-10 rs1800896 (-1082A/G) A/A genotype was more frequent in patients with sustained virological response (SVR). The decline in viral load over the first 12weeks of treatment was more pronounced in rs1800896 A/A genotype carriers, compared to G/G genotype carriers, and was irrespective of the treatment dosage. Carriage of rs1800896 A/A genotype was positively associated with improvement in viral load decline, which was simultaneous, with and without carriage of the common favourable IL-28B variant. Carriage of both IL-10 rs1800896 G/G and IL-28B non-favourable genotype was associated with twice the risk of getting slow decline of viral load during treatment. Haploview analysis identified ACGCTA and CCGCTG haplotypes to be linked with excellent PegIFN/RBV cure rate, and complete HCV eradication. On the other hand, ACGCTG and CCGCTA haplotypes were associated with resistance to PegIFN/RBV treatment. IL-10 rs1800896 variant markedly influences the clinical outcome of HCV infection, and is a determinant of the response to HCV treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype

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2012-01-01

Background IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined. Methods Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen. Results Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype. PMID:23145809

Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance

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Kempf, Brian J.; Peersen, Olve B.

2016-01-01

ABSTRACT RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3Dpol, as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3Dpol may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3Dpol-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3Dpol decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3Dpol increased the frequency of recombination. The 3Dpol Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G→A and C→U mutations in viral RNA. We conclude that 3Dpol Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance. IMPORTANCE Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a

Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C.

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Rodriguez-Torres, Maribel; Jeffers, Lennox J; Sheikh, Muhammad Y; Rossaro, Lorenzo; Ankoma-Sey, Victor; Hamzeh, Fayez M; Martin, Paul

2009-01-15

Race has been shown to be a factor in the response to therapy for hepatitis C virus (HCV) infection, and limited data suggest that ethnic group may be as well; however, Latinos and other ethnic subpopulations have been underrepresented in clinical trials. We evaluated the effect of Latino ethnic background on the response to treatment with peginterferon alfa-2a and ribavirin in patients infected with HCV genotype 1 who had not been treated previously. In a multicenter, open-label, nonrandomized, prospective study, 269 Latino and 300 non-Latino whites with HCV infection received peginterferon alfa-2a, at a dose of 180 microg per week, and ribavirin, at a dose of 1000 or 1200 mg per day, for 48 weeks, and were followed through 72 weeks. The primary end point was a sustained virologic response. We enrolled Latinos whose parents and grandparents spoke Spanish as their primary language; nonwhite Latinos were excluded. Baseline characteristics were similar in the Latino and non-Latino groups, although higher proportions of Latino patients were 40 years of age or younger, had a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of more than 27 or more than 30, and had cirrhosis. The rate of sustained virologic response was higher among non-Latino whites than among Latinos (49% vs. 34%, PLatino whites at week 4 (P=0.045) and throughout the treatment period (PLatino or non-Latino background was an independent predictor of the rate of sustained virologic response in an analysis adjusted for baseline differences in BMI, cirrhosis, and other characteristics. Adherence to treatment did not differ significantly between the two groups. The numbers of patients with adverse events and dose modifications were similar in the two groups, but fewer Latino patients discontinued therapy because of adverse events. Treatment with peginterferon alfa-2a and ribavirin for 48 weeks resulted in rates of sustained virologic response among patients

Management of hepatitis C infection in the era of direct-acting antiviral therapy

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Zain, L. H.; Sungkar, T.

2018-03-01

Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

Addition of ribavirin to daclatasvir plus asunaprevir for chronic hepatitis C 1b patients with baseline NS5A resistance-associated variants improved response.

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Hong, Chun-Ming; Liu, Chun-Jen; Yeh, Shiou-Hwei; Chen, Pei-Jer

2017-04-01

Daclatasvir is a nonstructural protein 5A inhibitor with potent activity against hepatitis C virus genotypes 1-6 in vitro, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate, the SVR rate in patients with baseline NS5A-L31/Y93H polymorphisms decreased to around 40%. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important. Whether the addition of ribavirin could improve the SVR rate among this group of patients remains unknown and hence our case series was reported. For six adult chronic hepatitis C 1b patients with a pre-existing NS5A-Y93H (>20%) polymorphism, we added ribavirin (800 mg/d) to daclatasvir/asunaprevir for 24 weeks and followed through 12-weeks post-treatment. Four of these patients received interferon/ribavirin treatment before but relapsed, while the other two were naïve cases. Two of them had liver cirrhosis and one had hepatocellular carcinoma postcurative therapy. The primary efficacy end-point was undetectable hepatitis C virus RNA (hepatitis C virus RNA level ofhepatitis C patients with NS5A-Y93H polymorphism, the addition of ribavirin to daclatasvir/asunaprevir may increase the SVR12 rate with minimal side effects, and thus deserves more comprehensive trials in resource-limited areas. Copyright © 2016. Published by Elsevier B.V.

Counteracting quasispecies adaptability: extinction of a ribavirin-resistant virus mutant by an alternative mutagenic treatment.

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Celia Perales

Full Text Available BACKGROUND: Lethal mutagenesis, or virus extinction promoted by mutagen-induced elevation of mutation rates of viruses, may meet with the problem of selection of mutagen-resistant variants, as extensively documented for standard, non-mutagenic antiviral inhibitors. Previously, we characterized a mutant of foot-and-mouth disease virus that included in its RNA-dependent RNA polymerase replacement M296I that decreased the sensitivity of the virus to the mutagenic nucleoside analogue ribavirin. METHODOLOGY AND PRINCIPAL FINDINGS: Replacement M296I in the viral polymerase impedes the extinction of the mutant foot-and-mouth disease virus by elevated concentrations of ribavirin. In contrast, wild type virus was extinguished by the same ribavirin treatment and, interestingly, no mutants resistant to ribavirin were selected from the wild type populations. Decreases of infectivity and viral load of the ribavirin-resistant M296I mutant were attained with a combination of the mutagen 5-fluorouracil and the non-mutagenic inhibitor guanidine hydrocloride. However, extinction was achieved with a sequential treatment, first with ribavirin, and then with a minimal dose of 5-fluorouracil in combination with guanidine hydrochloride. Both, wild type and ribavirin-resistant mutant M296I exhibited equal sensitivity to this combination, indicating that replacement M296I in the polymerase did not confer a significant cross-resistance to 5-fluorouracil. We discuss these results in relation to antiviral designs based on lethal mutagenesis. CONCLUSIONS: (i When dominant in the population, a mutation that confers partial resistance to a mutagenic agent can jeopardize virus extinction by elevated doses of the same mutagen. (ii A wild type virus, subjected to identical high mutagenic treatment, need not select a mutagen-resistant variant, and the population can be extinguished. (iii Extinction of the mutagen-resistant variant can be achieved by a sequential treatment of a

Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin.

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Barnard, Dale L; Day, Craig W; Bailey, Kevin; Heiner, Matthew; Montgomery, Robert; Lauridsen, Larry; Winslow, Scott; Hoopes, Justin; Li, Joseph K-K; Lee, Jongdae; Carson, Dennis A; Cottam, Howard B; Sidwell, Robert W

2006-08-01

Because of the conflicting data concerning the SARS-CoV inhibitory efficacy of ribavirin, an inosine monophosphate (IMP) dehydrogenase inhibitor, studies were done to evaluate the efficacy of ribavirin and other IMP dehydrogenase inhibitors (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), mizoribine, and mycophenolic acid) in preventing viral replication in the lungs of BALB/c mice, a replication model for severe acute respiratory syndrome (SARS) infections (Subbarao, K., McAuliffe, J., Vogel, L., Fahle, G., Fischer, S., Tatti, K., Packard, M., Shieh, W.J., Zaki, S., Murphy, B., 2004. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in the respiratory tract of mice. J. Virol. 78, 3572-3577). Ribavirin given at 75 mg/kg 4 h prior to virus exposure and then given twice daily for 3 days beginning at day 0 was found to increase virus lung titers and extend the length of time that virus could be detected in the lungs of mice. Other IMP dehydrogenase inhibitors administered near maximum tolerated doses using the same dosing regimen as for ribavirin were found to slightly enhance virus replication in the lungs. In addition, ribavirin treatment seemed also to promote the production of pro-inflammatory cytokines 4 days after cessation of treatment, although after 3 days of treatment ribavirin inhibited pro-inflammatory cytokine production in infected mice, significantly reducing the levels of the cytokines IL-1alpha, interleukin-5 (IL-5), monocyte chemotactic protein-1 (MCP-1), and granulocyte-macrophage colony stimulating factor (GM-CSF). These findings suggest that ribavirin may actually contribute to the pathogenesis of SARS-CoV by prolonging and/or enhancing viral replication in the lungs. By not inhibiting viral replication in the lungs of infected mice, ribavirin treatment may have provided a continual source of stimulation for the inflammatory response

Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection.

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Foster, Graham R; Pianko, Stephen; Brown, Ashley; Forton, Daniel; Nahass, Ronald G; George, Jacob; Barnes, Eleanor; Brainard, Diana M; Massetto, Benedetta; Lin, Ming; Han, Bin; McHutchison, John G; Subramanian, G Mani; Cooper, Curtis; Agarwal, Kosh

2015-11-01

We conducted an open-label, randomized, phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin, with and without peginterferon-alfa, in treatment-experienced patients with cirrhosis and hepatitis C virus (HCV) genotype 2 infection and treatment-naïve or treatment-experienced patients with HCV genotype 3 infection. The study was conducted at 80 sites in Europe, North America, Australia, and New Zealand Patients were randomly assigned (1:1:1) to groups given sofosbuvir and ribavirin for 16 weeks (n = 196); sofosbuvir and ribavirin for 24 weeks (n = 199); or sofosbuvir, peginterferon-alfa, and ribavirin for 12 weeks (n = 197). The primary end point was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (sustained virologic response [SVR12]). From October 2013 until April 2014, we enrolled and treated 592 patients-48 with genotype 2 HCV and compensated cirrhosis who had not achieved SVR with previous treatments and 544 with genotype 3 HCV (279 treatment-naïve and 265 previously treated). Overall, 219 patients (37%) had compensated cirrhosis. The last post-treatment week 12 patient visit was in January 2015. Rates of SVR12 among patients with genotype 2 HCV were 87% and 100%, for those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 94% for those receiving sofosbuvir, peginterferon, and ribavirin for 12 weeks. Rates of SVR12 among patients with genotype 3 HCV were 71% and 84% in those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 93% in those receiving sofosbuvir, peginterferon, and ribavirin. On-treatment virologic failure occurred in 3 patients with HCV genotype 3a receiving sofosbuvir and ribavirin for 24 weeks. The most common adverse events were fatigue, headache, insomnia, and nausea. Overall, 1% of patients discontinued treatment due to adverse events. Among patients with genotype 3 HCV infection, including a large proportion of treatment

Combination of α-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo.

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Chang, Jinhong; Schul, Wouter; Butters, Terry D; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A; Rayahin, Jamie E; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M

2011-01-01

Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. Copyright © 2010 Elsevier B.V. All rights reserved.

Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of Dengue virus infection in vitro and in vivo

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Chang, Jinhong; Schul, Wouter; Butters, Terry D.; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B.; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M.; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A.; Rayahin, Jamie E.; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M.

2010-01-01

Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. PMID:21073903

Combined pegylated interferon and ribavirin for the management of chronic hepatitis C in a prison setting.

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Sabbatani, Sergio; Giuliani, Ruggero; Manfredi, Roberto

2006-08-01

The elevated frequency of chronic hepatitis C virus (HCV) infection found among prison inmates, and the availability of improved pharmacological cure for this potentially life-threatening disorder, make investigations conducted in this somewhat neglected area very relevant, since only a few, open-label experiences have been reported till now. In the metropolitan prison of Bologna (Italy), HCV seroprevalence was found to be over 31% in 2003, so that a pilot feasibility study based on treatment with pegylated interferon plus ribavirin was initiated, after careful counseling carried out by a joint commission of health care personnel of the correctional facility and infectious diseases consultants. Thirty-nine patients were enrolled, and despite expected dropouts due to difficulty in maintaining the same level of counseling pressure over time, and the particularly unfavorable climatic conditions during Summer 2003, a sustained virological response was obtained for 8 out of the 21 patients who remained evaluable after the first three month follow-up, although we need to take into account that a high percentage of subjects (67%) were selected for therapy due to their favorable HCV genotypes (types 2 and 3). Our preliminary experience shows that an intrinsically complicated therapy, such as the administration of pegylated interferon plus ribavirin, can attain a relatively high success rate, even in a very unfavorable and uncomfortable context, such as a prison, where only enforced counseling, active participation of institutional health care operators, and patient's willingness to maintain an elevated level of co-operation and adherence, can overcome most structural and relational difficulties.

Development and validation of an assay for the simultaneous determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography-tandem mass spectrometry.

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Kromdijk, W; Pereira, S A; Rosing, H; Mulder, J W; Beijnen, J H; Huitema, A D R

2013-03-01

This paper describes the development and validation of an assay for the simultaneous quantification of the antiviral and antiretroviral drugs zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography coupled to tandem mass spectrometry. Sample pretreatment consisted of protein precipitation with 0.1% (v/v) formic acid in methanol, evaporation and reconstitution. Chromatographic separation was performed on a Synergy Polar reversed phase C18 column (150 mm × 2.0 mm ID, particle size 4 μm) using a stepwise gradient with 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in methanol at a flow rate of 300 μL/min. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for drug detection and quantification. Isotopically labeled zidovudine, lamivudine, tenofovir and ribavirin were used as internal standards. The method was validated over a clinical range of 20-2500 ng/mL for zidovudine, lamivudine and tenofovir, 4-500 ng/mL for abacavir and emtricitabine and 160-20,000 ng/mL for ribavirin. The inter and intra-assay accuracies and precisions were between -8.47% and 14.2% for zidovudine, emtricitabine and ribavirin. For abacavir, lamivudine and tenofovir, the inter and intra-assay accuracies and precisions at the lower limit of quantification were between -11.0% and 18.3%, whereas at all other levels these accuracies and precisions were between -11.7% and 12.0%. The described method is suitable for the determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma in clinical practice to monitor plasma concentrations in selected cases to optimize therapy. Copyright © 2013. Published by Elsevier B.V.

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis.

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Poordad, Fred; Nelson, David R; Feld, Jordan J; Fried, Michael W; Wedemeyer, Heiner; Larsen, Lois; Cohen, Daniel E; Cohen, Eric; Mobashery, Niloufar; Tatsch, Fernando; Foster, Graham R

2017-10-01

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis. Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported. In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2). This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients. Copyright © 2017 European

Serous Retinal Detachments Complicating Interferon-α and Ribavirin Treatment in Patients with Hepatitis C

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Giulio Modorati

2011-03-01

Full Text Available Purpose: To report the cases of two patients with chronic hepatitis C infection showing serous retinal detachments similar to Vogt-Koyanagi-Harada (VKH disease. Methods: We reviewed the clinical records of two patients who were diagnosed with VKH-like disease during combined interferon-α (IFNα and ribavirin treatment. Results: Interruption of IFNα and ribavirin treatment in association with oral corticosteroids resulted in a favorable visual outcome in the case of diffuse retinal detachment (case 1. On the contrary, visual acuity did not improve when late cicatricial stage disease was already present (case 2. Conclusion: There is increasing evidence of a link between hepatitis C virus infection treated with pegylated IFNα-2b and the development of VKH-like disease. Knowing the potential side effects of IFNα and ribavirin administration is fundamentally important, as is the need to closely follow up those patients that need to undergo this treatment.

Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC of hepatitis C patients during the first 10 weeks of treatment

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Edenberg Howard J

2008-11-01

Full Text Available Abstract Background and Aims This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron™ and ribavirin (administered by weight in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys™ and ribavirin were administered. Methods RNA was isolated from peripheral blood monocytes (PBMC from twenty treatment-naïve patients just before treatment (day 1 and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. Results The expression of many genes differed significantly (p ≤ 0.001 and changed at least 1.5-fold at days 3 (290 probes and 10 (255 probes, but the number dropped at days 6 (165 and 13 (142. Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1, TRAIL, IL1Rα and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1 was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. Conclusion The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our

In Vitro and In Vivo Phlebovirus Inhibition by Ribavirin

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1988-03-01

as x%%eliais oin the encephalutic disease in viaj rechnassociates. Inc. I Rockx ille. Md. i in dry- poxvder mice Indtuced by a neurotropic strain oft...1980. Ribavirin treatment of its capping of messenger RNA. Biochem. Biophys. Res. Com- toga. arena - and bunvavirus infections in subhuman prittiates

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

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Fanny Cosson

2017-04-01

Full Text Available An efficient synthetic pathway leading to two carbonated analogues of ribavirin is described. The key-steps in the synthesis of these ribosyltriazoles bearing a quaternary carbon atom in the 2’-position are an indium-mediated alkynylation and a 1,3-dipolar cyclization.

Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin

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Sperl, Jan; Horvath, Gabor; Halota, Waldemar

2016-01-01

daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA tier 1 safety event. RESULTS: The majority...... the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference...... pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. METHODS: This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once...

EVALUATION OF EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C, CAUSED BY HCV GENOTYPE 6

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D. A. Lioznov

2017-01-01

Full Text Available Objectives: Evaluating the effectiveness of 2 therapeutic schemes for chronic hepatitis C (genotype 6 which combined sofosbuvir and ribavirin, one of them also included pegylated interferon. Materials and methods: The study included 110 patients with chronic hepatitis C (genotype 6, who have undergone antiviral therapy (HTP in Hepatology Clinic inHo Chi Minh City,Vietnamfrom November 2015 to July 2016. 24 patients were treated by Pegylated interferon alfa-2a, ribavirin and sofosbuvir for 12 weeks, 86 patients – by sofosbuvir and ribavirin for 24 weeks. Non-interferon regimen was administered primarily to patients with contraindications to the use of interferon. To monitor the effectiveness of antiviral therapy, quantification of HCV RNA in serum was performed by PCR prior to treatment, at 4th, 12th or 24th week (depending on the observation group from the starting of treatment and at 12th, 24th week after completion of treatment. Results: All patients, who were treated with pegylated interferon, ribavirin and sofosbuvir, completed the full course of treatment and 100% of them are registered with sustained virological response at 12th and 24th week after the end of antiviral therapy (SVR-12 and SVR-24, respectively. In the group of patients, who treated with ribavirin and sofosbuvir, 97,7% of patients completed full course of treatment (SVR-12 was registered in 93% of patients, and SVR-24 – in 91,9% of patients. Of 75 patients without a history of HCC, SVR24 was registered in 74 people (98,7%, of 11 patients with HCC – in 5 patients (45,5%. SVR-24 was registered in 98% of patients with cirrhosis (F4 without HCC. Conclusion: The results can serve as a justification for the use of these schemes of antiviral therapy for special groups of patients and/or conditions when it is impossible to follow the latest recommendations, which will help to expand the access of patients to effective antiviral therapy for chronic hepatitis C.

A serial ¹⁸FDG-PET study of a patient with SSPE who had good prognosis by combination therapy with interferon alpha and ribavirin.

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Ohya, Takashi; Yamashita, Yushiro; Shibuya, Ikuhiko; Hara, Munetsugu; Nagamitsu, Shinichiro; Kaida, Hayato; Kurata, Seiji; Ishibashi, Masatoshi; Matsuishi, Toyojiro

2014-07-01

We describe a 15-year-old girl with subacute sclerosing panencephalitis (SSPE) in stage II who was treated with isoprinosine, intraventricular interferon alpha (IFN-α), and ribavirin for 3 years. She is alive at three years from onset and studies at school with the assistance of a special educational teacher. To assess residual brain function, serial (18)FDG-positron emission tomography (PET) was performed three times to measure cortical metabolism: at onset, a year later, and three years later. At onset, PET study revealed preserved glucose metabolism of the cerebral cortex. In serial PET study, glucose metabolism of the cerebral cortex was also preserved even after three years. Although SSPE is a progressive disease of the neuronal system, and typically leads to death in approximately 2-3 years, the neurological prognosis of our case was good. We consider that combination therapy in the very early stage without hypometabolism in the cerebral cortex may be effective for SSPE. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

A Produção Internacional em RBV: Características Gerais e Tratativa dos Recursos na Pesquisa em Organizações de Menor Porte

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Ricardo Lebbos Favoreto

2014-06-01

Full Text Available Desde a década de 80, a Resource-based View (RBV tem-se destacado como uma das principais correntes da estratégia. O volume e a complexidade da produção intelectual em RBV colocam àquele que se propõe transitar pela teoria o desafio de compreender suas características gerais. Sendo a teoria formatada preponderantemente a partir da análise da grande organização, acresce-se o desafio de entender a tratativa conferida aos recursos na pesquisa em organizações de menor porte. Perscrutando os acervos de alguns dos mais impactantes periódicos internacionais, a pesquisa relatada neste artigo tem por objetivo apresentar indicativos qualificadores e afigurações temáticas da produção em RBV. As análises apoiam-se em dados estatísticos e explorações textuais referentes ao conjunto considerado. Os resultados apontam para a larga prevalência de estudos quantitativos e, como objeto de pesquisa, de grandes organizações. A pesquisa em organizações de menor porte é, na sequência, analisada, e dela são extraídas as diretrizes norteadoras e as tratativas conferidas aos recursos. O artigo contribui, dessa forma, para o deslindamento da configuração da teoria, propondo, concomitantemente, sugestões para sua extensão. DOI:10.5585/riae.v13i2.2115

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

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Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

2008-09-01

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

Randomized, controlled trial of oral ribavirin for Japanese encephalitis in children in Uttar Pradesh, India.

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Kumar, Rashmi; Tripathi, Piyush; Baranwal, Madan; Singh, Sudhakar; Tripathi, Sanjeev; Banerjee, Gopa

2009-02-15

Japanese encephalitis is associated with high rates of mortality and disabling sequelae. To date, no specific antiviral has proven to be of benefit for this condition. We attempted to determine the efficacy of oral ribavirin treatment for reducing early mortality among children with Japanese encephalitis in Uttar Pradesh, India. Children (age, 6 months to 15 years) who had been hospitalized with acute febrile encephalopathy (a syrup through nasogastric tube or by mouth. The primary outcome was early mortality; secondary outcome measures were early (at hospital discharge; normal or nearly normal, independent functioning, dependent, vegetative state, or death) outcome, time to resolution of fever, time to resumption of oral feeding, duration of hospitalization, and late outcome (> or =3 months after hospital discharge). The study was double-blind, and analysis was by intention to treat. A total of 153 patients were enrolled during a 3-year period; 70 patients received ribavirin, and 83 received placebo. There was no statistically significant difference between the 2 groups in the early mortality rate: 19 (27.1%) of 70 ribavirin recipients and 21 (25.3%) of 83 placebo recipients died (odds ratio, 1.10; 95% confidence interval, 0.5-2.4). No statistically significant differences in secondary outcome measures were found. For the dosage schedule used in our study, oral ribavirin has no effect in reducing early mortality associated with Japanese encephalitis. ClinicalTrials.gov identifier: NCT00216268 .

Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

DEFF Research Database (Denmark)

Dore, Gregory J; Lawitz, Eric; Hézode, Christophe

2015-01-01

BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding d...

Predictive value of early viriological response for sustained viriological response in chronic hepatitis c with conventional interferon therapy

International Nuclear Information System (INIS)

Awan, A.; Umar, M.; Khaar, H.T.B.; Kulsoom, A.; Minhas, Z.; Ambreen, S.; Habib, N.; Mumtaz, W.; Habib, F.

2016-01-01

Background: Hepatitis is a major public health problem in Pakistan due to its strong association with liver failure and hepatocellular carcinoma. In Pakistan, conventional interferon therapy along with Ribavirin is favoured especially in Government funded programs for treatment of Hepatitis C, over the more expensive Pegylated Interferon and Ribavirin combination therapy as recommended by Pakistan society of Gastroenterology and GI endoscopy due to its favourable results observed in genotype 3 which is the dominant genotype of this region. Objective of our study was to assess the viriological responses with standard interferon therapy and to determine the predictive values of early viriological response (EVR) for Sustained Viriological Response (SVR) in chronic hepatitis C patients treated with standard interferon therapy. Methods: A cross sectional study was conducted on patients with chronic hepatitis C having received standard interferon and ribavirin therapy for six months. EVR and SVR were noted for analysis. Positive and negative predictive values of EVR on SVR were calculated. Results: Out of the total sample (N=3075), 1946 (63.3 percentage) patients were tested for EVR. 1386 (71.2 percentage) were positive while 560 (28.8 percentage) were negative while 516 (16.8 percentage) were tested for SVR. Two hundred and eighty-five (55.2 percentage) were positive while 231 (44.8 percentage) were negative. EVR and SVR tested were N=117. Positive predictive value of EVR on SVR was 67.1 percentage and negative predictive value was 65.8 percentage. Statistically significant association between EVR and SVR was determined with Chi square statistic of 11.8 (p-value <0.0001). Conclusion: EVR is a good predictor of response of patients to standard interferon and ribavirin therapy. In the absence of an EVR, it seems imperative to stop further treatment. Virilogical responses with conventional interferon therapy are comparable to those of pegylated interferon therapy so

Impact of duration of therapy on side effect profile of anti-HCV ...

African Journals Online (AJOL)

Purpose: To evaluate the plausible risks and adverse effects related to the duration of therapy in hepatitis C (HCV) patients in Lahore, Pakistan. Method: A retrospective observational study involving 250 HCV patients who received combination therapy with ribavirin and interferon was conducted. The patients were ...

Superiority of Interferon-Free Regimens for Chronic Hepatitis C

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Younossi, Zobair M.; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

2017-01-01

Abstract Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs. IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores. PMID:28207507

Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

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Nedeljković Nadežda

2012-01-01

Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

Ribavirin exposure induces histopathological changes in the seminiferous tubules of testes in albino rats

International Nuclear Information System (INIS)

Batool, A.

2013-01-01

Study objectives: The objectives of the study are to describe and compare histopathological changes in the seminiferous tubules of testes of rat, with different doses of Ribavirin at different time intervals. Introduction: The chemical disturbances may affect a vast number of potential sites in male reproductive system as well as its complex hormonal regulation. Testicular toxicity may reduce the fertility of the male. The current study was conducted to evaluate the effects of Ribavirin on the histological structure of seminiferous tubules in the testes of albino rats. Materials and Methods: Seventy two sexually mature adult male albino rats weighing 180-200gms were divided into four groups: A, B, C and D; each group having 18 rats. Ribavirin was administered intraperitoneally in different doses to these groups that were 20mg, 100mg and 200mg/kg body weight, while group A was control. Each group was further divided into three subgroups according to three time points which were selected for sacrifice that were 20th, 40th and 60th day from the last exposure to drug. Six randomly selected rats from each group were sacrificed on every sacrifice time. Results and Conclusion: The seminiferous tubules with degenerative changes like appearance of vacuole and necrotic material were observed in comparison to control groups, on 20th day of sacrifice in all groups. In rats sacrificed on day 40th and 60th, the sign of recovery in the form of regeneration of seminiferous epithelium was observed that was more marked in low dose groups than high dose groups which showed late recovery. We conclude that ribavirin being used as antiviral drug induces reversible degenerative changes in the seminiferous tubules of testes of albino rats. (author)

Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.

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Giulia Marchetti

Full Text Available Microbial translocation (MT through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS, host response to MT (sCD14, CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10 reduction from baseline after 12 weeks of therapy and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy. Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053 and no cirrhosis (p = 0.052. EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively, but similar T-cell activation compared to Non-EVR (Null Responders, NR and Non-SVR (N-SVR subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015. SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014.In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.

A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

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Braun, Dominique L; Rauch, Andri; Aouri, Manel; Durisch, Nina; Eberhard, Nadia; Anagnostopoulos, Alexia; Ledergerber, Bruno; Müllhaupt, Beat; Metzner, Karin J; Decosterd, Laurent; Böni, Jürg; Weber, Rainer; Fehr, Jan

2015-01-01

The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious

Determination of ribavirin in human serum using liquid chromatography tandem mass spectrometry

NARCIS (Netherlands)

van der Lijke, H.; Alffenaar, J.-W. C.; Kok, W.Th.; Greijdanus, B.; Uges, D.R.A.

2012-01-01

A method has been developed for the determination of ribavirin in human serum for therapeutic drug monitoring purposes, using liquid chromatography electrospray ionization mass spectrometry. Separation was obtained with a mobile phase gradient starting and ending in 100% aqueous conditions using a

Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States.

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Saint-Laurent Thibault, Catherine; Moorjaney, Divya; Ganz, Michael L; Sill, Bruce; Hede, Shalini; Yuan, Yong; Gorsh, Boris

2017-07-01

A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients. This study evaluated the cost-effectiveness of DCV + SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer. A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted. DCV + SOF was associated with lower costs and better effectiveness than SOF + RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV + SOF was less costly, but also slightly less effective than SOF + RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV + SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF + RBV. DCV + SOF is a dominant option compared with SOF + RBV in the US for the overall GT 3 HCV patient population.

Hepatitis C Eradication and Improvement of Cryoglobulinemia-Associated Rash and Membranoproliferative Glomerulonephritis with Interferon and Ribavirin after Kidney Transplantation

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Marilyn Zeman

2006-01-01

Full Text Available Postrenal transplant hepatitis C is increasing in frequency due to the high prevalence of hepatitis C among patients with renal failure. Despite this, there is still no standard hepatitis C treatment available for renal transplanted recipients. Combination antiviral hepatitis C therapy, the standard of care in the nontransplant population, is generally avoided because of documented renal graft rejection secondary to interferon treatment. A case of a male patient with postrenal transplant hepatitis C, which was associated with cryoglobulinemia and glomerulonephritis of the graft, is presented. He was treated with standard interferon with ribavirin. Sustained viral clearance was achieved despite ongoing evidence of cryoglobulinemia. Renal function, which had been deteriorating before treatment, improved as evidenced by the stabilization of serum creatinine and marked improvement of proteinuria. In conclusion, in selected patients, combination antiviral therapy may still be a viable option postrenal transplant.

Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve the immunological response in chronic hepatitis C patients.

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Kondo, Yasuteru; Ueno, Yoshiyuki; Wakui, Yuta; Ninomiya, Masashi; Kakazu, Eiji; Inoue, Jun; Kobayashi, Koju; Obara, Noriyuki; Shimosegawa, Tooru

2011-12-01

  The extracellular hepatitis C virus (HCV)-antigen, including HCV-Core protein, can suppress immune cells. Recently, the efficacy of double filtration plasmapheresis (DFPP) for chronic hepatitis C (CHC) was reported. However, the mechanism of efficacy of DFPP might not be only the reduction of HCV but also the effect of immune cells via direct and/or indirect mechanisms. The aim of this study is to analyze the virological and immunological parameters of difficult-to-treat HCV patients treated with DFPP combined with Peg-interferon and RBV (DFPP/Peg-IFN/RBV) therapy.   Twelve CHC patients were enrolled and treated with DFPP/Peg-IFN/RBV therapy. The immunological, virological and genetic parameters were studied.   All patients (4/4) treated with the major IL28B allele (T/T) could achieve complete early virological response (EVR). The amounts of HCV-Core antigen in the peripheral blood of EVR patients treated with DFPP/Peg-IFN/RBV rapidly declined in comparison to those of late virological response (LVR) patients treated with DFPP/Peg-IFN/RBV and EVR patients treated with Peg-IFN and RBV (Peg-IFN/RBV). The amount of IFN-γ produced from peripheral blood gradually increased. On the other hand, the amount of IL10 gradually decreased in the EVR patients. The frequencies of HCV-Core binding on CD3+ T cells rapidly declined in EVR patients treated with DFPP/Peg-IFN/RBV therapy. Moreover, the distributions of activated CD4(+) and CD8(+) T cells and CD16-CD56 high natural killer cells were significantly changed between before and after DFPP.   The rapid reduction of HCV-Core antigens and changes in the distribution of lymphoid cells could contribute to the favorable immunological response during DFPP/Peg-IFN/RBV therapy. © 2011 The Japan Society of Hepatology.

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

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Kamal SM

2014-06-01

Full Text Available Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL

Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

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Luis Jesuíno de Oliveira Andrade

Full Text Available Hepatitis C (HCV is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil.

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Perazzo, Hugo; Jorge, Marcelino Jose; Silva, Julio Castro; Avellar, Alexandre Monken; Silva, Patrícia Santos; Romero, Carmen; Veloso, Valdilea Gonçalves; Mujica-Mota, Ruben; Anderson, Rob; Hyde, Chris; Castro, Rodolfo

2017-11-23

Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. Treatment costs of GT1-HCV patients were PPP$ 43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$ 19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries.

Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir-experienced, NS5A treatment-naïve patients: Findings from two randomized trials.

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Tam, Edward; Luetkemeyer, Anne F; Mantry, Parvez S; Satapathy, Sanjaya K; Ghali, Peter; Kang, Minhee; Haubrich, Richard; Shen, Xianlin; Ni, Liyun; Camus, Gregory; Copans, Amanda; Rossaro, Lorenzo; Guyer, Bill; Brown, Robert S

2018-06-01

We report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens. The RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12 weeks of LDV/SOF or LDV/SOF + RBV. Compensated cirrhotic participants were randomized to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). Both studies used SVR at 12 weeks post-treatment (SVR12) as the primary endpoint. In the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF + RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF + RBV for 12 weeks or LDV/SOF for 24 weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n = 1; GT1a n = 5) and all attained SVR12, with no serious AEs or premature discontinuations. In this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gene expression profiles associated with anaemia and ITPA genotypes in patients with chronic hepatitis C (CH-C).

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Birerdinc, A; Estep, M; Afendy, A; Stepanova, M; Younossi, I; Baranova, A; Younossi, Z M

2012-06-01

Anaemia is a common side effect of ribavirin (RBV) which is used for the treatment of hepatitis C. Inosine triphosphatase gene polymorphism (C to A) protects against RBV-induced anaemia. The aim of our study was to genotype patients for inosine triphosphatase gene polymorphism rs1127354 SNP (CC or CA) and associate treatment-induced anaemia with gene expression profile and genotypes. We used 67 hepatitis C patients with available gene expression, clinical, laboratory data and whole-blood samples. Whole blood was used to determine inosine triphosphatase gene polymorphism rs1127354 genotypes (CC or CA). The cohort with inosine triphosphatase gene polymorphism CA genotype revealed a distinct pattern of protection against anaemia and a lower drop in haemoglobin. A variation in the propensity of CC carriers to develop anaemia prompted us to look for additional predictors of anaemia during pegylated interferon (PEG-IFN) and RBV. Pretreatment blood samples of patients receiving a full course of PEG-IFN and RBV were used to assess expression of 153 genes previously implicated in host response to viral infections. The gene expression data were analysed according to presence of anaemia and inosine triphosphatase gene polymorphism genotypes. Thirty-six genes were associated with treatment-related anaemia, six of which are involved in the response to hypoxia pathway (HIF1A, AIF1, RHOC, PTEN, LCK and PDGFB). There was a substantial overlap between sustained virological response (SVR)-predicting and anaemia-related genes; however, of the nine JAK-STAT pathway-related genes associated with SVR, none were implicated in anaemia. These observations exclude the direct involvement of antiviral response in the development of anaemia associated with PEG-IFN and RBV treatment, whereas another, distinct component within the SVR-associated gene expression response may predict anaemia. We have identified baseline gene expression signatures associated with RBV-induced anaemia and identified

PEGYLATED INTERFERON AND RIBAVIRIN FOR TREATMENT OF RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION: a single-liver transplant center experience in Brazil

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José Huygens Parente GARCIA

2015-09-01

Full Text Available BackgroundTreatment of hepatitis C virus infection in post-transplantation patients is a challenge due to poor tolerance and low success rates.ObjectiveTo determine the response rate to pegylated interferon and ribavirin in post-liver transplant patients with hepatitis C recurrence.MethodsBetween 18 May 2002 and 18 December 2011, 601 patients underwent liver transplantation at our service (Hospital Universitário Walter Cantídio, University of Ceará, 176 (29.2% of whom were hepatitis C virus positive. Forty received antiviral therapy and were included in this cohort study. Twenty-eight (70% completed the treatment protocol, which consisted of pegylated interferon and ribavirin for 48 weeks.ResultsThe sustained virological response rate was 55% according to intention-to-treat analysis. Recipient age and exposure to antiviral drugs prior to liver transplantation were associated with sustained virological response in the multivariate analysis. Patients were followed for 57 months on the average. Survival at 1 and 5 years was 100% in responders, versus 100% and 78%, respectively, in non-responders.ConclusionSustained virological response rates were satisfactory in our series of liver transplantation patients, and decreased with increasing recipient age. Non-exposure to antiviral drugs prior to liver transplantation was positively associated with sustained virological response. The overall survival of responders and non-responders was similar.

Benefit of hepatitis C virus core antigen assay in prediction of therapeutic response to interferon and ribavirin combination therapy.

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Takahashi, Masahiko; Saito, Hidetsugu; Higashimoto, Makiko; Atsukawa, Kazuhiro; Ishii, Hiromasa

2005-01-01

A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.

Daclatasvir and Sofosbuvir With or Without Ribavirin in Liver Transplant Recipients: A Single-Center Real-World Study.

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Mucenic, M; Bandeira de Mello Brandao, A; Marroni, C A; Medeiros Fleck, A; Zanotelli, M L; Kiss, G; Meine, M H; Leipnitz, I; Soares Schlindwein, E; Martini, J; Costabeber, A M; Sacco, F K F; Cracco Cantisani, G P

2018-04-01

Treatment with direct-acting antiviral drugs in interferon-free regimens is currently recommended for viral hepatitis C recurrence after liver transplantation. There are limited data regarding its results in this population, and no optimal treatment scheme has yet been singled out. We report our real-world results in liver transplant (LT) recipients. All patients were hepatitis C virus (HCV) monoinfected and completed a 12-week treatment course, followed 12 weeks later by HCV polymerase chain reaction testing with 12 IU/mL sensibility. Liver fibrosis was graded with the use of biopsies taken <12 months before treatment and stratified as early (0-1) or moderate to advanced (2-4) according to the Metavir score. Median postoperative time was 5.2 years. Genotype 3 was found in 66.7% of the sample. The following regimens were prescribed: daclatasvir-sofosbuvir with (n = 11) or without (n = 28) ribavirin. Genotypes 1 and 3 were evenly distributed between the regimens. Sustained virologic response (SVR) was obtained in 24 out of 28 patients (85.7%) who received daclatasvir-sofosbuvir and in all patients (100%) who received daclatasvir-sofosbuvir-ribavirin (global SVR 89.7%). All patients that failed treatment had genotype 3 HCV. Fibrosis was evaluated in 79.5% of the sample: 48.4% had early and 51.6% had moderate to advanced fibrosis, for which ribavirin was more commonly prescribed (P = .001). The SVR rate in our LT recipients was similar to that previously reported in the literature. The addition of ribavirin to DAA treatment appears to be justified in this population. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute hepatitis B in a patient with OLT during treatment with peg-interferon and ribavirin for hepatitis C recurrence.

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Biliotti, Elisa; Zacharia, Sabu; Grieco, Stefania; Spaziante, Martina; Giusto, Michela; Merli, Manuela; Gallinaro, Valentina; Taliani, Gloria

2012-12-01

The course and outcome of acute viral hepatitis in liver transplanted patients with hepatitis C recurrence are unknown. Here we describe a patient who presented with acute hepatitis B infection while on treatment with peg-interferon and ribavirin for hepatitis C recurrence after liver transplantation. A nucleoside analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV) infection and seroconverted to anti-HBs. In this case, the acute hepatitis B virus (HBV) infection might have contributed to the clearance of HCV, the concomitant immunosuppression might have lead to the slow clearance of HBV infection, and the combined antiviral therapy has helped in the resolution of both infections. Hepatitis B vaccination should be recommended in susceptible patients waiting for liver transplantation.

Case report: Ribavirin and vitamin A in a severe case of measles.

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Bichon, Amandine; Aubry, Camille; Benarous, Lucas; Drouet, Hortense; Zandotti, Christine; Parola, Philippe; Lagier, Jean-Christophe

2017-12-01

Despite a vaccine being widely available, measles continues to occur frequently, with sometimes lethal consequences. The mortality rate reaches 35% and measles represents 44% of the 1.4 million deaths which are due to preventable diseases. Severe forms of measles are reported, mainly in young, unvaccinated adults, and in specific populations. The risk factors for severe measles include no or incomplete vaccination and vitamin A deficiency. Apart from secondary measles-related infections, severe measles is mainly represented by neurological, respiratory, and digestive symptoms. Strengthening the hypothesis that there is a link between vitamin A deficiency and severe measles in this paper we report the case of a 25-year-old unvaccinated man hospitalized for severe and complicated measles. The evolution was good after administration of intramuscular vitamin A as well as intravenous ribavirin. Measles remains a fatal and serious disease. The early use of ribavirin and vitamin A shows significant improvements regarding morbimortality and should be systematic in severe cases. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy

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Badar Sadaf

2011-05-01

Full Text Available Abstract Background Hepatitis C virus roots a chronic liver disease. Currently approved treatment strategy includes administration of alpha interferon and ribavirin combined therapy for 24-48 weeks. One of the predictor of sustained virological response is an early virological response to treatment characterized as rapid response. Hyper variable region 1 (HVR1 of E2 protein is responsible for viral entry and acts as a target for neutralizing antibodies. Any mutation in this region would effect virus interaction with target cell and viral persistence. Methods Thirty one clones of six pre-treatment samples subjected to combination therapy were investigated. Three of the patients were rapid responders (R1, R2 and R3 and two were breakthrough responders (BT1 and BT2. Envelope 2 gene was amplified, cloned and sequenced. Amino acid substitution, frequency, composition and antigenic properties of HVR 1 of E2 protein were studied. Results In both rapid responders (R.R (14 amino acid sites and breakthrough responders (BT.R (13 amino acid sites half of the amino acid sites were either conserved or resistant to any physiochemical change due to amino acid substitution. It also indicated that average composition of hydrophilic and basic amino acids were comparatively lower in rapid responders than other samples affecting probable interaction of virus with target cells. A central non antigenic region was constant among the breakthrough responders but differed in length significantly among rapid responders reflecting the adaptive nature of HVR1 to the immune response. Conclusions We observed that although HVR1is quite variable region in HCV 3a patients responding differently to treatment it still maintains its physiochemical properties for its proper functioning and viability.

Nonarteritic anterior ischemic optic neuropathy associated with interferon and ribavirin in a patient with hepatitis C.

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Sharif, Walid; Sheikh, Khayam; De Silva, Ian; Elsherbiny, Samer

2017-04-01

To report a case of a temporal artery biopsy negative anterior ischemic optic neuropathy associated with a recently completed course of pegylated interferon 2 α with ribavirin for chronic hepatitis C. Despite the early presentation with symptoms and prompt treatment with systemic intravenous steroids the patient experienced deterioration of their optic neuropathy over the following few days. Although nonarteritic anterior ischemic optic neuropathy is a common disorder with known risk factors, the timing of onset of symptoms in our patient was suggestive of a possible etiology related to treatment with ribavirin and interferon 2 α, as found in the previously reported cases. There have been a few reported cases of the association between the use of interferon/ribavirin for treatment of chronic hepatitis with nonarteritic anterior ischemic optic neuropathy. In these cases stopping the drug caused some improvement of symptoms or halting the progression of optic neuropathy. Having reviewed the literature on previous cases, we postulate that there may be a dose related reaction to explain the delay and deterioration of vision in some cases despite stopping the drugs. We also advise that any person who is started on this treatment for chronic hepatitis are appropriately counselled as to the potential optic nerve side effect of the drug, based on the evidence reported in the literature.

Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell lines

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Sappok Anne

2011-12-01

Full Text Available Abstract Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1. The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis. In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines. In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction. Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies.

Hepatitis C treatment among racial and ethnic groups in the IDEAL trial.

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Muir, A J; Hu, K-Q; Gordon, S C; Koury, K; Boparai, N; Noviello, S; Albrecht, J K; Sulkowski, M S; McCone, J

2011-04-01

Previous studies of chronic hepatitis C virus (HCV) treatment have demonstrated variations in response among racial and ethnic groups including poorer efficacy rates among African American and Hispanic patients. The individualized dosing efficacy vs flat dosing to assess optimaL pegylated interferon therapy (IDEAL) trial enrolled 3070 patients from 118 United States centres to compare treatment with peginterferon (PEG-IFN) alfa-2a and ribavirin (RBV) and two doses of PEG-IFN alfa-2b and RBV. This analysis examines treatment response among the major racial and ethnic groups in the trial. Overall, sustained virologic response (SVR) rates were 44% for white, 22% for African American, 38% for Hispanic and 59% for Asian American patients. For patients with undetectable HCV RNA at treatment week 4, the positive predictive value of SVR was 86% for white, 92% for African American, 83% for Hispanic and 89% for Asian American patients. The positive predictive values of SVR in those with undetectable HCV RNA at treatment week 12 ranged from 72% to 81%. Multivariate regression analysis using baseline characteristics demonstrated that treatment regimen was not a predictor of SVR. Despite wide-ranging SVR rates among the different racial and ethnic groups, white and Hispanic patients had similar SVR rates. In all groups, treatment response was largely determined by antiviral activity in the first 12 weeks of treatment. Therefore, decisions regarding HCV treatment should consider the predictive value of the early on-treatment response, not just baseline characteristics, such as race and ethnicity. © 2010 Blackwell Publishing Ltd.

Side effects of antiviral therapy in hepatitis C virus infection-sarcoidosis - case report.

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Teodor, D; Teodor, Andra; Grigore, Lucia; Jugănariu, Gabriela; Dorobăţ, Carmen Mihaela; Miftode, Egidia; Azoicăi, Doina

2012-01-01

Standard therapy in chronic hepatitis C virus infection is still a combination of peginterferon alfa2a/2b and ribavirin for 48 weeks. As of side effects, there are organic side effects, such as hematologic disorders, and functional side effects, reflected in the quality of life of hepatitis C patients. Up to 30% of the patients develop specific side effects such as headache, fever, fatigue. Sarcoidosis, known as a granulomatous disease of uncertain cause, is an uncommon finding in this category of patients. This cause-effect relation is accounted for by the convergent action of peginterferon and ribavirin of stimulating type 1 T helper cells and reducing type 2 helper T cells activation. We present the case of male patient known with chronic hepatitis C who developed pulmonary sarcoidosis following antiviral therapy. The first manifestation of the disease was unexplained fever accompanied by pulmonary tract disease. The diagnosis was established by immunophenotyping in bronchial aspirate

The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin

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Younossi Zobair M

2012-02-01

Full Text Available Abstract Background Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients. Methods Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56 and was correlated with IL28B genotype (IL28B C/C or non-C/C over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP. Pathways were ranked based on number of gene involved separately per each study cohort. Results The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype. Conclusions IL28B CC genotype patients with CH-C show a sustained treatment-induced gene

The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin.

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Younossi, Zobair M; Birerdinc, Aybike; Estep, Mike; Stepanova, Maria; Afendy, Arian; Baranova, Ancha

2012-02-07

Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients. Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort. The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype. IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients

Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

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Galmozzi, E; Facchetti, F; Degasperi, E; Aghemo, A; Lampertico, P

2013-02-01

Recently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan(®) SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs. Copyright © 2012 Elsevier B.V. All rights reserved.

Peginterferon alfa-2a plus ribavirin for hemophilic patients with chronic hepatitis C virus infection in Taiwan

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Jung-An Lin

2014-10-01

Conclusion: Our study shows that the SVR rates are similar in hemophilic and nonhemophilic patients with chronic HCV infection who receive PEG-IFN-α-2a plus RBV in Taiwan. The rate of AEs also resembled other studies in nonhemophilic patients in Taiwan. No patient suffered from severe bleeding. However, large-scale, well-conducted studies are still needed to verify the treatment efficacy and safety.

Gestão do Conhecimento – GC – como recurso estratégico e fonte de Vantagem Competitiva Sustentável – VCS – na perspectiva Resource-based view – RBV – Knowledge Management – KM – used as a strategic resource and source of Sustainable Competitive Advantage – SCA – in the Resource-based view – RBV –

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Virginia Aparecida Castro

2012-06-01

Full Text Available A Gestão do Conhecimento – GC – busca integrar toda a organização ao conhecimento que pode ser criado, compartilhado e armazenado. Desta forma, este trabalho tem por objetivo evidenciar de que maneira a GC é utilizada como recurso estratégico e fonte de Vantagem Competitiva Sustentável – VCS – na perspectiva Resource based view – RBV –. É feito um levantamento na forma de censo junto aos alunos das turmas de pós-graduação lato sensu (MBA da FAGEN – Faculdade de Gestão e Negócios – da UFU – Universidade Federal de Uberlândia –, os quais atuam no mercado como gestores e possuem pelo menos um subordinado sob a sua liderança. Após uma revisão da literatura sobre GC e VCS estruturou-se o instrumento de pesquisa a partir do Diagnóstico de Gestão do Conhecimento criado por Bukowitz e Williams (2002 e do Framework VRIO proposto por Barney (1991,1995. Ao considerar o critério de desempenho global de 55%, o cálculo da média aponta um percentual de 70%. Porém, a GC é utilizada em um nível preliminar, pois nota-se que os gestores necessitam, além de reconhecerem a importância da GC, trabalharem para a sua efetiva implantação. Assim, a GC, alinhada ao plano estratégico global da empresa, poderá ser utilizada como recurso estratégico e fonte de VCS na perspectiva RBV.The Knowledge Management – KM – searches to integrate organization to the knowledge that can be created, shared and stored. This study aims to show how the KM is used as a strategic resource and source of Sustainable Competitive Advantage – SCA – in the Resource based view – RBV – perspective. We made a survey in the form of census with the students of  Master Business Administration – MBA of FAGEN – Faculdade de Gestão e Negócios – da UFU – Universidade Federal de Uberlândia –. This students are managers and have employees with your leadership. After a review of the literature on KM and SCA, we have structured the

Cathodic adsorptive stripping voltammetric determination of Ribavirin in pharmaceutical dosage form, urine and serum

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Ahmed A. Abdel Gaber

2017-05-01

Full Text Available A sensitive, simple and rapid square-wave adsorptive stripping voltammetric method was developed and validated for the determination of Ribavirin in pharmaceutical formulations. The proposed method was based on the electrochemical reduction of Ribavirin at a hanging mercury drop electrode in Britton Robinson buffer at pH 10. A well-defined peak was observed at 880 mV with 30 s of accumulation time and 50 mV of accumulation potential. Under these optimized conditions, the square-wave adsorptive stripping voltammetric peak current showed a linear correlation on drug concentration over the range of 1 × 10−10–2 × 10−7 mol L−1 with a correlation coefficient of 0.9995 for the proposed method. The detection and quantitation limits for this method were 2.02 × 10−10 and 6.80 × 10−10 mol L−1, respectively. The results obtained for intra-day and inter-day precision (as RSD % were between 0.447% and 1.024%. This method was applied successfully for the determination of Ribavirin in its pharmaceutical dosage forms with mean recoveries of 99.68 ± 0.13 with RSD % of 0.81% and 99.20 ± 0.24 with RSD % of 0.49% for two concentrations 5 × 10−9 and 5 × 10−8 mol L−1, respectively for 200 mg capsules. The results obtained from the developed square-wave adsorptive stripping voltammetric method were compared with those obtained by the analytical method reported in the literature.

Onset of Celiac Disease after Treatment of Chronic Hepatitis C with Interferon Based Triple Therapy

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Amandeep Singh

2015-01-01

Full Text Available Background. Patients treated with interferon (IFN based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disease (CD as a result of triple therapy (interferon, ribavirin, and boceprevir for chronic HCV. Case. 53-year-old Caucasian female with past medical history of IV drug abuse was referred for abnormal LFTs. Laboratory data showed HCV RNA of 4,515,392 IU/mL, HCV genotype 1a, with normal LFTs. She was treated with 4 weeks of pegylated interferon alfa-2a plus ribavirin, followed by triple therapy using boceprevir for a total of 28 weeks. Approximately 4 weeks after initiation of triple therapy patient developed loose nonbloody bowel movements and was also found to have anemia. Biopsies from first and second portions of the duodenum were consistent with CD. The patient was treated with a gluten-free diet. Her intestinal symptoms improved and the hemoglobin returned to normal. Conclusion. Chronic HCV patients being treated with interferon alfa can develop celiac disease during or after therapy. For patients with positive autoantibodies, all-oral-IFN-free regimens should be considered. Celiac disease should be considered in patients who develop CD-like symptoms while on and shortly after cessation of interferon alfa therapy.

Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies.

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Mizokami, M; Dvory-Sobol, H; Izumi, N; Nishiguchi, S; Doehle, B; Svarovskaia, E S; De-Oertel, S; Knox, S; Brainard, D M; Miller, M D; Mo, H; Sakamoto, N; Takehara, T; Omata, M

2016-10-01

High rates of sustained virologic response (SVR) has been achieved in Japanese patients with chronic hepatitis C virus (HCV) genotype (GT)1 and GT2 infection treated with ledipasvir/sofosbuvir (LDV/SOF) ±ribavirin (RBV) and SOF+RBV, respectively. We evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS5A and NS5B genes was performed for all GT1 patients. Deep sequencing of NS5A (GT1 only) and NS5B (GT1 and GT2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU/mL). In patients with HCV GT1 infection, 22.3% (GT1a: 2/11; GT1b: 74/330) had ≥1 baseline NS5A RAV. The most frequent NS5A RAVs in GT1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS5A RAVs at baseline, 100% and 97% of patients achieved SVR12, compared with 100% and 99% for those with no NS5A RAVs with LDV/SOF and LDV/SOF+RBV, respectively. All patients with NS5B RAVs at baseline achieved SVR12. Of the 153 patients with GT2 infection (GT2a 60.1%, GT2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS5B RAVs were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV/SOF and SOF+RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT1 and GT2 infection. The presence of baseline NS5A RAVs did not impact treatment outcome in GT1 Japanese patients treated with LDV/SOF for 12 weeks. © 2016 John Wiley & Sons Ltd.

Early gene expression profiles of patients with chronic hepatitis C treated with pegylated interferon-alfa and ribavirin.

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Younossi, Zobair M; Baranova, Ancha; Afendy, Arian; Collantes, Rochelle; Stepanova, Maria; Manyam, Ganiraju; Bakshi, Anita; Sigua, Christopher L; Chan, Joanne P; Iverson, Ayuko A; Santini, Christopher D; Chang, Sheng-Yung P

2009-03-01

Responsiveness to hepatitis C virus (HCV) therapy depends on viral and host factors. Our aim was to assess sustained virologic response (SVR)-associated early gene expression in patients with HCV receiving pegylated interferon-alpha2a (PEG-IFN-alpha2a) or PEG-IFN-alpha2b and ribavirin with the duration based on genotypes. Blood samples were collected into PAXgene tubes prior to treatment as well as 1, 7, 28, and 56 days after treatment. From the peripheral blood cells, total RNA was extracted, quantified, and used for one-step reverse transcription polymerase chain reaction to profile 154 messenger RNAs. Expression levels of messenger RNAs were normalized with six "housekeeping" genes and a reference RNA. Multiple regression and stepwise selection were performed to assess differences in gene expression at different time points, and predictive performance was evaluated for each model. A total of 68 patients were enrolled in the study and treated with combination therapy. The results of gene expression showed that SVR could be predicted by the gene expression of signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signaling-1 in the pretreatment samples. After 24 hours, SVR was predicted by the expression of interferon-dependent genes, and this dependence continued to be prominent throughout the treatment. Early gene expression during anti-HCV therapy may elucidate important molecular pathways that may be influencing the probability of achieving virologic response.

Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C La respuesta inmune T1 inducida durante el tratamiento con PEG-IFNα mαs ribavirina controla la replicaciσn viral en pacientes con hepatitis crónica C

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M. Trapero

2005-07-01

Full Text Available Objectives: to analyze the T1/T2 cytokine profile in CD8 T cells from peripheral blood mononuclear cells from patients with genotype-1 CHC during treatment with pegylated interferon (Peg-IFN α2a plus ribavirin (RBV. To correlate Th1/Th2 balance with virological response. Patients and methods: in this prospective longitudinal study, a total of 28 naïve genotype-1 CHC patients received Peg-IFNα2a (180 µg/week plus RBV (1-1.2 g/day for 48 weeks. All patients (mean age 45 ± 8 years completed treatment and follow-up: 12 (43% achieved a sustained virological response (SVR, 13 relapsed after end of treatment (47%, and only 3 (10% were non-responders. Sixteen healthy controls were also analyzed (mean age 39 ± 17 years. The production of IL-4, IIFNγ, and TTNFα by CD8 T cells was measured by intracytoplasmic detection using flow cytometry in both resting and stimulated cells with a phorbol ester. Statistics: Student's t test for independent values, χ2 test, and ANOVA test were used; relapsers and non-responders were joined to achieve a higher statistical power. Results: at third month during treatment, phorbol ester-stimulated-IL-4 levels tend to be lower in patients who presented with SVR versus those who did not (0.97 vs 2.58; p = 0.1. No statistically significant differences were found in IIFNγ and TTNFα levels at month 3. At EOT, the stimulated-IIFNγ production was significantly higher in patients with SVR (20 vs. 8; p Objetivos: analizar el perfil de citocinas T1/T2 producidas por los linfocitos T CD8+ de sangre periférica en pacientes con hepatitis crónica C (HCC y genotipo 1 durante el tratamiento con interferón pegilado (Peg-IFN α2a y ribavirina (RBV y compararlos con controles sanos. Correlacionar el balance T1/T2 con la respuesta virológica al tratamiento combinado. Pacientes y métodos: en este estudio prospectivo longitudinal se incluyeron 28 pacientes naïve con HCC genotipo 1 tratados con Peg-IFNα2a (180 µg/semana más RBV

Frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin for chronic hepatitis C

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Shakoor, A.; Shafqat, F.; Mehmud, T.H.; Akram, M.; Riaz, S.; Iqbal, Z.; Khan, A.A.

2010-01-01

Large numbers of patients suffering from Chronic Hepatitis C (HCV) are seeking treatment with interferon alpha (IFN) because of significant advances in overall improvement in the course of HCV and its complications. Objectives were to estimate the frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin treatment for chronic hepatitis C. Methods: It was an observational study conducted in the out-patient Department of Gastroenterology Shaikh Zayed Hospital, Lahore during a period of three months, i.e., from September to November 2008. One hundred consecutive patients undergoing interferon alpha/ ribavirin treatment for chronic HCV were included in the study. All patients, irrespective of age, sex or duration of treatment were administered with a check list of common physical complaints and DSM-IV symptoms for Major Depressive Episode. Results: Out of a total of 100 subjects 37 were male and 63 were female. In all, 39 (39%) patients fulfilled the diagnostic criteria of DSM-IV for Major Depressive Episode. Major Depression was more common in female 28 (44.4%) as compared to male 11 (28.7%) patients. Somatic symptoms were common in all the patients but they were reported more frequently by patients with Major Depression compared to those without Major Depression. Myalgias, headache, joint pain, nausea/vomiting, abdominal pain and palpitation were the most common physical symptoms. Conclusion: Major Depression and somatic complaints are a common consequence of interferon alpha/ribavirin treatment for chronic hepatitis C. All patients receiving this treatment should be periodically assessed for the detection of these side effects to promptly address relevant treatment options. (author)

Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients

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Mustafa Mubin

2012-08-01

Full Text Available Abstract Background Hepatitis C virus (HCV infection is one of the leading causes of chronic liver disease (CLD. About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism, may develop in HCV-infected patients although altered alanine amino transferase (ALT enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin. The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy levels in HCV patients in addition to other parameters. Methods 532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP, lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon α plus ribavirin treatment and sustained virologic response (SVR was determined 6–9 months post-therapy. Results Hyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders; 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients. The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients. Conclusion

Stock indexing and Potato virus Y elimination from potato plants cultivated in vitro Indexação de matrizes e eliminação do Potato virus Y em plantas de batata cultivadas in vitro

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Luciana Cordeiro Nascimento

2003-01-01

Full Text Available Potato cultivars (Solanum tuberosum L. have shown degeneration or run out caused by viruses after several cycles of propagation using seed tubers from commercial fields. This work reports the occurrence of single and mixed infections of four potato viruses in Paraíba-Brazil and presents a method for Potato virus Y (PVY elimination, by using thermo-and chemotherapies. Plants of potato cv. Baraka were tested by direct antigen coating ELISA. Antisera against PVY, Potato virus X (PVX, Potato virus S (PVS, and Potato leafroll virus (PLRV were used. Materials with positive reaction to PVY were treated for virus elimination. Single node cuttings (1.0 cm length were excised and inoculated in Murashige & Skoog (MS medium, supplemented with 1.0 mg L-1 of kinetin, 0.001 mg L-1 of naphthalene acetic acid (NAA and 0.1 mg L-1 of gibberellic acid (GA3. The thermotherapy at approximately 37ºC, during 30 and 40 days, resulted in 20.0 and 37.5% PVY elimination, respectively. Chemotherapy was undertaken with Ribavirin (RBV, 5-Azacytidine (AZA, and 3-Deazauridine (DZD. The RBV showed the highest rate of virus eradication, with 55.5% virus-free plants. Simultaneous thermo and chemotherapy had higher efficiency for the elimination of PVY, reaching rates of healthy plants of 83.3% with RBV, 70.0% with AZA, and 50.0% with DZD.Cultivares de batata (Solanum tuberosum L. têm mostrado degenerescência causada por vírus após ciclos sucessivos do uso de tubérculos de campos comerciais como material propagativo. Este trabalho verifica a ocorrência de infecção simples e mista de quatro vírus da batata na Paraíba e apresenta adequação da técnica de cultivo in vitro para obtenção de material livre de Potato virus Y (PVY, incluindo uso de microestacas, termo e quimioterapia. Plantas de batata do cv. Baraka foram submetidas à indexação sorológica pelo teste "direct antigen coating" ELISA. Utilizaram-se antissoros contra o PVY, Potato virus X (PVX, Potato virus

T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen

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Hartling, Hans Jakob; Birch, Carsten; Gaardbo, Julie C

2015-01-01

Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T......-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were...... compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T-cell homeostasis during treatment were...

Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin.

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Jimenez-Sousa, Maria Angeles; Almansa, Raquel; de la Fuente, Concha; Caro-Paton, Agustín; Ruiz, Lourdes; Sanchez-Antolín, Gloria; Gonzalez, Jose Manuel; Aller, Rocio; Alcaide, Noelia; Largo, Pilar; Resino, Salvador; de Lejarazu, Raul Ortiz; Bermejo-Martin, Jesus F

2010-06-01

Hepatitis C virus causes significant morbidity and mortality worldwide. The infection induces up-regulation of cytokine and chemokines commonly linked to the development of cellular and pro-inflammatory antiviral responses. The current standard in hepatitis C treatment consists of combination regimens of pegylated interferon-alpha plus ribavirin. The impact of combined treatment in the host immune response is still poorly understood. In the present study, we profiled 27 cytokines, chemokines and growth factors involved in the innate and adaptive responses to the virus in the serum of 27 hepatitis C virus-infected patients, before and after 12 weeks of combined treatment, and compared them to 10 healthy controls. Hepatitis C virus infection induced not only the secretion of chemokines and cytokines participating in Th1 responses (MIP-1 alpha, IP-10, TNF-alpha, IL-12p70, IL-2), but also cytokines involved in the development of Th17 responses (IL-6, IL-8, IL-9 and IL-17) and two pro-fibrotic factors (FGF-b, VEGF). The most important increases included MIP-1 alpha (4.7-fold increase compared to the control group), TNF-alpha (3.0-fold), FGF-b (3.4-fold), VEGF (3.5-fold), IP-10 (3.6-fold), IL-17 (107.0-fold), IL-9 (7.5-fold), IL-12p70 (7.0-fold), IL-2 (5.6-fold) and IL-7 (5.6-fold). Combined treatment with pegylated interferon-alpha plus ribavirin down-modulated the secretion of key Th1 and Th17 pro-inflammatory mediators, and pro-fibrotic growth factors as early as 12 weeks after treatment initiation. MIP-1 alpha, FGF-b, IL-17 decreased in a more dramatic manner in the group of responder patients than in the group of non-responders (fold-change in cEVR; fold-change in NcEVR): MIP-1 alpha (4.72;1.71), FGF-b (4.54;1.21), IL-17 (107.1;1.8). Correlation studies demonstrated that the decreases in the levels of these mediators were significantly associated with each other, pointing to a coordinated effect of the treatment on their secretion (r coefficient; p value): [ FGF

Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience

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Hernandez, Maria Del Pilar; Vance, Evan; Gilinski, Dani; Youtseff, Helen; Toro, Maribel; Antoine, Marie; Jeffers, Lennox J.; Peyton, Adam

2016-01-01

Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection. One hundred patients with HCV genotype 1 infection were treated between December 2013 and June 2014. Eighty-six patients were treated with sofosbuvir and simeprevir, with or without ribavirin, for 12 weeks; 12 patients were treated with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks; and 2 patients were treated with sofosbuvir and ribavirin for 24 weeks. Overall, treatment was well tolerated and feasible, with compliance rates over 95% in patients treated with all-oral therapy. The sustained virologic response (SVR) rate for sofosbuvir and simeprevir (88.4%) was superior to the rate for sofosbuvir, pegylated interferon, and ribavirin (50.0%). Subgroup analysis showed diminished SVR rates in cirrhotic patients vs noncirrhotic patients. There were no significant differences in SVR when comparing treatment with or without ribavirin or among genotype subtypes. In conclusion, this study demonstrated excellent completion rates for all-oral treatment of veterans with chronic HCV infection. Additionally, treatment was highly effective, nearing a 90% cure rate. Thus, we recommend that the VA health care system continue to incorporate new HCV medications into its formulary so as to expand HCV treatment for US veterans. PMID:27917084

In vitro antiviral efficacy of caffeic acid against canine distemper virus.

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Wu, Zong-Mei; Yu, Zhen-Jiang; Cui, Zhen-Qiang; Peng, Lu-Yuan; Li, Hao-Ran; Zhang, Chun-Lei; Shen, Hai-Qing; Yi, Peng-Fei; Fu, Ben-Dong

2017-09-01

Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC 50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 μg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection. Copyright © 2017. Published by Elsevier Ltd.

Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection

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Hézode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne

2015-01-01

OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30...

Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis.

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Georg Dultz

Full Text Available In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18 ± 2.72 were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240 weeks, ± SD 136 weeks.Eighteen patients (26.5% achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001.Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.

Gene expression profiles associated with depression in patients with chronic hepatitis C (CH-C).

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Birerdinc, Aybike; Afendy, Arian; Stepanova, Maria; Younossi, Issah; Baranova, Ancha; Younossi, Zobair M

2012-09-01

The standard treatment for CH-C, pegylated interferon-α and ribavirin (PEG-IFN + RBV), is associated with depression. Recent studies have proposed a new role for cytokines in the pathogenesis of depression. We aimed to assess differential gene expression related to depression in CH-C patients treated with PEG-IFN + RBV. We included 67 CH-C patients being treated with PEG-IFN+RBV. Of the entire study cohort, 22% had pre-existing depression, while another 37% developed new depression in course of the treatment. Pretreatment blood samples were collected into PAXgene™ RNA tubes, the RNAs extracted from peripheral blood mononuclear cells (PBMCs) were used for one step RT-PCR to profile 160 mRNAs. Differentially expressed genes were separated into up- and down-regulated genes according to presence or absence of depression at baseline (pre-existing depression) or following the initiation of treatment (treatment-related depression). The mRNA expression profile associated with any depression and with treatment-related depression included four and six genes, respectively. Our data demonstrate a significant down-regulation of TGF-β1 and the shift of Th1-Th2 cytokine balance in the depression associated with IFN-based treatment of HCV infection. We propose that TGF-β1 plays an important role in the imbalance of Th1/Th2 in patients with CH-C and depression. With further validation, TGF-β1 and other components of Th1/Th2 regulation pathway may provide a future marker for CH-C patients predisposed to depression.

Inhibition of bovine viral diarrhea virus RNA synthesis by thiosemicarbazone derived from 5,6-dimethoxy-1-indanone.

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Castro, Eliana F; Fabian, Lucas E; Caputto, María E; Gagey, Dolores; Finkielsztein, Liliana M; Moltrasio, Graciela Y; Moglioni, Albertina G; Campos, Rodolfo H; Cavallaro, Lucía V

2011-06-01

In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV).

Meta-analysis of mutations in the NS5A gene and hepatitis C virus resistance to interferon therapy: uniting discordant conclusions

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Schinkel, Janke; Spaan, Willy J. M.; Kroes, Aloys C. M.

2004-01-01

Hepatitis C virus genotype 1B responds poorly to treatment with interferon, in contrast to the more interferon-sensitive genotypes 2 and 3. Studies on combination therapy regimens with PEG-interferon and ribavirin report sustained response rates that generally do not exceed 50%, in contrast to

Cost-effectiveness of elbasvir/grazoprevir use in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States.

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Elbasha, E; Greaves, W; Roth, D; Nwankwo, C

2017-04-01

Among patients with chronic kidney disease (CKD) in the United States, HCV infection causes significant morbidity and mortality and results in substantial healthcare costs. A once-daily oral regimen of elbasvir/grazoprevir (EBR/GZR) for 12 weeks was found to be a safe and efficacious treatment for HCV in patients with CKD. We evaluated the cost-effectiveness of EBR/GZR in treatment-naïve and treatment-experienced CKD patients compared with no treatment (NoTx) and pegylated interferon plus ribavirin (peg-IFN/RBV) using a computer-based model of the natural history of chronic HCV genotype 1 infection, CKD and liver disease. Data on baseline characteristics of the simulated patients were obtained from NHANES, 2000-2010. Model inputs were estimated from published studies. Cost of treatment with EBR/GZR and peg-INF/RBV were based on wholesale acquisition cost. All costs were from a third-party payer perspective and were expressed in 2015 U.S. dollars. We estimated lifetime incidence of liver-related complications, liver transplantation, kidney transplantation, end-stage live disease mortality and end-stage renal disease mortality; lifetime quality-adjusted life years (QALY); and incremental cost-utility ratios (ICUR). The model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV genotype 1 infection and CKD compared with NoTx or use of peg-IFN/RBV. EBR/GZR-based regimens resulted in higher average remaining QALYs and higher costs (11.5716, $191 242) compared with NoTx (8.9199, $156 236) or peg-INF/RBV (10.2857, $186 701). Peg-IFN/RBV is not cost-effective, and the ICUR of EBR/GZR compared with NoTx was $13 200/QALY. Treatment of a patient on haemodialysis with EBR/GZR resulted in a higher ICUR ($217 000/QALY). Assuming a threshold of $100 000 per QALY gained for cost-effectiveness, use of elbasvir/grazoprevir to treat an average patient with CKD can be considered cost

Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

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Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

2012-01-01

Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

Major drivers influencing adherence and quality of life during antiviral triple therapy in patients with chronic hepatitis C

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Suceveanu Andra I.

2016-05-01

Full Text Available Background & Aims. Triple therapy with Peg-IFNs, Ribavirin and protease inhibitors raise the treatment success for hepatitis C up to 83%, but also bring together with the significantly higher rates of sustained virologic response (SVR more side effects, interfering with patient’s quality of life (QoL and work productivity. We aimed to analyze the factors influencing the adherence and the QoL during triple therapy using Peg-IFNs, Ribavirin and protease inhibitors in 50 patients diagnosed with chronic hepatitis C with first line therapy failure. Multivariate Cox proportional hazards regression was used to analyze determinants of retreatment initiation and treatment compliance, according to patient features. Results: We identified as major drivers of retreatment initiation the younger age, the female gender, the urban provenience, the high income, and the psychiatric and alcohol or drugs abuse history. The adherence and the QoL during retreatment therapy were similar, despite the regimen used, and obvious lower in patients with history of previous abandon, drugs and alcohol abuse or hematologic/ psychiatric decompensation. A lower capacity to work and a temporary withdrawal from job necessary to continue the therapy were seen similar in patients taking Boceprevir/Telaprevir. Abandon of therapy without a known reason was more frequent in males, with alcohol and drugs intake history, from rural region, with low income, and with psychiatric disturbances in personal history. Conclusion. Physicians should focus to develop medical strategies or drugs to increase the adherence and to provide a better QoL for patients with chronic hepatitis C making antiviral therapy.

Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study.

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Molina, Jean-Michel; Orkin, Chloe; Iser, David M; Zamora, Francisco-Xavier; Nelson, Mark; Stephan, Christoph; Massetto, Benedetta; Gaggar, Anuj; Ni, Liyun; Svarovskaia, Evguenia; Brainard, Diana; Subramanian, G Mani; McHutchison, John G; Puoti, Massimo; Rockstroh, Jürgen K

2015-03-21

Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1-4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77-91) in patients with genotype-1 HCV, 88% (69-98) in patients with genotype-2 HCV, 89% (81-94) in patients with genotype-3 HCV, and 84% (66-95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67-99] and 91% [81-97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36-100] and 86% [73-94], respectively). There was no emergence of sofosbuvir-resistance mutations

Pegylated interferon fractal pharmacokinetics: individualized dosing for hepatitis C virus infection.

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Jain, Mamta K; Pasipanodya, Jotam G; Alder, Lara; Lee, William M; Gumbo, Tawanda

2013-03-01

Despite recent advances in hepatitis C virus (HCV) therapeutics, the combination of pegylated interferon and ribavirin (PEGIFN/RBV) remains the cornerstone of treatment. Optimization and individualization of PEGIFN dosing could improve outcomes. Week one PEGIFN serum concentrations in 42 HCV genotype 1-infected patients treated with conventional PEGIFN/RBV were analyzed using multicompartmental pharmacokinetic models. For each patient, pharmacokinetic parameter estimates, weight, age, interleukin-28B (IL-28B) single-nucleotide polymorphism, CD4 count, baseline HCV RNA, gender, race, and HIV status were examined using classification and regression tree analysis to identify factors predictive of sustained viral response (SVR). Survival analysis was performed to compare the time to undetectable viral load in patients with and without the highest scoring predictor. PEGIFN concentrations varied at least 87-fold. Pharmacokinetics were best described by a two-compartment model with an 8.4-h absorption lag. Patient weight correlated with PEGIFN systemic clearance based on fractal geometry relationships. SVR was achieved in 36% of patients; a PEGIFN cumulative 1-week area under the curve (AUC) of ≤0.79 mg · h/liter scored highest in predicting poor response, followed by a weight of ≥93.7 kg. Patients with a PEGIFN AUC of >0.79 mg · h/liter achieved undetectable viral load more rapidly than those with a lower AUC (hazard ratio, 1.63; 95% confidence interval, 1.21 to 2.04). PEGIFN exhibits wide pharmacokinetic variability, mainly driven by patient weight, so that the standard dose may not reach levels needed to achieve SVR. Optimizing dose to patient weight and PEGIFN AUC in the first week offers a solution to improve SVR and to potentially shorten duration of therapy.

New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials.

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Lee, L Y; Tong, C Y W; Wong, T; Wilkinson, M

2012-04-01

Hepatitis C virus (HCV) affects approximately 3% of the world population. The current standard of care for treatment of HCV is a combination of pegylated interferon and ribavirin. Approximately 10% of patients will stop treatment and 30% of patients require dose reduction because of side effects. For genotype 1 HCV-infected patients, only 40% of patients will achieve undetectable viral load 26 weeks posttreatment. The objectives of this review were to identify new treatments that are in clinical trials. These include boceprevir and telaprevir which are in routine clinical use and form part of the American Association for the Study of Liver Diseases (AASLD) 2011 guidelines as well as drugs based on observational studies, improving/modifying ribavirin or interferon-based therapies, modifying the host response and finally the use of direct-acting antiviral agents (DAA).   MEDLINE and EMBASE databases were searched from 2008 to 2011 for treatments for hepatitis C. Furthermore, abstracts and poster presentations for the annual European Association Study of the Liver, AASLD, Digestive Disease Week and Asian Pacific Association for the study of the Liver were searched for relevant material. All four classes of DAA; NS3/NS4a serine protease inhibitors, cyclophilin inhibitors, NS5b polymerase inhibitors and NS5a inhibitors, show good success rates. Trials have been performed without ribavirin or interferon and demonstrate good antiviral activity with a decreased side effect profile. Combinations of DAA are a promising area of research with a high success rate. Clinical trials show that future HCV therapy could be personalised, achieve higher success rates with decreased adverse incidents. © 2012 Blackwell Publishing Ltd.

Make or Buy in a Mature Industry? Models of Clientsupplier Relationships under TCT and RBV Perspectives

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Manuel Portugal Ferreira

2010-01-01

Full Text Available In this paper, we use the transaction cost theory [TCT] and the resource-based view [RBV] to discuss three propositions on the models of client-supplier relationships in mature industries. The two theories seem to advance different organizational forms of the client-supplier relationships, and in some instances are contradictory. How should firms organize to prosper and grow, namely in the international markets? Through the case study of three Portuguese packaging firms, with primary (interviews and secondary data, we discuss how the three firms deploy three distinct strategic organization models in a mature industry. One firm utilizes marketbased governance mechanisms, and concentrates its production in a few selected locations. Another firm vertically integrates almost the entire value chain of the product to provide full service to its clients. The third firm operates in a model of integrated outsourcing, with the installation wall to wall with its clients. The clientsupplier models adopted by these firms are based on efficient, stable, and trustworthy relationships that permit them to focus on their core competences and reduce transaction costs. The superior performance of firms requires a proper alignment of hierarchical and relational governance, taking the dimensions of their transactions into consideration.

Insulin resistance and response to telaprevir plus peginterferon alpha and ribavirin in treatment-naive patients infected with HCV genotype 1

NARCIS (Netherlands)

Serfaty, L.; Forns, X.; Goeser, T.; Ferenci, P.; Nevens, F.; Carosi, G.; Drenth, J.P.H.; Lonjon-Domanec, I.; DeMasi, R.; Picchio, G.; Beumont, M.; Marcellin, P.

2012-01-01

OBJECTIVE: Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured

FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC³ program.

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Poynard, Thierry; Munteanu, Mona; Colombo, Massimo; Bruix, Jordi; Schiff, Eugene; Terg, Ruben; Flamm, Steven; Moreno-Otero, Ricardo; Carrilho, Flair; Schmidt, Warren; Berg, Thomas; McGarrity, Thomas; Heathcote, E Jenny; Gonçales, Fernando; Diago, Moises; Craxi, Antonio; Silva, Marcelo; Boparai, Navdeep; Griffel, Louis; Burroughs, Margaret; Brass, Clifford; Albrecht, Janice

2011-02-01

EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p ≤ 0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p ≤ 0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12 weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin.

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Abbate, Isabella; Lo Iacono, Oreste; Di Stefano, Rosa; Cappiello, Giuseppina; Girardi, Enrico; Longo, Roberta; Ferraro, Donatella; Antonucci, Giorgio; Di Marco, Vito; Solmone, Mariacarmela; Craxì, Antonio; Ippolito, Giuseppe; Capobianchi, Maria R

2004-05-01

HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha 2b or STD-IFN alpha 2b plus RBV. HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients. Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.

Inhibition of Bovine Viral Diarrhea Virus RNA Synthesis by Thiosemicarbazone Derived from 5,6-Dimethoxy-1-Indanone▿

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Castro, Eliana F.; Fabian, Lucas E.; Caputto, María E.; Gagey, Dolores; Finkielsztein, Liliana M.; Moltrasio, Graciela Y.; Moglioni, Albertina G.; Campos, Rodolfo H.; Cavallaro, Lucía V.

2011-01-01

In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV). PMID:21430053

Significance of iron reduction for the therapy of chronic hepatitis C

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Nožić Darko

2005-01-01

Full Text Available Background. It has been established that many patients with chronic hepatitis C have elevated serum iron, feritin levels and iron deposits in the liver. Therefore, the liver damage due to hepatitis C virus may be aggravated with iron overload. In many studies higher levels of iron in the blood and the liver were connected with the decreased response to interferon-alfa therapy for chronic viral hepatitis C. Recent introduction of pegylated interferons plus ribavirin has improved the therapeutic response, so it is now possible to cure more than 50% of the patients. Case report. Three patients with chronic hepatitis C and iron overload were presented. Iron reduction therapy using phlebotomy or eritrocytapheresis with plasmapheresis was done at different times in regard to specific antiviral therapy or as a sole therapy. Conclusion. It has been shown that iron reduction, sole or combined with antiviral therapy, led to the deacreased aminotransferase serum activity and might have slow down the evolution of chronic hepatitis C viral infection.

End-of-Treatment-Response in Patients Treated for Hepatitis C Virus with Standard Interferon and Ribavirin Based on Viral Load

International Nuclear Information System (INIS)

Rathore, M. A.; Hussain, A. B.; Ghani, E.

2015-01-01

Objective: To determine the End-of-Treatment-Response (ETR) to standard interferon and ribavirin based regimen in patients of chronic hepatitis C and to compare the ETR response in low and high viral load groups. Study Design: Descriptive study. Place and Duration of Study: Virology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2012 to May 2013. Methodology: Patients with chronic hepatitis C virus infection were included in the study. Pre-treatment viral load was determined by RoboGene Quantification kit. Based on viral load, the 400 patients were divided into two equal groups of low viral load (< 800,000 IU/ml) and high viral load (> 800,000 IU/ml). The patients were treated with standard interferon alpha (3 million units subcutaneously thrice weekly) and ribavirin (10.6 mg/kg body weight) for 6 months. ETR was measured using Sacace Biotechnologies Qualitative kit. Chi-square test was used to compare the ETR in the two viral load groups. P-value < 0.05 was considered as significant. Results: Out of 400 patients, 206 (51.5%) were males and 194 (48.5%) were females. Two hundred seventy (67.5%) patients achieved ETR and 130 (35.5%) failed to do so. In low viral load group, 145 (72.5%) patients achieved and 55 (27.5%) patients did not achieve ETR. In high viral load group, 123 (61.5%) patients achieved and 77 (38.5%) did not achieve ETR. The difference in ETR between low and high viral load groups was statistically significant (p=0.019). Conclusion: End-of-treatment-response in patients treated for hepatitis C virus with standard interferon and ribavirin was greater in patients with low viral load as compared to patients with high viral load. (author)

A Review of Adverse Cutaneous Drug Reactions Resulting from the Use of Interferon and Ribavirin

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Nisha Mistry

2009-01-01

Full Text Available Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.

Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: a Danish nationwide cohort study

DEFF Research Database (Denmark)

Hansen, Nanna; Obel, Niels; Christensen, Peer

2011-01-01

The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim...

Effectiveness of combined antyviral therapy in children with chronic hepatitis C

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G. P. Martynova

2013-01-01

Full Text Available The paper presents the results of the research on effectiveness of combined antiviral therapy conducted with pegylated interferon alpha 2b of prolonged action (Peginterferon alpha 2b at a dose of 60 mcg/m2 per week and Rebetol (Ribavirin at a dose of 15 mg/kg per day in 26 children with chronic viral hepatitis C aged from 3 to 17, who underwent regular medical check-ups in City Clinical Hospital № 20 named after I.S. Berzon in Krasnoyarsk. Evaluation of effectiveness of combined antiviral therapy revealed that patients with genotype 1 had an immediate virologic response in 78,5% of cases, 83,3% of patients with genotype 2, 3 had a stable virologic response.

难治性慢性丙型肝炎患者抗病毒治疗中NK细胞和Treg细胞的动态变化

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CHEN Xiaoyun

2014-06-01

Full Text Available ObjectiveTo investigate the changes in NK cells and regulatory T (Treg cells among patients with refractory chronic hepatitis C (CHC during antiviral therapy and to analyze antiviral effect-related immunological factors. MethodsA total of 41 patients with refractory CHC (30 treatment-naive patients and 11 treatment-unresponsive patients and 11 healthy controls (HC were enrolled in this prospective open cohort study. Naive patients received pegylated interferon α-2a (Peg-IFN-α-2a 180 μg/week and ribavirin (RBV 10.6-15 mg/kg/day for 48 weeks, while unresponsive patients received Peg-IFN-α-2a 180 μg/week and RBV 15 mg/kg/day for 72 weeks. Blood cells and serum were dynamically collected to measure HCV RNA, liver function, NK cells and Treg cells and to analyze curative effect-related immunological factors. Continuous variables were analyzed by t-test or rank sum test, and discrete variables were analyzed by chi-square test. ResultsAll patients finished antiviral treatment and 24-week follow-up survey. Seventeen naive patients (56.7% and 3 unresponsive patients (27.2% achieved a sustained virologic response (SVR. The other 13 naive patients and 8 unresponsive patients without SVR were named response-free patients. At baseline, the percentage of NK cells in patients was lower than that in the HC group, while the percentage of Treg cells in patients was higher than that in the HC group. During antiviral therapy, in naive patients with SVR, the percentage of NK cells increased at week 24 of treatment, as compared with the baseline and week 4, and the percentage of Treg cells decreased at week 24, as compared with the baseline and week 4; In naive patients without SVR, the percentage of Treg cells increased at week 24, as compared with the baseline and week 4; no significant change in the percentage of NK cells or Treg cells was observed in unresponsive patients without SVR.ConclusionDecrease in NK cells and increase in Treg cells are related to

Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin.

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Scherzer, Thomas-Matthias; Hofer, Harald; Staettermayer, Albert Friedrich; Rutter, Karoline; Beinhardt, Sandra; Steindl-Munda, Petra; Kerschner, Heidrun; Kessler, Harald H; Ferenci, Peter

2011-05-01

Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients. rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400mg with 800 mg ribavirin/day. HCV RNA was determined at weeks 2 and 4 of 180 μg/week peginterferon alfa-2a/ribavirin treatment. Sixty-nine patients completed the treatment and follow-up. rs12979860 genotyping revealed that 27 (37.5%) patients had C/C, 39 (54.2%) T/C, and 5 (6.9%) T/T. Thirteen patients (18.1%) became HCV RNA negative at week 2 and an additional 30 (41.7%) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8%; T/C or T/T: 50.0%). Irrespective of the ribavirin dose, the viral load decline was larger than in those with the T allele (T/C or T/T) (week 2: 4.46; [0.36-6.02] median; [range] vs. 3.50; [0.14-5.62]; log IU HCV-RNA/ml; p<0.001; week 4: 4.97; [1.21-6.20] vs. 4.49; [1.16-6.23]; p=0.003). Despite the faster initial viral response in C/C carriers, SVR rates were not different compared to T-allele carriers. Results of the SNP in the rs8099917 region were similar. IL28B polymorphisms modulate early virologic response to peginterferon/ribavirin treatment. In contrast to HCV genotype 1 patients, no effect on SVR rates was observed in genotype 3 patients. The clinical relevance of an earlier viral decline in C/C patients needs to be determined. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

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Birerdinc, A; Afendy, A; Stepanova, M; Younossi, I; Manyam, G; Baranova, A; Younossi, Z M

2010-10-01

Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-β pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-β pathways are associated with some predictors of response. �

Detection of bcl-2 translocation in patients with chronic hepatitis C and its possible relation to antiviral therapy: preliminary study

International Nuclear Information System (INIS)

Ibrahim, N.S.; Hanna, M.O.F.; Farid, R.J.; Zayed, N.A.; Hunter, S.S.; Esmat, J.

2007-01-01

It has been suggested that t(14; 18) translocation of bcl-2 to the immunoglobulin heavy chain (IgH) locus may contribute to the pathogenesis of lymphoproliferative disorders (LPD) related to hepatitis C virus (HCV) infection. The present study aimed to assess the prevalence of bcl-2 translocation in Egyptian chronic HCV patients and to investigate the effect of combination antiviral therapy of interferon a and ribavirin on t(14;18). Fifty five chronic HCV patients were studied for the prevalence of t(l4; 18). These patients were classified into 2 groups, 33 non treated HCV patients and 22 treated HCV patients with antiviral therapy as well as control group of age and sex matched individuals. The bcl-2/IgH rearrangement was detected in peripheral blood mononuclear cells (PBMCs) by nested polymerase chain reaction. All patients have undergone HCV viral determination by real time PCR. Bcl-2/IgH translocation was detected in 21 (38.2%) of all 55 chronically infected HCV patients. Considering all patients with chronic HCV-infection, bcl-2 rearrangement was slightly more frequent in the non treated group than in those who underwent treatment with interferon plus ribavirin but the difference was not statistically significant, although treated patients showed biochemical and virologic response at the end of 6 months of antiviral therapy. In conclusion, t(l4;18) in PBMCs is a frequent finding in chronic HCV infection

Hepatitis C Therapy – Related Haematological Side Effects are Associated with Treatment Outcome / Hematološka Neželjena Dejstva Terapije Hepatitisa C Su Povezana Sa Ishodom Lecenja

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Vukovic Vuk R.

2016-03-01

Full Text Available Treatment of patients suffering from chronic hepatitis C with standard pegylated interferon alpha 2a plus ribavirin has limited efficacy. Therapy outcome is dependent on several factors of both the host and virus, including age, sex, stage of fibrosis, viral genotype, viral load, and occurrence of haematological adverse events during chronic hepatitis C treatment. The aim of this study was to determine the relationship between the viral and host factors and the haematological side effects of therapy with sustained virological response.

Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

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Curtis L Cooper

2010-01-01

Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

[Bilateral non-arteritic ischemic optic neuropathy during treatment of viral hepatitis C with pegylated interferon and Ribavirin].

Science.gov (United States)

Iferkhass, S; Elasri, F; Chatioui, S; Khoyaali, A; Bargach, T; Reda, K; Oubaaz, A

2015-01-01

Hepatitis C is a serious viral infection, for which the current treatment is based on the combination of pegylated interferon (IFN) and Ribavirin(®). Ophthalmic complications observed with PEG-IFN are infrequent and of variable prognosis. They often include an ischemic retinopathy with typical cotton-wool spots, hemorrhage and retinal edema, and rarely acute non-arteritic anterior ischemic optic neuropathy as illustrated by our report. We report the case of a 51-year-old man followed for chronic active hepatitis C, who presented in the fourth month of treatment with pegylated interferon and vidarabine with a sharp decline in visual acuity secondary to acute bilateral non-arteritic anterior ischemic optic neuropathy. The hepatitis C treatment was discontinued. His course was notable by the third week for a significant regression of papilledema with improvement in visual acuity in the right eye and no change in the left eye, remaining at counting fingers. After regressing for four years, the disease progressed to bilateral temporal optic atrophy without change in visual acuity. Pegylated interferon and Ribavirin(®) are commonly used in the treatment of chronic hepatitis C. They are the source of various ophthalmologic complications of varied severity. The pathophysiology of this ocular toxicity currently remains hypothetical. Non-arteritic ischemic optic neuropathy is still a relatively rare complication with a poor functional prognosis, often requiring discontinuation of treatment. Thus, careful ophthalmologic monitoring before and during antiviral treatment of patients with hepatitis C appears necessary. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection.

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Collison, Meadhbh; Chin, Jun Liong; Abu Shanab, Ahmed; Mac Nicholas, Ross; Segurado, Ricardo; Coughlan, Suzie; Connell, Jeff; Carr, Michael J; Merriman, Raphael B; McCormick, P Aiden; Hall, William W

2015-02-01

Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

Science.gov (United States)

Zeuzem, S; Flisiak, R; Vierling, J M; Mazur, W; Mazzella, G; Thongsawat, S; Abdurakhmanov, D; Van Kính, N; Calistru, P; Heo, J; Stanciu, C; Gould, M; Makara, M; Hsu, S-J; Buggisch, P; Samuel, D; Mutimer, D; Nault, B; Merz, M; Bao, W; Griffel, L H; Brass, C; Naoumov, N V

2015-10-01

Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens. © 2015 John Wiley & Sons Ltd.

[Hepatitis C treatment in special patient groups].

Science.gov (United States)

Berenguer, Marina; Jorquera, Francisco; Ángel Serra, Miguel; Sola, Ricard; Castellano, Gregorio

2014-07-01

The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects. These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

TO THE QUESTION ABOUT IMMUNOLOGIES CRITERIAS OF EFFICIENCY OF ANTIVIRUS THERAPY OF A CHRONIC VIRUS HEPATITES C

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L. Ph. Sklyar

2006-01-01

Full Text Available Abstract. The group of patients in amount 45 person received the standard combined therapy by preparations of recombinant IFN-α in combination with ribavirin. The positive effect of standard antivirus treatment at patients with chronic HCV-infection associated with increase of level of IL-2, decrease of levels of TNF-α, IL-1α, IL-12р40, IL-12р70 and IL-10 in peripheral serum. It has allowed to use them as noninvasive markers of the steady virologic answer during treatment of a chronic HCV-infection.

Drug Pricing Evolution in Hepatitis C.

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Vernaz, Nathalie; Girardin, François; Goossens, Nicolas; Brügger, Urs; Riguzzi, Marco; Perrier, Arnaud; Negro, Francesco

2016-01-01

We aimed to determine the association between the stepwise increase in the sustained viral response (SVR) and Swiss and United States (US) market prices of drug regimens for treatment-naive, genotype 1 chronic hepatitis C virus (HCV) infection in the last 25 years. We identified the following five steps in the development of HCV treatment regimens: 1) interferon (IFN)-α monotherapy in the early '90s, 2) IFN-α in combination with ribavirin (RBV), 3) pegylated (peg) IFN-α in combination with RBV, 4) the first direct acting antivirals (DAAs) (telaprevir and boceprevir) in combination with pegIFN-α and RBV, and 5) newer DAA-based regimens, such as sofosbuvir (which is or is not combined with ledipasvir) and fixed-dose combination of ritonavir-boosted paritaprevir and ombitasvir in combination with dasabuvir. We performed a linear regression and mean cost analysis to test for an association between SVRs and HCV regimen prices. We conducted a sensitivity analysis using US prices at the time of US drug licensing. We selected randomized clinical trials of drugs approved for use in Switzerland from 1997 to July 2015 including treatment-naïve patients with HCV genotype 1 infection. We identified a statistically significant positive relationship between the proportion of patients achieving SVRs and the costs of HCV regimens in Switzerland (with a bivariate ordinary least square regression yielding an R2 measure of 0.96) and the US (R2 = 0.95). The incremental cost per additional percentage of SVR was 597.14 USD in Switzerland and 1,063.81 USD in the US. The pricing of drugs for HCV regimens follows a value-based model, which has a stable ratio of costs per achieved SVR over 25 years. Health care systems are struggling with the high resource use of these new agents despite their obvious long-term advantages for the overall health of the population. Therefore, the pharmaceutical industry, health care payers and other stakeholders are challenged with finding new drug

Entrepreneurship in the Context of the Resource-Based View of the Firm

DEFF Research Database (Denmark)

Foss, Nicolai Juul

This chapter discusses entrepreneurship in the context of the RBV. What does the RBV have to say that the study of entrepreneurship may usefully draw on? And, conversely, how can entrepreneurship research further the RBV? I begin by sketching the RBV. I then discuss the relation between the RBV a...... and entrepreneurship research, before I characterize a new research stream that has emerged over the last decade or so in the intersection of the RBV and entrepreneurship research, namely “strategic entrepreneurship.”......This chapter discusses entrepreneurship in the context of the RBV. What does the RBV have to say that the study of entrepreneurship may usefully draw on? And, conversely, how can entrepreneurship research further the RBV? I begin by sketching the RBV. I then discuss the relation between the RBV...

Sofosbuvir and daclatasvir therapy in patients with hepatitis C-related advanced decompensated liver disease (MELD ≥ 15).

Science.gov (United States)

McCaughan, G W; Thwaites, P A; Roberts, S K; Strasser, S I; Mitchell, J; Morales, B; Mason, S; Gow, P; Wigg, A; Tallis, C; Jeffrey, G; George, J; Thompson, A J; Parker, F C; Angus, P W

2018-02-01

Antiviral therapy for hepatitis C has the potential to improve liver function in patients with decompensated cirrhosis. To examine the virological response and effect of viral clearance in patients with decompensated hepatitis C cirrhosis all with MELD scores ≥15 following sofosbuvir/daclatasvir ± ribavirin. We prospectively collected data on patients who commenced sofosbuvir/daclatasvir for 24-weeks under the Australian patient supply program (TOSCAR) and analysed outcomes including sustained viral response at 12 weeks (SVR12), death and transplant. 108 patients (M/F, 79/29; median age 56years; Child-Pugh 10; MELD 16; genotype 1/3, 55/47) received sofosbuvir/daclatasvir and two also received ribavirin. On intention-to-treat, the SVR12 rate was 70% (76/108). Seventy-eight patients completed 24-weeks therapy. SVR12 was achieved in 56 of these patients on per-protocol-analysis (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR12, median MELD and Child-Pugh fell from 16(IQR15-17) to 14(12-17) and 10(9-11) to 8(7-9), respectively (P<.001). In those who died, MELD increased from 16 to 23 at death (P=.036). Patients who required transplantation had a significantly higher baseline MELD (20) compared to those patients completing treatment (16) (P=.0010). The odds ratio for transplant in patients with baseline MELD ≥20 was 13.8(95%CI 2.78-69.04). SVR12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child-Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post-transplant. © 2017 John Wiley & Sons Ltd.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness two years after treatment with Ombitasvir/Paritaprevir/Ritonavir ±Dasabuvir ±Ribavirin in the AMBER, real-world experience study.

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Flisiak, Robert; Janczewska, Ewa; Łucejko, Mariusz; Karpińska, Ewa; Zarębska-Michaluk, Dorota; Nazzal, Khalil; Bolewska, Beata; Białkowska, Jolanta; Berak, Hanna; Fleischer-Stępniewska, Katarzyna; Tomasiewicz, Krzysztof; Karwowska, Kornelia; Simon, Krzysztof; Piekarska, Anna; Tronina, Olga; Tuchendler, Ewelina; Garlicki, Aleksander

2018-06-11

We followed for 2 years patients treated with Direct Acting Agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction of liver stiffness (LS), and risk of hepatocellular carcinoma (HCC).The study included patients from 16 hepatologic centers involved in the AMBER, investigators initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. A total of 204 patients among 209 from the primary study were enrolled; 200 with available testing at 2 years follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 non-responders retreated). During 2yFU 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses was lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, two-years follow-up confirmed durability of virologic response after treatment of HCV infection with Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics, that support the need for longer than 2-year monitoring for possible disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

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Hee Chul Nam

2016-06-01

Full Text Available Background/Aims: The treatment strategy for hepatitis C virus (HCV has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV and asunaprevir (ASV. We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. Methods: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12 and safety. Results: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN and ribavirin (RBV treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation occurring in two patients. Conclusion: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An Open-Label Study.

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Feld, Jordan J; Ramji, Alnoor; Shafran, Stephen D; Willems, Bernard; Marotta, Paul; Huchet, Emmanuelle; Vachon, Marie-Louise; Svarovskaia, Evguenia S; Huang, K C; Hyland, Robert H; Yun, Chohee; Massetto, Benedetta; Brainard, Diana M; McHutchison, John G; Tam, Edward; Bailey, Robert; Cooper, Curtis; Yoshida, Eric M; Greenbloom, Susan; Elkhashab, Magdy; Borgia, Sergio; Swain, Mark G

2017-07-01

Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection. We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance. Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%-94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%). In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis. NCT02413593. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

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Yoan Antonio Sánchez Rodríguez

2011-03-01

main cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplantation worldwide. OBJECTIVE: to identify the side effects of a combined therapy of recombinant interpheron alpha 2b plus ribavirin during the treatment and up to 8 weeks afterwards, as well as the main effects related to temporary or definitive withdrawal. METHODS: a pharmacological surveillance study was performed in which 122 patients with chronic hepatitis C, who had been seen at the Institute of Gastroenterology from May 2001 to May 2006, were included. Recombinant interferon alpha 2b (3 million units administered 3 times a week plus ribavirin (1 000 or 1 200 mg daily depending on the body weight was the therapy used for 48 weeks. RESULTS: of the total number of cases, 88.5 % had side effects; 79.5 % of which corresponded to pseudocold syndrome followed by hematological, neuropsychiatric and gastrointestinal manifestations, and other less frequent ailments. In the studied group, 6.6% had to interrupt their treatment temporarily due to some side effect different from anemia whereas 4 patients gave up the study, three affected by severe hemolytic anemia and one with uncontrollable hyperthyroidism. CONCLUSIONS: the combined therapy of recombinant interferon alpha 2b plus ribavirin proved to be safe; the most frequent side effect was pseudocold syndrome in the majority of cases. The hematological manifestations that made the patients to give up the study led to recommend a strict follow-up of hemoglobin levels and thorough diagnosis and treatment of the main side effects found in other systems and associated to this combined therapy.

O planejamento estratégico e a visão baseada em recursos (RBV: uma avaliação da tecnologia da informação na gestão hospitalar [doi: 10.5329/RECADM.2013006

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Saulo Barbara de Oliveira

2013-04-01

Full Text Available O artigo apresenta os resultados de uma pesquisa empírica conduzida em cinco hospitais públicos da cidade do Rio de Janeiro. Traz em destaque o caso de um hospital público que poderá servir de benchmarking para outros hospitais brasileiros, uma vez que tem na Tecnologia da Informação (TI e no Planejamento Estratégico (PE um valioso ativo para o desenvolvimento de suas competências, indo ao encontro da teoria RBV (resource-based view. A pesquisa, de natureza qualitativa e exploratória analisa a percepção dos gestores de hospitais sobre a situação em que se encontram a consciência, as ações e as práticas da gestão estratégica de TI. Os dados de campo foram coletados em entrevistas feitas com os gestores de TI e de infraestrutura desses hospitais. O estudo possibilitou identificar carências e problemas relativos ao PE, seleção, implantação e uso da TI, e de outras ferramentas nos hospitais investigados. Os resultados são preocupantes e apresentam relatos do quanto a gestão hospitalar precisa ser aprimorada, especialmente no tocante ao reconhecimento da TI como recurso valioso para o desenvolvimento de competências organizacionais e inovações.   Palavras-chave Gestão Hospitalar, Visão Baseada em Recursos, Planejamento Estratégico, Tecnologia da informação.     THE STRATEGIC PLAN AND THE RESOURCE-BASED VIEW (RBV: AN EVALUATION OF INFORMATION TECHNOLOGY IN HOSPITAL MANAGEMENT   ABSTRACT This article presents the results of empirical research conducted in five public hospitals of Rio de Janeiro city. It Highlights the case of a public hospital that can serve as a benchmarking for other brazilian hospitals since it has in information technology (IT and in strategic planning (SP a valuable asset for the development of their skills, going to meet the RBV theory (resource-based view. This qualitative and exploratory study examines the hospitals managers’ perception on the situation of strategic awareness

Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir, dasabuvir ± ribavirin for hepatitis C genotype 1 - final results of the REV1TAL study.

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Lubel, John; Strasser, Simone; Stuart, Katherine A; Dore, Gregory; Thompson, Alexander; Pianko, Stephen; Bollipo, Steven; Mitchell, Joanne L; Fragomeli, Vincenzo; Jones, Tracey; Chivers, Sarah; Gow, Paul; Iser, David; Levy, Miriam; Tse, Edmund; Gazzola, Alessia; Cheng, Wendy; Nazareth, Saroj; Galhenage, Sam; Wade, Amanda; Weltman, Martin; Wigg, Alan; MacQuillan, Gerry; Sasadeusz, Joe; George, Jacob; Zekry, Amany; Roberts, Stuart K

2017-01-01

Limited data exist on the outcomes of ritonavir-boosted paritaprevir with ombitasvir and dasabuvir (PrOD) ± ribavirin in a real-world setting. The aim of this study was to compare the efficacy and safety of PrOD-based therapy in hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre-treatment factors predictive of sustained viral response (SVR) and serious adverse events (SAEs) on treatment. 451 patients with hepatitis C genotype 1 treated in 20 centres across Australia were included. Baseline demographic, clinical and laboratory information, on-treatment biochemical, virological and haematological indices and details on serious adverse events were collected locally. Cirrhosis was present in 340 patients (75.4%). Overall SVR was 95.1% with no differences in SVR between the cirrhosis and non-cirrhosis groups (94.7% versus 96.4%). SVR in subgenotypes 1a and 1b was 93.1% and 99.2%, respectively. On multivariate analysis, baseline bilirubin level and early treatment cessation predicted SVR. SAEs occurred in 10.9% of patients including hepatic decompensation (2.7%) and hepatocellular carcinoma (1.8%). On multivariate analysis of factors predictive of SAEs in the overall group, Child-Turcotte-Pugh (CTP) B was the only significant factor, while in those with cirrhosis, baseline albumin and creatinine levels were significant. In this large real-world cohort of HCV genotype 1 subjects, treatment with PrOD was highly effective and similar to clinical trials. Important determinants of reduced SVR include early cessation of therapy and baseline bilirubin concentration. SAEs were not infrequent with CTP B patients being at greatest risk.

Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin

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Pei-yuan Su

2016-07-01

Full Text Available The lower limits of virus detection of hepatitis C virus (HCV RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR] in predicting sustained virological response (SVR in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90 and detectable but not quantifiable (< 12 IU/mL, n = 27. All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p < 0.001. We determined 4th week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002 and a good predictor of SVR [area under the curve (AUC = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4th week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks with PEG-IFN and ribavirin.

Entrepreneurship in the Context of the Resource-based View of the Firm

OpenAIRE

Foss, Nicolai J.

2011-01-01

This chapter discusses entrepreneurship in the context of the RBV. What does the RBV have to say that the study of entrepreneurship may usefully draw on? And, conversely, how can entrepreneurship research further the RBV? I begin by sketching the RBV. I then discuss the relation between the RBV and entrepreneurship research, before I characterize a new research stream that has emerged over the last decade or so in the intersection of the RBV and entrepreneurship research, namel...

The impact of pegylated interferon and ribavirin combination treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients.

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Jung, Hee Jae; Kim, Young Seok; Kim, Sang Gyune; Lee, Yun Nah; Jeong, Soung Won; Jang, Jae Young; Lee, Sae Hwan; Kim, Hong Soo; Kim, Boo Sung

2014-03-01

Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment. In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of β cells (HOMA-β) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx). A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0 ± 11.2 years, mean ± SD; non-SVR, 56.6 ± 9.9 years; PC) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-β were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group. LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).

Drug Pricing Evolution in Hepatitis C

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Vernaz, Nathalie; Girardin, François; Goossens, Nicolas; Brügger, Urs; Riguzzi, Marco; Perrier, Arnaud; Negro, Francesco

2016-01-01

Objective We aimed to determine the association between the stepwise increase in the sustained viral response (SVR) and Swiss and United States (US) market prices of drug regimens for treatment-naive, genotype 1 chronic hepatitis C virus (HCV) infection in the last 25 years. We identified the following five steps in the development of HCV treatment regimens: 1) interferon (IFN)-α monotherapy in the early '90s, 2) IFN-α in combination with ribavirin (RBV), 3) pegylated (peg) IFN-α in combination with RBV, 4) the first direct acting antivirals (DAAs) (telaprevir and boceprevir) in combination with pegIFN-α and RBV, and 5) newer DAA-based regimens, such as sofosbuvir (which is or is not combined with ledipasvir) and fixed-dose combination of ritonavir-boosted paritaprevir and ombitasvir in combination with dasabuvir. Design We performed a linear regression and mean cost analysis to test for an association between SVRs and HCV regimen prices. We conducted a sensitivity analysis using US prices at the time of US drug licensing. We selected randomized clinical trials of drugs approved for use in Switzerland from 1997 to July 2015 including treatment-naïve patients with HCV genotype 1 infection. Results We identified a statistically significant positive relationship between the proportion of patients achieving SVRs and the costs of HCV regimens in Switzerland (with a bivariate ordinary least square regression yielding an R2 measure of 0.96) and the US (R2 = 0.95). The incremental cost per additional percentage of SVR was 597.14 USD in Switzerland and 1,063.81 USD in the US. Conclusion The pricing of drugs for HCV regimens follows a value-based model, which has a stable ratio of costs per achieved SVR over 25 years. Health care systems are struggling with the high resource use of these new agents despite their obvious long-term advantages for the overall health of the population. Therefore, the pharmaceutical industry, health care payers and other stakeholders are

Effects of Interferon Therapy on Heart

International Nuclear Information System (INIS)

Faisal, A. W. K.; Ali, S. A.; Nisar, S.; Ahmad, F.

2016-01-01

Background: Hepatitis C virus (HCV) infection is a major health problem worldwide. Around 185 million people are suffering from HCV infection all over the world, out of which 10 million people are residing in Pakistan. 4.7 percent (2-14 percent by different studies) of Pakistanis are suffering from this deadly disease. Interferon+Ribavarin IFN/RIB is the mainstay of treatment for this infection. Various cardiovascular adverse reactions have been reported of this therapy. We conducted this study at Punjab Institute of cardiology to look for the cardiac safety of interferon therapy in our population. Methods: We studied HCV infected patients planned for interferon therapy between 21st of November 2012 to 20th of August 2014. Echocardiography was performed before, during and after the completion of therapy. Pegylated interferon once a week plus ribavirin therapy was given to the patients. Patients received 16-40 injections of pegylated interferon depending upon the decision of hepatologist. Patients with prior structural heart disease, patients who did not start the treatment or patients who did not turn up on follow up were excluded from the study. Results: A total of 102 patients planned to have interferon therapy were screened echocardiographically. One patient died after 5 injections due to infection (a non-cardiac cause). 46 patients completed the treatment and the follow up. None of the patients had any acute cardiac event. All patients had normal biventricular systolic function at the end of study. None of the patients had significant valvular heart disease or pulmonary hypertension. Reversal of E/A ratio or E/A ratio>2, parameters of diastolic dysfunction and mild pericardial effusion were noted in a statistically significant number of patients. Conclusion: Interferon therapy for HCV infection is cardiac safe in patients who have structurally normal heart. Female patients have propensity of adverse events like severe diastolic dysfunction and mild pericardial

Celiac disease onset after pegylated interferon and ribavirin treatment of chronic hepatitis C Doença celíaca após tratamento de hepatite C crônica com interferon peguilado e ribavirina

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Elson V. Martins Jr.

2004-06-01

Full Text Available AIM: Report of a case of a woman patient who developed celiac disease after pegylated interferon alpha-2a and ribavirin use for chronic hepatitis C. PATIENT AND METHOD: A 34-year-old woman with chronic hepatitis C, genotype 3, receiving pegylated interferon alpha-2a and ribavirin for 6 months, developed progressive malaise and anemia 6 months after the end of treatment. RESULT: Additional investigation revealed duodenal villous atrophy and positivity for anti-endomysium and anti-gliadin antibodies. Celiac disease diagnosis was performed and symptoms and laboratory abnormalities improved after gluten-free diet. CONCLUSION: Celiac disease must be ruled out in patients with malabsorption complaints in or after interferon (or pegylated interferon therapy. Screening for celiac disease with detection of anti-endomysium antibodies would be done in susceptible patients.OBJETIVO: Relatar caso de doença celíaca ocorrendo após uso de interferon peguilado e ribavirina em paciente com hepatite C crônica. PACIENTE E MÉTODO: Mulher de 34 anos com hepatite C crônica, genótipo 3, tratada com interferon peguilado alfa-2a e ribavirina durante 6 meses, desenvolveu quadro de astenia e anemia após 6 meses do término do tratamento. RESULTADO: Investigação complementar revelou atrofia vilositária à biopsia duodenal e detecção de anticorpos anti-endomísio e anti-gliadina, realizando-se diagnóstico de doença celíaca. Dieta isenta de glúten foi instituída, observando-se boa resposta clínica e laboratorial. CONCLUSÃO: Doença celíaca deve ser afastada em pacientes com quadro de má absorção durante ou após uso de interferon (ou interferon peguilado. Rastreamento de doença celíaca através da realização de anticorpo anti-endomísio pode ser considerado em populações susceptíveis.

A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service.

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Westerhout, Kirsten; Treur, Maarten; Mehnert, Angelika; Pascoe, Katie; Ladha, Imran; Belsey, Jonathan

2015-01-01

Triple therapy using a protease inhibitor (PI) with peginterferon and ribavirin (PR) is increasingly used in patients with chronic hepatitis C virus (HCV) infection. The most recently introduced PI, simeprevir (SMV), offers high levels of viral eradication combined with a reduced overall duration of therapy. The objective of this study was to compare the cost-effectiveness of SMV + PR vs PR alone or in combination with telaprevir (TVR) or boceprevir (BOC) in patients infected with genotype 1 HCV Method: A cost-utility model was constructed, incorporating two phases, capturing the efficacy of therapy in an initial treatment phase, followed by a long-term post-treatment Markov phase, capturing lifetime outcomes according to whether a sustained viral response (SVR) had been achieved on treatment. Dosage regimens were based on the EMA approved label for each treatment. SVR estimates and adverse event rates were derived from a mixed treatment comparison. Baseline characteristics were drawn from an analysis of a UK HCV data-set and clinician opinion. Health state transition probabilities, utilities, and health state costs were drawn from previously published economic analyses. The model considered direct health costs only, and the perspective was that of the UK National Health Service. The model yielded an ICER for SMV + PR vs PR alone of £9725/QALY for treatment-naïve and £7819/QALY for treatment-experienced. Benefit was driven by increased likelihood of achieving SVR, with consequent long-term utility gains. SMV + PR dominated TVR + PR and BOC + PR in both patient groups. This principally reflected the QALY benefit of an increased likelihood of SVR with SMV, combined with lower overall drug costs, due to reduced mean treatment duration. Compared to other currently licensed treatment options, SMV + PR represents a cost effective treatment option for patients with chronic genotype 1 HCV infection.

Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin

NARCIS (Netherlands)

Kanter, C.T.M.M. de; Luin, M. van; Solas, C.; Burger, D.M.; Vrolijk, J.M.

2014-01-01

A 46-year old man with a chronic hepatitis C virus infection received triple therapy with ribavirin, pegylated interferon and telaprevir. The patient also received simvastatin. One month after starting the antiviral therapy, the patient was admitted to the hospital because he developed

Triple therapy in chronic hepatitis C: initial series in a public health program in the South of Brazil.

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Almeida, Paulo R L; Fonseca, Carla Bortolin; Koch, Vivian W; Souza, Amanda M; Feltrin, Alberi A; Tovo, Cristiane Valle

2015-01-01

Chronic hepatitis C has great impact on world's health. Current therapy for genotype 1 hepatitis C virus includes protease inhibitors boceprevir and telaprevir, associated to standard therapy - peginterferon alfa + ribavirin. There are no published data in Brazil on the results of this new therapy, and it is interesting an evaluation of what was accomplished up to this moment. Objectives To evaluate virologic response to triple therapy, as well as the safety profile and tolerability. This study is a clinical series of patients receiving triple therapy for C hepatitis in a single center of a Public Health System of South Brasil. Out of the 121 patients that initiated the triple therapy, the first patients that finished the treatment and evaluated the sustained virological response (24 weeks after the end of treatment) were included. Twenty four genotype 1 chronic hepatitis C monoinfected patients were included. Nineteen (79.2%) patients had been previously treated. Thirteen (54.2%) patients were cirrhotic. Nineteen (79.2%) patients completed the planned therapy. By the end of the treatment, 14 (58.3%) out of 24 patients had undetectable viral load. Sustained virologic response occurred in 12 (50.0%) out of 24 patients, 07 (58.3%) in telaprevir group and 05 (41.7%) in boceprevir group. Out of 24 patients under triple therapy, 58% (n=14) presented anemia. In conclusion, despite the small number of patients treated with triple therapy evaluated in the current study, it possibly reflects the population under this therapy in real-life.

Treatment of Decompensated Cirrhosis Secondary to Hepatitis C with Antiviral Therapy

International Nuclear Information System (INIS)

Khokhar, N.; Qureshi, M.O.; Niazi, T.K.

2013-01-01

Objective: To treat decompensated hepatitis C patient with interferon, ribavirin and amantidine to ascertain the sustained viral response. Study Design: Descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2007 to January 2012. Methodology: HCV PCR patients with decompensated hepatitis C, who had developed a complication like ascites, encephalopathy or variceal bleeding were included in the study. Those with uncontrolled ascites or other complications were excluded. Treatment with standard interferon 3 miU subcutaneously three times a week along with ribavirin 800 mg to 1200 mg and amantidine 100 mg b.i.d. was administered for 12 months. Patients were followed every month with CBC and ALT and HCV PCR was performed after 3 months to document early viral response. They had HCV PCR at the end of the treatment to document end of treatment response. All were further followed for another 6 months at monthly intervals and HCV PCR was performed at the end of this period to document sustained viral response. Results: In all, 165 patients were treated. Treatment had to be discontinued in 42 (26%) patients. Out of these, 16 patients died. Thus, 123 completed treatment. Sustained viral response was documented in 58 out of the 123 (47%) patients. Hepatic encephalopathy, gastrointestinal bleeding, sepsis and development of ascites were the major complications during treatment. Conclusion: Forty seven percent of patients with decompensated hepatitis C cirrhosis were able to achieve sustained viral response after one year treatment with anti-viral therapy. However, complications developed during treatment and, therefore, frequent and close monitoring is necessary in these patients. (author)

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

Science.gov (United States)

Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

2009-06-15

Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Critical evaluation of blood volume measurements during hemodialysis.

Science.gov (United States)

Dasselaar, Judith J; van der Sande, Frank M; Franssen, Casper F M

2012-01-01

Devices that continuously measure relative blood volume (RBV) changes during hemodialysis (HD) are increasingly used for the prevention of dialysis hypotension and fine-tuning of dry weight. However, RBV measurements are subject to various limitations. First, RBV devices provide information on relative blood volume changes but not on absolute blood volume. Since blood volume varies with the hydration status, identical reductions of RBV may result in very different absolute blood volumes at the end of HD. Second, RBV changes underestimate the change of total blood volume due to translocation of lower-hematocrit blood from the microcirculation to the central circulation. Third, changes in posture before and during HD, food intake, exercise, and administration of intravenous fluids may influence the validity of the RBV measurement. Fourth, results obtained by various RBV devices show large interdevice differences. Finally, although a fall in blood volume is an important factor in dialysis hypotension, frank dialysis hypotension only occurs when the cardiovascular compensatory mechanisms can no longer compensate for the reduction in blood volume. Therefore, the dialysis staff should not exclusively focus on RBV, but also search for opportunities in the dialysis prescription to facilitate cardiovascular compensatory mechanisms, e.g. by lowering dialysate temperature. In the opinion of the authors, routine RBV monitoring should be used with caution until the major conceptual and methodological problems that are inherent to the indirect RBV estimation are clarified. Copyright © 2012 S. Karger AG, Basel.

Retreatment with sofosbuvir/velpatasvir in cirrhotic patients with genotype-4 who failed a previous interferon-free regimen: a case series.

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Boglione, Lucio; Pinna, Simone Mornese; Lupia, Tommaso; Cariti, Giuseppe; Di Perri, Giovanni

2018-02-14

The novel available interferon (IFN)-free regimens significantly improved the sustained virological response (SVR) in patients with chronic hepatitis C (CHC), without important side effects and with shorter duration of treatment. In a subset of patients, however, the treatment failure (TF) was due to the presence of resistance-associated substitutions (RAS) that lead to virological breakthrough (BT) or relapse. We analysed in this case series the role of RAS on the TF in cirrhotic patients with genotype (GT)4, treated with a previous IFN-free regimen, and retreated with the combination of sofosbuvir (SOF)/velpatasvir (VEL) for 12 or 24 weeks, without ribavirin (RBV). We included in this analysis all patients with GT4 who failed a previous IFN-free treatment, with the presence of RAS at BT or relapse. All patients were retreated with a fixed combination of SOF/VEL for 12/24 weeks, without RBV. We evaluated the SVR and the MELD score change after the treatment. Seven patients were described. All were cirrhotic, Child-Pugh A (n=5), B (n=2); baseline RAS were detected in 4/7 subjects; at post-treatment detection, NS5 RAS were: F28S (n=1), Q30K (n=2), S30G (n=1), NS3 were: S122R (n=1), S122G (n=2), D168V (n=3). All retreated patients gained SVR. MELD score improved in all subjects with a median change of 3 points. No significant side effects or adverse events were reported. The combination SOF/VEL could be considered for the retreatment of cirrhotic GT4 patients who failed a previous IFN-free treatment with the presence of RAS in NS3 or NS5 regions.

Retreatment with sofosbuvir/velpatasvir in cirrhotic patients with genotype 4 who failed a previous interferon-free regimen: a case series.

Science.gov (United States)

Boglione, Lucio; Pinna, Simone Mornese; Lupia, Tommaso; Cariti, Giuseppe; Di Perri, Giovanni

2018-02-14

The novel available interferon (IFN)-free regimens significantly improved the sustained virological response (SVR) in patients with chronic hepatitis C (CHC), without important side-effects and with shorter duration of treatment. In a subset of patients, however, the treatment failure (TF) was due to the presence of resistance-associated substitutions (RAS) that lead to virological breakthrough (BT) or relapse. We analyzed in this case-series the role of RAS on the TF in cirrhotic patients with GT4, treated with a previous IFN-free regimen, and retreated with the combination of sofosbuvir (SOF)/velpatasvir (VEL) for 12 or 24 weeks, without ribavirin (RBV). We included in this analysis all patients with GT4 who failed a previous IFN-free treatment, with the presence of RAS at BT or relapse. All patients were retreated with a fixed combination of SOF/VEL for 12/24 weeks, without RBV. We evaluated the SVR and the MELD score change after the treatment. Seven patients were described. All were cirrhotic, Child-Pug A (n=5), B (n=2); baseline RAS were detected in 4/7 subjects; at post-treatment detection, NS5 RAS were: F28S (n=1), Q30K (n=2), S30G (n=1), NS3 were: S122R (n=1), S122G (n=2), D168V (n=3). All retreated patients gained the SVR. MELD score improved in all subjects with a median change of 3 points. No significant side-effects or adverse events were reported. The combination SOF/VEL could be considered for the retreatment of cirrhotic GT4 patients who failed a previous IFN-free treatment with the presence of RAS in NS3 or NS5 regions.

Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting

Science.gov (United States)

Ramos, Huascar; Linares, Pedro; Badia, Ester; Martín, Isabel; Gómez, Judith; Almohalla, Carolina; Jorquera, Francisco; Calvo, Sara; García, Isidro; Conde, Pilar; Álvarez, Begoña; Karpman, Guillermo; Lorenzo, Sara; Gozalo, Visitación; Vásquez, Mónica; Joao, Diana; de Benito, Marina; Ruiz, Lourdes; Jiménez, Felipe; Sáez-Royuela, Federico; Asociación Castellano y Leonesa de Hepatología (ACyLHE)

2017-01-01

AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus (HCV). METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response (SVR) as well as serious adverse events (SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial (CT-met and CT-unmet, respectively). RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir (36.4%), followed by sofosbuvir/ledipasvir (24.9%) and ombitasvir/paritaprevir/ritonavir (r)/dasabuvir (19.9%). Ribavirin (RBV) was administered in 198 patients (42.9%). SVRs occurred in 437/462 patients (94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CT-met group vs 91.9% patients in the CT-unmet group (P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure (P = 0.04). Eleven patients (2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively (P = 0.003). CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized. PMID:28533924

Chronic hepatitis C treatment in a cystic fibrosis patient in the pulmonary pre-transplant stage Tratamiento de hepatitis crónica C en un paciente con fibrosis quística en situación de pretrasplante pulmonar

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L. Adán Merino

2010-10-01

Full Text Available The standard treatment of chronic hepatitis C, pegylated interferon and ribavirin (pegI/R, has many limitations in both effectiveness and secondary effects, which makes it unsuitable or even contraindicated for some patients. In hepatitis C virus-infected cystic fibrosis patients this treatment could increase respiratory infections with subsequent pulmonary function deterioration. On the contrary, hepatitis C virus (HCV infection may make lung transplant (LT unfeasible. We present the case of a cystic fibrosis-young man diagnosed with HCV infection during LT assessment who was treated with pegI/R. In spite of the lung function worsening and respiratory infections, he managed to complete treatment and even sustained virological response (SVR. At present he is on LT waiting list.El tratamiento estándar de la hepatitis crónica C, interferón pegilado (INF-peg y ribavirina (RBV, puede ser inadecuado o incluso estar contraindicado en algunos pacientes debido a sus limitaciones en cuanto a eficacia y efectos adversos. En pacientes con fibrosis quística infectados por el virus de la hepatitis C (VHC el tratamiento antiviral podría aumentar las infecciones respiratorias con el consiguiente empeoramiento de la función pulmonar. Por contra, la infección por VHC podría desestimar a estos pacientes para un necesario trasplante pulmonar. Presentamos el caso de un varón con fibrosis quística diagnosticado de infección VHC durante su evaluación previa al trasplante pulmonar. El paciente fue tratado con INF-peg y RBV. A pesar del empeoramiento en la función pulmonar y numerosas infecciones respiratorias intercurrentes, logró completar el tratamiento y obtener respuesta viral sostenida, encontrándose actualmente en lista de espera.

Results of interferon-based treatments in Alaska Native and American Indian population with chronic hepatitis C

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Stephen E. Livingston

2016-03-01

Full Text Available Background: There have been few reports of hepatitis C virus (HCV treatment results with interferon-based regimens in indigenous populations. Objective: To determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI population. Design: In an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined. Results: Sustained virologic response (SVR with standard interferon was 16.7% (3/18 and with standard interferon and ribavirin was 29.7% (11/37. Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%, including 10 of 46 with genotype 1 (21.7%, 38 of 51 with genotype 2 (74.5% and 13 of 22 with genotype 3 (59.1%. By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p=0.002, estimated duration of infection (p=0.034 and HCV genotype (p<0.0001. There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%. Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%. Conclusions: We had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1.

Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.

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Luis F López-Cortés

Full Text Available Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR, SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.ClinicalTrials.gov NCT00553930.

Critical Evaluation of Blood Volume Measurements during Hemodialysis

NARCIS (Netherlands)

Dasselaar, Judith J.; van der Sande, Frank M.; Franssen, Casper F. M.

2012-01-01

Devices that continuously measure relative blood volume (RBV) changes during hemodialysis (HD) are increasingly used for the prevention of dialysis hypotension and fine-tuning of dry weight. However, RBV measurements are subject to various limitations. First, RBV devices provide information on

Knowledge mobilization in healthcare organizations: a view from the resource-based view of the firm.

Science.gov (United States)

Ferlie, Ewan; Crilly, Tessa; Jashapara, Ashok; Trenholm, Susan; Peckham, Anna; Currie, Graeme

2015-03-01

This short literature review argues that the Resource-Based View (RBV) school of strategic management has recently become of increased interest to scholars of healthcare organizations. RBV links well to the broader interest in more effective Knowledge Mobilization (KM) in healthcare. The paper outlines and discusses key concepts, texts and authors from the RBV tradition and gives recent examples of how RBV concepts have been applied fruitfully to healthcare settings. It concludes by setting out a future research agenda.

Effect of high and low ultrafiltration volume during hemodialysis on relative blood volume

NARCIS (Netherlands)

Dasselaar, JJ; de Jong, PE; Huisman, RM; Franssen, CFM

2006-01-01

Achieving an optimal posthemodialysis hydration status may be difficult because objective criteria for dry weight are lacking. Both relative blood volume changes (Delta RBV) at the end of hemodialysis and Delta RBV normalized for ultrafiltration volume (Delta RBV/UF ratio) have been reported to

Resource based view: a promising new theory for healthcare organizations: Comment on "Resource based view of the firm as a theoretical lens on the organisational consequences of quality improvement".

Science.gov (United States)

Ferlie, Ewan

2014-11-01

This commentary reviews a recent piece by Burton and Rycroft-Malone on the use of Resource Based View (RBV) in healthcare organizations. It first outlines the core content of their piece. It then discusses their attempts to extend RBV to the analysis of large scale quality improvement efforts in healthcare. Some critique is elaborated. The broader question of why RBV seems to be migrating into healthcare management research is considered. They conclude RBV is a promising new theory for healthcare organizations.

Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY)

DEFF Research Database (Denmark)

Sulkowski, Mark; Hezode, Christophe; Gerstoft, Jan

2015-01-01

BACKGROUND: Both hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected patients are in need of safe, effective, all-oral HCV regimens. In a phase 2 study we aimed to assess the efficacy and safety of grazoprevir (MK-5172; HCV NS3/4A protease inhibitor) and two doses of elbasvir (MK-8742......; HCV NS5A inhibitor) in patients with HCV mono-infection and HIV/HCV co-infection. METHODS: The C-WORTHY study is a phase 2, multicentre, randomised controlled trial of grazoprevir plus elbasvir with or without ribavirin in patients with HCV; here, we report findings for previously untreated (genotype......%) and was associated with emergence of resistance-associated variants to one or both drugs. The safety profile of grazoprevir plus elbasvir with or without ribavirin was similar in mono-infected and co-infected patients. No patient discontinued due to an adverse event or laboratory abnormality. The most common adverse...

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

Science.gov (United States)

Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

2017-08-01

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4 + T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

INFECTIOUS AETIOLOGY OF MARGINAL ZONE LYMPHOMA AND ROLE OF ANTI-INFECTIVE THERAPY

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Salvatore Perrone

2016-01-01

Full Text Available Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood, however the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because recapitulates a cancer cured only by antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus rising hope that new available drugs, extremely effective against HCV replication, could improve outcome also in HCV-driven lymphomas. The rare cases of MZL localized to orbital fat and eye conjunctivas have been associated with Chlamydia psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer thain gastric MALT. Finally some case-reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.

HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127 and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection

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Sarrazin C

2016-11-01

Full Text Available Christoph Sarrazin,1 Francesco Castelli,2 Pietro Andreone,3 Maria Buti,4 Massimo Colombo,5 Stanislas Pol,6 Filipe Calinas,7 Massimo Puoti,8 Antonio Olveira,9 Mitchell Shiffman,10 Jerry O Stern,11 George Kukolj,12 Michael Roehrle,13 Stella Aslanyan,11 Qiqi Deng,11 Richard Vinisko,11 Federico J Mensa,11 David R Nelson,14 on behalf of the HCVerso1 and 2 study groups 1Department of Internal Medicine 1, JW Goethe University Hospital, Frankfurt, Germany; 2Department of Infectious and Tropical Diseases, University of Brescia, Brescia, 3Department of Medical and Surgical Sciences, Università di Bologna and Azienda Ospedaliero-Universitaria, Policlinico Sant‘Orsola-Malpighi, Bologna, Italy; 4Department of Internal Medicine, Hospital Universitari Vall d’Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain; 5Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 6University Paris Descartes, Department of Hepatology, Hospital Cochin, APHP and INSERM UMS-20, Institut Pasteur, Paris, France; 7Department of Gastroenterology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal; 8Department of Infectious Diseases, AO Ospedale Niguarda Cà Granda, Milan, Italy; 9Liver Unit, Hospital Universitario La Paz, CIBERehd, Madrid, Spain; 10Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, USA; 11Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 12Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada; 13Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 14Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA Abstract: The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2 in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including

Aminoadamantanes for chronic hepatitis C

NARCIS (Netherlands)

Lamers, M.H.; Broekman, M.; Drenth, J.P.H.; Gluud, C.

2014-01-01

BACKGROUND: Around 3% of the world's population (approximately 160 million people) are chronically infected with hepatitis C virus. The proportion of infected people who develop clinical symptoms varies between 5% and 40%. Combination therapy with pegylated interferon-alpha plus ribavirin eradicates

Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

LENUS (Irish Health Repository)

Bull, S J

2009-12-01

Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Histopathology in Chronic Hepatitis C Genotype 2 and 3

DEFF Research Database (Denmark)

Rembeck, Karolina; Alsiö, Asa; Christensen, Peer Brehm

2012-01-01

Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present stu...

Cost-utility analysis of ledipasvir/sofosbuvir for the treatment of genotype 1 chronic hepatitis C in Japan.

Science.gov (United States)

Igarashi, Ataru; Tang, Wentao; Guerra, Ines; Marié, Lucile; Cure, Sandrine; Lopresti, Michael

2017-01-01

Hepatitis C is the result of a ribonucleic acid (RNA) virus (hepatitis C virus; HCV). The Japan Society of Hepatology (JSH) estimated that 1.5-2 million people in Japan carry HCV. Six major HCV genotypes (GT) and a large number of subtypes have been described in the literature. In Japan, around 70% to 80% of people are infected with HCV genotype 1b. The progress of the disease primarily affects the liver and may lead to liver cirrhosis, hepatocellular carcinoma (HCC) and death. Sofosbuvir (SOF) is a nucleotide analogue NS5B inhibitor and ledipasvir (LDV) is an inhibitor of the HCV NS5A protein. They are combined in a single tablet regimen for the treatment of GT1 patients and resulted in sustained virological response (SVR) above 94% in large phase III trials. This analysis assesses the cost-utility of LDV/SOF in GT1 patients in Japan. A cohort of 10,000 patients was followed through a Markov model until they reached 100 years of age. GT1 treatment-naïve and experienced, non-cirrhotic and cirrhotic patients were studied separately. LDV/SOF was compared to several treatment regimens containing pegylated interferon (PEGIFN), telaprevir (TVR), simeprevir (SMV), daclatasvir (DCV), asunaprevir (ASV) and ribavirin (RBV). Discount rates of 2% were applied to costs and outcomes according to the Japanese guidelines. LDV/SOF was cost-effective against most comparators with incremental cost-effectiveness ratios (ICERs) below JPY 5,000,000. By applying a societal perspective, LDV/SOF was the dominant treatment strategy in all cases. Moreover, LDV/SOF reduced the number of cases of advanced liver disease. These results were robust to sensitivity analyses. LDV/SOF was cost-effective compared to most of the currently recommended treatments. Furthermore, LDV/SOF extends treatments to HCV-infected patients who are ineligible for interferon and RBV-based regimens. LDV/SOF thus has the potential to help reduce the burden of HCV in Japan.

Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C

DEFF Research Database (Denmark)

Leutscher, Peter Derek Christian; Lagging, Martin; Buhl, Mads Rauning

2010-01-01

The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa-2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI...

Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.

Directory of Open Access Journals (Sweden)

Ming V Lin

Full Text Available The prevalence of Hepatitis C Virus (HCV infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79% with a median age of 60 years (range 34-70 years, median creatinine of 1.2 mg/dL (0.66-1.76, and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%. All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin, ledipasvir (7 patients without and 1 patient with ribavirin or ribavirin alone (4 patients. The overall sustained virologic response (SVR12 was 91% (21 out of 23 patients. One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46% and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective

Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.

Science.gov (United States)

Lin, Ming V; Sise, Meghan E; Pavlakis, Martha; Amundsen, Beth M; Chute, Donald; Rutherford, Anna E; Chung, Raymond T; Curry, Michael P; Hanifi, Jasmine M; Gabardi, Steve; Chandraker, Anil; Heher, Eliot C; Elias, Nahel; Riella, Leonardo V

2016-01-01

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post

Reactivation of Herpesvirus in Patients With Hepatitis C Treated With Direct-Acting Antiviral Agents.

Science.gov (United States)

Perelló M, Christie; Fernández-Carrillo, Carlos; Londoño, María-Carlota; Arias-Loste, Teresa; Hernández-Conde, Marta; Llerena, Susana; Crespo, Javier; Forns, Xavier; Calleja, José Luis

2016-11-01

We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. We collected data from 576 patients with HCV infection treated with DAA combinations at 3 hospitals in Spain, from November 2014 through November 2015. We also collected data from a control population (230 HCV-infected patients, matched for sex and age; 23 untreated and 213 treated with interferon-based regimens). Herpesvirus was reactivated in 10 patients who received DAA therapy (7 patients had cirrhosis and 3 patients had received liver transplants), a median of 8 weeks after the therapy was initiated. None of the controls had herpesvirus reactivation. Patients with herpesvirus reactivation were receiving the DAA agents sofosbuvir with ledipasvir (with or without ribavirin, 7/10), ombitasvir with paritaprevir and ritonavir plus dasabuvir (with or without ribavirin, 2/10), or sofosbuvir with simeprevir plus ribavirin (1/10). Two of the 10 patients developed postherpetic neuralgia and 1 patient developed kerato-uveitis. All 10 patients with herpesvirus reactivation achieved a sustained virologic response. Immune changes that follow clearance of HCV might lead to reactivation of other viruses, such as herpesvirus. Patients with HCV infection suspected of having herpesvirus infection should be treated immediately. Some groups also might be screened for herpesvirus infection. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Telaprevir for previously treated chronic HCV infection

NARCIS (Netherlands)

McHutchison, John G.; Manns, Michael P.; Muir, Andrew J.; Terrault, Norah A.; Jacobson, Ira M.; Afdhal, Nezam H.; Heathcote, E. Jenny; Zeuzem, Stefan; Reesink, Hendrik W.; Garg, Jyotsna; Bsharat, Mohammad; George, Shelley; Kauffman, Robert S.; Adda, Nathalie; Di Bisceglie, Adrian M.; Heathcote, E. J.; Kaita, K.; Ma, M.; Myers, R.; Sherman, M.; Yoshida, E.; Berg, T.; Manns, M. P.; Zeuzem, S.; de Knegt, R.; van Hoek, B.; Afdhal, N. H.; Arora, S.; Bernstein, D.; Cochran, J.; Di Bisceglie, A. M.; Dickson, R.; Dieterich, D. T.; Etzkorn, K.; Everson, G. T.; Faruqui, S.; Ghalib, R.; Gitlin, N.; Godofsky, E.; Gordon, S.; Hassanein, T.; Jacobson, I. M.; Kilby, A.; Kugelmas, M.; Kwo, P. Y.; Lawitz, E. S.; Lindsay, K.; Maillard, M.; Nelson, D. R.; Nyberg, L.

2010-01-01

Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment. We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after

Impact of donor and recipient single nucleotide polymorphisms of IL28B rs8099917 in living donor liver transplantation for hepatitis C.

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Nobuhiro Harada

Full Text Available Single nucleotide polymorphisms of interleukin-28B (IL28B rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR and sustained virologic response (SVR were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.

Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders

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Loftis Jennifer M

2007-01-01

Full Text Available Abstract Background Individuals with substance use disorders (SUDs are at increased risk for hepatitis C viral infection (HCV, and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20 of the Veterans Healthcare Administration (VHA between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN or combination therapy (IFN and ribavirin who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group and patients without a history of SUD (SUD- Group. Results Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%, and if they had genotypes 1 and 4 (39.5% vs. 39.9%. Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8% and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%. Conclusion Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

Sequence diversity of hepatitis C virus 6a within the extended interferon sensitivity-determining region correlates with interferon-alpha/ribavirin treatment outcomes.

Science.gov (United States)

Zhou, Daniel X M; Chan, Paul K S; Zhang, Tiejun; Tully, Damien C; Tam, John S

2010-10-01

Studies on the association between sequence variability of the interferon sensitivity-determining region (ISDR) of hepatitis C virus and the outcome of treatment have reached conflicting results. In this study, 25 patients infected with HCV 6a who had received interferon-alpha/ribavirin combination treatment were analyzed for the sequence variations. 14 of them had the full genome sequences obtained from a previous study, whereas the other 11 samples were sequenced for the extended ISDR (eISDR). This eISDR fragment covers 192 bp (64 amino acids) upstream and 201 bp (67 amino acids) downstream from the ISDR previously defined for HCV 1b. The comparison between interferon-alpha resistance and response groups for the amino acid mutations located in the full genome (6 and 8 patients respectively) as well as the mutations located in the eISDR (10 and 15 patients respectively) showed that the mutations I2160V, I2256V, V2292I (Pc) 2010 Elsevier B.V. All rights reserved.

Treatment of Hantavirus Pulmonary Syndrome

Science.gov (United States)

2007-10-14

femoral artery and vein. The bed is versity of New Mexico. . Antiviral therapy Ribavirin was tested for efficacy in HFRS patients in China nd shown to...Weis- senbacher, M.C., 1996. Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina (B. Aires) 56, 709–711

A Review of Hepatitis C Virus (HCV) and the Current Management ...

African Journals Online (AJOL)

Background: Chronic Hepatitis C virus (HCV) is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end- stage liver disease. The addition of protease inhibitor with peginterferon alfa and ribavirin (triple therapy) for genotype 1 infected patients, are the current standard of care. Method: Data was sourced ...

Outcomes of treatment with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation.

Science.gov (United States)

Honda, Masaki; Sugawara, Yasuhiko; Watanabe, Takehisa; Tateyama, Masakuni; Tanaka, Motohiko; Uchida, Koushi; Kawabata, Seiichi; Yoshii, Daiki; Miura, Kouhei; Isono, Kaori; Hayashida, Shintaro; Ohya, Yuki; Yamamoto, Hidekazu; Sasaki, Yutaka; Inomata, Yukihiro

2017-10-01

The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT). A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis. Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12 weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4 months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment. The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12 weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection. © 2016 The Japan Society of Hepatology.

Boceprevir: a protease inhibitor for the treatment of hepatitis C.

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Chang, Mei H; Gordon, Lori A; Fung, Horatio B

2012-10-01

Boceprevir is a protease inhibitor indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in combination with peginterferon and ribavirin for treatment-naive patients and those who previously failed to improve with interferon and ribavirin treatment. This article provides an overview of the mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of boceprevir. Relevant information was identified through a search of PubMed (1990-July 2012), EMBASE (1990-July 2012), International Pharmaceutical Abstracts (1970-July 2012), and Google Scholar using the key words boceprevir, SCH 503034, non-structural protein 3 (NS3) serine protease inhibitor, and direct-acting antiviral agent (DAA). Additional information was obtained from the US Food and Drug Administration's Web site, review of the reference lists of identified articles, and posters and abstracts from scientific meetings. Clinical efficacy of boceprevir was assessed in 2 Phase III trials, Serine Protease Inhibitor Therapy-2 (SPRINT-2) for treatment-naive patients and Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) for treatment-experienced patients. In SPRINT-2, patients were randomized to receive peginterferon + ribavirin (PR) or peginterferon + ribavirin + boceprevir (PRB); duration of boceprevir therapy varied from 24, 32, to 44 weeks on the basis of HCV RNA results. The primary endpoint was achievement of sustained virologic response (SVR; lower limit of detection, 9.3 IU/mL). The addition of boceprevir was shown to be superior, with overall SVR rates ranging from 63% to 66% compared with 38% with PR (P < 0.001). Results of SVR in SPRINT-2 were also reorganized to monitor SVRs in black and non-black patients. Treatment-experienced patients were assessed in RESPOND-2; however, null responders were excluded. Patients were again randomized to PR or PRB; duration of boceprevir therapy varied from

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

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Rosângela Teixeira

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

2013-04-01

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Ya'aba et al.

African Journals Online (AJOL)

Christy

Dieterich DT., Purow JM and Rajapaksa R (1999): Activity of combination therapy with interferon alfa-2b plus ribavirin in chronic hepatitis C patients co-infected with HIV. Semin. Liver Diseases. 19(supplement. 1):87-94. 5. Federal Ministry of Health Nigeria (2004). National HIV/AIDS and Reproductive Health Survey.

Resistance-Associated NS5A Variants of Hepatitis C Virus Are Susceptible to Interferon-Based Therapy.

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Jun Itakura

Full Text Available The presence of resistance-associated variants (RAVs of hepatitis C virus (HCV attenuates the efficacy of direct acting antivirals (DAAs. The objective of this study was to characterize the susceptibility of RAVs to interferon-based therapy.Direct and deep sequencing were performed to detect Y93H RAV in the NS5A region. Twenty nine genotype 1b patients with detectable RAV at baseline were treated by a combination of simeprevir, pegylated interferon and ribavirin. The longitudinal changes in the proportion of Y93H RAV during therapy and at breakthrough or relapse were determined.By direct sequencing, Y93H RAV became undetectable or decreased in proportion at an early time point during therapy (within 7 days in 57% of patients with both the Y93H variant and wild type virus at baseline when HCV RNA was still detectable. By deep sequencing, the proportion of Y93H RAV against Y93 wild type was 52.7% (5.8%- 97.4% at baseline which significantly decreased to 29.7% (0.16%- 98.3% within 7 days of initiation of treatment (p = 0.023. The proportion of Y93H RAV was reduced in 21 of 29 cases (72.4% and a marked reduction of more than 10% was observed in 14 cases (48.7%. HCV RNA reduction was significantly greater for Y93H RAV (-3.65±1.3 logIU/mL/day than the Y93 wild type (-3.35±1.0 logIU/mL/day (p<0.001.Y93H RAV is more susceptible to interferon-based therapy than the Y93 wild type.

Resistance-Associated NS5A Variants of Hepatitis C Virus Are Susceptible to Interferon-Based Therapy.

Science.gov (United States)

Itakura, Jun; Kurosaki, Masayuki; Higuchi, Mayu; Takada, Hitomi; Nakakuki, Natsuko; Itakura, Yoshie; Tamaki, Nobuharu; Yasui, Yutaka; Suzuki, Shoko; Tsuchiya, Kaoru; Nakanishi, Hiroyuki; Takahashi, Yuka; Maekawa, Shinya; Enomoto, Nobuyuki; Izumi, Namiki

2015-01-01

The presence of resistance-associated variants (RAVs) of hepatitis C virus (HCV) attenuates the efficacy of direct acting antivirals (DAAs). The objective of this study was to characterize the susceptibility of RAVs to interferon-based therapy. Direct and deep sequencing were performed to detect Y93H RAV in the NS5A region. Twenty nine genotype 1b patients with detectable RAV at baseline were treated by a combination of simeprevir, pegylated interferon and ribavirin. The longitudinal changes in the proportion of Y93H RAV during therapy and at breakthrough or relapse were determined. By direct sequencing, Y93H RAV became undetectable or decreased in proportion at an early time point during therapy (within 7 days) in 57% of patients with both the Y93H variant and wild type virus at baseline when HCV RNA was still detectable. By deep sequencing, the proportion of Y93H RAV against Y93 wild type was 52.7% (5.8%- 97.4%) at baseline which significantly decreased to 29.7% (0.16%- 98.3%) within 7 days of initiation of treatment (p = 0.023). The proportion of Y93H RAV was reduced in 21 of 29 cases (72.4%) and a marked reduction of more than 10% was observed in 14 cases (48.7%). HCV RNA reduction was significantly greater for Y93H RAV (-3.65±1.3 logIU/mL/day) than the Y93 wild type (-3.35±1.0 logIU/mL/day) (p<0.001). Y93H RAV is more susceptible to interferon-based therapy than the Y93 wild type.

Effective oral favipiravir (T-705 therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever.

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Michelle Mendenhall

2011-10-01

Full Text Available Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed.Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV to further preclinical development of T-705 (Favipiravir, a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD(50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity.Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based on challenge with highly pathogenic arenaviruses

Resource-Based View of Information Systems: Sustainable and Transient Competitive Advantage Perspectives

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Gaurav Gupta

2018-01-01

Full Text Available The resource-based view (RBV, or resource-based theory, is one of the oldest and most influential theories in the field of information systems. This paper contends that it is timely to revisit, reflect on, and reposition RBV to ensure its continued disciplinary relevance and progress. In doing so, this paper (i provides a succinct and sharp evaluation of the conventional RBV of information systems that firms use to establish sustainable competitive advantage, and (ii makes an original contribution by introducing a contemporary RBV of information systems that firms can use to establish transient competitive advantage. Both these contributions should advance the current and future understanding of information systems as (a an internal firm resource, (b a source of competitive advantage, and (c a driver of firm performance.

Towards a Dynamic Resource-Based View: Insights from Austrian capital and Entrepreneurship Theory

DEFF Research Database (Denmark)

Foss, Nicolai Juul; Ishikawa, Ibuki

The dominant view in the strategic management field is the resource-based view ("RBV"). It has often been observed that the RBV is lacking in the dynamic dimension. For example, processes of building competitive advantages by means of combining existing complementary resources in novel ways...... are not inquired into. We argue that the RBV may profitably draw on Austrian (Misesian) and Knightian insights in entrepreneurship and capital theory, particularly in its Lachmannian manifestation, in order to strengthen its dynamic components. We link the RBV and Austrian ideas in the context of the theory...... of complex systems pioneered by Herbert Simon. We draw a number of implications for strategic management from this synthesis, notably into resource value and sustainability of competitive advantage.JEL Code: B53, D21, L23, M1...

Serial Changes in Alpha-Fetoprotein Levels During Therapy for Chronic Hepatitis C

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Altug Senol

2014-12-01

Full Text Available Aim: Alpha-fetoprotein (AFP has been widely used as a diagnostic marker for hepatocellular carcinoma. Some patients with hepatitis C show high AFP values, but no evidence of hepatocellular carcinoma. The aim of this study is to assess the influence of antiviral treatment on the serum AFP in patients with chronic hepatitis C without hepatocellular carcinoma. Material and Method: Thirty seven chronic hepatitis C patients (20 females and 17 males were included in the study. All patients were given a combined treatment of pegylated or conventional interferon (IFN and ribavirin. Serum AFP was measured at baseline and on months 3-6-12 of the therapy. Results: Compared to the pretreatment levels of ALT (88,59 ± 57,22 IU, those at 3, 6 and 12 months were statistically lower (p0,05, to 4,34 ± 4,64 (p>0,05 and to 2,63 ± 2,17 (p10 ng/ml. In these patients, mean serum AFP levels were decreased from pretreatment level of 15,09 ± 5,92 ng/ml to 11,39±3,30, to 6,97±2,53 (p

Epidemiological characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infection.

Science.gov (United States)

Roulot, D; Bourcier, V; Grando, V; Deny, P; Baazia, Y; Fontaine, H; Bailly, F; Castera, L; De Ledinghen, V; Marcellin, P; Poupon, R; Bourlière, M; Zarski, J P; Roudot-Thoraval, F

2007-07-01

Hepatitis C virus genotype 4 (HCV-4) infection is progressing in Europe, where epidemiology and sustained virological response (SVR) seem to be different than in the Middle East. We analysed epidemiological features and SVR rates in a retrospective study of 1532 HCV-4-infected patients, including 1056 patients infected in France, 227 immigrants infected in Egypt and 249 in sub-Saharan Africa. SVR rates were assessed in 242 naive patients of the 1532, who received peginterferon plus ribavirin for 48 weeks. HCV subtype 4a or 4d was the most common among patients infected in France, where the predominant route of transmission was intravenous drug abuse. The 4a subtype was largely predominant (93%) among patients infected in Egypt, where transmission was mostly because of parenteral treatment for schistosomiasis. More than seven different subtypes and no predominant route of infection were found in patients infected in sub-Saharan Africa. Liver fibrosis was significantly less severe in patients infected in France and Africa than in patients infected in Egypt. SVR rates were higher in patients infected in Egypt, compared with those infected in France or Africa (54.9%, 40.3% and 32.4%, respectively, P < 0.05). An overall better response was observed in patients infected with the 4a subtype. In multivariate analysis, two factors were associated independently with SVR: the Egyptian origin of transmission and the absence of severe fibrosis. In conclusion, the distribution of HCV-4 subtypes varies with the geographical origin of transmission and affects the SVR following antiviral treatment.

Hydrogen 1 (1H) magnetic resonance spectroscopy (MRS) of 3.0T in ...

African Journals Online (AJOL)

Ninety chronic hepatitis C patients undergoing antiviral therapy with interferon and ribavirin underwent 1H MR spectroscopy at 3.0T before treatment, 6 month after the start of treatment and one year after the start of treatment. Peak value of lipid, area under the peak of lipid, peak ratio of lipid, water and area ratio under the ...

New Therapies, Evidence, and Guidance in Hepatitis C Management: Expert Practices and Insights from an Educational Symposium at the AMCP 27th Annual Meeting Expo.

Science.gov (United States)

Terrault, Norah; Monto, Alex; Stinchon, Michael R; Rusie, Erica; Moreo, Kathleen

2015-09-01

The 2013-2014 approvals of new direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection have engendered a paradigm shift in HCV treatment and management, offering the potential for a cure at a population level. The availability of the highly effective and relatively safe DAAs prompted revisions to guidance recommendations based on new clinical trial evidence. In the context of this paradigm shift and considerations of the costs associated with the new DAAs, managed care professionals face new questions and challenges regarding HCV treatment and management approaches. To address the continuing education needs of this group, PRIME Education, Inc. (PRIME) conducted a symposium on HCV at the 27th Annual Meeting Expo of the Academy of Managed Care Pharmacy. Moderated by Michael R. Stinchon, Jr., RPh, the program panel featured 2 internationally recognized leaders in hepatitis C treatment and research: Norah Terrault, MD, MPH, and Alex Monto, MD.  To summarize the educational symposium presentations and discussions. This article is organized by key questions that the panelists and attendees raised for discussion during the 2-hour symposium. The questions addressed methods for assessing liver fibrosis; comprehensive patient assessment to inform treatment decisions; the influence of viral load on decisions about treatment duration; the role of ribavirin in optimizing treatment efficacy; unmet treatment needs for patients with HCV genotype 3 or advanced liver disease; and managed care strategies for patient education, adherence promotion, and care coordination. In answering attendee questions on these issues, the expert panelists presented established evidence, and recognizing limitations to current evidence and guidance recommendations, they discussed applications of clinical judgment and offered their views and practices regarding individualized care for patients with HCV.  In response to questions about the utility of noninvasive methods for

Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients

Directory of Open Access Journals (Sweden)

Chen Z

2017-08-01

Full Text Available Zhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Background: Direct-acting antiviral (DAA resistance-associated substitutions (RASs can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV. The selection pressure by pegylated-interferon (Peg-IFN plus ribavirin (P/R treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group and those previously treated with P/R (post-IFN group. The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]. The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%. The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%–5%. Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not

Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.

Science.gov (United States)

Chayama, Kazuaki; Hayes, C Nelson; Yoshioka, Kentaro; Moriwaki, Hisataka; Okanoue, Takashi; Sakisaka, Shotaro; Takehara, Tetsuo; Oketani, Makoto; Toyota, Joji; Izumi, Namiki; Hiasa, Yoichi; Matsumoto, Akihiro; Nomura, Hideyuki; Seike, Masataka; Ueno, Yoshiyuki; Yotsuyanagi, Hiroshi; Kumada, Hiromitsu

2011-04-01

Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy. We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment. When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%. Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.

The Challenges of Teaching Strategic Management: Working toward Successful Inclusion of the Resource-Based View

Science.gov (United States)

Schneider, Marguerite; Lieb, Pamela

2004-01-01

The industrial organization economics (IOE) and resource-based view (RBV) schools contribute uniquely to the strategic management curriculum. However, presentation of the RBV is often inadequate or ineffective, in part due to faculty habit, students' conceptualization of knowledge as objective and readily transferable, and course pedagogy. We…

Een resource-based portfoliobenadering : strategieën op basis van de resource-based view

NARCIS (Netherlands)

Santema, S.C.; Rijt, van de J.

1999-01-01

In dit artikel wordt met behulp van de Resourcebased View (RBV) een portfoliomodel voor resources ontwikkeld. De RBV kenmerkt zich tot op heden als een theorie met een eenzijdige focus op sterke, niet-imiteerbare, immobiele resources. In dit artikel wordt weergegeven hoe een onderneming kan omgaan

Synergistic antiviral activity of gemcitabine and ribavirin against enteroviruses

NARCIS (Netherlands)

Kang, Hyunju; Kim, Chonsaeng; Kim, Dong-Eun; Song, Jae-Hyoung; Choi, Miri; Choi, Kwangman; Kang, Mingu; Lee, Kyungjin; Kim, Hae Soo; Shin, Jin Soo; Kim, Janghwan; Han, Sang-Bae; Lee, Mi-Young; Lee, Su Ui; Lee, Chong-Kyo; Kim, Meehyein; Ko, Hyun-Jeong; van Kuppeveld, Frank J M; Cho, Sungchan

2015-01-01

Enteroviruses are major causative agents of various human diseases, and some of them are currently considered to be an enormous threat to public health. However, no effective therapy is currently available for the treatment of these infections. We identified gemcitabine, a nucleoside-analog drug

Trombose de veia central da retina em paciente usuária de interferon e ribavirina: relato de caso Central vein occlusion in a patient using interferon and ribavirin: case report

Directory of Open Access Journals (Sweden)

John Helal Jr.

2006-08-01

Full Text Available O interferon alfa (INF alfa é droga atualmente utilizada no tratamento de várias doenças sistêmicas, como a hepatite C crônica. A ribavirina quando associada ao interferon alfa aumenta muito a resposta ao tratamento. Estima-se que a infecção crônica pelo vírus da hepatite C afete 170 milhões de pessoas no mundo, muitas delas em uso dessas medicações. A forma típica da retinopatia associada ao interferon alfa apresenta exsudatos algodonosos e hemorragias intra-retinianas. Há vários relatos de alterações oculares associadas ao uso do interferon alfa. Este trabalho descreve um caso de oclusão de veia central da retina em olho direito, com hemorragias no olho contralateral, em paciente usuária dessas medicações por dois anos. O caso descrito expõe em um dos olhos o quadro mais freqüente da retinopatia associada ao uso de interferon alfa (hemorragias de fundo e no olho contralateral, uma apresentação muito mais atípica (trombose de veia central da retina. O quadro fundoscópico apresentou melhora com a interrupção da medicação.Interferon and ribavirin are medications widely used in the treatment of some systemic diseases, mainly hepatitis C. Ribavirin when associated with interferon increases the rate of success of this treatment. There are about 170 million patients with chronic hepatitis C in the world, many in use of these medications. The classic associated retinopathy is described as cotton wool exudates and hemorrhages. Since the first reports, several different ocular disturbances were described in association with interferon. The present case shows a patient whose right eye presented with central retinal vein occlusion and whose left eye presented the typical findings of hemorrhages; prompt resolution after the medications were discontinued.

The Future of HCV Therapy: NS4B as an Antiviral Target

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Hadas Dvory-Sobol

2010-11-01

Full Text Available Chronic hepatitis C virus (HCV infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors.

Sofosbuvir treatment and hepatitis C virus infection

Science.gov (United States)

Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

2016-01-01

Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

The Resource-Based View and Value: The Customer-Based View of the Firm

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Clulow, Val; Barry, Carol; Gerstman, Julie

2007-01-01

Purpose: The resource-based view (RBV) explores the role of key resources, identified as intangible assets and capabilities, in creating competitive advantage and superior performance. To a great extent the conceptual analysis and empirical research within the RBV has focused on the firm's perspective of key resources and the value to the firm of…

Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

Science.gov (United States)

Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

2014-05-01

Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

Interleukin 28B gene variation at rs12979860 determines early viral kinetics during treatment in patients carrying genotypes 2 or 3 of hepatitis C virus

DEFF Research Database (Denmark)

Lindh, Magnus; Lagging, Martin; Färkkilä, Martti

2011-01-01

Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon λ3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n...... = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P

The Comparative Effects of Transaction Cost Economics and Resource Based View: A Technological Alliance Motivational Perspective

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Hwan Jin Kim

2016-06-01

Full Text Available This paper examines the impact of two main alliance motivation theories, transaction cost economics (TCE and resource based view (RBV, on alliance processes among Korean manufacturing high-tech ventures. Results show that TCE and RBV are complimentarily explaining the formation of inter-firm alliances. TCE variables are more related with alliance partner characteristics while RBV is more linked with partner capabilities. Both show positive effects on performance. No significant effect is found on determining an alliance governance structure. While selecting appropriate technological alliance partners show positive effects on performance, no significant effect is found between alliance governance structure and performance. Factors of both theories impacting each alliance stage and analytical explanations of such impacts are discussed.

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

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Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

2013-01-01

Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

Directory of Open Access Journals (Sweden)

Julie Nemecek

Full Text Available Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA to amplify abnormal prion protein (PrP(TSE from highly diluted variant Creutzfeldt-Jakob disease (vCJD-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE in tissues and blood. Macaque vCJD PrP(TSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA. Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV, a close relative of the bank vole, seeded with macaque vCJD PrP(TSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N. We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE. Meadow vole brain (170N/N PrP genotype was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE was more permissive than human PrP(TSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE from brains of humans and macaques with vCJD. PrP(TSE signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

Effect of Antiviral Therapy on Markers of Fibrogenesis in Patients with Chronic Hepatitis C

DEFF Research Database (Denmark)

Nøjgaard, C.; Johansen, J.S.; Krarup, H.B.

2003-01-01

BACKGROUND: The possible markers of liver fibrosis (plasma YKL-40, PIIINP, MMP-2 and TIMP-1) were measured at the start (t0) and end of treatment (t12) with alpha-interferon and ribavirin and repeated at 6-months follow-up (t18) in 51 patients with chronic hepatitis C. METHODS: We evaluated 1...... significantly increased in patients compared to normal controls. In responders (n = 30), plasma YKL-40 (P

The effect of combined drugs therapy on the course of clinical rabies infection in a murine model.

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Smreczak, Marcin; Orłowska, Anna; Marzec, Anna; Trębas, Paweł; Kycko, Anna; Reichert, Michał; Koraka, Penelope; Osterhaus, Albert D M E; Żmudziński, Jan Franciszek

2018-04-09

Rabies is a fatal disease of all mammals causing almost 60,000 human deaths every year. To date, there is no effective treatment of clinical rabies once the symptoms appear. Here, we describe the promising effect of combination therapy composed of molecules that target replication of the rabies virus (RV) at different stages of life cycle and molecules that inhibit some pathways of the innate host immune response accompanied by a blood-brain barrier opener on the outcome of RV infection. The study reports statistically significant extension of survival of mice treated with the drug cocktail containing T-705, ribavirin, interferon α/β, caspase-1 inhibitor, TNF-α inhibitor, MAPKs inhibitor and HRIG compared to the survival of mice in the virus control group (p = 0.0312). Furthermore, the study points to the significant impact of interferon α/β on the survival of RV-infected mice. We have shown a significant down regulation of pro-inflammatory molecules (caspase-1 and TNF-a) in the CNS in RV-infected mice treated with a combination of drugs including interferon α/β. Copyright © 2018. Published by Elsevier Ltd.

A Framework for Prediction of Response to HCV Therapy Using Different Data Mining Techniques

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Enas M. F. El Houby

2014-01-01

Full Text Available Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV. The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients’ response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

Management of the infant with respiratory syncytial virus.

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Corey, M A; Clore, E R

1991-04-01

This article examines updated clinical information concerning respiratory syncytial virus (RSV) infection including epidemiology, pathology, clinical manifestations, diagnosis, treatment, nosocomial infection, and prognosis. Also presented is current information on ribavirin therapy, its side effects, and precautions. Research related to the most effective isolation methodology is discussed, as well as nursing diagnoses based on Gordon's Functional Health Patterns and interventions for the infant hospitalized with RSV bronchiolitis and/or pneumonia.

Treatment response in HCV related chronic hepatitis

International Nuclear Information System (INIS)

Hussain, A.B.; Hussain, T.; Hussain, S.; Masood, A.; Kazmi, Y.; Tariq, W.Z.; Karamat, K.A.

2004-01-01

Objective: To evaluate the virological response to treatment with interferon and ribavirin in-patients with hepatitis C related liver disease. Material and Methods: Two hundred seventy-nine patients were included in the study. These patients had taken interferon and ribavirin treatment for HCV related chronic hepatitis, and were referred to AFIP for HCV RNA testing by polymerase chain reaction (PCR) between January 2002 and September 2002. Out of 279 cases, 229 had taken the treatment for 06 or 12 months and were tested for end-of-treatment response (ETR). Fifty patients had completed there treatment regimens of 6 or 12 months treatment, at least 24 weeks before their PCR test and were having follow-up testing for sustained viral response (SVR). The sera of these patients were tested for HCV RNA by PCR, using a commercial kit of Amplicor (Roche) for qualitative detection of HCV RNA. Results: Out of 229 cases tested for end-of-treatment response, 198 (86.5%) had no detectable HCV RNA (responders) and 31 (13.50%) were PCR positive (non-responders). Thirty-eight out of 50 cases, tested for a sustained viral response, had a negative result for HCV PCR thus showing sustained response rate of 76%. Conclusion: The viral remission/response to interferon and ribavirin combination therapy in our patients was better than that quoted in other regions. (author)

Bioavailability of iron in cottonseed meal, ferric sulfate, and two ferrous sulfate by-products of the galvanizing industry.

Science.gov (United States)

Boling, S D; Edwards, H M; Emmert, J L; Biehl, R R; Baker, D H

1998-09-01

Iron depletion-repletion assays were carried out with young chicks to establish Fe bioavailability values for Fe2(SO4)3.7H2O (22.7% Fe), Fe-ZnSO4.H2O (20.2% Fe, 13.0% Zn), Zn-FeSO4.H2O (20.2% Zn, 14.2% Fe), and cottonseed meal (200 mg Fe/kg). Standard hemoglobin response curves were established using feed-grade FeSO4.H2O (28.8% Fe) or reagent-grade FeSO4.7H2O (20.1% Fe) as standards such that relative bioavailability (RBV) could be assessed for the experimental sources of Fe. Weight gain, hemoglobin, and hematocrit responded linearly (P 0.10) from the standard. However, evaluation of all criteria of response (hemoglobin, hematocrit, weight gain) suggested that neither Fe-ZnSO4.H2O nor Zn-FeSO4.H2O had different Fe RBV values than FeSO4.H2O. Standard-curve calculations were used for assessment of Fe RBV in Fe2(SO4)3.7H2O and cottonseed meal, as only a single level of Fe addition was studied for each of these products. Iron RBV in Fe2(SO4)3.7H2O was estimated to be 37%, whereas Fe RBV in cottonseed meal was found to be 56%. Both of these values were lower (P galvanizing industry, are excellent sources of bioavailable Fe, whereas ferric sulfate and cottonseed meal are relatively poor sources of usable Fe.

Correlation between a single nucleotide polymorphism (G/T at nt ...

African Journals Online (AJOL)

Jane

2011-10-12

Oct 12, 2011 ... correlated to achieving sustained virological response (SVR) after pegylated interferon alpha and ribavirin ... ribavirin. Key words: Hepatitis C virus (HCV), interferon (IFN), myxovirus resistance protein (Mx1 protein), myxovirus .... long injection of interferon alpha 2b plus daily oral dose of ribavirin). If SVR is ...

Validation of a questionnaire to monitor symptoms in HIV-infected patients during hepatitis C treatment.

Science.gov (United States)

Cachay, Edward R; Ballard, Craig; Colwell, Bradford; Torriani, Francesca; Hicks, Charles; Mathews, Wm Christopher

2017-09-20

Clinicians are incorporating patient-reported outcomes in the management of HIV-infected persons co-infected with hepatitis C virus (HCV), but there are no validated inventories to monitor symptoms of patients during HCV therapy. Five-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV. The HCV symptom-inventory (HCV-SI) was administered before, during, and after HCV treatment. Discriminant validity was assessed, separately, in mixed model linear regression of HCV-SI T-scores on treatment regimens (pegylated-interferon and ribavirin; pegylated-interferon, ribavirin, and telaprevir; and interferon-free antivirals); and side effect-related premature treatment discontinuation (SE-DC). From the 103 patients who completed the HCV-SI, 7% were female, 26% non-white, 32% cirrhotics and 91% had undetectable HIV viral loads. Most had genotype 1 (83%) and were HCV treatment-naïve (78%). We treated 19% of patients with pegylated-interferon and ribavirin, 22% with pegylated-interferon, ribavirin, and telaprevir and 59% received interferon-free antivirals. Overall, 77% achieved a sustained virologic response, and 6% discontinued HCV treatment due to side effects. In the treatment discrimination model, compared to the no treatment period, HCV-SI scores were significantly (p < 0.01) lower for interferon-free antivirals and higher for interferon-containing regimens. In the SE-DC model, the total HCV-SI, somatic and neuropsychiatric scores significantly predicted those patients who prematurely discontinued HCV treatment (P < 0.05). The HCV-SI effectively differentiated among treatment regimens known to vary by side effect profiles and between patients with and without treatment discontinuation due to side effects. The HCV-SI may have value as a patient-reported outcome instrument predicting the risk of HCV treatment discontinuation.

Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C.

Science.gov (United States)

Bruix, Jordi; Poynard, Thierry; Colombo, Massimo; Schiff, Eugene; Burak, Kelly; Heathcote, Elizabeth J L; Berg, Thomas; Poo, Jorge-Luis; Mello, Carlos Brandao; Guenther, Rainer; Niederau, Claus; Terg, Ruben; Bedossa, Pierre; Boparai, Navdeep; Griffel, Louis H; Burroughs, Margaret; Brass, Clifford A; Albrecht, Janice K

2011-06-01

Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program. Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n=311) or no treatment (controls, n=315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event. There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P=.016). There were no new safety observations. Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Compliance with therapy in patients with chronic hepatitis C: associations with psychiatric symptoms, interpersonal problems, and mode of acquisition.

Science.gov (United States)

Kraus, M R; Schäfer, A; Csef, H; Faller, H; Mörk, H; Scheurlen, M

2001-10-01

Tolerance of interferon-a therapy for hepatitis C is often poor and medication is expensive. Compliance with diagnostic procedures and, even more important, with medical treatment is obviously critical to minimize the rate of dropouts and to maximize cost efficiency. Moreover, a good concordance with scheduled follow-ups is important for early recognition and treatment of interferon-associated side effects. Therefore, we investigated psychiatric symptoms, interpersonal problems, different modes of acquisition, and sociodemographic factors in HCV-infected patients as possible predictor variables of good versus poor compliance. In a longitudinal study, 74 patients with chronic hepatitis C (CHC) who fulfilled the criteria for treatment with interferon (IFN)-alpha-2b with or without ribavirin were investigated prospectively to identify those at risk for poor compliance during IFN medication. To assess predictive factors, we used both IIP-C (Inventory of Interpersonal Problems) and SCL-90-R (Symptom Check List 90 Items Revised) as psychometric instruments. Sociodemographic and somatic variables as well as compliance during IFN therapy were also evaluated. Poor compliance before or during medication was demonstrated by 23% (N = 17) of HCV patients. Sociodemographic factors and mode of acquisition, particularly former intravenous drug (IVD) abuse were not significantly linked with compliance. Logistic regression analysis demonstrated that the subgroup of patients with compliance problems was best identified by both pretherapeutic psychiatric symptoms and interpersonal problems. Predictive value was best and significant for anger-hostility (P = 0.009), intrusive (P = 0.014), depression (P = 0.015), and phobic anxiety (P = 0.049). Adopting this statistical prediction model, sensitivity was 47.1%, but specificity reached 98.3%. In total, 86.5% of cases were classified correctly. In situations of unclear indication for IFN therapy, psychological variables assessment of before

Ribavirin

Science.gov (United States)

... difficulty concentrating difficulty falling asleep or staying asleep memory loss rash dry, irritated, or itchy skin sweating ... is important to keep all medication out of sight and reach of children as many containers (such ...

Image-guided radiotherapy of bladder cancer: bladder volume variation and its relation to margins

DEFF Research Database (Denmark)

Muren, Ludvig; Redpath, Anthony Thomas; Lord, Hannah

2007-01-01

: The correlation between the relative bladder volume (RBV, defined as repeat scan volume/planning scan volume) and the margins required to account for internal motion was first studied using a series of 20 bladder cancer patients with weekly repeat CT scanning during treatment. Both conformal RT (CRT) and IGRT......BACKGROUND AND PURPOSE: To control and account for bladder motion is a major challenge in radiotherapy (RT) of bladder cancer. This study investigates the relation between bladder volume variation and margins in conformal and image-guided RT (IGRT) for this disease. MATERIALS AND METHODS...... these patients were given fluid intake restrictions on alternating weeks during treatment. RESULTS: IGRT gave the strongest correlation between the RBV and margin size (R(2)=0.75; p10mm were required in only 1% of the situations when the RBV1, whereas isotropic margins >10...

[Novel methods of hepatitis C treatment and prevention].

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Chmielewska, Alicja M; Rychłowska, Małgorzata; Król, Ewelina; Solarz, Karolina; Bieńkowska-Szewczyk, Krystyna

2015-08-19

Despite available treatment, Hepatitis C remains one of most serious burdens to public health. Current therapy based on pegylated interferon-alpha and ribavirin has significant side effects and its effectiveness varies for different genotypes of the virus. Four novel drugs - viral protease inhibitors (telaprevir, boceprevir, simeprevir) and polymerase inhibitor - sofosbuvir have been introduced in last years for use in combination with standard-of-care treatment. For the first time interferon free therapies were approved with the use of combination of sofosbuvir+ribavirin. New therapies improve virological response rates but also increase the cost, side effects and raise the issue of drug resistance. Numerous novel anti-HCV compounds have been evaluated in advanced clinical trials including inhibitors of viral proteins (protease, polymerase and NS5A) and inhibitors of host factors involved in HCV replication (cyclophilin A, microRNA - miR-122). New interferon-free therapies reducing severe side effects are expected to enter the market within few months. At the same time efforts are undertaken to determine the host and viral factors with predictive value for HCV treatment response, enabling personalized therapy approach. The main success in this field was the discovery of interleukin IL28B polymorphism, which correlates with positive standard-of-care treatment response. An effective vaccination may be an alternative for antiviral drugs, but no anti-HCV vaccine is available currently. It is well proved that successful vaccination should induce antibody and T-cell responses specific against a range of HCV genotypes. With this aim, new subunit and genetic candidate vaccines have been evaluated in I and II phase clinical trials. This review summarizes the recent developments in the field of new drug development and vaccine studies against hepatitis C virus.

Novel methods of hepatitis C treatment and prevention

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Alicja M. Chmielewska

2015-08-01

Full Text Available Despite available treatment, Hepatitis C remains one of most serious burdens to public health. Current therapy based on pegylated interferon-alpha and ribavirin has significant side effects and its effectiveness varies for different genotypes of the virus. Four novel drugs – viral protease inhibitors (telaprevir, boceprevir, simeprevir and polymerase inhibitor – sofosbuvir have been introduced in last years for use in combination with standard-of-care treatment. For the first time interferon free therapies were approved with the use of combination of sofosbuvir+ribavirin. New therapies improve virological response rates but also increase the cost, side effects and raise the issue of drug resistance. Numerous novel anti-HCV compounds have been evaluated in advanced clinical trials including inhibitors of viral proteins (protease, polymerase and NS5A and inhibitors of host factors involved in HCV replication (cyclophilin A, microRNA – miR-122. New interferon-free therapies reducing severe side effects are expected to enter the market within few months. At the same time efforts are undertaken to determine the host and viral factors with predictive value for HCV treatment response, enabling personalized therapy approach. The main success in this field was the discovery of interleukin IL28B polymorphism, which correlates with positive standard-of-care treatment response. An effective vaccination may be an alternative for antiviral drugs, but no anti-HCV vaccine is available currently. It is well proved that successful vaccination should induce antibody and T-cell responses specific against a range of HCV genotypes. With this aim, new subunit and genetic candidate vaccines have been evaluated in I and II phase clinical trials. This review summarizes the recent developments in the field of new drug development and vaccine studies against hepatitis C virus.

Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

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Pan, Calvin Q; Tiongson, Benjamin C; Hu, Ke-Qin; Han, Steven-Huy B; Tong, Myron; Chu, Danny; Park, James; Lee, Tai Ping; Bhamidimarri, Kalyan Ram; Ma, Xiaoli; Xiao, Pei Ying; Mohanty, Smruti R; Wang, Dan

2018-06-16

Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

De novo Cryoglobulinaemic Mononeuritis Multiplex during Treatment of Chronic Hepatitis C Infection: A Viral Effect or Induced by Pegylated Interferon Alpha

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J.R. Potts

2012-03-01

Full Text Available Cryoglobulinaemic mononeuritis multiplex (MNM is an extrahepatic manifestation of chronic hepatitis C virus (HCV infection for which interferon-based antiviral therapy is currently the treatment of choice. Rarely MNM can be associated with HCV treatment though generally in the setting of pre-existing cryoglobulinaemia and detectable HCV viraemia. We report an unusual case of de novo MNM occurring late during the course of pegylated interferon and ribavirin therapy for chronic HCV infection, following a prolonged period of viral suppression. The patient had no evidence of cryoglobulinaemia prior to HCV treatment and undetectable HCV RNA levels at the time of presentation with MNM. The case raises the possibility that MNM could develop as an adverse immunomodulatory effect of pegylated interferon therapy.

Interferon-Mediated Regression of Fibrosis During Antiviral Therapy for Chronic Hepatitis C in Different Variants of IL28B Gene Polymorphism

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D.Ye. Telegin

2014-02-01

Full Text Available The article considers the relationship between the degree of reduction of HCV-induced liver fibrosis by the end of antiviral therapy (AVT for chronic hepatitis C (CHC and the main variants of IL28b gene polymorphism. Materials and Methods. Retrospectively we analyzed the outcomes of treatment of 324 patients who received standard antiviral therapy (a combination of pegylated interferons PegIFN-alpha2b or PegIFN-alpha2a and ribavirin for CHC genotype 1b. The total duration of treatment was 12 months. We evaluated three types of virologic response: rapid (RVR, 4th week of AVT, early (EVR, 12th week of AVT and sustained (SVR, 24th week after the AVT. Results and Discussion. All types of detected changes of fibrosis stages by the end of antiviral treatment in comparison with baseline values were distributed into the following groups : 1 — a significant reduction of fibrosis (25 % of treated patients, 2 — moderate decrease in fibrosis (64 % patients, 3 — unchanged degree of fibrosis (7.6 %, increased fibrosis (3.4 %. A comparison of fibrosis dynamics during antiviral therapy was carried out in the two groups of patients: without (N = 110 and with (N = 214 T-allele of the gene IL28b. The most significant decrease in the degree of fibrosis detected among patients with favorable CC gene IL28b variant, because exactly in this group of patients the frequency of SVR was highest. Among those who have reached sustained aviremia, the lowest degree of reduction of fibrosis was found in T-allele carriers of the gene IL28b. Conclusions. The findings suggest that not all patients with CHC who achieved sustained virologic response escape the risks associated with the effects of viral persistence of HCV.

Prevention and treatment of respiratory syncytial virus bronchiolitis and postbronchiolitic wheezing

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Kimpen Jan LL

2002-06-01

Full Text Available Abstract Respiratory syncytial virus (RSV is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.

Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France.

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Aherfi, Sarah; Solas, Caroline; Motte, Anne; Moreau, Jacques; Borentain, Patrick; Mokhtari, Saadia; Botta-Fridlund, Danielle; Dhiver, Catherine; Portal, Isabelle; Ruiz, Jean-Marie; Ravaux, Isabelle; Bregigeon, Sylvie; Poizot-Martin, Isabelle; Stein, Andreas; Gérolami, René; Brouqui, Philippe; Tamalet, Catherine; Colson, Philippe

2014-11-01

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy. © 2014 Wiley Periodicals, Inc.

Clinical importance of pharmacogenetics in the treatment of hepatitis C virus infection.

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Kamal, Adina Maria; MitruŢ, Paul; Kamal, Kamal Constantin; Tica, Oana Sorina; Niculescu, Mihaela; Alexandru, Dragoş Ovidiu; Tica, Andrei Adrian

2016-01-01

Globally, over 4% of the world population is affected by hepatitis C virus (HCV) infection. The current standard of care for hepatitis C infection is combination therapy with pegylated interferon and ribavirin for 48 weeks, which yield a sustained virological response in only a little over half of the patients with genotype 1 HCV. We investigated the clinical importance of pharmacogenetics in treatment efficacy and prediction of hematotoxicity. A total of 148 patients infected with HCV were enrolled. All patients were treated for a period of 48 weeks or less with pegylated interferon and ribavirin. Four genotypes were investigated: inosine triphosphatase (ITPA) rs1127354, C20orf194 rs6051702, interferon lambda (IFNL)3 rs8099917, IFNL3÷4 rs12979860 in the population from southwestern Romania. Genetic variants for rs129798660 and rs6051702 proved once more to represent an indisputable clinical tool for predicting sustained virological response (SVR) (69.23%, chi-square p=0.007846, ppharmacogenetics should play a constant role in treatment decisions for patients infected with hepatitis C virus.

A Bibliometric Study of the Resource-based View (RB V in International Business Research Using Barney (1991 as a Key Marker

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Manuel Portugal Ferreira

2016-06-01

Full Text Available In this study we examine how the RBV has been included in IB research over the past twenty years using Barney’s (1991 article as a key marker. Bibliometric techniques analyzing citations, co-citations and research themes delved into, were applied to the articles published between 1991 and 2010 in five leading IB journals. Data was collected from the Social Science Citation Index (SSCI of the Institute for Scientific Information (ISI. We conclude that the RBV has been having an important impact on most of IB research themes and has been driving a large portion of current thought on the multinational corporations’ strategies, location choices and internationalization. Although, we also find areas that have been explored to much lesser extent. In addition to identify the stock of accumulated knowledge, this study contributes to highlight areas for future inquiry on how IB studies may further benefit from an RBV-oriented perspective.

Chronic hepatitis E infection with an emerging virus strain in a heart transplant recipient successfully treated with ribavirin: a case report.

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Waldenström, Jesper; Castedal, Maria; Konar, Jan; Karason, Kristjan; Lagging, Martin; Norder, Helene

2015-08-26

During the last decade hepatitis E infections have been recognized as a health problem in high-income countries, where hepatitis E virus genotype 3 is endemic. The infection is often self-limiting, but may develop into chronic infection in immunocompromised patients, especially in solid organ recipients. If these patients or patients with underlying liver disease get hepatitis E infection, they may develop liver failure and cirrhosis. Hepatitis E virus is occasionally found in blood products and transfusion transmission has been reported. We present the first case of chronic hepatitis E infection in a heart transplant recipient in Sweden. A 63-year-old Swedish white man presented with highly elevated liver enzymes 6 months after heart transplantation. Polymerase chain reaction revealed chronic hepatitis E infection, caused by a virus strain found infecting symptomatic cases in Sweden and other European countries. During transplantation, he received blood products from 17 donors, and transfusion transmission is highly likely. The only detectable marker for hepatitis E infection was hepatitis E virus ribonucleic acid for more than 2 months before anti-hepatitis E virus developed. He was treated successfully with ribavirin and decreased immunosuppression. Our patient was probably infected through contaminated blood products and subsequently developed chronic infection, which was cured upon treatment. This highlights the need for evaluating the problem with chronic hepatitis E infection in immunocompromised patients, and for discussion concerning screening of blood products. Polymerase chain reaction-based methods are recommended for diagnosing hepatitis E infection in patients with compromised immunity. In addition, knowledge needs to be gained on the infecting virus strain, which may be more virulent than other strains.

Assessment of cost of innovation versus the value of health gains associated with treatment of chronic hepatitis C in the United States: The quality-adjusted cost of care.

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Younossi, Zobair M; Park, Haesuk; Dieterich, Douglas; Saab, Sammy; Ahmed, Aijaz; Gordon, Stuart C

2016-10-01

New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. A decision-analytic Markov model. Published literature and clinical trial data. Life Time. Third-party payer. This study compared four approved regimens in treatment-naïve genotype 1 chronic hepatitis C patients, including pegylated interferon and ribavirin (PR), first generation triple therapy (boceprevir + PR and telaprevir + PR), second generation triple therapy (sofosbuvir + PR and simeprevir + PR) and all-oral DAA regimens (ledipasvir/sofosbuvir and ombitasvir + paritaprevir/ritonavir + dasabuvir ± ribavirin). Quality-adjusted cost of care (QACC). QACC was defined as the increase in treatment cost minus the increase in the patient's quality-adjusted life years (QALYs) when valued at $50,000 per QALY. All-oral therapy improved the average sustained virologic response (SVR) rate to 96%, thereby offsetting the high drug acquisition cost of $85,714, which resulted in the highest benefit based on the efficiency frontier. Furthermore, while oral therapies increased HCV drug costs by $48,350, associated QALY gains decreased quality-adjusted cost of care by $14,120 compared to dual therapy. When the value of a QALY was varied from $100,000 to $300,000, the quality adjusted cost of care compared to dual therapy ranged from - $21,234 to - $107,861, - $89,007 to - $293,130, - $176,280 to - $500,599 for first generation triple, second generation triple, and all-oral therapies, respectively. Primary efficacy and safety measurements for drug regimens were sourced from clinical trials data rather than a real

Stable replication of the EBNA1/OriP-mediated baculovirus vector and its application to anti-HCV gene therapy

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Chang Myint OO

2009-10-01

Full Text Available Abstract Background Hepatitis C virus (HCV is one of the main causes of liver-related morbidity and mortality. Although combined interferon-α-ribavirin therapy is effective for about 50% of the patients with HCV, better therapies are needed and preventative vaccines have yet to be developed. Short-hairpin RNAs (shRNAs inhibit gene expression by RNA interference. The application of transient shRNA expression is limited, however, due to the inability of the shRNA to replicate in mammalian cells and its inefficient transduction. The duration of transgene (shRNA expression in mammalian cells can be significantly extended using baculovirus-based shRNA-expressing vectors that contain the latent viral protein Epstein-Barr nuclear antigen 1 (EBNA1 and the origin of latent viral DNA replication (OriP sequences. These recombinant vectors contain compatible promoters and are highly effective for infecting primary hepatocyte and hepatoma cell lines, making them very useful tools for studies of hepatitis B and hepatitis C viruses. Here, we report the use of these baculovirus-based vector-derived shRNAs to inhibit core-protein expression in full-length hepatitis C virus (HCV replicon cells. Results We constructed a long-term transgene shRNA expression vector that contains the EBV EBNA1 and OriP sequences. We also designed baculovirus vector-mediated shRNAs against the highly conserved core-protein region of HCV. HCV core protein expression was inhibited by the EBNA1/OriP baculovirus vector for at least 14 days, which was considerably longer than the 3 days of inhibition produced by the wild-type baculovirus vector. Conclusion These findings indicate that we successfully constructed a long-term transgene (shRNA expression vector (Ac-EP-shRNA452 using the EBNA1/OriP system, which was propagated in Escherichia coli and converted into mammalian cells. The potential anti-HCV activity of the long-term transgene (shRNA expression vector was evaluated with the view

Changes in forearm muscle temperature alter renal vascular responses to isometric handgrip.

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Kuipers, Nathan T; Sauder, Charity L; Kearney, Matthew L; Ray, Chester A

2007-12-01

The purpose of the present study was to examine the effect of heating and cooling the forearm muscles on renal vascular responses to ischemic isometric handgrip (IHG). It was hypothesized that heating and cooling the forearm would augment and attenuate, respectively, renal vascular responses to IHG. Renal vascular responses to IHG were studied during forearm heating at 39 degrees C (n = 15, 26 +/- 1 yr) and cooling at 26 degrees C (n = 12, 26 +/- 1 yr). For a control trial, subjects performed the experimental protocol while the forearm was normothermic (approximately 34 degrees C). Muscle temperature (measured by intramuscular probe) was controlled by changing the temperature of water cycling through a water-perfused sleeve. The experimental protocol was as follows: 3 min at baseline, 1 min of ischemia, ischemic IHG to fatigue, and 2 min of postexercise muscle ischemia. At rest, renal artery blood velocity (RBV; Doppler ultrasound) and renal vascular conductance (RVC = RBV/mean arterial blood pressure) were not different between normothermia and the two thermal conditions. During ischemic IHG, there were greater decreases in RBV and RVC in the heating trial. However, RBV and RVC were similar during postexercise muscle ischemia during heating and normothermia. RVC decreased less during cooling than in normothermia while the subjects performed the ischemic IHG protocol. During postexercise muscle ischemia, RVC was greater during cooling than in normothermia. These results indicate that heating augments mechanoreceptor-mediated renal vasoconstriction whereas cooling blunts metaboreceptor-mediated renal vasoconstriction.

Interferon-alpha-induced destructive thyroiditis followed by Graves' disease in a patient with chronic hepatitis C: a case report.

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Kim, Bu Kyung; Choi, Young Sik; Park, Yo Han; Lee, Sang Uk

2011-12-01

Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-α) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-α therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-α (pegIFN-α) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-α and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-α therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-α therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-α therapy and remained weakly positive after IFN-α therapy was discontinued.

Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.

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Manuel Romero-Gómez

Full Text Available Virological response to peginterferon + ribavirin (P+R at week 4 can predict sustained virological response (SVR. While patients with rapid virological response (RVR do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L should have treatment discontinued due to low SVR rate.To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R.In this prospective and multicenter study, HCV mono-infected (n=538 and HCV/HIV co-infected (n=186 patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model and a validation cohort (to validate the model.D1L was reached in 509 (80.2% and RVR in 148 (22.5% patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86 in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79 in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88 in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88 in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.The combination of genetic (IL28B polymorphism and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.

Boceprevir in genotype 1 chronic hepatitis C: First experiences in Serbia

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Simonović-Babić Jasmina

2015-01-01

Full Text Available Introduction. The triple therapy which consists of one of the protease inhibitor plus pegylated interferon and ribavirin (P/R is the standard of care for the treatment of chronic hepatitis C virus (HCV genotype 1(G1 infection both in treatment-naпve and experienced patients. Objective. The aim of this study was to analyze the efficacy and tolerability of this regime in hospital practice in Serbia. Methods. From July 2012 to October 2012, 20 previously treated patients with advanced fibrosis and HCV G1 infection were included in the triple antiviral regimen in six referral centers in Serbia. All patients were treated with response guide therapy (RGT regime according to the boceprevir treatment protocol. During the 4-week lead-in period all patients received peginterferon plus ribavirin. After the lead-in period boceprevir was added in the dosage of 800 mg three times a day orally. The subsequent treatment varied according to virologic response and fibrosis. During the therapy HCV RNA level was measured at week 4, 8, 12, 24 of the treatment for the assessment of virologic response profile. All patients who completed therapy were assessed at the end of the treatment and at the end of an additional 24-week treatment-free period for a sustained virologic response (SVR. Results. The total of 20 patients with advanced fibrosis was treated. Among patients with an undetectable HCV RNA level at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level <1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was 55%. The safety profile of the treatment regimen was good. Anemia was reported in 25% of patients. There was no life-threatening treatment adverse event. Conclusion. Boceprevir in combination with P/R achieved fairly good SVR rates in patients that were “most difficult to treat” who failed on dual therapy and was effective among patients with cirrhosis.

Project management as a competitive advantage for the internationalization of Brazilian companies

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Andre Luiz Spinelli Schelini

2017-12-01

Full Text Available This study focuses on three theoretical axes: project management (PM, internationalization of companies and the resource-based view (RBV. It aimed to analyze if, and in what way, PM maturity contributes to the international strategy of Brazilian companies from the RBV perspective. The research strategy adopted in three Brazilian companies constituted a multiple case study with a descriptive exploratory approach through intercase and intracase analysis. As an unprecedented result, the study identified five characteristics of mature project management: project sustainability, stakeholder engagement, goal setting and strategy, change management, and risk management. Furthermore, all of these contributed to the internationalization of the companies in question, with an impact on competitive advantage, considering the RBV-VRIO analysis. Thus, the study contributes to the field by aiding companies that are beginning or intend to begin internationalization processes, enabling them to obtain better results through PM. A limitation of the study is the small number of cases investigated, which may be viewed as an opportunity for conducting further studies.

The Resource-Based View and The Concept of Value: The Role of Emergence in Value Creation

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Luis Armando Luján Salazar

2017-02-01

Full Text Available This theoretical paper deals with the concept of value. It asserts that value is the only and necessary condition in the resource-based view (RBV. It also argues that no resource or strategy is valuable per se: it is related to a configuration of resources, routines, and embedded assets. For example, concerning the RBV attribute of imitation, we can ask to what extent a valuable resource is independent of the rest of resources, and by extension, to what extent a configuration of resources is rare by itself. This paper discusses the emergence of value and it is embeddedness in a configuration of resources. Revising the concept of value could challenge the other main conditions in the RBV: rarity and cost of imitation, impossibility to replace with strategic substitutes. If the relations of these attributes with the rest of the resources are taken into account, we might have a better understanding of how value emerges and how a firm’s resources and capabilities are related with the creation of value.

Interferon-induced central retinal vein thrombosis

International Nuclear Information System (INIS)

Nazir, L.; Husain, A.; Haroon, W.; Shaikh, M.I.; Mirza, S.A.; Khan, Z.

2012-01-01

A middle-aged lady presented with sudden onset of unilateral central retinal vein thrombosis after completing 6 months course of interferon and ribavirin for chronic hepatitis C infection. She had no risk factors and all her thrombophilia workup was normal, however, she was found to be dyslipidemic which may have contributed to atherosclerosis and predispose to thrombosis. Despite anticoagulation, her visual acuity deteriorated. This case illustrates the possibility of unpredictable visual complication of interferon. Frequent eye examination should be undertaken in patients having underlying risk factors like diabetes, hypertension or dyslipidemia undergoing interferon therapy. (author)

Interferon-induced central retinal vein thrombosis

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Nazir, L; Husain, A; Haroon, W; Shaikh, M I; Mirza, S A; Khan, Z

2012-11-15

A middle-aged lady presented with sudden onset of unilateral central retinal vein thrombosis after completing 6 months course of interferon and ribavirin for chronic hepatitis C infection. She had no risk factors and all her thrombophilia workup was normal, however, she was found to be dyslipidemic which may have contributed to atherosclerosis and predispose to thrombosis. Despite anticoagulation, her visual acuity deteriorated. This case illustrates the possibility of unpredictable visual complication of interferon. Frequent eye examination should be undertaken in patients having underlying risk factors like diabetes, hypertension or dyslipidemia undergoing interferon therapy. (author)

Antiviral Polymer Therapeutics

DEFF Research Database (Denmark)

Smith, Anton Allen Abbotsford

2014-01-01

polymerized in a controlled manner with carrier monomers of historically proven biocompatible polymers. The carrier polymers, the loading of ribavirin as well as the size of the polymer were varied systematically with the aid of an automated synthesis platform. These polymers were tested in a cellular assay...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein...... is mediated through specific transporters, it is thought that the accumulation can be alleviated through the attachment of ribavirin to a macromolecule. To this end, ribavirin was enzymatically modified into a monomer compatible with controlled polymerization techniques. The ribavirin monomers were...

Particle Size, Surface Area, and Amorphous Content as Predictors of Solubility and Bioavailability for Five Commercial Sources of Ferric Orthophosphate in Ready-To-Eat Cereal.

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Dickmann, Robin S; Strasburg, Gale M; Romsos, Dale R; Wilson, Lori A; Lai, Grace H; Huang, Hsimin

2016-03-01

Ferric orthophosphate (FePO₄) has had limited use as an iron fortificant in ready-to-eat (RTE) cereal because of its variable bioavailability, the mechanism of which is poorly understood. Even though FePO₄ has desirable sensory properties as compared to other affordable iron fortificants, few published studies have well-characterized its physicochemical properties. Semi-crystalline materials such as FePO₄ have varying degrees of molecular disorder, referred to as amorphous content, which is hypothesized to be an important factor in bioavailability. The objective of this study was to systematically measure the physicochemical factors of particle size, surface area, amorphous content, and solubility underlying the variation in FePO₄ bioavailability. Five commercial FePO₄ sources and ferrous sulfate were added to individual batches of RTE cereal. The relative bioavailability value (RBV) of each iron source, determined using the AOAC Rat Hemoglobin Repletion Bioassay, ranged from 51% to 99% (p Solubility in dilute HCl accurately predicted RBV (R² = 0.93, p = 0.008). Amorphous content measured by Dynamic Vapor Sorption ranged from 1.7% to 23.8% and was a better determinant of solubility (R² = 0.91; p = 0.0002) than surface area (R² = 0.83; p = 0.002) and median particle size (R² = 0.59; p = 0.12). The results indicate that while solubility of FePO₄ is highly predictive of RBV, solubility, in turn, is strongly linked to amorphous content and surface area. This information may prove useful for the production of FePO₄ with the desired RBV.

Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent.

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Park, Joonsoo; Kwon, Osung; An, Hyun-Jin; Park, Kwan Kyu

2018-04-01

Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl ( p =0.026) and 40 mg/100 µl ( p =0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl ( p =0.000) and 300 µl/100 µl ( p =0.030). The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.

Lessons learnt from the management of a case of Lassa fever and follow-up of nosocomial primary contacts in Nigeria during Ebola virus disease outbreak in West Africa.

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Iroezindu, Michael O; Unigwe, Uche S; Okwara, Celestine C; Ozoh, Gladys A; Ndu, Anne C; Ohanu, Martin E; Nwoko, Ugochukwu O; Okoroafor, Uwadiegwu W; Ejimudo, Esinulo; Tobin, Ekaete A; Asogun, Danny A

2015-11-01

To describe our experiences in the management of a case of Lassa fever (LF) and follow-up of nosocomial primary contacts during the 2014 Ebola outbreak in West Africa. Clinical management of the index case and infection control/surveillance activities for primary contacts are described. Laboratory confirmation was by Lassa virus-specific reverse-transcriptase PCR. A 28-year-old man with a 10-day history of febrile illness was referred to a major tertiary hospital in south-east Nigeria from a city that previously experienced a LF outbreak and was recently affected by Ebola. On observation of haemorrhagic features, clinicians were at a crossroads. Diagnosis of LF was confirmed at a National Reference Centre. The patient died despite initiation of ribavirin therapy. Response activities identified 121 primary contacts comprising 78 (64.5%) hospital staff/interns, 19 (15.7%) medical students, 18 (14.9%) inpatients and 6 (5.0%) relatives. Their mean age was 32.8 ± 6.6 years, and 65.3% were women. Twenty (16.5%) had high-risk exposure and were offered ribavirin as post-exposure prophylaxis. No secondary case of LF occurred. Fatigue (43.8%) and dizziness (31.3%) were the commonest side effects of ribavirin. Response activities contained nosocomial spread of LF, but challenges were experienced including lack of a purpose-built isolation facility, absence of local Lassa virus laboratory capacity, failure to use appropriate protective equipment and stigmatisation of contacts. A key lesson is that the weak health systems of Africa should be comprehensively strengthened; otherwise, we might win the Ebola battle but lose the one against less virulent infections for which effective treatment exists. © 2015 John Wiley & Sons Ltd.

Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris.

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Ueda, Youki; Mori, Kyoko; Satoh, Shinya; Dansako, Hiromichi; Ikeda, Masanori; Kato, Nobuyuki

2014-05-02

Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as statins and teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with interferon-α or ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM, cordycepin, but not ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin. Copyright © 2014 Elsevier Inc. All rights reserved.

Competitive advantage: an analytical framework based on entrepreneurship

Institute of Scientific and Technical Information of China (English)

LIU Zhibiao

2006-01-01

This article observes and studies the role and effect of entrepreneurship within the theoretical framework of resource-based view(RBV).It advances competitive advantage theory based on entrepreneurship by proving the distinctiveness of entrepreneurship. Distinctive cognition competence of entrepreneurs provides them with personal specific assets,which determines both the competence to explore new business opportunities and the competence to integrate resources for risk activities.The characteristics of such intangible resource as entrepreneurship,such as its distinctiveness,limitedness of competition,and incomplete mobility of factors,are the most important sources of competitive advantage of enterprises in the strategic management theory of RBV.

IMPACT OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C ON CYTOKINE SYNTHESIS AND HEPATIC FIBROSING PROCESSES

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V. V. Shchekotov

2015-01-01

Full Text Available Objective: to estimate the time course of changes in the levels of tumor necrosis factor-α (TNF-α, interleukin-4 (IL-4, IL-6, and the hepatic fibrosis indicators hyaluronic acid (HA and liver elasticity index during combined antiviral therapy (AVT with interferon alpha-2b and ribavirin in patients with chronic hepatitis C (CHC. Subjects and methods. Fifty patients with CHC were examined. Serum TNF-α, IL-6, IL-4, and HA were estimated using an enzyme immunoassay. The stage of hepatic fibrosis was determined by fibroelastography with the liver elastic index being measured; the time course of changes in the indicators was assessed in 20 patients at the end of AVT. A virological response was monitored at therapy completion and 6 months later. Results. The patients with CHC in the reactivation phase were found to have enhanced TNF-α, IL-6, and IL-4 activities in 84, 60, and 100 % of the cases, respectively (р < 0.001, р = 0.01, р < 0.001, respectively. The median serum concentration of HA in CHC was 1.8-fold higher than that in the control group (p = 0.03; the liver elastic index averaged 6.5 kPa. TNF-α and IL-6 levels correlated with viremia, transaminases, and hepatic fibrosis indicators. At combined AVT completion, the virological response rate was as high as 85 %, which was attended by a considerable reduction in cytolysis, HA concentrations, and liver density index to 5.4 kPa (3.6–6.8 kPa (p < 0.04, and in the activity of the examined cytokines. The sustained virological response rate was 80 %. Only IL-4 levels decreased and TNF-α and IL-6 concentration remained at the baseline level in patients unresponsive to AVT. Conclusion. It is expedient to monitor TNF-α, IL-4, IL-6, and HA to evaluate the severity of liver involvement in CHC and to predict the efficiency of AVT.

Telaprevir: Changing the standard of care of chronic hepatitis C

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A K Rajani

2013-01-01

Full Text Available Chronic hepatitis C is a major public health problem and its burden is expected to increase in the near future. Out of six genotypes of hepatitis C virus (HCV identified, genotype 1 is the most prevalent genotype in America and Europe. With peg-interferon alpha and ribavirin dual therapy, sustained virological response (SVR is achieved in less than half of the patients infected with HCV genotype 1. Moreover, this dual therapy also causes many intolerable adverse effects. Telaprevir is an HCV protease inhibitor approved for chronic hepatitis C genotype 1 mono-infection. It is a type of direct acting antiviral drug acting through inhibition of viral non-structural 3/4A protease. It can be safely administered in mild hepatic dysfunction. Due to inhibition of CYP3A4 and P-glycoprotein, significant drug-drug interactions are possible with telaprevir. Trials have shown significantly higher SVR rates when telaprevir is added to peg-interferon alpha and ribavirin, particularly in patients with unfavorable prognostic factors. It is approved for use in treatment-naïve and previously treated patients. Rash and anemia are the major troublesome side-effects. Next-generation protease inhibitors may overcome the drawbacks of telaprevir and another approved HCV protease inhibitor - boceprevir. Evidence from small scale studies suggests that telaprevir may be used in conditions like HIV co-infection, post-transplantation and some HCV non-1 genotype infections also. Preliminary data show higher SVR rates with triple therapy even in patients with unfavorable interleukin-28B (IL28B genotype. With development of other direct acting antivirals, it might be possible to treat chronic hepatitis C with interferon-free regimens in future. This article briefly reviews the properties of telaprevir and its status in the context of rapidly evolving aspects of management of chronic hepatitis C.

Is response-guided therapy being applied in the clinical setting? The hepatitis C example.

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Harris, Jennifer B; Ward, Melea A; Schwab, Phil

2015-02-01

Response-guided therapy (RGT) is a treatment model that bases adjustments to therapeutic regimens on individualized patient physiologic response. This approach is applied to patients with chronic hepatitis C virus (HCV) infection who are treated with a triple therapy regimen of boceprevir or telaprevir in combination with pegylated interferon and ribavirin. As RGT expands in other pharmacologic regimens, including the treatment of breast cancer and acute myeloid leukemia, a measurement of how this approach is applied in clinical practice is important to determine whether the benefits of RGT are being optimized. To measure adherence to the RGT guidelines and to the treatment futility rules based on the drug labeling information for boceprevir and for telaprevir in the treatment of patients with chronic HCV infection. A retrospective observational cohort study was conducted using the large Humana research database, which includes pharmacy, medical, and laboratory claims, as well as enrollment data for more than 1.5 million fully insured commercial members, 1.9 million Medicare Advantage members, and 2.4 million Medicare Part D members from all 50 states. The study population included patients aged ≥18 years to <90 years who were fully insured with commercial or Medicare Advantage coverage. A pharmacy claim for boceprevir or telaprevir was used to identify patients receiving triple therapy for HCV infection. Medical, pharmacy, and laboratory claims were reviewed from the date of the first boceprevir or telaprevir pharmacy claim between May 2011 and February 2012 through a 32-week follow-up period, during which patients were required to have continuous health plan enrollment eligibility. This time period allowed for the occurrences of required HCV RNA laboratory monitoring and the assessment of treatment patterns. The use of RGT for boceprevir and telaprevir includes the monitoring of HCV RNA levels at routine intervals to determine how to proceed with therapy

Particle Size, Surface Area, and Amorphous Content as Predictors of Solubility and Bioavailability for Five Commercial Sources of Ferric Orthophosphate in Ready-To-Eat Cereal

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Robin S. Dickmann

2016-03-01

Full Text Available Ferric orthophosphate (FePO4 has had limited use as an iron fortificant in ready-to-eat (RTE cereal because of its variable bioavailability, the mechanism of which is poorly understood. Even though FePO4 has desirable sensory properties as compared to other affordable iron fortificants, few published studies have well-characterized its physicochemical properties. Semi-crystalline materials such as FePO4 have varying degrees of molecular disorder, referred to as amorphous content, which is hypothesized to be an important factor in bioavailability. The objective of this study was to systematically measure the physicochemical factors of particle size, surface area, amorphous content, and solubility underlying the variation in FePO4 bioavailability. Five commercial FePO4 sources and ferrous sulfate were added to individual batches of RTE cereal. The relative bioavailability value (RBV of each iron source, determined using the AOAC Rat Hemoglobin Repletion Bioassay, ranged from 51% to 99% (p < 0.05, which is higher than typically reported. Solubility in dilute HCl accurately predicted RBV (R2 = 0.93, p = 0.008. Amorphous content measured by Dynamic Vapor Sorption ranged from 1.7% to 23.8% and was a better determinant of solubility (R2 = 0.91; p = 0.0002 than surface area (R2 = 0.83; p = 0.002 and median particle size (R2 = 0.59; p = 0.12. The results indicate that while solubility of FePO4 is highly predictive of RBV, solubility, in turn, is strongly linked to amorphous content and surface area. This information may prove useful for the production of FePO4 with the desired RBV.

Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1 as Predictors for Response to Interferon Therapy in HCV Genotype 4

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Olfat Shaker

2013-01-01

Full Text Available Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66% of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C.

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Muratori, Paolo; Muratori, Luigi; Guidi, Marcello; Granito, Alessandro; Susca, Micaela; Lenzi, Marco; Bianchi, Francesco B

2005-02-15

Hepatitis C virus (HCV)-related chronic hepatitis is frequently associated with non-organ-specific autoantibodies (NOSAs), but available data about the relationship between NOSA positivity and the effect of antiviral therapy in persons with hepatitis C are few and controversial. Our aim was to evaluate the impact of NOSA positivity on the outcome of combined antiviral therapy in HCV-positive patients. A total of 143 consecutive adult patients with hepatitis C were studied. Antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomal antibody type 1 (LKM1) were detected by indirect immunofluorescence. All patients were treatment naive and received combined antiviral therapy (interferon [IFN]-ribavirin) after enrollment in the study. Patients were classified as nonresponders if HCV RNA was detectable after 6 months of therapy, as relapsers if abnormal transaminase levels and reactivation of HCV replication were observed after the end of treatment, and as long-term responders if transaminase levels were persistently normal and HCV RNA was undetectable 6 months after the end of treatment. Thirty-seven patients (25%) were NOSA positive (SMA was detected in 19 patients, ANA in 10, ANA and SMA in 4, LKM1 in 3, and SMA and LKM1 in 1). The prevalence of long-term response was similar between NOSA-positive patients and NOSA-negative patients (48.6% vs. 56.6%; P=not significant). Compared with HCV genotype 1 (HCV-1), HCV genotypes other than 1 were more often associated with long-term response among NOSA-positive patients (93.3% vs. 30%; P=.0017). The overall rate of long-term response, irrespective of NOSA status, was 54.5%. Detection of HCV-1 and elevated gamma-glutamyl transpeptidase serum levels were independent negative prognostic factors of treatment response (P=.007 and P=.026, respectively). Combined antiviral treatment (IFN-ribavirin) is safe and effective in NOSA-positive patients with hepatitis C, even if long-term response is

A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.

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Rubén Agudo

2010-08-01

Full Text Available Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S in the viral polymerase (3D. The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin -by avoiding the biased repertoire of transition mutations produced by this purine analogue-and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP, as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure.

Management and Treatment of Hepatitis C Virus in Patients with HIV and Hepatitis C Virus Coinfection: A Practical Guide for Health Care Professionals

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Pierre Côté

2007-01-01

Full Text Available Concomitant HIV and hepatitis C virus (HCV is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment.

Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals.

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Côté, Pierre; Baril, Jean-Guy; Hébert, Marie-Nicole; Klein, Marina; Lalonde, Richard; Poliquin, Marc; Rouleau, Danielle; Therrien, Rachel; Vézina, Sylvie; Willems, Bernard; Dion, Harold; Junod, Patrice; Lapointe, Normand; Lévesque, Dominic; Pinault, Lyse; Tremblay, Cécile; Trottier, Benoît; Trottier, Sylvie; Tsoukas, Chris; Piché, Alain

2007-09-01

Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment.

Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals

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Côté, Pierre; Baril, Jean-Guy; Hébert, Marie-Nicole; Klein, Marina; Lalonde, Richard; Poliquin, Marc; Rouleau, Danielle; Therrien, Rachel; Vézina, Sylvie; Willems, Bernard; Dion, Harold; Junod, Patrice; Lapointe, Normand; Lévesque, Dominic; Pinault, Lyse; Tremblay, Cécile; Trottier, Benoît; Trottier, Sylvie; Tsoukas, Chris; Piché, Alain

2007-01-01

Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment. PMID:18923731

Significant correlation between spleen volume and thrombocytopenia in liver transplant patients: a concept for predicting persistent thrombocytopenia.

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Ohira, Masahiro; Ishifuro, Minoru; Ide, Kentaro; Irei, Toshimitsu; Tashiro, Hirotaka; Itamoto, Toshiyuki; Ito, Katsuhide; Chayama, Kazuaki; Asahara, Toshimasa; Ohdan, Hideki

2009-02-01

Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P or= 400), persistent thrombocytopenia is predictable after LTx. (c) 2009 AASLD.

COMPETITIVENESS OF THE PORT OF SINES: THE RBV CONTRIBUTION

OpenAIRE

Azevedo, Susana; Ferreira, João

2008-01-01

The main objective of this paper is to analyze the competitiveness of the main maritime Port sited in Portugal - Port of Sines. This paper is developed under the Resource-based view approach. A literature review about the Resource-based view is presented with a special highlight on the contribution of organizations owns’ resources to the competitiveness. With this paper we intend to emphasize the applicability of a management theory to a different type of organizations which only recently st...

Resource-Based View (RBV of Unincorporated Social Economy Organizations

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Kunle Akingbola

2013-05-01

Full Text Available This article examines three related questions about unincorporated social economy organizations (USEOs: What are the characteristics of these social economy organizations? What is the unique bundle of resources that gives rise to and sustains their operations? Is there evidence of bricolage in these organizations? The findings suggest that USEOs are driven foremost by a social mission. USEOs provide diverse services and products including economic and specialized social activities, which are integral to the social fabric of society. The results also show that they combine and leverage two core resources – social capital and human capital – to support the operations of their organizations. Moreover they appear to draw on whatever resources are at their disposal to support the activities of the organization. This suggests that USEOs are involved in bricolage activities, which could explain the longevity of many of the organizations.RÉSUMÉCet article répond à trois questions étroitement liées sur les organismes d’économie sociale non constitués en société : Quelles sont les caractéristiques de ces organismes? Quelles sont les ressources particulières qui leur permettent de fonctionner? Ces organismes ont-ils recours au bricolage (dans le sens que Claude Lévi-Strauss prête à ce mot? Les résultats indiquent qu’une mission sociale est ce qui motive les organismes d’économie sociale non enregistrés. Ces derniers fournissent une diversité de produits et services, y compris des activités économiques et sociales spécialisées qui sont essentielles pour la solidarité sociale. Les résultats montrent aussi que ces organismes combinent deux ressources clés – le capital social et le capital humain – afin d’appuyer le bon fonctionnement de leurs organisations. En outre, pour ce faire, ils ont apparemment recours à toute ressource qui soit à leur portée. Cette dernière pratique indique que les organismes d’économie sociale non constitués en société mènent vraisemblablement des activités de bricolage, ce qui pourrait expliquer pourquoi bon nombre de leurs organisations ont si longue vie.

Indirect comparison of the antiviral efficacy of peginterferon alpha 2a plus ribavirin used with or without simeprevir in genotype 4 hepatitis C virus infection, where common comparator study arms are lacking: a special application of the matching adjusted indirect comparison methodology.

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Van Sanden, Suzy; Pisini, Marta; Duchesne, Inge; Mehnert, Angelika; Belsey, Jonathan

2016-01-01

The need to assess relative efficacy in the absence of comparative clinical trials is a problem that is often encountered in economic modeling. The use of matching adjusted indirect comparison (MAIC) in this situation has been suggested. We present the results of a MAIC used to evaluate the incremental benefit offered by adding simeprevir (SMV) to standard therapy in the treatment of patients infected with genotype 4 hepatitis C virus (HCV). Individual patient data for a single arm study evaluating the use of SMV with peginterferon alfa 2a + ribavirin (PR) in genotype 4 HCV were available (RESTORE study). A systematic literature review was used to identify studies of PR alone used in the same patient group. By applying the inclusion criteria for each study in turn to the RESTORE dataset and then applying the published MAIC covariate matching algorithm, a series of pseudosamples from RESTORE were generated. After assessment of the matching outcomes, the best matched comparisons were used to derive estimates of efficacy for SMV + PR in patients equivalent to those participating in the PR trial. Five potential comparator studies were identified. After applying the matching process, two emerged as offering the greatest equivalence with the generated RESTORE pseudosamples and were used to estimate SMV + PR efficacy, expressed as the percentage of patients achieving sustained viral response (SVR). In one comparison, SVR in the SMV + PR group was 85% versus 63% for PR alone. In the second comparison, the corresponding SVRs were 77% and 44% respectively. After matching for varying baseline characteristics, both comparisons of RESTORE versus studies of PR alone yielded a benefit for SMV + PR vs PR alone in genotype 4 HCV-infected patients. The incremental gain in SVR associated with use of SMV ranged from 22% to 33%. In the absence of direct comparative studies, the MAIC gives a better perspective than simple comparison of absolute SVR from individual

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

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Backx, M; Lewszuk, A; White, J R; Cole, J; Sreedharan, A; van Sanden, S; Diels, J; Lawson, A; Neal, K R; Wiselka, M J; Ito, T; Irving, W L

2014-03-01

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection. © 2013 John Wiley & Sons Ltd.

Iron bioavailability in Wistar rats fed with fortified rice by Ultra Rice technology with or without addition of yacon flour (Smallanthus sonchifolius).

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Della Lucia, Ceres M; Vaz Tostes, Maria das Graças; Silveira, Carlos Mário M; Bordalo, Lívia A; Rodrigues, Fabiana C; Pinheiro-Sant'Ana, Helena Maria; Martino, Hércia S D; Costa, Neuza Maria B

2013-03-01

This study aimed to evaluate iron (Fe) bioavailability in Wistar rats fed with rice fortified with micronized ferric pyrophosphate (FP) by Ultra Rice (UR) technology with or without addition of yacon flour as a source of 7.5% of fructooligosaccharides (FOS). Diets were supplied with 12 mg iron/kg from the following sources: ferrous sulfate (FS - control diet), fortified rice with micronized ferric pyrophosphate (Ultra Rice) (UR diet), ferrous sulfate + yacon flour (FS + Y diet) or Ultra Rice + yacon flour (UR + Y diet). Blood samples were collected at the end of depletion and repletion stages for determination of hemoglobin concentration and calculation of the relative biological value (RBV). Also, the content of short chain fatty acids (SCFA) (acetic, propionic and butyric acids) from animals' stools and caecum weight were determined. The UR diet showed high iron bioavailability (RBV = 84.7%). However, the addition of yacon flour in the diet containing fortified rice (UR + Y diet) decreased RBV (63.1%) significantly below the other three groups (p flour showed higher acetic acid values compared to those who did not. In conclusion, fortified UR with micronized ferric pyrophosphate showed high iron bioavailability but the addition of yacon flour at 7.5% FOS reduced iron bioavailability despite increased caecum weight and SCFA concentration.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

Science.gov (United States)

Coelho-Borges, Silvia; Cheinquer, Hugo; Wolff, Fernando Herz; Cheinquer, Nelson; Krug, Luciano; Ashton-Prolla, Patricia

2012-01-01

Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

ORGANISATIONAL CAPABILITIES, COMPETITIVE ADVANTAGE AND PERFORMANCE IN SUPPORTING INDUSTRIES IN VIETNAM

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Nham Phong Tuan

2010-01-01

Full Text Available This paper focuses on applying the resource-based view (RBV of firms to explain performance in supporting industries in Vietnam. Specifically, we based our research on the comprehensive framework of RBV and reviewed previous empirical researches before deciding on adopting a dynamic capabilities approach to test relationships among organisational capabilities, competitive advantage and performance. A multivariate analysis of survey responses of 102 firms belonging to supporting industries in Vietnam indicates that the organisational capabilities are related to the competitive advantage, that the competitive advantage is related to performance, and that the competitive advantage mediates the relationship between organizational capabilities and performance. These findings have considerable implications for academics as well as practitioners. Finally, this study also provides directions for future research.

Necessary but Not Sufficient…; Comment on “Knowledge Mobilization in Healthcare Organizations: A View From the Resource-Based View of the Firm”

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Gill Harvey

2015-12-01

Full Text Available The challenge of mobilizing knowledge to improve patient care, population health and ensure effective use of resources is an enduring one in healthcare systems across the world. This commentary reflects on an earlier paper by Ferlie and colleagues that proposes the resource-based view (RBV of the firm as a useful theoretical lens through which to study knowledge mobilization in healthcare. Specifically, the commentary considers 3 areas that need to be addressed in relation to the proposed application of RBV: the definition of competitive advantage in healthcare; the contribution of macro level theory to understanding knowledge mobilization in healthcare; and the need to embrace and align multiple theories at the micro, meso, and macro levels of implementation.

Necessary but Not Sufficient… Comment on "Knowledge Mobilization in Healthcare Organizations: A View From the Resource-Based View of the Firm".

Science.gov (United States)

Harvey, Gill; Kitson, Alison

2015-08-25

The challenge of mobilizing knowledge to improve patient care, population health and ensure effective use of resources is an enduring one in healthcare systems across the world. This commentary reflects on an earlier paper by Ferlie and colleagues that proposes the resource-based view (RBV) of the firm as a useful theoretical lens through which to study knowledge mobilization in healthcare. Specifically, the commentary considers 3 areas that need to be addressed in relation to the proposed application of RBV: the definition of competitive advantage in healthcare; the contribution of macro level theory to understanding knowledge mobilization in healthcare; and the need to embrace and align multiple theories at the micro, meso, and macro levels of implementation. © 2015 by Kerman University of Medical Sciences.

Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C

DEFF Research Database (Denmark)

Hauser, Goran; Awad, Tahany; Brok, Jesper

2014-01-01

events leading to treatment discontinuation, other adverse events, and quality of life. Our secondary outcome was sustained virological response in serum, that is, undetectable hepatitis C virus RNA in serum by sensitive tests six months after the end of treatment. DATA COLLECTION AND ANALYSIS: Two...... review authors independently used a standardised data collection form. We meta-analysed data with both fixed-effect and random-effects models. For each outcome, we calculated the odds ratio (OR) (for liver-related morbidity or all-cause mortality) or the risk ratio (RR) along with 95% confidence interval...... (CI) based on intention-to-treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risk of random errors (play of chance).For each outcome, we calculated the RR with 95% CI based on intention-to-treat analysis. Effects...

Use of medicinal plants as the additional therapy of viral hepatitis

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I.B. Ershova

2017-04-01

Full Text Available Dear colleagues, continuing the rubric of the journal about the treatment of infectious diseases by medicinal plants, we want to present the methods of using medicinal plants as an additional therapy for treatment of viral hepatitis in addition to the main treatment according to the generally clinical standards of antiviral therapy. Viral hepatitis compiles a large group of human infectious diseases characterized by a predominant liver damage. “Currently, viral hepatitis is recognized as a major public health problem requiring urgent action”, said Dr Margaret Chan, WHO Director-General (WHO Global hepatitis report, 2017. Treatment of viral hepatitis is a complex task and involves the use of generally clinical recommendations or standards. There are criteria for determining the need for pharmacotherapy and the most rational scheme for antiviral treatment in every case of viral hepatitis. The purpose of antiviral therapy is to achieve a stable virologic response, to prevent the progression of the disease, the development of cirrhosis and hepatocellular carcinoma. However, at the present stage a stable virologic response in the general population of patients can be achieved in approximately 60 % of cases. In addition, standard antiviral drugs have side effects, are of high cost and are contraindicated in a number of clinical situations, for example, with a decrease in the number of blood elements (thrombocytopenia, leukopenia, anemia, at the stage of decompensated liver cirrhosis. Probably, all this induces to use alternative methods of therapy, which remain popular both among general practitioners and patients with this infection. The question of the treatment of viral hepatitis with medicinal herbs has been studied for a long time. According to some authors, there is no scientific evidence that hepatitis C can be cured by herbs. The only scientifically proven method of fighting the virus is antiviral therapy. However, there are other points

A PARTICIPAÃÃO NA LISTA DE EMPRESAS COM MELHORES PRÃTICAS PARA COM OS FUNCIONÃRIOS E SEU IMPACTO NA PERFORMANCE: UM ESTUDO EMPÃRICO SOB A LÃGICA DA RBV (RESOURCE-BASED VIEW

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Ludwig Miguel Agurto Berdejo

2009-09-01

Full Text Available Neste trabalho empírico, procuram-se evidências do impacto na performance das empresas decorrente da participação da organização na lista de empresas com melhores práticas para com os seus empregados (MPE. O trabalho sustenta-se no construto da resource-based view (RBV da empresa, estruturado em Barney (1991, entendendo a presença da empresa nas listagens de MPE como um recurso idiossincrático e difícil de ser imitado, o que leva a considerar este recurso como uma fonte de vantagem competitiva sustentável. O objetivo deste trabalho é verificar se a presença constante na lista de MPE no período de 2004 a 2006 proporciona uma performance financeira, medida pelo ROA e ROE, e de mercado, medida pelo Q de Tobin, superior em relação a um grupo de empresas comparáveis incluídas dentro de um grupo de controle. O período completo da análise compreende de 2001 a 2006, tendo sido testados 26 pares de empresas. Usando o Teste Wilcoxon, observouse que, para o ano de 2006, as amostras apresentam uma diferença significativa ao nível de 5% para o ROA e de 3% para o ROE evidenciando um melhor desempenho das empresas pertencentes à lista de MPE. Adicionalmente, usando a técnica de dados em painel, observou-se que a variável que denota a quantidade de participações que a empresa possui na listagem das MPE para o período de 2001 a 2006 apresenta significância para um nível menor do que 10%, contribuindo para o modelo do valor da empresa medido pelo Q de Tobin. Desta forma, este trabalho traz evidências que contribuem para demonstrar que a performance foi positivamente impactada pela sustentação de capacidades intangíveis e socialmente complexas. Com a sustentação destas capacidades podendo dificultar a sua imitação por concorrentes atuais e futuros.

[Therapy-resistant and therapy-refractory arterial hypertension].

Science.gov (United States)

Wallbach, M; Koziolek, M J

2018-05-02

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

A network meta-analysis to compare simeprevir with boceprevir and telaprevir in combination with peginterferon-α and ribavirin in patients infected with genotype 1 Hepatitis C virus.

Science.gov (United States)

Taieb, Vanessa; Pacou, Maud; Ho, Sophia; Pettré, Ségolène; Van Sanden, Suzy; Pisini, Marta; Ustianowski, Andrew; Mehnert, Angelika

2015-01-01

To conduct a network meta-analysis (NMA) to assess the relative efficacy and safety of simeprevir, a second generation oral protease inhibitor (PI), compared to telaprevir and boceprevir in combination with pegylated interferon-α and ribavirin (PR) in patients with chronic hepatitis C. A systematic literature review and NMA of randomized controlled trials involving anti-virals added to PR were conducted. Electronic database searches and hand searches were conducted to identify relevant publications. Outcomes of interest included sustained virologic response (SVR), incidence of adverse events (AEs), and discontinuation due to AEs. Networks were based on treatment-, dose-, and duration-specific nodes. Sub-group analyses were conducted to investigate heterogeneity, based on Metavir scores, sub-genotypes 1a/1b, and prior response. A total of 15 publications were considered for the base case of the meta-analysis. Simeprevir was associated with higher SVR rates than PR alone. Compared to telaprevir and boceprevir, SVR rates tended to be higher for simeprevir, with odds ratios ranging from 1.27 [0.81-2.00] to 2.61 [1.44-4.74] in treatment-naïve and from 1.04 [0.78-1.38] to 1.74 [0.84-3.61] in treatment-experienced patients, respectively. In terms of safety, the risks of anemia and discontinuations due to AEs were lower for simeprevir compared to PR alone, telaprevir, and boceprevir. The risk of rash was lower for simeprevir compared to telaprevir, and similar compared to PR alone and boceprevir. This NMA in genotype 1 HCV patients suggests a similar or better efficacy and tolerability profile for simeprevir compared to telaprevir and boceprevir.

A Localização Geográfica como Recurso Organizacional: Utilização de Sistemas Especialistas para Subsidiar a Tomada de Decisão Locacional do Setor Bancário

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Ana Maria dos Santos Carnasciali

2011-01-01

Full Text Available The location of a business site is a material resource and, along with its financial and technological resources, may provide a company with a distinguished position in comparison with its competitors. Deciding on the best location of a business site is a major task and requires several studies This paper proposes the integration of a Geographic Information System and an Expert System (SES to support decision-making regarding the choice of the best location to open a branch of bank so that location constitutes a competition material resource for the organization. In this paper, we develop a system called the Realty Prospecting System for the Banking Sector (RPS, which allows these variables to be detailed in terms of value, rarity and difficulty to imitate and substitute. Assuming that the resource based view (RBV emphasizes the strategic choice by the recovery of important actions such as identifying, developing and deploying key resources for the management of the organization to maximize returns, an analysis of the prospected properties in terms of competitive advantage was also conducted, concluding that the RBV is the element that contributes to the SPI. It increases ability to analyze the system beyond the question of location, i.e., the RBV allows prospected properties to be examined in terms of competitive advantage.

Baseline prediction of combination therapy outcome in hepatitis C virus 1b infected patients by discriminant analysis using viral and host factors.

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Saludes, Verónica; Bracho, Maria Alma; Valero, Oliver; Ardèvol, Mercè; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Martró, Elisa

2010-11-30

Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy -especially among genotype 1 infected patients-, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1-E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A "leave-one-out" cross-validation method was used to assess the reliability of the discriminant models. Lower alanine transaminase levels (ALT, p=0.009), a higher number of quasispecies variants in the E1-E2 region (number of haplotypes, nHap_E1-E2) (p=0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p=0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1-E2, and gamma-glutamyl transferase and ALT levels. Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this

Effect of antiviral treatment and host susceptibility on positive selection in hepatitis C virus (HCV).

Science.gov (United States)

Jiménez-Hernández, Nuria; Sentandreu, Vicente; Castro, José A; Torres-Puente, Manuela; Bracho, Alma; García-Robles, Inmaculada; Ortega, Enrique; Del Olmo, Juan; Carnicer, Fernando; González-Candelas, Fernando; Moya, Andrés

2008-02-01

We have conducted a large sequence study of the E1-E2 and NS5A regions of the HCV, subtypes 1a and b, both in patients previously treated with interferon, and untreated patients, who later responded, or not, to a combination therapy based on interferon plus ribavirin. We have examined the role played by the number of positively selected sites on disease progression and its relationship with several variables such as patients' age, sex and their risk of acquiring the disease. We have detected three groups of patients that respond or not to combination therapy: responders of intermediate age, older non-responders and young non-responders, they possess an increasing average number of positively selected sites in the E1-E2 region, respectively. We conclude that the host's genetic factors play an important role in whether the disease is contained or becomes chronic.

Association of Oral Lichen Planus with Chronic C Hepatitis. Review of the Data in Literature

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GHEORGHE, Carmen; MIHAI, Lelia; PARLATESCU, Ioanina; TOVARU, Serban

2014-01-01

The relationship between chronic hepatitis C virus infection (HCV) and oral lichen planus (OLP) is a current topic in the field of oral medicine. Many studies of this association have been made over time. The geographic variation of the hepatitis C prevalence proved to be an important factor influencing the statistical results of the studies analyzing the association of the oral plan lichen with the hepatitis C virus. Approaching this issue is not to be neglected. Treatment outcomes in patients with oral lichen planus associated with chronic hepatitis C virus are often unsatisfactory compared to patients suffering from idiopathic oral lichen planus. Also, the evolution of oral lesions is often fluctuating, with repeated periods of relapse according to the degree of liver function decompensation. Background therapy for liver disease itself may influence lichen planus lesions. Thus, during therapy with interferon and ribavirin oral lesions may appear or become acute. PMID:25553136

Hepatitis C virus protease inhibitor-resistance mutations: our experience and review.

Science.gov (United States)

Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Imazeki, Fumio; Yokosuka, Osamu

2013-12-21

Direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection are one of the major advances in its medical treatment. The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States, Europe, and Japan. When combined with peginterferon plus ribavirin, these agents increase sustained virologic response rates to 70%-80% in treatment-naïve patients and previous-treatment relapsers with chronic HCV genotype 1 infection. Without peginterferon plus ribavirin, DAA mono-therapies increased DAA-resistance mutations. Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future. However, it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases. Furthermore, these mutations exhibit cross-resistance to multiple drugs. The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown, and it is as yet uncertain whether such variants are sensitive to DAAs. We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors. Here, we reviewed the literature on resistance variants of HCV protease inhibitors in treatment naïve patients with chronic HCV genotype 1, as well as our experience.

Art Therapy: What Is Art Therapy?

Science.gov (United States)

... individual, couples, family, and group therapy formats. Art therapy is an effective treatment for people experiencing developmental, medical, educational, and social or psychological impairment. Individuals who benefit from art therapy include ...

Relative biological value of 1α-hydroxycholecalciferol to 25-hydroxycholecalciferol in broiler chicken diets.

Science.gov (United States)

Han, J C; Chen, G H; Zhang, J L; Wang, J G; Qu, H X; Yan, Y F; Yang, X J; Cheng, Y H

2017-07-01

This study was conducted to evaluate the relative biological value (RBV) of 1α-hydroxycholecalciferol (1α-OH-D3) to 25-hydroxycholecalciferol (25-OH-D3) in one- to 21-day-old broiler chickens fed calcium (Ca)- and phosphorus (P)-deficient diets. On the d of hatch, 450 male Ross 308 broiler chickens were weighed and randomly allotted to 9 treatments with 5 replicates of 10 birds per replicate. The basal diet contained 0.50% Ca and 0.25% non-phytate phosphorus (NPP) but was not supplemented with cholecalciferol (vitamin D3). The levels of Ca and NPP in basal diets were lower than those recommended by NRC (1994). 25-OH-D3 was fed at zero, 1.25, 2.5, 5.0, and 10.0 μg/kg, and 1α-OH-D3 was fed at 0.625, 1.25, 2.5, and 5.0 μg/kg. The RBV of 1α-OH-D3 to 25-OH-D3 based on vitamin D intake was determined by the slope ratio method. Results showed that 25-OH-D3 or 1α-OH-D3 improved the growth performance and decreased the mortality in one- to 21-day-old broilers. A linear relationship was observed between the level of 25-OH-D3 or 1α-OH-D3 and mineralization of the femur, tibia, or metatarsus. The RBV of 1α-OH-D3 to 25-OH-D3 were 234, 253, and 202% when the weight, ash weight, and Ca percentage of femur were used as criteria. The corresponding RBV of 1α-OH-D3 to 25-OH-D3 were 232 to 263% and 245 to 267%, respectively, when tibia and metatarsus mineralization were used as criteria. These data indicate that when directly feeding a hormonally active form of vitamin D as 1α-OH-D3 proportionally less is needed than when using the precursor (25-OH-D3) in diets deficient in Ca and P. © 2017 Poultry Science Association Inc.

Investigating the organisational impacts of quality improvement: a protocol for a realist evaluation of improvement approaches drawing on the Resource Based View of the Firm.

Science.gov (United States)

Burton, Christopher R; Rycroft Malone, Jo; Robert, Glenn; Willson, Alan; Hopkins, Angela

2014-07-31

Little is understood about the role of quality improvement in enabling health organisations to survive and thrive in the contemporary context of financial and economic challenges. We will draw on the theoretical foundations of the 'Resource Based View of the Firm' (RBV) to develop insights into why health organisations engage in improvement work, how impacts are conceptualised, and 'what works' in delivering these impacts. Specifically, RBV theorises that the mix and use of resources across different organisations may explain differences in performance. Whether improvement work influences these resources is unclear. Case study research will be conducted across health organisations participating in four approaches to improvement, including: a national improvement programme; a multiorganisational partnership around implementation; an organisational strategy for quality improvement; and a coproduction project designed to enhance the experience of a clinical service from the perspective of patients. Data will comprise in-depth interviews with key informants, observation of key events and documents; analysed within and then across cases. Adopting a realist perspective, the core tenets of RBV will be evaluated as a programme theory, focusing on the interplay between organisational conditions and behavioural or resource responses that are reported through engagement in improvement. The study has been approved by Bangor University Ethics Committee. The investigation will not judge the relative merits of different approaches to healthcare quality improvement. Rather, we will develop unique insights into the organisational consequences, and dependencies of quality improvement, providing an opportunity to add to the explanatory potential of RBV in this and other contexts. In addition to scientific and lay reports of the study findings, research outputs will include a framework for constructing the economic impacts of quality improvement and practical guidance for health

Conversão do conhecimento é fonte de Vantagem Competitiva Sustentável? uma análise empírica sob a perspectiva da Resource-based View Is knowledge conversion a source of Competitive Sustainable Advantage? an empirical analysis based from a Resource-based View perspective

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Silvio Popadiuk

2011-01-01

Full Text Available Distinções entre Vantagem Competitiva (VC e Vantagem Competitiva Sustentável (VCS, apresentadas por Wernerfelt (1984, 1995, Barney (1986a, 1986b, 1991 e Barney e Arikan (2001, indicam que a VCS tende a resistir às tentativas de duplicação. Com o presente estudo, foi analisado se o modelo SECI de conversão do conhecimento (NONAKA; TAKEUCHI, 2004 é avaliado pelos gestores organizacionais como uma fonte de VCS, segundo a perspectiva da Resource-based View (RBV. Por meio de estudo de campo, mediante a aplicação de um questionário estruturado fechado junto a 200 gestores, concluiu-se que a visão do gestor é divergente dos indicadores conceituais que qualificam o modelo SECI como vetor de Vantagem Competitiva Sustentável na perspectiva da RBV. Em outras palavras, enquanto a literatura afirma que o modelo SECI é gerador VCS, no presente estudo identificou-se que a opinião dos gestores não converge para essa afirmação, sugerindo que, na prática, a teoria é outra.The distinction between competitive advantage and competitive sustainable advantage (CSA as presented by Wernerfelt (1984, 1995, Barney (1986a, 1986b, 1991, and Barney and Arikan (2001 indicates that CSA tends to resist duplication. The purpose of the present study is to analyze how the SECI model (Nonaka and Takeuchi, 2004 has been evaluated by managers as a CSA source using from a Resource-based View perspective (RBV. A structured questionnaire with closed questions was administered to 200 managers. The questionnaire allowed the analysis of the manager´s view about the indicators that qualify the SECI model as a CSA source according to a RBV perspective. In other words, while the literature supports the idea that the SECI model develops CSA, the present study identified that the managers have a divergent view. This suggests that practices differ from theory.

75 FR 50880 - TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech Therapy

Science.gov (United States)

2010-08-18

... 0720-AB36 TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech... referrals of beneficiaries to the Military Health System for physical therapy, occupational therapy, and... practitioners will be allowed to issue referrals to patients for physical therapy, occupational therapy, and...

[Significance of non-organ-specific autoantibodies in HCV-related chronic hepatitis].

Science.gov (United States)

Guidi, Marcello; Muratori, Paolo; Granito, Alessandro; Muratori, Luigi; Pappas, Georgios; Bianchi, Francesco B

2005-12-01

The preliminary question regarding the clinical issue of the antiviral therapy in the HCV related chronic hepatitis patients is: is it mandatory the research for the autoantibodies in the eligible patients for the antiviral treatment? This issue is of particular interest at the light of the the reported cases of HCV positive patients with positivity for liver kidney microsome type 1 antibody who developed a hepatitic flare during the antiviral treatment. The data from literature about the efficacy and safety on the antiviral treatment in patients with autoantibodies are few and controversial, particularly if the ones regarding antiviral drugs and more recent treatment regimens are taking into account (peg-interferon, combined therapy of interferon and ribavirin). Large and prospective studies are needed for a thorough evaluation about the potential impact of autoantibodies reactivity on the therapeutic outcome. To date, it must be confirmed that a strict monitoring of hepatic parameters is to recommend during the whole treatment phase. This in the light of a potential appearance of significant flares of aminotransferases, particularly in subjects with anti LKM-1 autoantibodies, during interferon therapy.

Markov random field and Gaussian mixture for segmented MRI-based partial volume correction in PET

International Nuclear Information System (INIS)

Bousse, Alexandre; Thomas, Benjamin A; Erlandsson, Kjell; Hutton, Brian F; Pedemonte, Stefano; Ourselin, Sébastien; Arridge, Simon

2012-01-01

In this paper we propose a segmented magnetic resonance imaging (MRI) prior-based maximum penalized likelihood deconvolution technique for positron emission tomography (PET) images. The model assumes the existence of activity classes that behave like a hidden Markov random field (MRF) driven by the segmented MRI. We utilize a mean field approximation to compute the likelihood of the MRF. We tested our method on both simulated and clinical data (brain PET) and compared our results with PET images corrected with the re-blurred Van Cittert (VC) algorithm, the simplified Guven (SG) algorithm and the region-based voxel-wise (RBV) technique. We demonstrated our algorithm outperforms the VC algorithm and outperforms SG and RBV corrections when the segmented MRI is inconsistent (e.g. mis-segmentation, lesions, etc) with the PET image. (paper)

New preclinical antimalarial drugs potently inhibit hepatitis C virus genotype 1b RNA replication.

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Youki Ueda

Full Text Available BACKGROUND: Persistent hepatitis C virus (HCV infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8 were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251 showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect. CONCLUSIONS/SIGNIFICANCE: We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.

HCV IRES-mediated core expression in zebrafish.

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Ye Zhao

Full Text Available The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism.

Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

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de Bruijn, Winnie; Ibáñez, Cristina; Frisk, Pia; Bak Pedersen, Hanne; Alkan, Ali; Vella Bonanno, Patricia; Brkičić, Ljiljana S.; Bucsics, Anna; Dedet, Guillaume; Eriksen, Jaran; Fadare, Joseph O.; Fürst, Jurij; Gallego, Gisselle; Godói, Isabella P.; Guerra Júnior, Augusto A.; Gürsöz, Hakkı; Jan, Saira; Jones, Jan; Joppi, Roberta; Kerman, Saim; Laius, Ott; Madzikwa, Newman; Magnússon, Einar; Maticic, Mojca; Markovic-Pekovic, Vanda; Massele, Amos; Ogunleye, Olayinka; O'Leary, Aisling; Piessnegger, Jutta; Sermet, Catherine; Simoens, Steven; Tiroyakgosi, Celda; Truter, Ilse; Thyberg, Magnus; Tomekova, Kristina; Wladysiuk, Magdalena; Vandoros, Sotiris; Vural, Elif H.; Zara, Corinne; Godman, Brian

2016-01-01

Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes

Introduction and utilisation of high priced HCV medicines across Europe; implications for the future

Directory of Open Access Journals (Sweden)

Winnie de Bruijn

2016-07-01

Full Text Available Background: Infection with the Hepatitis C Virus (HCV is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs boceprevir (BCV and telaprevir (TVR in addition to ribavirin and pegylated interferon (pegIFN. Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR among European countries from 2008 to 2013. Utilisation measured in defined daily doses (DDDs/ 1000 patients/ quarter (DIQs and expenditure in Euros/ DDD. Health authority activities to influence treatments categorised using the 4E methodology (Education, Engineering, Economics and Enforcement. Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilisation of the new PIs versus ribavirin indicates differences in dual versus triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilisation of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1 with potentially an appreciable budget impact. These concerns have resulted in different prices negotiations across countries, with their impact

COMPETÊNCIAS ORGANIZACIONAIS E GESTÃO ESTRATÉGICA: UM ESTUDO EM INSTITUIÇÕES FINANCEIRAS PÚBLICAS SOB A ÓTICA DA VISÃO BASEADA EM RECURSOS [doi: 10.5329/RECADM.20100902004

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Nemias Figueiredo Cardoso

2010-11-01

Full Text Available Diego M. Coraiola 12.00 Normal 0 21 false false false PT-BR X-NONE X-NONE RESUMO Este trabalho procura analisar as competências organizacionais de duas instituições financeiras públicas como recursos estratégicos para o alcance de vantagens competitivas que permitam o cumprimento da sua missão. Analisa as competências essenciais e distintivas de cada uma das organizações, estabelecendo uma análise comparativa entre estas. A pesquisa foi qualitativa, descritiva e realizada em dois bancos públicos localizados em Fortaleza. O instrumento de coleta utilizado foi a entrevista semi-estruturada e os dados foram tratados comparativamente, para possibilitar uma visão da situação das organizações. O referencial teórico adotado para a pesquisa considera o conceito de competências organizacionais (Hamel; Prahalad, 1995, Fleury; Fleury, 2001 articulado com a abordagem estratégia da visão baseada em recursos (RBV, de Barney (1991. Os resultados apontaram que, do ponto de vista da vantagem competitiva sustentável à luz da visão baseada em recursos (RBV, pode-se afirmar que o Banco A detém maior competitividade em relação ao Banco B, pois seus recursos e competências classificados como vantagem competitiva sustentável nos recursos organizacionais e nas competências essenciais em serviços financeiros são: conhecimentos, sistemas e, em relação aos serviços financeiros, apenas o processamento de transações apresenta vantagem competitiva, porém a mesma é de natureza temporária.   Palavras-Chave Competência organizacional, visão baseada em recursos (RBV, gestão estratégica por competências.     ORGANIZATIONAL COMPETENCIES AND STRATEGIC MANAGEMENT: A STUDY IN PUBLIC FINANCIAL INSTITUTIONS UNDER OPTICS OF THE RESOURCE BASED VIEW   ABSTRACT This study analyzes the organizacionais abilities of two public financial institutions as strategical resources for the reach of competitive advantages that allow the fulfilment of its

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

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Silvia Coelho-Borges

2012-03-01

Full Text Available CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS: A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2 and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week and ribavirin (1.000 mg, daily for 24 weeks. RESULTS: Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis and BclI (H63D mutation analysis in 16 (37% patients, all heterozygous (11 H63D, 2 C282Y and 3 both. Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41% of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test. CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Significance of occult hbv infection in patients with chronic hepatitis c

International Nuclear Information System (INIS)

Anwar, W.; Sarwar, M.; Saif, M.; Hussain, A.B.; Tariq, W.Z.

2006-01-01

Objective: To determine the frequency of occurrence of occult Hepatitis B infection in chronic hepatitis C patients and its impact (if any) on the effectivity of standard chronic hepatitis C treatment. Design: Quasi-experimental study. Place and Duration of Study: The study was conducted at the Department of Medicine, Military Hospital, Rawalpindi, and Virology Department, Armed Forces Institute of Pathology, Rawalpindi, for a period of nine months from January 2003 to September 2003. Patients and Methods: This study was conducted on 30 HBsAg negative patients with chronic hepatitis C liver disease who were receiving combination therapy with interferon and ribavirin. Occult hepatitis B infection was assessed by carrying out HBV DNA by polymerase chain reaction (PCR) in the sera of these patients. Markers of previous hepatitis B infection Le; anti-HBs and total anti-HBc antibodies were also tested. Response to treatment for hepatitis C (with interferon and ribavirin) was assessed at the end of six months of therapy by measuring ALT levels and HCV RNA by PCR in the serum. Results: In our study only one patient (3.33%) was found to be harbouring HBV DNA in the serum detectable by PCR, with markers of previous HBV infection (both anti HBc antibodies and anti HBs antibodies were positive). A total 14 patients (46.67%) had markers of previous HBV infection, while 16 patients (53.33%) had no such sero markers. Twenty five out of 30 patients (83.33%) responded to treatment and 5 (16.66%) turned out to be non-responders. The single case of occult hepatitis B detected in this study responded to hepatitis C treatment. Conclusion: Occult hepatitis B is not a common occurrence in chronic hepatitis C patients and it did not alter the outcome of treatment for hepatitis C in our study. (author)

Humanistic therapies versus other psychological therapies for depression

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Churchill, Rachel; Davies, Philippa; Caldwell, Deborah; Moore, Theresa HM; Jones, Hannah; Lewis, Glyn; Hunot, Vivien

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all humanistic therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different humanistic therapy models (person-centred, gestalt, process-experiential, transactional analysis, existential and non-directive therapies) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all humanistic therapies compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. PMID:25278809

Gene therapy and radionuclides targeting therapy in mammary carcinoma

International Nuclear Information System (INIS)

Song Jinhua

2003-01-01

Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.

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Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

2011-08-11

A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case.

Intensity-modulated radiation therapy: dynamic MLC (DMLC) therapy, multisegment therapy and tomotherapy. An example of QA in DMLC therapy

International Nuclear Information System (INIS)

Webb, S.

1998-01-01

Intensity-modulated radiation therapy will make a quantum leap in tumor control. It is the new radiation therapy for the new millennium. The major methods to achieve IMRT are: 1. Dynamic multileaf collimator (DMLC) therapy, 2. multisegment therapy, and 3. tomotherapy. The principles of these 3 techniques are briefly reviewed. Each technique presents unique QA issues which are outlined. As an example this paper will present the results of a recent new study of an important QA concern in DMLC therapy. (orig.) [de

Physical Therapy and Occupational Therapy in Progeria

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Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation ... Inc. All rights reserved. Page 2 of 5 Physical and Occupational Therapy in Progeria Hutchinson-Gilford Progeria ...

Determinants of Export Performance of Small and Medium-sized Manufacturing Brazilian Enterprises from the Perspective of Resource-based View and Uppsala Model

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Edson Wilson Torrens

2014-12-01

Full Text Available Studies of the determinants of export performance include companies located in developed countries and emerging economies. A predominance of studies focusing on large companies in developed countries was observed. The studies tested the RBV and the Uppsala model in isolated ways. The combined use of variables in the models of RBV and Uppsala studies of Brazilian SMEs appear as a gap to be filled in organizational research. This research contributes to theoretical and empirical knowledge involving the phenomena related to the internationalization of Brazilian SMEs by proposing a model integrating these approaches. This research aims identify the determinants of export performance of SMEs in the perspective of RBV and the Uppsala Model. On a survey with 84 SMEs were employed multiple statistical techniques (factor analysis, linear and logistic regression and structural equation modeling. Resources influenced by the idiosyncrasies of the company and its stage of internationalization affected the export performance. Managerial resources were prevalent on organizational resources. Stage of internationalization and exporting time influenced the relationship between export performance and resources. Size and technological intensity not mediated export performance. Resources and stage of internationalization affect the export performance of SMEs. The following question was developed: What are the determinants of export performance of Brazilian manufacturing SMEs? SMEs in emerging countries arouse the attention of governments worldwide since its economic, employment and income opportunities that provide and challenges facing to innovate, promote sustainability, establish and consolidate its internationalization.

Gestalt Therapy and Cognitive Therapy - Contrasts or Complementarities?

DEFF Research Database (Denmark)

Tønnesvang, Jan; Sommer, Ulla; Hammink, James

2010-01-01

The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued...... that gestalt therapy, defined as a fieldtheoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual...... between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. Keywords: integrative therapy, gestalt...

[Antiviral activity of different drugs in vitro against viruses of bovine infectious rhinotracheitis and bovine diarrhea].

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Glotov, A G; Glotova, T I; Sergeev, A A; Belkina, T V; Sergeev, A N

2004-01-01

In vitro experiments studied the antiviral activity of 11 different drugs against viruses of bovine infective rhinotracheitis (BIRT) and bovine viral diarrhea (BVD). The 50% inhibiting concentrations of the test agents were determined in the monolayers of MDBK and KCT cell cultures. Only did phosprenyl show a virucidal activity against BIRT virus. All the tested drugs significantly inhibited the reproduction of BIRT virus in the sensitive MDBK cell cultures. Thus, bromuridin, acyclovir, ribavirin and methisazonum inhibited the virus by > or = 100,000 times; liposomal ribavirin, gossypolum, anandinum, polyprenolum, phosprenyl, by 1000-10,000 times; eracond and argovit, by 100 times. In experiments on BVD virus, the cultured KCT cells displayed the antiviral activity of bromuridin, phosprenil, polyprenolum, methisazonum, acyclovir, gossypolum, argovit, and ribavirin (in two variants), which caused a statistically significant (100-10,000-fold) decrease in the productive activity of this virus. Eracond and anandid proved to be ineffective.

Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

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Kazi Abdus Salam

2013-01-01

Full Text Available Currently, hepatitis C virus (HCV infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin. The new therapy has significantly improved sustained virologic response (SVR; however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.

LENUS (Irish Health Repository)

Moreau, Isabelle

2012-02-03

Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF). Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.

Music Therapy: A Career in Music Therapy

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About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, cognitive, emotional, and social functioning. Music therapists work with children and adults with developmental ...

SCREENING OF PROTEASE INHIBITORS RESISTANCE MUTATIONS IN HEPATITIS C VIRUS ISOLATES INFECTING ROMANIAN PATIENTS UNEXPOSED TO TRIPLE THERAPY.

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Dinu, Sorin; Calistru, Petre-Iacob; Ceauşu, Emanoil; Târdeil, Graţiela; Oprişan, Gabriela

2015-01-01

Although the European recommendations include the use of new antiviral drugs for the treatment of hepatitis C, in Romania the current treatment remains interferon plus ribavirin. First generation viral protease inhibitors (i.e. boceprevir, telaprevir), which have raised the chances of obtaining viral clearance in up to 70% of infection cases produced by genotype 1 isolates, have not been introduced yet as standard treatment in our country. The success of these new antivirals is limited by the occurrence and selection of resistance mutations during therapy. We set-up a molecular study aiming to detect any resistance mutations to boceprevir and telaprevir harbored by hepatitis C isolates infecting Romanian patients naïve to viral protease inhibitors. Since these new antivirals are efficient and approved for genotype 1 infection, viral samples were genotyped following a protocol previously developed by our research group. We analyzed by both population sequencing and molecular cloning and sequencing the NS3 protease region of hepatitis C virus isolates infecting patients which were not previously exposed to boceprevir and telaprevir. All the analyzed samples were subtype 1b and resembled the samples collected in recent years from Romanian patients. Molecular cloning followed by sequencing showed great intra-host diversity, which is known to represent the source of isolates with different resistance phenotypes. Both population sequencing and molecular cloning followed by clone sequencing revealed two boceprevir resistance mutations (T54S and V55A), respectively, a telaprevir resistance mutation (T54S) in the sequences obtained from a patient with chronic hepatitis C. To our knowledge, this is the first study indicating the existence of pre-treatment resistance mutations to boceprevir and telaprevir in hepatitis C virus isolates infecting Romanian patients.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.

Science.gov (United States)

Angelo, Ana Luiza Dias; Cavalcante, Lourianne Nascimento; Abe-Sandes, Kiyoko; Machado, Taísa Bonfim; Lemaire, Denise Carneiro; Malta, Fernanda; Pinho, João Renato; Lyra, Luiz Guilherme Costa; Lyra, Andre Castro

2013-10-01

Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (pC/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined

Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

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Vigani A.G.

2005-01-01

Full Text Available Hepatitis C virus (HCV is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy, cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week and ribavirin (500 mg orally, twice a day for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis c Genotype 1b Naïve Patients in Chile.

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Constanza L Vargas

Full Text Available Daclatasvir and Asunaprevir (DCV/ASV have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources.A Markov model was built to estimate the expected costs in Chilean pesos (CL$ and converted to US dollars (US$ and benefits in quality adjusted life years (QALYs in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs and Peginterferon plus Ribavirin (PR. Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed.PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$ 16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$ 6,375/QALY at a price of US$ 38,710; and US$ 1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$ 38,710 was 91.6% while there is a 21.43% probability that DCV/ASV dominates PR if the total treatment price was US$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita.DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system.

Competitively Distinct Operations as a Key for Superior and Sustainable Business Performance: An Example from Walmart

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Binod Timilsina

2015-09-01

Full Text Available Existing research on the resource-based view (RBV has provided limited evidence on how firms achieve superior and sustainable business performance; this failure is because current literature de-emphasizes the importance of operations. This paper argues that to gain and sustain superior business performance, a firm’s sustainable competitive advantage is not enough, its operations also needs to be competitively distinct. Therefore, through unifying the necessary conditions of superior and sustainable business performance the paper presents a better understanding of the RBV. The success story of Walmart, from existing literature, is considered as an example to support the proposed framework. The paper concludes that the cost of operations, opportunity cost, cost of resources and possible output are the crucial factors in resource choice and operations decision to secure competitively distinct operations. Finally, theoretical and managerial implications, research limitations and future research possibilities are discussed.

Family Therapy

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Family therapy Overview Family therapy is a type of psychological counseling (psychotherapy) that can help family members improve communication and resolve conflicts. Family therapy is usually provided by a psychologist, ...

The effect of resource based view on sustainable capability advantage

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Mostafa Jafari

2014-12-01

Full Text Available Nowadays, it is important to achieve and to sustain an organization’s competitive advantage in complex environments. This paper evaluates different concepts that have led to such benefits. The study sheds light on resource based view (RBV and its role to reach sustainable competitive advantage (SCA within banking industry of Iran. A valid research instrument was utilized to conduct a survey of 150 top- and middle-level managers from Mellat bank of Iran. With a response rate of 81.3 percent, 122 questionnaires were returned while a number of valid and usable questionnaires were 101. In order to determine validity of questionnaire, the content validity and Cronbach's alpha were used to determine the reliability of the questionnaire (RBV questionnaire 0.934, SCA questionnaire 0.843. The study utilized structural equation modelling, and a series of exploratory and confirmatory factor analyses and they tested the integrated model of MKM and SCA. Statistical support was found for the hypothesized relationships. Moreover it has been shown that RBV had the greatest effect on the market centered SCA, while it had the least influence on the financial centered. The findings offer valuable insights on the generalizability of MKM in a research setting. Structural equation modeling has been implemented and the study also used freedman test to rank the factors and the results show that communication was the most important factor (4.41, followed by process (4.03, knowledge implementation (2.79, decision making (2.54 and human resources (1.22 was the last important factor.

Meaning of dancing therapy in therapy of clients with psychological diseases

OpenAIRE

NĚMCOVÁ, Barbora

2010-01-01

Bachelor thesis deals with meaning and effects of Dance therapy in frame of medical therapy of clients with psychical disease. Theoretical part defines words like dance, movement and Dance therapy. This part also describes history of dance, meaning and aims of Dance therapy, its school, aims and divisions. Mensioned are person of dance therapist, personalities connected with dance and Dance therapy, target groups of clients suitable for Dance therapy, importance of Dance therapy for clients w...

Strategic Management of Network Resources

DEFF Research Database (Denmark)

Antero, Michelle; Riis, Philip Holst

2011-01-01

This paper applies the resource-based view (RBV) theory to a case study aimed at identifying the complementary resources among partners in the ERPCorp ecosystem of development and implementation of Enterprise Resource Planning (ERP) for small and medium enterprises (SMEs) in Denmark. The paper an...

Scientific Progress in Strategic Management

DEFF Research Database (Denmark)

Foss, Nicolai Juul

Does the RBV represent a case of scientific progress? And has it emerged as the dominant approach to the analysis of competitive advantage for this reason? Conventional criteria for scientific progress, notably those of the growth of knowledge literature, are not particularly helpful for understa...

Resources and Transaction Costs

DEFF Research Database (Denmark)

Foss, Kirsten; Foss, Nicolai Juul

2004-01-01

resources depends on the propertyrights that she holds to those resources and on the transaction costs of exchanging,defining and protecting the relevant property rights. While transaction costs aremajor sources of value dissipation, value may be created by reducing suchdissipation. Implications for the RBV...

基于交易价值视角的供应链联盟模式研究

DEFF Research Database (Denmark)

Jie, Zhou; Li, Peter Ping

2013-01-01

As a new unique form that combines the advantages of market and hierarchy, supply chain alliance has attracted attention from both academia and practitioners. The extant research on supply chain alliance is rooted in transaction cost economics (TCE) and resource-based theories (RBV). Both TCE...

Complementary Theories to Supply Chain Management

DEFF Research Database (Denmark)

Halldorsson, Arni; Hsuan, Juliana; Kotzab, Herbert

Borrowing from complementary theories has become an important part of theorizing SCM. We build upon principal-agent theory (PAT), transaction cost analysis (TCA), network theory (NT), and resource-based view (RBV) to provide insights on how to structure a supply chain and manage it. Through...

Entrepreneurship, Transaction Costs, and Resource Attributes

DEFF Research Database (Denmark)

Foss, Kirsten; Foss, Nicolai Juul

transaction costs and property rights shape the process of entrepreneurial discovery. We provide a sketch of the mechanisms that link entrepreneurship, property rights, and transaction costs in a resource-based setting, contributing further to the attempt to take the RBV in a more dynamic direction....

Behaviour therapy for obesity treatment considering approved drug therapy

Directory of Open Access Journals (Sweden)

Wasem, Jürgen

2008-05-01

Full Text Available Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two, six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the

Sex Therapy

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Sex therapy Overview Sex therapy is a type of psychotherapy — a general term for treating mental health problems by talking with a mental health professional. Through sex therapy, you can address concerns about sexual function, ...

What Is Music Therapy?

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American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is ...

Gestalt therapy and cognitive therapy--contrasts or complementarities?

Science.gov (United States)

Tønnesvang, Jan; Sommer, Ulla; Hammink, James; Sonne, Mikael

2010-12-01

The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued that gestalt therapy, defined as a field-theoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual and contextual aspects of therapeutic change processes, toward different levels of memory involved in these processes, and toward the relationship between basic needs, sensation and cognition in therapeutic work. Further, a dialogue between the two approaches will pave the way for addressing the connection between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Therapy with radionuclides. Radionuklid-Therapie

Energy Technology Data Exchange (ETDEWEB)

Biersack, H.J.; Hotze, A.L. (Bonn Univ. (Germany). Klinik fuer Nuklearmedizin)

1992-12-01

Radioiodine therapy of benign and malignant thyroid diseases is a well-established procedure in Nuclear Medicine. However, the therapeutic use of radioisotopes in other diseases is relatively unknown among our refering physicians. The therapeutic effects of intraarticular (rheumatoid arthritis) and intracavitary (pleural and peritoneal carcinosis) applications yields good results. The radiophosphorus therapy in polycythemia vera rubra has always to be considered as an alternative to chemotherapy. The use of analgetics may be reduced by pain therapy of bone metastasis by injection of bone-seeking beta emitters like Rh-186 HEDP. Other procedures like therapeutic application of meta-iodo-benzylguanidine in neuroblastoma and malignant pheochromocytoma resulted in at least remissions of the disease. Radioimmunotherapy needs further evaluation before it can be recommended as a routine procedure. (orig.).

Gene Therapy

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Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

Food therapy and medical diet therapy of Traditional Chinese Medicine

OpenAIRE

Qunli Wu; Xiaochun Liang

2018-01-01

Food therapy of traditional Chinese medicine aims to maintain balanced nutrition through diet. Medical diet therapy, however, is to achieve the balance of Yin and Yang through the combination of nutrition and medicine. Either “food therapy” or “medical diet therapy” aims to keep health, prevent disease, remove illness and slow aging. In recent years, both food therapy and medical diet therapy have been increasingly applied in clinical nutrition therapy. In terms of traditional Chinese food th...

Current perspectives of radiation therapy. History of radiation therapy

International Nuclear Information System (INIS)

Itami, Jun

2011-01-01

More than 100 years have passed since the discovery of X-Strahlen by Roentgen. The history of radiation therapy has evolved under mutual stimulating relationships of the external beam radiation therapy by X-ray tubes and accelerators, and the internal radiation therapy employing radium and other radionuclides. The currently employed technologies in radiation therapy have its origin already till nineteen sixties and the development of physics and engineering have realized the original concept. (author)

Achieving Shared Triple Bottom Line (TBL) Value Creation

DEFF Research Database (Denmark)

Tate, Wendy; Bals, Lydia

2016-01-01

are revisited to lay the theoretical foundation for exploring how the social dimension might be addressed. Social capabilities are then explored by looking at the social entrepreneurship literature and illustrative cases with the purpose of elaborating RBV toward a social resource-based view (SRBV) of the firm...

Resources and transaction costs

DEFF Research Database (Denmark)

Foss, Kirsten; Foss, Nicolai Juul

2005-01-01

from resources depends on the property rights that he or she holds and on the transaction costs of exchanging, defining, and protecting them. While transaction costs are a major source of value dissipation, reducing such dissipation may create value. Implications for the RBV analysis of sustained...

Internet Usage and Competitive Advantage: The Impact of the Internet on an Old Economy Industry in Spain.

Science.gov (United States)

del Aguila Obra, Ana Rosa; Bruque Camara, Sebastian; Padilla Melendez, Antonio

2002-01-01

Considers whether Internet technologies have led to competitive advantage for companies operating in traditional industries. Highlights include a literature review; using the resource-based view (RBV) of firms as a theoretical framework for an empirical investigation; and a survey that investigated Internet technologies and competitive advantage…

Resource based view of the firm: measures of reputation among health service-sector businesses.

Science.gov (United States)

Smith, Alan D

2008-01-01

Application of the strategic leverage of Resource Based View of the Firm (RBV) directly advocates that a company's competitive advantage is derived from its ability to assemble and exploit an appropriate combination of resources (both tangible and intangible assets). The three companies that were selected were Pittsburgh-based companies that were within relatively easy access, representing healthcare service-related industries, and can be reviewed for the principles of the RBV. The particular firms represented a variety of establishments and included Baptist Homes (a long-term care facility), University of Pittsburgh Medical Center (UPMC)(a provider of hospital and other health services), and GlaxoSmithKline, Consumer Healthcare, North America (GSK-CHNA)(a global provider of healthcare products and services). Through the case studies, it was found that not all intangible assets are strategic, and by extension, not all measures of reputation are strategic either. For an intangible asset to be considered strategic, in this case reputation, it must be valuable, rare, imperfectly imitable, and non-substitutable.

Detection of turbidity dynamics in Tampa Bay, Florida using multispectral imagery from ERTS-1

Science.gov (United States)

Coker, A. E.; Higer, A. L.; Goodwin, C. R.

1973-01-01

In 1970, Congress authorized the deepening of the Tampa Bay channel (Rivers and Harbors Act of 1970) from 34 to 44 feet. In order to determine the effects of this deepening on circulation, water quality, and biota, during and after the construction, the U.S. Geological Survey, in cooperation with the Tampa Port Authority, has collected data and developed a digital simulation model of the bay. In addition to data collected using conventional tools, use is being made of data collected from ERTS-1. Return beam vidicon (RBV) multispectral data were collected, while a shell dredging barge was operating in the bay, and used for turbidity recognition and unique spectral signatures representative of type and amount of material in suspension. A three-dimensional concept of the dynamics of the plume was achieved by superimposing the parts of the plume recognized in each RBV band. This provides a background for automatic computer processing of ERTS data and three-dimensional modeling of turbidity plumes.

THE CONCEPT OF POSITION AND MODULE IN QUESTION FOR INDIVIDUALS PROPOSED FOR THE NEW TIMES.

Directory of Open Access Journals (Sweden)

Maciel Manoel Queiroz

2012-12-01

Full Text Available This paper addresses the competitive factors in the logistics service providers (LSPs industry in Brazil, through analysis based substantiated on Resource Based View (RBV, which associates the competitive advantage of an organization to its resources and their capacities. A sample of the largest providers of logistics services, operating in the Brazilian market, according to its annual gross revenues in 2010 was key point to this study that can be classified methodologically as a content analysis. The objective was to identify and to reflect on the key factors related to competitiveness and organizations revenues, categorized according to the RBV approach, in resources, strategic resources and competitive advantage. The results indicated that the main resources were (1 ownership for storage and fleet, the most common strategic resources (2: computer application processes assisted by simulation and operations optimization and the perspective for competitive advantage (3: the diversification of the kind of business offered.

Feminist Therapy.

Science.gov (United States)

Laidlaw, Toni; Malmo, Cheryl

1991-01-01

Traces roots of feminist therapy and its independence from traditional and prevalent theories and therapy practices. Asserts that Freudian theory and humanistic assumptions are sexist and contribute to powerlessness of women. In contrast, feminist therapy is seen as dealing directly with client-counselor relationships, trust, advocacy, and…

Emotion Regulation in Schema Therapy and Dialectical Behavior Therapy

NARCIS (Netherlands)

Fassbinder, E.; Schweiger, U.; Martius, D.; Brand-de Wilde, O.; Arntz, A.

2016-01-01

Schema therapy (ST) and dialectical behavior therapy (DBT) have both shown to be effective treatment methods especially for borderline personality disorder. Both, ST and DBT, have their roots in cognitive behavioral therapy and aim at helping patient to deal with emotional dysregulation. However,

Three-dimensional conformal radiation therapy: the tomo-therapy approach

International Nuclear Information System (INIS)

Linthout, N.; Verellen, D.; Coninck, P. de; Bel, A.; Storme, G.

2000-01-01

Conformal radiation therapy allows the possibility of delivering high doses at the tumor volume whilst limiting the dose to the surrounding tissues and diminishing the secondary effects. With the example of the conformal radiation therapy used at the AZ VU8 (3DCRT and tomo-therapy), two treatment plans of a left ethmoid carcinoma will be evaluated and discussed in detail. The treatment of ethmoid cancer is technically difficult for both radiation therapy and surgery because of the anatomic constraints and patterns of local spread. A radiation therapy is scheduled to be delivered after surgical resection of the tumor. The treatment plan for the radiation therapy was calculated on a three-dimensional (3D) treatment planning system based on virtual simulation with a beam's eye view: George Sherouse's Gratis. An effort was made to make the plan as conformal and as homogeneous as possible to deliver a dose of 66 Gy in 33 fractions at the tumor bed with a maximum dose of 56 Gy to the right optic nerve and the chiasma. To establish the clinical utility and potential advantages of tomo-therapy over 3DCRT for ethmoid carcinoma, the treatment of this patient was also planned with Peacock Plant. For both treatment plans the isodose distributions and cumulative dose volume histograms (CDVH) were computed. Superimposing the CDVHs yielded similar curves for the target and an obvious improvement for organs at risk such as the chiasma, brainstem and the left eye when applying tomo-therapy. These results have also been reflected in the tumor control probabilities (equal for both plans) and the normal tissue complication probabilities (NTCP), yielding significant reductions in NTCP for tomo-therapy. The probability of uncomplicated tumor control was 52.7% for tomo-therapy against 38.3% for 3DCRT. (authors)

Medical Art Therapy

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Birgul Aydin

2012-03-01

Full Text Available Art therapy is a form of expressive therapy that uses art materials. Art therapy combines traditional psychotherapeutic theories and techniques with an understanding of the psychological aspects of the creative process, especially the affective properties of the different art materials. Medical art therapy has been defined as the clinical application of art expression and imagery with individuals who are physically ill, experiencing physical trauma or undergoing invasive or aggressive medical procedures such as surgery or chemotherapy and is considered as a form of complementary or integrative medicine. Several studies have shown that patients with physical illness benefit from medical art therapy in different aspects. Unlike other therapies, art therapy can take the patients away from their illness for a while by means of creative activities during sessions, can make them forget the illness or lost abilities. Art therapy leads to re-experiencing normality and personal power even with short creative activity sessions. In this article definition, influence and necessity of medical art therapy are briefly reviewed.

Impact of a rectal and bladder preparation protocol on prostate cancer outcome in patients treated with external beam radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Maggio, A.; Bresciani, S.; Di Dia, A.; Miranti, A.; Poli, M.; Stasi, M. [Candiolo Cancer Institute - FPO, IRCCS, Medical Physic Department, Candiolo (Italy); Gabriele, D. [Candiolo Cancer Institute - FPO, IRCCS, Radiotherapy Department, Candiolo (Italy); University of Sassari, Division of Radiation Oncology, Sassari (Italy); Garibaldi, E.; Delmastro, E.; Gabriele, P. [Candiolo Cancer Institute - FPO, IRCCS, Radiotherapy Department, Candiolo (Italy); Varetto, T. [Candiolo Cancer Institute - FPO, IRCCS, Nuclear Medicine Department, Candiolo (Italy)

2017-09-15

Vorbereitungsprotokoll mit leerem Rektum und angenehm voller Blase (Rektum-Blasen-Vorbereitung [RBV]) angewendet, bei den weiteren 319 Patienten kam kein Protokoll zur Vorbereitung von Rektum und Blase (NRBV) zur Anwendung. Patienten mit RBV hatten im Vergleich zu NRBV-Patienten ein signifikant hoeheres BDFS (64 % vs. 48 % nach 10 Jahren), CDFS (81 % vs. 70,5 % nach 10 Jahren) und PCSS (95 % vs. 88 % nach 10 Jahren; log-Rang-Test p < 0,001). Die multivariate Analyse (MVA) aller behandelten Patienten und der Patienten mit moderat hohem Risiko zeigte, dass der Gleason-Score (GS) und die Rektum-Blasen-Vorbereitung die wichtigsten prognostischen Faktoren des PCSS, CDFS und BDFS waren. Hinsichtlich der Patienten mit hohem und sehr hohem Risiko waren in der univariaten Analyse (UVA) GS, RBV, Prostatakarzinom-Staging und Strahlentherapiedosis Praediktoren fuer PCSS, CDFS und BDFS. Wie unsere Studie deutlich belegt, verringert die RBV signifikant die biochemischen und klinischen Rueckfaelle und die Wahrscheinlichkeit eines prostatakarzinombedingten Tods bei Patienten ohne taegliche bildgefuehrte Prostatalokalisierung, vermutlich weil die Patienten mit RBV im Vergleich zu NRBV-Patienten waehrend der gesamten Behandlung reproduzierbar ein leeres Rektum und eine angenehm volle Blase haben. (orig.)

42 CFR 410.35 - X-ray therapy and other radiation therapy services: Scope.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false X-ray therapy and other radiation therapy services... Other Health Services § 410.35 X-ray therapy and other radiation therapy services: Scope. Medicare Part B pays for X-ray therapy and other radiation therapy services, including radium therapy and...

Personal therapy for undergraduate music therapy students: a survey of AMTA program coordinators.

Science.gov (United States)

Gardstrom, Susan C; Jackson, Nancy A

2011-01-01

The primary purpose of this study was to gather information in order to understand if and how various modalities of personal therapy are employed with undergraduate music therapy students in the United States. AMTA degree program coordinators were asked about 3 therapy modalities, in particular: verbal therapy, music therapy, and expressive arts therapy (excluding music therapy). It was predicted that less than a quarter of the respondents would indicate that personal therapy of any modality was required in their undergraduate curricula, but that a larger percentage would indicate that it was encouraged. Both hypotheses were supported, with just over 14% of the respondents indicating that they require some form of personal therapy and 32% indicating that they encourage it, with 73% of this latter subgroup encouraging verbal therapy and 46% encouraging music therapy. It was further predicted that, when therapy was required or encouraged, it was most often provided by an individual who was associated with the college/university and that therapy was usually provided in a group format. Respondent comments related to these 2 questions revealed considerable confusion between experiential exercises and personal therapy, leading to dubious validity of some of the numerical data. Qualitative treatment of narrative responses illuminated 4 salient issues regarding personal therapy for undergraduate music therapy students, as follows: (a) the legal and ethical feasibility of making personal therapy a requirement; (b) the cost and availability of qualified professionals; (c) the benefits of personal therapy as an integral facet of undergraduate music therapy training and education; and (d) the appropriateness of personal therapy at the undergraduate level of training.

The Resource-Based View: A Review and Assessment of Its Critiques

NARCIS (Netherlands)

Kraaijenbrink, Jeroen; Spender, J.C.; Groen, Arend J.

2010-01-01

The resource-based view (RBV) of the firm has been around for over 20 years—during which time it has been both widely taken up and subjected to considerable criticism. The authors review and assess the principal critiques evident in the literature, arguing they fall into eight categories. They

Strategic Management in the Healthcare Sector: The Debate About the Resource-Based View Flourishes in Response to Recent Commentaries

Directory of Open Access Journals (Sweden)

Ewan Ferlie

2016-02-01

Full Text Available There is increasing interest in – and debate about – the extent to which key concepts from the resource-based view (RBV of the Firm school of strategic management can be usefully applied to study knowledge mobilization (KM processes in healthcare and other public services settings.

Comparison of dose-volume histograms for Tomo therapy, linear accelerator-based 3D conformal radiation therapy, and intensity-modulated radiation therapy

International Nuclear Information System (INIS)

Ji, Youn-Sang; Dong, Kyung-Rae; Kim, Chang-Bok; Choi, Seong-Kwan; Chung, Woon-Kwan; Lee, Jong-Woong

2011-01-01

Highlights: → Evaluation of DVH from 3D CRT, IMRT and Tomo therapy was conducted for tumor therapy. → The doses of GTV and CTV were compared using DVHs from 3D CRT, IMRT and Tomo therapy. → The GTV was higher when Tomo therapy was used, while the doses of critical organ were low. → They said that Tomo therapy satisfied the goal of radiation therapy more than the others. - Abstract: Evaluation of dose-volume histograms from three-dimensional conformal radiation therapy (3D CRT), intensity-modulated radiation therapy (IMRT), and Tomo therapy was conducted. These three modalities are among the diverse treatment systems available for tumor therapy. Three patients who received tumor therapy for a malignant oligodendroglioma in the cranium, nasopharyngeal carcinoma in the cervical neck, and prostate cancer in the pelvis were selected as study subjects. Therapy plans were made for the three patients before dose-volume histograms were obtained. The doses of the gross tumor volume (GTV) and the clinical target volume (CTV) were compared using the dose-volume histograms obtained from the LINAC-based 3D CRT, IMRT planning station (Varian Eclipse-Varian, version 8.1), and Tomo therapy planning station. In addition, the doses of critical organs in the cranium, cervix, and pelvis that should be protected were compared. The GTV was higher when Tomo therapy was used compared to 3D CRT and the LINAC-based IMRT, while the doses of critical organ tissues that required protection were low. These results demonstrated that Tomo therapy satisfied the ultimate goal of radiation therapy more than the other therapies.

A Play Therapy Approach Focusing on Parent-Child Relationship: Filial Therapy

Directory of Open Access Journals (Sweden)

Banu Tortamis Ozkaya

2015-06-01

Full Text Available Filial therapy is a structured, short-term, and evidence-based play therapy model that aims to train and supervise parents in conducting child-centered play therapy sessions with their children. Filial therapy strengthens the relationship among all family members -in particular the relationship between the parent and the child- and helps parents acquire new and effective parenting skills. Thus parents gain a powerful tool to cope with the difficulties they experience even after therapy sessions end. In this review, filial therapy is explained within the context of its theoretical background and therapy process. Several adaptations of the model and research studies on its effectiveness are also discussed briefly. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 208-220

THE EFFECTIVENESS OF PLAY THERAPY AND MUSICAL THERAPY IN REDUCING THE HOSPITALIZATION STRESS

Directory of Open Access Journals (Sweden)

Yuni Sufyanti Arief

2017-07-01

Full Text Available Introduction: Hospitalization in pediatric patients may caused an anxiety and stress in all age levels. Several techniques can be applied to reduced hospitalization stress in children, such as playing therapy and music therapy. The objective of this study was to analyze the difference of effectiveness between both therapies in reducing the hospitalization stress in 4-6 years old children. Method: A quasy-experimental pre-posttest design was used in this study. There were 18 respondents, divided into three groups, i.e. group one receiving playing therapy, group two receiving music therapy and the last group as control group. Data were collected by using observation sheet before and after intervention to recognize the hospitalization stress. Data were analyzed by using Wilcoxon Signed Rank Test and Mann Whitney U Test with significance level of α<0.05. Result: Result showed that playing therapy and music therapy had significant effect to reduce the hospitalization stress with p=0.027 for play therapy, p=0.024 for musical therapy, and p=0.068 for control. Mann Whitney U Test revealed that there were no difference in the effectiveness of play therapy and musical therapy in reducing the hospitalization stress with p=0.009 for play therapy and control group, p=0.012 for music therapy and control group, and p=0.684 for playing therapy and musical therapy. Discussion: It can be concluded that play therapy and musical therapy are equally effective to reduce the hospitalization stress in children. It’s recommended for nurses in pediatric ward to do  playg therapy and musical therapy periodically.

Adaptive therapy.

Science.gov (United States)

Gatenby, Robert A; Silva, Ariosto S; Gillies, Robert J; Frieden, B Roy

2009-06-01

A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the "cost" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant

Hypoxia in Prostate Cancer: Correlation of BOLD-MRI With Pimonidazole Immunohistochemistry-Initial Observations

International Nuclear Information System (INIS)

Hoskin, Peter J.; Carnell, Dawn M.; Taylor, N. Jane; Smith, Rowena E.; Stirling, J. James; Daley, Frances M.; Saunders, Michele I.; Bentzen, Soren M.; Collins, David J.; D'Arcy, James A.; Padhani, Anwar P.

2007-01-01

Purpose: To investigate the ability of blood oxygen level-dependent (BOLD) MRI to depict clinically significant prostate tumor hypoxia. Methods and Materials: Thirty-three patients with prostate carcinoma undergoing radical prostatectomy were studied preoperatively, using gradient echo sequences without and with contrast medium enhancement, to map relative tissue oxygenation according to relaxivity rates and relative blood volume (rBV). Pimonidazole was administered preoperatively, and whole-mount sections of selected tumor-bearing slices were stained for pimonidazole fixation and tumor and nontumor localization. Histologic and imaging parameters were independently mapped onto patient prostate outlines. Using 5-mm grids, 861 nontumor grid locations were compared with 237 tumor grids (with >50% tumor per location) using contingency table analysis with respect to the ability of imaging to predict pimonidazole staining. Results: Twenty patients completed the imaging and histologic protocols. Pimonidazole staining was found in 33% of nontumor and in 70% of tumor grids. The sensitivity of the MR relaxivity parameter R 2 * in depicting tumor hypoxia was high (88%), improving with the addition of low rBV information (95%) without changing specificity (36% and 29%, respectively). High R 2 * increased the positive predictive value for hypoxia by 6% (70% to 76%); conversely, low R 2 * decreased the likelihood of hypoxia being present by 26% (70% to 44%) and by 41% (71% to 30%) when combined with rBV information. Conclusion: R 2 * maps from BOLD-MRI have high sensitivity but low specificity for defining intraprostatic tumor hypoxia. This together with the negative predictive value of 70% when combined with blood volume information makes BOLD-MRI a potential noninvasive technique for mapping prostatic tumor hypoxia

Bioavailability of elemental iron powders to rats is less than bakery-grade ferrous sulfate and predicted by iron solubility and particle surface area.

Science.gov (United States)

Swain, James H; Newman, Samuel M; Hunt, Janet R

2003-11-01

Foods are fortified with elemental forms of iron to reduce iron deficiency. However, the nutritional efficacy of current, commercially produced elemental iron powders has not been verified. We determined the bioavailability of six commercial elemental iron powders and examined how physicochemistry influences bioavailability. Relative biological value (RBV) of the iron powders was determined using a hemoglobin repletion/slope ratio method, treating iron-deficient rats with repletion diets fortified with graded quantities of iron powders, bakery-grade ferrous sulfate or no added iron. Iron powders were assessed physicochemically by measuring iron solubility in hydrochloric acid at pH 1.0 and 1.7, surface area by nitrogen gas adsorption and surface microstructure by electron microscopy. Bioavailability from the iron powders, based on absolute iron intake, was significantly less than from FeSO4 (100%; P Electrolytic (54%; A-131, U.S.) > Electrolytic (46%; Electrolytic Iron, India) > H-Reduced (42%; AC-325, U.S.) > Reduced (24%; ATOMET 95SP, Canada) > CO-Reduced (21%; RSI-325, Sweden). Solubility testing of the iron powders resulted in different relative rankings and better RBV predictability with increasing time at pH 1.7 (R2 = 0.65 at 150 min). The prediction was improved with less time and lower pH (R2 = 0.82, pH 1.0 at 30 min). Surface area, ranging from 90 to 370 m2/kg, was also highly predictive of RBV (R2 = 0.80). Bioavailability of iron powders is less than bakery-grade ferrous sulfate and varies up to three times among different commercial forms. Solubility at pH 1.0 and surface area were predictive of iron bioavailability in rats.

Daclatasvir: potential role in hepatitis C

Directory of Open Access Journals (Sweden)

Lee C

2013-10-01

Full Text Available Choongho Lee College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea  Abstract: Chronic hepatitis C virus (HCV infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly. Keywords: hepatitis C virus, nonstructural protein 5A, NS5A inhibitor, hepatitis C treatment

Hepatitis C virus host cell interactions uncovered

DEFF Research Database (Denmark)

Gottwein, Judith; Bukh, Jens

2007-01-01

  Insights into virus-host cell interactions as uncovered by Randall et al. (1) in a recent issue of PNAS further our understanding of the hepatitis C virus (HCV) life cycle, persistence, and pathogenesis and might lead to the identification of new therapeutic targets. HCV persistently infects 180...... million individuals worldwide, causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The only approved treatment, combination therapy with IFN- and ribavirin, targets cellular pathways (2); however, a sustained virologic response is achieved only in approximately half of the patients...... treated. Therefore, there is a pressing need for the identification of novel drugs against hepatitis C. Although most research focuses on the development of HCV-specific antivirals, such as protease and polymerase inhibitors (3), cellular targets could be pursued and might allow the development of broad...

Aminoadamantanes for chronic hepatitis C

DEFF Research Database (Denmark)

Lamers, Mieke H; Broekman, Mark; Drenth, Joost Ph

2014-01-01

BACKGROUND: Around 3% of the world's population (approximately 160 million people) are chronically infected with hepatitis C virus. The proportion of infected people who develop clinical symptoms varies between 5% and 40%. Combination therapy with pegylated interferon-alpha plus ribavirin...... response in genotype 1 infected patients to at least 70%. There is therefore an unmet need for drugs that can achieve a higher proportion of sustained virological response. Aminoadamantanes are antiviral drugs used for treatment of patients with chronic hepatitis C. OBJECTIVES: To assess the beneficial...... and harmful effects of aminoadamantanes for patients with chronic hepatitis C infection by conducting a systematic review with meta-analyses of randomised clinical trials, as well as trial sequential analyses. SEARCH METHODS: We conducted electronic searches of the Cochrane Hepato-Biliary Group Controlled...

Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in Denmark: identification of viral resistance mutations.

Science.gov (United States)

Sølund, Christina; Krarup, Henrik; Ramirez, Santseharay; Thielsen, Peter; Røge, Birgit T; Lunding, Suzanne; Barfod, Toke S; Madsen, Lone G; Tarp, Britta; Christensen, Peer B; Gerstoft, Jan; Laursen, Alex L; Bukh, Jens; Weis, Nina

2014-01-01

The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.

CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults

Science.gov (United States)

Hull, Mark; Klein, Marina; Shafran, Stephen; Tseng, Alice; Giguère, Pierre; Côté, Pierre; Poliquin, Marc; Cooper, Curtis

2013-01-01

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. OBJECTIVE: To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context. METHODS: A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale. RESULTS: All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2–6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients. DISCUSSION: Recommendations may not supersede individual clinical judgement. PMID:24489565

Proton therapy

International Nuclear Information System (INIS)

Smith, Alfred R

2006-01-01

Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

Proton-therapy and hadron-therapy ionization chambers

International Nuclear Information System (INIS)

Boissonnat, Guillaume

2015-01-01

In the framework of the ARCHADE project (Advanced Resource Center for Hadron-therapy in Europe), a research project in Carbone ion beam therapy and clinical Proton-therapy, this work investigates the beam monitoring and dosimetry aspects of ion beam therapy. The main goal, here, is to understand the operating mode of air ionization chambers, the detectors used for such applications. This study starts at a very fundamental level as the involved physical and chemical parameters of air were measured in various electric field conditions with dedicated setups and used to produce a simulation tools aiming at reproducing the operating response in high intensity PBS (Pencil Beam Scanning) coming from IBA's (Ion Beam Applications) next generation of proton beam accelerators. In addition, an ionization chamber-based dosimetry equipment was developed, DOSION III, for radiobiology studies conducted at GANIL under the supervision of the CIMAP laboratory. (author)

Hepatitis C Variability, Patterns of Resistance, and Impact on Therapy

Directory of Open Access Journals (Sweden)

Cristina Simona Strahotin

2012-01-01

Full Text Available Hepatitis C (HCV, a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, is the most common indication for liver transplantation in the United States. Although annual incidence of infection has declined since the 1980s, aging of the currently infected population is expected to result in an increase in HCV burden. HCV is prone to develop resistance to antiviral drugs, and despite considerable efforts to understand the virus for effective treatments, our knowledge remains incomplete. This paper reviews HCV resistance mechanisms, the traditional treatment with and the new standard of care for hepatitis C treatment. Although these new treatments remain PEG-IFN-α- and ribavirin-based, they add one of the newly FDA approved direct antiviral agents, telaprevir or boceprevir. This new “triple therapy” has resulted in greater viral cure rates, although treatment failure remains a possibility. The future may belong to nucleoside/nucleotide analogues, non-nucleoside RNA-dependent RNA polymerase inhibitors, or cyclophilin inhibitors, and the treatment of HCV may ultimately parallel that of HIV. However, research should focus not only on effective treatments, but also on the development of a HCV vaccine, as this may prove to be the most cost-effective method of eradicating this disease.

Measuring Organisational Capabilities in the Higher Education Sector

Science.gov (United States)

Bobe, Belete J.; Kober, Ralph

2015-01-01

Purpose: Drawing on the resource-based view (RBV), the purpose of this paper is to develop a framework and instrument to measure the organisational capabilities of university schools/departments. In doing so, this study provides evidence of the way competitive resources are bundled to generate organisational capabilities that give university…

Radon therapy; Radon in der Therapie

Energy Technology Data Exchange (ETDEWEB)

Spruck, Kaija [Technische Hochschule Mittelhessen, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

2017-04-01

Radon therapies are used since more than 100 years in human medicine. Today this method is controversially discussed due to the possible increase of ionizing radiation induced tumor risk. Although the exact mode of biological radiation effect on the cell level is still not known new studies show the efficiency of the radon therapy without side effect for instance for rheumatic/inflammatory or respiratory disorders.

Combined tumor therapy

International Nuclear Information System (INIS)

Wrba, H.

1990-01-01

This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

Brain Stimulation Therapies

Science.gov (United States)

... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

The perfect marriage: Solution-focused therapy and motivational interviewing in medical family therapy

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Gage Stermensky

2014-01-01

Full Text Available Medical family therapy has many potential uses in behavioral medicine and primary care. Current research was reviewed to determine the most advantageous way to apply solution-focused therapy and motivational interviewing as a perfect marriage in medical family therapy. An extensive literature review was done in the following databases for medical family therapy: Proquest, EBSCO, Medline, and PsychInfo. The search resulted in 86 relevant articles, of which 46 of the most recent were selected for review. Medical family therapy lacks current research that supports solution-focused therapy or motivational interviewing. However, evidence supports the use of solution-focused therapy as a brief format, as well as the closely related intervention, motivational interviewing. While medical family therapy presents many hopeful possibilities in the fields of behavioral medicine, psychology, and marriage and family therapy, little evidence currently exists for the most effective implementation. This review found evidence supporting solution-focused therapy and motivational interviewing as the perfect marriage of the collaborative team approaches for the future implementation and use of specific interventions in medical family therapy.

Music Therapy and Music Therapy Research. Response

DEFF Research Database (Denmark)

Pedersen, Inge Nygaard

2002-01-01

This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

Treatment of Recurrent Chordomas by Percutaneous Ethanol Injection Therapy and Radiation Therapy

International Nuclear Information System (INIS)

Nakajo, M.; Ohkubo, K.; Fukukura, Y.; Nandate, T.; Nakajo, M.

2006-01-01

We report a case of recurrent sacral chordomas that have been successfully controlled by the combination therapy of percutaneous ethanol injection therapy (PEIT) and radiation therapy in a 71-year-old man. PEIT may be one of the adjuvant therapies for recurrent chordomas

Dystonia: Physical Therapy

Science.gov (United States)

... Online Support Frequently Asked Questions Faces of Dystonia Physical Therapy Physical therapy may be an important component of treating ... everyday tasks, Since dystonia is a neurological disorder, physical therapy does not treat the dystonia directly but ...

Physical therapy and occupational therapy in Parkinson's disease

NARCIS (Netherlands)

Radder, D.L.M.; Sturkenboom, I.H.W.M.; Nimwegen, M. van; Keus, S.H.; Bloem, B.R.; Vries, N.M. de

2017-01-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in

CAM therapies among primary care patients using opioid therapy for chronic pain

Directory of Open Access Journals (Sweden)

Mundt Marlon P

2007-05-01

Full Text Available Abstract Background Complementary and alternative medicine (CAM is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Results Patients were treated for a variety of pain problems including low back pain (38.4%, headaches (9.9%, and knee pain (6.5%; the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248, chiropractic treatment (17.8%, n = 162, acupuncture (7.6%, n = 69, yoga (6.1%, n = 55, herbs and supplements (6.8%, n = 62, and prolotherapy (5.9%, n = 54. CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8% and prolotherapy (87.7%, whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. Conclusion This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.

CAM therapies among primary care patients using opioid therapy for chronic pain.

Science.gov (United States)

Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F

2007-05-16

Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.

[Music therapy and depression].

Science.gov (United States)

Van Assche, E; De Backer, J; Vermote, R

2015-01-01

Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy.

Physical Therapy (For Parents)

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Physical Therapy KidsHealth / For Parents / Physical Therapy Print en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) ...

Effectiveness of hypnosis therapy and Gestalt therapy as depression treatments

Directory of Open Access Journals (Sweden)

Elizabeth González-Ramírez

2017-03-01

Full Text Available We analyzed the effectiveness of two psychological therapies to treat depression in the Culiacan population, Mexico. According to criteria of MINI (international Neuropsychiatric interview, 30 individuals from a total of 300 were selected and diagnosed with some kind of depression. Patients were divided in three groups: 1 treatment with hypnosis therapy, 2 treatment with Gestalt-hypnosis therapy, and 3 control group. Before and after the treatments the Beck Anxiety Inventory (BAI was applied to know the depression level of the analyzed groups. The results show that the three groups were presenting a moderated level of depression. The groups under hypnosis therapy and Gestalt-hypnosis therapy show statistical differences between pre-test and post-test. The hypnosis therapy shows significant statistic differences to treat depression with respect to the other two groups. In conclusion, the therapeutic hypnosis is an effective treatment and has relevance to treat depression, while other therapeutic treatments tend to be slow and with minor result. This study is the first of this kind carried out in Culiacan in Sinaloa, Mexico.

Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase.

Science.gov (United States)

Kaushik, Nidhi; Subramani, Chandru; Anang, Saumya; Muthumohan, Rajagopalan; Shalimar; Nayak, Baibaswata; Ranjith-Kumar, C T; Surjit, Milan

2017-11-01

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. IMPORTANCE Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used

Efficacy of Scutellaria baicalensis for the Treatment of Hand, Foot, and Mouth Disease Associated with Encephalitis in Patients Infected with EV71: A Multicenter, Retrospective Analysis

Directory of Open Access Journals (Sweden)

Hailong Lin

2016-01-01

Full Text Available This study aimed to evaluate the clinical efficacy and safety of using the traditional Chinese herbal medicine Scutellaria baicalensis for the treatment of severe HFMD in 725 patients aged >1 year in a multicenter, retrospective analysis. The patients were divided into the S. baicalensis and ribavirin groups, and the temperatures, presence or absence of skin rashes and oral lesions, nervous system (NS involvement, and viral loads of the patients, as well as the safety of the treatments, were evaluated. The median duration of fever, median time to NS involvement, and the number of patients with oral ulcers and/or vesicles, as well as skin rashes, were decreased in the S. baicalensis group compared with the ribavirin group. In addition, the EV71 viral loads were decreased in the S. baicalensis group, suggesting that S. baicalensis exerted more potent antiviral effects compared with ribavirin. The present study demonstrated that S. baicalensis was suitable for the treatment of severe HFMD in patients aged >1 year, since it was shown to rapidly relieve fever, attenuate oral lesions and rashes, and improve NS involvement. Furthermore, it was demonstrated to be relatively safe for topical application.

Peginterferon Lambda-1a Is Associated with a Low Incidence of Autoimmune Thyroid Disease in Chronic Hepatitis C.

Science.gov (United States)

Fredlund, Paul; Hillson, Jan; Gray, Todd; Shemanski, Lynn; Dimitrova, Dessislava; Srinivasan, Subasree

2015-11-01

Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 μg) or alfa interferon (180 μg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both PLambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, PLambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin.

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

Science.gov (United States)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

Alternative Therapy of Animals – Homeopathy and Other Alternative Methods of Therapy

Directory of Open Access Journals (Sweden)

Løken Torleiv

2002-03-01

Full Text Available Alternative therapy of animals is described, in the meaning of alternatives to veterinary therapy traditionally accepted by veterinary faculties and schools and included in their curricula. Alternative therapy composes of different disciplines, of which homeopathy is emphasised in this presentation. Information is given on the use and interest of such therapy among veterinarians and animal owners. Homeopathy as other alternative therapies, may offer great advances, if they induce any effect. Some of the disciplines are based on a scientifically accepted documentation. Others, and homeopathy in particular, are missing such a documentation of effect. The justification of including alternative therapy in treating animals is discussed. Research in alternative therapy of animals is greatly needed, in particular to evaluate therapeutic methods which are in extensive use without any documented effect. An ongoing research project in Norway on the effect of homeopathic treatment of mastitis in cows is shortly presented.

Chemotherapy and molecular target therapy combined with radiation therapy