Influence of hepatitis C virus and IL28B genotypes on liver stiffness.

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Lene Fogt Lundbo

Full Text Available Liver fibrosis has been associated with hepatitis C virus (HCV genotype and genetic variation near the interleukin 28B (IL28B gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.This cross-sectional study consists of 369 patients with chronic hepatitis C (CHC. Liver stiffness was evaluated using transient elastograhy (TE. Factors associated with development of liver fibrosis were identified by logistic regression analysis.We identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR 5.7-12.1. HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log10 IU/mL, p = 0.03. Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9-14.5 compared to genotype 1 (6.9 kPa; IQR, 5.4-10.9 and 2 (6.7 kPa; IQR, 4.9-8.8 (p = 0.02. Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04. However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR 1.09 (95% confidence interval (CI, 1.05-1.14 per year increment, ALT (OR 1.01 (95% CI, 1.002-1.011, per unit increment and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19-4.81, were consistently associated with cirrhosis (TE>17.1 kPa.Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study.

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response

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Hallager, Sofie; Ladelund, Steen; Christensen, Peer Brehm

2017-01-01

Background: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained......, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted...... elevated in patients with alcohol overuse after SVR. Conclusion: Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients...

Impact of PNPLA3 and IFNL3 polymorphisms on hepatic steatosis in Asian patients with chronic hepatitis C.

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Chao-Min Huang

Full Text Available A recent meta-analysis revealed that the genotype PNPLA3 rs738409 GG is associated with a higher risk of hepatic steatosis (HS in Caucasian patients with chronic hepatitis C (CHC. However, controversial results were found regarding Asian populations. Furthermore, previous studies have shown a negative association between interferon lambda 3 (IFNL3 rs12979860 CC and HS in Caucasian CHC patients, but there have been no reports indicating any such association in Asian populations. In this study, then, we investigated the association of PNPLA3 and IFNL3 polymorphisms with HS in Asian CHC patients.We enrolled consecutive CHC patients who underwent liver biopsy prior to antiviral therapy. We excluded those patients with decompensated liver disease, any co-existing chronic liver disease, or HIV or HBV co-infection.1080 CHC patients were enrolled, and HS was found in 453 (41.9% patients. The frequency distribution of the G allele was significantly associated with HS (P<0.001, and this conferred a higher risk to G allele homozygotes (OR: 2.06, 95% CI: 1.46-2.88, P <0.001 than to G allele carriers (OR: 1.98, 95% CI: 1.52-2.58, P<0.001. There was a borderline significant difference in the prevalence of HS in rs12979860 CC versus non-CC (40.8% versus 49.3%, P = 0.059. After adjustment for age, sex, body mass index, diabetes, and excessive alcohol intake, the rs738409 G allele homozygote carriers still carried a higher risk for HS (OR: 1.93, 95% CI: 1.35-2.77, P = 0.003.The PNPLA3 rs738409 GG genotype is positively associated with HS, while the IFNL3 rs 12979860 CC genotype may be negatively associated with HS, in Asian CHC patients.

[Catalase gene rs1001179 polymorphism and oxidative stress in patients with chronic hepatitis C and ulcerative colitis].

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Bulatova, I A; Tretyakova, Yu I; Shchekotov, V V; Shchekotova, A P; Ulitina, P V; Krivtsov, A V; Nenasheva, O Yu

2015-01-01

To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory. Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients. In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047). The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

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Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

2017-05-01

In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

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Petta, S; Di Marco, V; Di Stefano, R; Cabibi, D; Cammà, C; Marchesini, G; Craxì, A

2011-07-01

The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load. © 2011 Blackwell Publishing Ltd.

Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis patients with chronic Hepatitis C (genotype 4: A single-center study

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Bahaa El-Din Moustafa Zayed

2017-01-01

Full Text Available Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC can help to evaluate the long-term prognosis, complications of hepatitis C virus (HCV as well as eligibility for renal transplantation,. Our aim was to assess liver fibrosis in Egyptian hemodialysis (HD patients infected with CHC genotype 4 using a fibroscan. This cross-sectional observational study was conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at Kasr Al Ainy Hospital. All patients were subjected to routine laboratory evaluation including, hepatitis B surface antigen, hepatitis B core antibody, hepatitis Be antigen, hepatitis C antibody (HCVAb and human immunodeficiency virus antibody, quantitative polymerase chain reaction (PCR for both HCV and hepatitis B virus (HBV, serum hyaluronic acid level, and alpha-fetoprotein (AFP. Fibroscan was performed on all HCV-positive patients. The mean age was 47.43 ± 12.65 years, 50.7% were male, and 49.3% were female. The most common causes of end-stage renal disease were hypertensive nephropathy (32.1% and diabetic nephropathy (18.7%. HCVAb was positive in 57.5% of the patients and HBV was positive in 3%. Forty HCV-positive patients (57.1% who underwent fibroscan had mild to significant fibrosis, and thirty patients (42.9% had advanced fibrosis. There was significant correlation between HCV PCR and duration on HD, number of blood transfusions, and hyaluronic acid (HA level. In addition, there was a significant correlation between serum HA and HD duration as well as liver fibrosis. No significant correlation was found between duration on HD and fibrosis stage (P = 0.619; also, no significant correlation was noted between the age of the patients and HA level or stage of fibrosis (P = 0.970. Fibro-scan is a simple noninvasive test that can be used to assess liver fibrosis in HD patients with CHC. Most of the study patients had mild to significant fibrosis.

Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity.

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Chang, Ming-Ling; Kuo, Chia-Jung; Huang, Hsin-Chih; Chu, Yin-Yi; Chiu, Cheng-Tang

2016-01-01

The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown. A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels. Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and multivariate analyses showed that sex (pre- and post-therapy, pimmune and metabolic homeostasis through association with C4 and TC. Positive alterations in C4 and TC levels reflect viral clearance after therapy in CHC patients.

Determinants of successful chronic hepatitis C case finding among patients receiving opioid maintenance treatment in a primary care setting.

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Senn, Oliver; Seidenberg, André; Rosemann, Thomas

2009-12-01

Injection drug users are at high risk for chronic hepatitis C virus infection (CHC). Opioid maintenance treatment (OMT) offers a unique opportunity to screen for CHC. This study proposed the hypothesis that a general practitioner (GP) with special interest in addiction medicine can achieve CHC screening rates comparable to specialized centres and aimed to investigate determinants for a successful CHC case finding in a primary care setting. Retrospective medical record analysis of 387 patients who received opioid maintenance therapy between 1 January 2002 and 31 May 2008 in a general practice in Zurich, Switzerland. Successful CHC assessment was defined as performance of hepatitis C virus (HCV) serology with consecutive polymerase chain reaction-based RNA and genotype recordings. The association between screening success and patient characteristics was assessed using multiple logistic regression. findings: Median (interquartile range) age and duration of OMT of the 387 (268 males) patients was 38.5 (33.6-44.5) years and 34 (11.3-68.0) months, respectively. Fourteen patients (3.6%) denied HCV testing and informed consent about screening was missing in 13 patients (3.4%). In 327 of 360 patients (90.8%) with informed consent a successful CHC assessment has been performed. Screening for HCV antibodies was positive in 136 cases (41.6%) and in 86 of them (63.2%) a CHC was present. The duration of OMT was an independent determinant of a successful CHC assessment. In addicted patients a high CHC assessment rate in a primary care setting in Switzerland is feasible and opioid substitution provides an optimal framework.

Synthesis and preliminary biodistribution studies of [131I]SIB-PEG4-CHC in tumor-bearing mice

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Xiaobei Zheng; Jing Yang; Xiaojiang Duan; Tingting Niu; Wangsuo Wu; Jianjun Wang; Feng Dong

2011-01-01

This work reports the synthesis and preliminary biodistribution results of [ 131 I]SIB-PEG 4 -CHC in tumor-bearing mice. The tributylstannyl precursor ATE-PEG 4 -CHC was synthesized by conjugation of ATE to amino pegylated colchicine NH 2 -PEG 4 -CHC. [ 131 I]SIB-PEG 4 -CHC was radiosynthesized by electrophilic destannylation of the precursor with a yield of ∼44%. The radiochemical purity (RCP) appeared to be >95% by a Sep-Pak cartridge purification. [ 131 I]SIB-PEG 4 -CHC was lipophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [ 131 I]SIB-PEG 4 -CHC cleared from background rapidly, and didn't deiodinate in vivo. However, the poor tumor localization excluded it from further investigations as a tumor-targeted radiopharmaceuticals. (author)

The i148m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls

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Valenti Luca

2012-08-01

Full Text Available Abstract Background Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD and steatohepatitis (NASH, and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3 polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. Methods To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ genotype. PNPLA3 rs738409 (I148M and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT of 35 obese subjects undergoing bariatric surgery. Results Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148 M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p = 0.03, and in healthy subjects (p = 0.04. At multivariate analysis, PNPLA3 148 M alleles were associated with low adiponectin levels (ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148 M allele. The p.148 M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p PNPLA3 and ADIPOQ genotypes and viral features. Conclusions The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum

Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

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Sikorska, Katarzyna; Stalke, Piotr; Romanowski, Tomasz; Rzepko, Robert; Bielawski, Krzysztof Piotr

2013-08-01

Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

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Gamal Badra

2006-01-01

Full Text Available Chronic hepatitis C virus (HCV infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4 is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5% patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32% previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.

[Study on the anti-Lewis lung carcinoma effect of metformin combined with MCT1 inhibitor CHC].

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Guo, Fu-Chun; Wang, Li-Qiang; Zhang, Jing; Wang, Yong-Sheng

2013-05-01

To investigate the antitumor effect of the combination of metformin with alpha-cyano-4-hydroxycinnamic acid (CHC, a MCT1 inhibitor) in the treatment of Lewis lung cancer. In vitro, the utilization of lactate acid was measured by lactate assay in cultured medium and the inhibition of LL/2 cell proliferation of four groups [control group, metformin group (1 mmol/L and 5 mmol/L), CHC group (5 mmol/L) and the combination group (metformin 5 mmol/L and CHC 5 mmol/L)] was detected in 24 h, 48 h, and their apoptosis in 24 h was also detected. In vivo, twenty eight C57BL/6 mice bearing LL/2 (5 x 10(5)) subcutaneous Lewis lung cancer on the right flank was established and then randomly assigned into four groups: control, metformin (200 mg/kg body mass in 0.1 mL i. g. with NS 0.1 mL i. p.), CHC (100 mg/kg body mass in 0.1 mL i.p. with NS 0.1 mL i. g. ) and the combination (metformin 200 mg/kg body mass in 0.1 mL i.g. with CHC 100 mg/kg body mass in 0.1 mL i. p.). Tumor volume was measured. The pathologic observation and apoptotic analysis of tumors was assessed by TUNEL assay. Compared to the contorl, metformin or CHC alone, combination of two drugs leaded to a significant lactate acid production in cultured medium and the inhibition of LL/ 2 cell viability (P used alone in early stage (P metformin and CHC transformed the lactic acid metabolism in LL/2 cells and induced cell apoptosis and showed the antitumor effect.

Establishing ultrasound based transient elastography cutoffs for different stages of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis C patients.

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Elsharkawy, Aisha; Alboraie, Mohamed; Fouad, Rabab; Asem, Noha; Abdo, Mahmoud; Elmakhzangy, Hesham; Mehrez, Mai; Khattab, Hany; Esmat, Gamal

2017-12-01

Transient elastography is widely used to assess fibrosis stage in chronic hepatitis C (CHC). We aimed to establish and validate different transient elastography cut-off values for significant fibrosis and cirrhosis in CHC genotype 4 patients. The data of 100 treatment-naive CHC patients (training set) and 652 patients (validation set) were analysed. The patients were subjected to routine pretreatment laboratory investigations, liver biopsy and histopathological staging of hepatic fibrosis according to the METAVIR scoring system. Transient elastography was performed before and in the same week as liver biopsy using FibroScan (Echosens, Paris, France). Transient elastography results were correlated to different stages of hepatic fibrosis in both the training and validation sets. ROC curves were constructed. In the training set, the best transient elastography cut-off values for significant hepatic fibrosis (≥F2 METAVIR), advanced hepatic fibrosis (≥F3 METAVIR) and cirrhosis (F4 METAVIR) were 7.1, 9 and 12.2 kPa, with sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%, respectively. The application of these cut-offs in the validation set showed sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01% for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, respectively. Transient elastography performs well for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut-offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption.

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Vădan, Roxana; Gheorghe, Liana; Becheanu, Gabriel; Iacob, Răzvan; Iacob, Speranţa; Gheorghe, Cristian

2003-09-01

Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus. We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis. From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis. Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy induced clearance in Egyptian chronic HCV patients.

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Hamdy, Marwa; Kassim, Samar Kamal; Khairy, Eman; Maher, Mohsen; Mansour, Khaled Amr; Albreedy, Ashraf M

2018-04-05

Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients. Copyright © 2018 Elsevier B.V. All rights reserved.

[Detection and the production mechanism of antinuclear antibodies (ANA) and anti-liver/kidney microsomal tpe 1 antibodies (anti-LKM1) in patients with chronic hepatitis C].

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Bai, Li; Lu, Hai-Ying; Feng, Zhen-Ru; Yu, Min; Li, Wen-Gang; Gong, Wei-Bo; Zhao, Nu-en-ji-ya; Xu, Xiao-Yuan

2009-08-01

To investigate the prevalence of antinuclear antibodies (ANA) and anti-liver/ kidney microsomal type 1 antibodies (anti-LKM1) in patients with chronic hepatitis C (CHC)and to explore the mechanism of production of these autoantibodies. Serum samples were collected from 360 patients with CHC (case group), 69 patients with chronic hepatitis B (CHB) and 69 patients with autoimmune hepatitis (AIH) (control group). Serum ANA and anti-LKM1 were detected by indirect immunofluorescence (HF) technique and enzyme-linked immunosorbent assay (ELISA), respectively. Multi-factor analysis was performed to explore the correlations of the production of autoantibodies with some factors such as age, sex, viral loads, HCV genotype, biochemical parameters and clinical characteristics. Fifty-four (15%) of 360 patients infected with HCV were positive in autoantibodies. The prevalence of ANA and anti-LKM1 were 12.5% (45/360) and 2.5% (9/ 360), respectively. The positive rate of autoantibodies in patients with CHC was significantly higher than that in patients with CHB (15% vs 2.9%, P = 0.006), but significantly lower than that in patients with AIH (15% vs 47.9%, P 0.05). Autoantibodies related to AIH can be detected in CHC patients; interferon may not induce the production of autoantibodies; it is very likely that HCV infection induces the autoimmune reaction and the production of autoantibodies.

Sexual dysfunction and dissatisfaction in chronic hepatitis C patients

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Bruno Cópio Fábregas

2014-10-01

Full Text Available Introduction The prevalence of sexual dysfunction (SD and dissatisfaction with sexual life (DSL in patients with chronic hepatitis C virus infection (CHC was jointly investigated via a thorough psychopathological analysis, which included dimensions such as fatigue, impulsiveness, psychiatric comorbidity, health-related quality of life (HRQL and sociodemographic and clinical characteristics. Methods Male and female CHC patients from an outpatient referral center were assessed using the Brief Fatigue Inventory, the Barrat Impulsiveness Scale, the Beck Depression Inventory (BDI, the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale (HAM-A, and the World Health Organization Quality of Life Scale-Brief Version (WHOQOL-BREF. Structured psychiatric interviews were performed according to the Mini-International Neuropsychiatric Interview. SD was assessed based on specific items in the BDI (item 21 and the HAM-A (item 12. DSL was assessed based on a specific question in the WHOQOL-BREF (item 21. Multivariate analysis was performed according to an ordinal linear regression model in which SD and DSL were considered as outcome variables. Results SD was reported by 60 (57.1% of the patients according to the results of the BDI and by 54 (51.4% of the patients according to the results of the HAM-A. SD was associated with older age, female gender, viral genotype 2 or 3, interferon-α use, impulsiveness, depressive symptoms, antidepressant and benzodiazepine use, and lower HRQL. DSL was reported by 34 (32.4% of the patients and was associated with depressive symptoms, anxiety symptoms, antidepressant use, and lower HRQL. Conclusions The prevalence of SD and DSL in CHC patients was high and was associated with factors, such as depressive symptoms and antidepressant use. Screening and managing these conditions represent significant steps toward improving medical assistance and the HRQL of CHC patients.

Comorbidities and medications of patients with chronic hepatitis C under specialist care in the UK

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Hudson, Benjamin; Walker, Alex J.

2017-01-01

Designing services with the capacity and expertise to meet the needs of the chronic hepatitis C (CHC) population in the era of direct acting antivirals (DAAs), and widening access to such treatments, requires detailed understanding of the characteristics and healthcare needs of the existing patient population. In this retrospective analysis of data from the National HCV Research UK Biobank between March 2012 and October 2014, the characteristics of the CHC population currently under specialist care in the UK were evaluated—with specific focus upon use of medications, adverse lifestyle choices, and comorbidities. Demographic data, risk factors for CHC acquisition, HCV genotype, liver disease status, lifestyle factors, comorbidities, and medication classes were collected. Data were analyzed by history of injecting drug use (IDU), age, and severity of liver disease. A total of 6278 patients (70.5% white; median age, 52 years) from 59 UK specialist centres were included; 59.1% of patients had acquired HCV through IDU. The prevalence of adverse lifestyle factors was significantly lower in non‐IDU compared with previous IDU or recent IDU patients. Depression was common in the previous (50.8%) and recent IDU (68.1%) groups, compared with 27.6% in non‐IDU patients. Cirrhosis was common (23.6%), and prevalence increased with age. We describe a heterogeneous, polymorbid, and aging population of CHC patients in secondary care, and demonstrate underrepresentation of injecting drug users within the current system. The implications of this present significant challenges to physicians and healthcare commissioners in designing services which are fit for purpose inthe DAA era. PMID:28480974

Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

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Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

2012-01-01

Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

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Stella M Martinez

Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

Naturally occurring hepatitis C virus protease inhibitors resistance-associated mutations among chronic hepatitis C genotype 1b patients with or without HIV co-infection.

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Cao, Ying; Zhang, Yu; Bao, Yi; Zhang, Renwen; Zhang, Xiaxia; Xia, Wei; Wu, Hao; Xu, Xiaoyuan

2016-05-01

The aim of this study was to measure the frequency of natural mutations in hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected protease inhibitor (PI)-naive patients. Population sequence of the non-structural (NS)3 protease gene was evaluated in 90 HCV mono-infected and 96 HIV/HCV co-infected PI treatment-naive patients. The natural prevalence of PI resistance mutations in both groups was compared. Complete HCV genotype 1b NS3 sequence information was obtained for 152 (81.72%) samples. Seven sequences (8.33%) of the 84 HCV mono-infected patients and 21 sequences (30.88%) of the 68 HIV/HCV co-infected patients showed amino acid substitutions associated with HCV PI resistance. There was a significant difference in the natural prevalence of PI resistance mutations between these two groups (P = 0.000). The mutations T54S, R117H and N174F were observed in 1.19%, 5.95% and 1.19% of HCV mono-infected patients. The mutations F43S, T54S, Q80K/R, R155K, A156G/V, D168A/E/G and V170A were found in 1.47%, 4.41%, 1.47%/1.47%, 2.94%, 23.53%/1.47%, 1.47%/1.47%/1.47% and 1.47% of HIV/HCV co-infected patients, respectively. In addition, the combination mutations in the NS3 region were detected only in HIV/HCV genotype 1b co-infected patients. Naturally occurring HCV PI resistance mutations existed in HCV mono-infected and HIV/HCV co-infected genotype 1b PI-naive patients. HIV co-infection was associated with a greater frequency of PI resistance mutations. The impact of HIV infection on baseline HCV PI resistance mutations and treatment outcome in chronic hepatitis C (CHC) patients should be further analyzed. © 2015 The Japan Society of Hepatology.

Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

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Dmitry Konstantinov

2016-09-01

Full Text Available The purpose of the study was to examine the clinical and epidemiological data in patients with chronic hepatitis C (CHC and hepatocellular carcinoma (HCC before they sought specialized medical care. The study included 92 patients with CHC. All patients were divided into 2 groups: Group 1 consisted of CHC patients with HCC (n=45, and Group 2 (n=47 consisted of CHC patients without HCC. With the development of HCC in CHC patients, clinical manifestations were absent only in 2.2% of patients. Determining factors in HCC development are male sex, mature age, the maintained HCV replication, moderate and severe fibrosis, disease duration of more than 10 years, and the lack of effect of antiviral treatment.

Inducible protein-10 as a predictive marker of antiviral hepatitis C treatment

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Neesgaard, Bastian; Ruhwald, Morten; Weis, Nina

2017-01-01

AIM: To investigate interferon-γ-inducible protein-10's (IP-10) potential to anticipate rapid (RVR)- and sustained virological responses (SVR) to chronic hepatitis C (CHC) treatment. METHODS: We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC, in patients...... treatment free for at least six months, with genotype 1 or 4, and in relation to 24 wk treatment for genotype 2 and 3, with pegylated interferon in combination with ribavirin. Patients had to have both a baseline IP-10 level as well as a hepatitis C virus (HCV)-RNA determination 4 wk after treatment...... initiation or 24 wk after end of treatment. Studies including patients with liver diseases other than CHC, human immunodeficiency virus-infection, treatment with immunosuppresents or cytostatica, alcohol dependency or active intravenous drug-use were excluded. We found 81 articles by searching the MEDLINE...

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).

Increased risk of hepatocellular carcinoma in patients with chronic hepatitis C

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Hallager, Sofie; Weis, Nina

2014-01-01

Chronic hepatitis C (CHC) frequently leads to cirrhosis with an increased risk of hepatocellular carcinomas (HCC). CHC therapy is currently changing for the better whereas prognosis for HCC remains dismal if not detected early and thus regular screening in cirrhotic CHC patients for HCC...... is recommended. CHC is known to be underdiagnosed in Denmark where it is up to the involved physician to screen for risk factors for CHC and increase the patient's chance of a cure for CHC with therapy....

Sex-specific genotype-by-environment interactions for cuticular hydrocarbon expression in decorated crickets, Gryllodes sigillatus: implications for the evolution of signal reliability.

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Weddle, C B; Mitchell, C; Bay, S K; Sakaluk, S K; Hunt, J

2012-10-01

Phenotypic traits that convey information about individual identity or quality are important in animal social interactions, and the degree to which such traits are influenced by environmental variation can have profound effects on the reliability of these cues. Using inbred genetic lines of the decorated cricket, Gryllodes sigillatus, we manipulated diet quality to test how the cuticular hydrocarbon (CHC) profiles of males and females respond across two different nutritional rearing environments. There were significant differences between lines in the CHC profiles of females, but the effect of diet was not quite statistically significant. There was no significant genotype-by-environment interaction (GEI), suggesting that environmental effects on phenotypic variation in female CHCs are independent of genotype. There was, however, a significant effect of GEI for males, with changes in both signal quantity and content, suggesting that environmental effects on phenotypic expression of male CHCs are dependent on genotype. The differential response of male and female CHC expression to variation in the nutritional environment suggests that these chemical cues may be under sex-specific selection for signal reliability. Female CHCs show the characteristics of reliable cues of identity: high genetic variability, low condition dependence and a high degree of genetic determination. This supports earlier work showing that female CHCs are used in self-recognition to identify previous mates and facilitate polyandry. In contrast, male CHCs show the characteristics of reliable cues of quality: condition dependence and a relatively higher degree of environmental determination. This suggests that male CHCs are likely to function as cues of underlying quality during mate choice and/or male dominance interactions. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Predictors of high healthcare resource utilization and liver disease progression among patients with chronic hepatitis C.

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LaMori, Joyce; Tandon, Neeta; Laliberté, François; Germain, Guillaume; Pilon, Dominic; Lefebvre, Patrick; Prabhakar, Avinash

2016-01-01

Since hepatitis C virus therapy is typically prioritized for patients with more advanced disease, predicting which patients will progress could help direct scarce resources to those likely to benefit most. This study aims to identify demographics and clinical characteristics associated with high healthcare resource utilization (HRU) and liver disease progression among CHC patients. Using health insurance claims (January 2001-March 2013), adult patients with ≥2 CHC claims (ICD-9-CM: 070.44 or 070.54), and ≥6 months of continuous insurance coverage before and ≥36 months after the first CHC diagnosis were included. Patients with human immunodeficiency virus were excluded. Generalized estimating equations were used to identify the demographic and clinical characteristics of being in the 20% of patients with the highest HRU. Factors predicting liver disease progression were also identified. In the study population (n = 4898), liver disease severity and both CHC- and non-CHC-related comorbidities and conditions were strong predictors of high healthcare costs, with odds ratios (ORs; 95% confidence interval [CI]) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities/conditions of 2.78 (2.48-3.12) and 2.19 (1.76-2.72), respectively. CHC- and non-CHC-related comorbidities and conditions were also strong predictors of liver disease progression with ORs (95% CI) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities and conditions of 2.18 (1.83-2.60) and 1.50 (1.14-1.97), respectively. Potential inaccuracies in claims data, information or classification bias, and findings based on a privately insured population. This study suggests that CHC patients with high healthcare resource utilization have a high level of comorbidity at baseline and also that non-CHC comorbidities and conditions are strong predictors of high HRU. Non-cirrhotic CHC patients with one or more comorbidities are at high risk of progressing to cirrhosis or end-stage liver disease.

Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.

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Salvatore Petta

Full Text Available BACKGROUND AND AIMS: Serum levels of γ-glutamyl-transpeptidase(γ-GT were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD, genotype 1 chronic hepatitis C (G1CHC and chronic hepatitis B (CHB, we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR and severity of liver fibrosis. METHODS: 843 consecutive patients with chronic liver disease (CLD(193 NAFLD, 481 G1CHC, 169 CHB were evaluated by liver biopsy (Kleiner and Scheuer scores and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT. RESULTS: By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120-6.564,p = 0.02, G1CHC (OR3.461,CI2.138-5.603,p80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079-15.970,p = 0.03 for NAFLD; OR2.250,CI1.211-4.181,p = 0.01 for G1CHC; OR3.096,CI2.050-34.220,p = 0.01 for CHB. CONCLUSIONS: In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.

Negotiating substance use stigma: the role of cultural health capital in provider-patient interactions.

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Chang, Jamie; Dubbin, Leslie; Shim, Janet

2016-01-01

Diverse aspects of life and lifestyles, including stigmatised attributes and behaviors are revealed as providers and patients discuss health. In this article, we examine how the stigma associated with substance use issues shapes clinical interactions. We use the theoretical framework of cultural health capital (CHC) to explain how substance use stigma is created, reinforced and sometimes negotiated as providers and patients engage in health interactions. We present two main findings using examples. First, two theoretical concepts--habitus and field--set the social position and expectations of providers and patients in ways that facilitate the stigmatisation of substance use. Second, we found both providers and patients actively exchanged CHC as a key strategy to reduce the negative effects of stigma. In some clinical encounters, patients possessed and activated CHC, providers acknowledged patient's CHC and CHC was successfully exchanged. These interactions were productive and mutually satisfying, even when patients were actively using substances. However, when CHC was not activated, acknowledged and exchanged, stigma was unchallenged and dominated the interaction. The CHC theoretical framework allows us to examine how the stigma process is operationalized and potentially even counteracted in clinical interactions. © 2015 Foundation for the Sociology of Health & Illness.

Impaired platelet aggregation and rebalanced hemostasis in patients with chronic hepatitis C virus infection

DEFF Research Database (Denmark)

Nielsen, Nick S.; Jespersen, Sofie; Gaardbo, Julie C.

2017-01-01

Increased risk of both cardiovascular disease (CVD) and bleeding has been found in patients with chronic hepatitis C (CHC) infection, and a re-balanced hemostasis has been proposed. The aim of this study was to investigate functional whole blood coagulation and platelet function in CHC infection....... The prospective study included 82 patients with CHC infection (39 with advanced liver fibrosis and 43 with no or mild liver fibrosis) and 39 healthy controls. A total of 33 patients were treated for CHC infection and achieved sustained virological response (SVR). Baseline and post-treatment blood samples were...... collected. Hemostasis was assessed by both standard coagulation tests and functional whole blood hemostatic assays (thromboelastograhy (TEG), and platelet aggregation (Multiplate). Patients with CHC and advanced fibrosis had impaired platelet aggregation both compared to patients with no or mild fibrosis...

Study of Various HCV Genotypes in Patients Managing by Referral Clinic in Yazd Province

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M Pedarzadeh

2012-02-01

Full Text Available Introduction: Determining virus genotype is a major factor for initiation of treatment because various kinds of genotypes need different antiviral drugs. Distribution of hepatitis C genotype in the word is variable in each country or even in each province. So we need to determine distribution pattern of hepatitis C genotype in our region. This study was performed in referral clinic of Yazd province. Methods: This was a descriptive study conducted between 2007 and 2010 on patients who were observed by Yazd referral clinic (the clinic for evaluating and management of patients with high risk behaviors. Ninety two patients who had positive RIBA test for hepatitis C infection were randomly selected and entered the study. Genotyping was performed using RT-PCR method. The primer was "universal primer HCV". Prevalence of various genotypes was analyzed according to gender, addiction and co- existence of HCV-HIV infection. Personal information and laboratory results were analyzed using SPSS. Results: The most common genotype in our study was genotype 3a (65% of cases, followed by 1a (35%. Globally 83% of patients were IV drug addict. Genotype distribution in these patients was similar to others. Fifteen patients had co-infection of HCV-HIV, and 47% of them were contaminated by genotype 1a and 53% with 3a. We could not find any patient contaminated with genotypes 2 or 4. No other genotypes except 1 & 3 or mixed genotype infection could be determined in our patients. Twenty three percent of patients had negative PCR despite positive RIBA test. This indicates that self improvement from acute hepatitis C infection in IV drug addict patients is similar to other people. Conclusion: According to the results of our study, about 2/3 of patients were infected by genotype 3a. This kind of chronic hepatitis C shows a better response to treatment comparing genotype 1a (or 1b with shorter duration and lower cost drugs. But despite higher incidence of genotype 3a, we

Carcinoma hepatocelular (CHC. Factores de riesgo, diagnóstico y tratamiento. Hospital Pablo Tobón Uribe, 1995-2000

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Gonzálo Correa Arango

2001-04-01

Full Text Available

Por estudios epidemiológicos sabemos que el CHC es el octavo
cáncer más frecuente en el mundo; también que es 3 veces más
frecuente en hombres que en mujeres tanto en el mundo como en
Antioquia (1,2 y que se presentan 350.000 casos nuevos cada año.
Nuestro objetivo es describir el comportamiento clínico y epidemiológico del CHC en la población usuaria del HPTU entre enero de 1995 y julio del 2000.

Qualitative analysis of patient-centered decision attributes associated with initiating hepatitis C treatment.

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Zuchowski, Jessica L; Hamilton, Alison B; Pyne, Jeffrey M; Clark, Jack A; Naik, Aanand D; Smith, Donna L; Kanwal, Fasiha

2015-10-01

In this era of a constantly changing landscape of antiviral treatment options for chronic viral hepatitis C (CHC), shared clinical decision-making addresses the need to engage patients in complex treatment decisions. However, little is known about the decision attributes that CHC patients consider when making treatment decisions. We identify key patient-centered decision attributes, and explore relationships among these attributes, to help inform the development of a future CHC shared decision-making aid. Semi-structured qualitative interviews with CHC patients at four Veterans Health Administration (VHA) hospitals, in three comparison groups: contemplating CHC treatment at the time of data collection (Group 1), recently declined CHC treatment (Group 2), or recently started CHC treatment (Group 3). Participant descriptions of decision attributes were analyzed for the entire sample as well as by patient group and by gender. Twenty-nine Veteran patients participated (21 males, eight females): 12 were contemplating treatment, nine had recently declined treatment, and eight had recently started treatment. Patients on average described eight (range 5-13) decision attributes. The attributes most frequently reported overall were: physical side effects (83%); treatment efficacy (79%), new treatment drugs in development (55%); psychological side effects (55%); and condition of the liver (52%), with some variation based on group and gender. Personal life circumstance attributes (such as availability of family support and the burden of financial responsibilities) influencing treatment decisions were also noted by all participants. Multiple decision attributes were interrelated in highly complex ways. Participants considered numerous attributes in their CHC treatment decisions. A better understanding of these attributes that influence patient decision-making is crucial in order to inform patient-centered clinical approaches to care (such as shared decision-making augmented

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.

Helicobacter pylori genotyping from positive clotests in patients with duodenal ulcer

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Mattar Rejane

2000-01-01

Full Text Available Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5%; only two (5% patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5% patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.

Prevalence of hepatic steatosis and associated factors in Iranian patients with chronic hepatitis C

OpenAIRE

Poortahmasebi, Vahdat; Emami Aleagha, Mohammad Sajad; Amiri, Mehdi; Qorbani, Mostafa; Farahmand, Mohammad; Asayesh, Hamid; Alavian, Seyed Moayed

2016-01-01

Background: Hepatic steatosis is commonly observed in patients with chronic hepatitis C (CHC). Many studies indicate a relationship between steatosis and fibrosis progression. The aim of this study was to analyze the prevalence of hepatic steatosis and related factors in Iranian CHC patients. Methods: One hundred and fifteen consecutive patients with CHC were enrolled which were treatment- na?ve. The patients were divided into groups with and without steatosis according to the result of liver...

Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses

DEFF Research Database (Denmark)

Pedersen, Jannie; Jensen, Tanja B; Carlsen, Thomas H R

2013-01-01

, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23) or non-sustained virologic response (n = 16) were enrolled. Samples taken prior to treatment were tested for their ability...... to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1). The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer). We observed no genotype or subtype specific differences in NAb50-titers between......The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1...

Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection

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Nick S. Nielsen

2017-05-01

Full Text Available Increased risk of both cardiovascular disease (CVD and bleeding has been found in patients with chronic hepatitis C (CHC infection, and a re-balanced hemostasis has been proposed. The aim of this study was to investigate functional whole blood coagulation and platelet function in CHC infection. The prospective study included 82 patients with CHC infection (39 with advanced liver fibrosis and 43 with no or mild liver fibrosis and 39 healthy controls. A total of 33 patients were treated for CHC infection and achieved sustained virological response (SVR. Baseline and post-treatment blood samples were collected. Hemostasis was assessed by both standard coagulation tests and functional whole blood hemostatic assays (thromboelastograhy (TEG, and platelet aggregation (Multiplate. Patients with CHC and advanced fibrosis had impaired platelet aggregation both compared to patients with no or mild fibrosis and to healthy controls. Patients with CHC and advanced fibrosis also had lower antithrombin, platelet count, and coagulation factors II-VII-X compared to healthy controls. In contrast, TEG did not differ between groups. In treated patients achieving SVR, post-treatment platelet count was higher than pre-treatment counts (p = 0.033 and ADPtest, ASPItest, and RISTOhightest all increased post treatment (all p < 0.05. All Multiplate tests values, however, remained below those in the healthy controls. CHC-infected patients displayed evidence of rebalanced hemostasis with only partly hemostatic normalization in patients achieving SVR. The implications of rebalanced hemostasis and especially the impact on risk of CVD and bleeding warrants further studies.

Risk factors and genotypes of hepatitis C virus infection in libyan patients.

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Alashek, Wa; Altagdi, M

2008-12-01

The prevalence and incidence of HCV infection varies geographically due to exposure to different risk factors. Identification of HCV genotype is important to defining the epidemiology of the disease. The objective of this study was to describe genotype distribution and its relation to risk factors among HCV infected patients attending virology clinic of the Department of Infectious Diseases at the Tripoli Medical Centre. The medical records of 891 Libyan chronic HCV infected patients registered and followed up from January 2003 to January 2007 were reviewed. Data gathered includes patient's age, gender, risk factors and family history of HCV infection. Statistical analysis was performed using t, x2 and contingency coefficient tests. The mean age was 40.22±13.09 years. Two thirds of patients were males. Normal alanine aminotransferase (ALT) at diagnosis was found in 62% of the patients. HCV RNA<2 million copies at diagnosis was found among 54% of patients. HCV genotype 1 (G1) was the most frequent (30.9%), followed by G4 (29.2%). Genotype 2 affected 19.3% and G3 13.6%. No classification of HCV genotype was available for 2% of the patients. Many subtypes of HCV were detected with different frequencies (G1a and b, G2a, b, c and a/c, G3a and G4a and c/d). All genotypes of HCV were more common among males (P<0.001). Genotype 3 was the most frequent among male patients (88.6%). Regarding the risk factors, 33% of patients had a history of hospitalization and/or surgical procedures, and 22.7% had a history of blood transfusion. A past history of intravenous drug abuse (IVDA) was reported by 15% of the patients, and 15.9% reported a history of dental procedures. The relationship between the genotype of HCV and risk factors was statistically significant (P<0.001). No history of risky exposure was found among 10.8% of patients. Genotypes 1 and 4 were more predominant among HCV infected patients. Males were affected more than females and they presented themselves to the

The Impact of Cooperative Learning on CHC Students' Achievements and Its Changes over the Past Decade

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Chen, Qiuxian; Liu, Yuan

2017-01-01

Informed by emergent learning theories and multiple evidenced benefits, cooperative learning has developed into a widely accepted organization mode of class in the Western context. For the same reason, cooperative learning is transferred, during the past decade, into classrooms of Confucian Heritage Culture (CHC) contexts. Concerns, however, are…

Prevalence of mixed hepatitis C virus (HCV genotypes among recently diagnosed dialysis patients with HCV infection

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Mohammed A Al Balwi

2011-01-01

Full Text Available Hepatitis C virus (HCV infection is considered a major health problem recognized globally. HCV is a major cause of chronic liver disease that may lead to cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate the prevalence of multiple (mixed HCV genotypes in Saudi patients recently diagnosed with HCV infection and their association with various clinical risk factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz Medical City, Riyadh. The clinical and laboratory data of the study patients were collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR technology to assist in the follow-up and management of HCV-infected patients undergoing antiviral therapy. Twenty-two patients (1.7% were found to have mixed HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in 19 patients (86%, mixed genotypes associated with genotype-1 were found in 68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed genotypes associated with genotype-1 were seen in three cases (13.6%; they were associated with genotype-2 in two (66.7% and with genotype-5 in one patient (33.3%. In conclusion, the prevalence rate of mixed HCV genotypes in the cohort of the newly infected Saudi patients was 1.7%, with genotype-4 being the most frequent genotype encountered.

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

Science.gov (United States)

Buti, M; Domínguez-Hernández, R; Oyagüez, I; Casado, M A; Esteban, R

2017-09-01

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings. © 2017 John Wiley & Sons Ltd.

The design decisions of breeding zone sub-module for testing in ITER in order to validate the CHC TBM concept

International Nuclear Information System (INIS)

Leshukov, A.Yu.; Kapyshev, V.K.; Kartashev, I.A.; Kovalenko, V.G.; Razmerov, A.V.; Sviridenko, M.N.; Strebkov, Yu.S.

2010-01-01

Russian Federation has adopted the strategy to participate in the TBM Program on the rights of 'Partner' in the development of ceramic helium-cooled (CHC) test blanket module (TBM) concept. In this connection one of the possible collaboration scenarios is to integrate the characteristic design element of RF concept in the structure of 'Leader's' TBM and to test it in ITER environment. According to the collaboration in the framework of Test Blanket Working Group (TBWG) the 'Leader' and 'Partner' should develop together the selected (DEMO-relevant) TBM concept which will not disturb the ITER operation. Because of the analogue in the design principles, testing objectives and parameters of the EU CHC TBM concept ('Leader') and of the RF one, the RF specialists have developed the design options of breeding zone sub-module (BZSM) to be integrated in one of the EU TBM cells for further testing in ITER. There are four BZSM design options (according to four types of TBM to be tested) have been developed. Brief explanation of RF strategy in the partnership for the development of CHC blanket concept is presented in this paper. This paper also contains the description of all the four BZSM designs and some technological features.

Risk Factors and Genotypes of Hepatitis C Virus Infection in Libyan Patients

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Alashek WA

2008-01-01

Full Text Available Background: The prevalence and incidence of HCV infection varies geographically due to exposureto different risk factors. Identification of HCV genotype is important to defining the epidemiology of thedisease. The objective of this study was to describe genotype distribution and its relation to riskfactors among HCV infected patients attending virology clinic of the Department of InfectiousDiseases at the Tripoli Medical Centre. Methods: The medical records of 891 Libyan chronic HCVinfected patients registered and followed up from January 2003 to January 2007 were reviewed. Datagathered includes patient's age, gender, risk factors and family history of HCV infection. Statisticalanalysis was performed using t, x2 and contingency coefficient tests. Results: The mean age was40.22±13.09 years. Two thirds of patients were males. Normal alanine aminotransferase (ALT atdiagnosis was found in 62% of the patients. HCV RNA < 2 million copies at diagnosis was foundamong 54% of patients. HCV genotype 1 (G1 was the most frequent (30.9%, followed by G4(29.2%. Genotype 2 affected 19.3% and G3 13.6%. No classification of HCV genotype was availablefor 2% of the patients. Many subtypes of HCV were detected with different frequencies (G1a and b,G2a, b, c and a/c, G3a and G4a and c/d. All genotypes of HCV were more common among males(P<0.001. Genotype 3 was the most frequent among male patients (88.6%. Regarding the riskfactors, 33% of patients had a history of hospitalization and/or surgical procedures, and 22.7% had ahistory of blood transfusion. A past history of intravenous drug abuse (IVDA was reported by 15% ofthe patients, and 15.9% reported a history of dental procedures. The relationship between thegenotype of HCV and risk factors was statistically significant (P<0.001. No history of risky exposurewas found among 10.8% of patients. Conclusion: Genotypes 1 and 4 were more predominantamong HCV infected patients. Males were affected more than females and

Hearing impairment in genotyped Wolfram syndrome patients.

NARCIS (Netherlands)

Plantinga, R.F.; Pennings, R.J.E.; Huygen, P.L.M.; Bruno, R.; Eller, P.; Barrett, T.G.; Vialettes, B.; Paquis-Fluklinger, V.; Lombardo, F.; Cremers, C.W.R.J.

2008-01-01

OBJECTIVES: Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment.

Blood group genotyping: from patient to high-throughput donor screening.

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Veldhuisen, B; van der Schoot, C E; de Haas, M

2009-10-01

Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platelet antigens is known. In many laboratories, blood group genotyping assays are routinely used for diagnostics in cases where patient red cells cannot be used for serological typing due to the presence of auto-antibodies or after recent transfusions. In addition, DNA genotyping is used to support (un)-expected serological findings. Fetal genotyping is routinely performed when there is a risk of alloimmune-mediated red cell or platelet destruction. In case of patient blood group antigen typing, it is important that a genotyping result is quickly available to support the selection of donor blood, and high-throughput of the genotyping method is not a prerequisite. In addition, genotyping of blood donors will be extremely useful to obtain donor blood with rare phenotypes, for example lacking a high-frequency antigen, and to obtain a fully typed donor database to be used for a better matching between recipient and donor to prevent adverse transfusion reactions. Serological typing of large cohorts of donors is a labour-intensive and expensive exercise and hampered by the lack of sufficient amounts of approved typing reagents for all blood group systems of interest. Currently, high-throughput genotyping based on DNA micro-arrays is a very feasible method to obtain a large pool of well-typed blood donors. Several systems for high-throughput blood group genotyping are developed and will be discussed in this review.

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.

Mortality Rates in Patients With Chronic Hepatitis C and Cirrhosis Compared With the General Population

DEFF Research Database (Denmark)

Hallager, Sofie; Brehm Christensen, Peer; Ladelund, Steen

2017-01-01

Background: Knowledge about mortality rates (MRs) in patients with chronic hepatitis C (CHC) with cirrhosis is limited. This study aimed to estimate all-cause MRs among patients with CHC with or without cirrhosis in Denmark compared with the general population. Methods: Patients registered...... in the Danish Database for Hepatitis B and C with CHC and a liver fibrosis assessment were eligible for inclusion. Liver fibrosis was assessed by means of liver biopsy, transient elastography, and clinical cirrhosis. Up to 20 sex- and age-matched individuals per patient were identified in the general population....... Data were extracted from nationwide registries. Results: A total of 3410 patients with CHC (1014 with cirrhosis), and 67 315 matched individuals were included. Adjusted MR ratios (MRRs) between patients with or without cirrhosis and their comparison cohorts were 5.64 (95% confidence interval [CI], 4...

Glucose abnormalities in Asian patients with chronic hepatitis C.

Science.gov (United States)

Bo, Qingyan; Orsenigo, Roberto; Wang, Junyi; Griffel, Louis; Brass, Clifford

2015-01-01

Many studies have demonstrated a potential association between type 2 diabetes (T2D) and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D) and their risk factors between Asian and non-Asian chronic hepatitis C (CHC) patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries). This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025) as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%), and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08). Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had no impact on viral response to peginterferon plus ribavirin.

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.

Science.gov (United States)

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

Hepatitis C virus Genotypes in Patients with End-Stage Renal Disease in East Azerbaijan, Iran

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Somi Mohammad

2008-01-01

Full Text Available Information about the genotypes and associated risk factors in hepatitis C virus (HCV infected patients in Iran is limited. The aim of this study was to identify the HCV genotypes and associated risk factors in a group of HCV infected patients on dialysis therapy in Iran. The sera of 753 patients with chronic renal failure from fifteen dialysis units in East Azerbaijan Province were screened for anti-HCV antibodies as well as HCV RNA; viral RNA was extracted for the genotype specific primer approach. Patients were questioned concerning documented risk factors. Genotyping analysis was performed in 55 patients with positive anti-HCV and HCV-RNA. Genotypes 1 and 3 were found in 46 (83.7% and three (5.5% patients, respectively. The most frequent HCV subtype was 1a (76.4%, followed by 3a and 1b and 1b (5.5% each while one patient was infected with both 1a and 1b. There was no statistically significant difference between the risk factors analyzed and the acqui-sition of HCV infection. This study gives added evidence of the predominant HCV genotypes in Iran, which is different than reports from other Arab countries and similar with the pattern of genotype in both Europe and United States.

Hepatic fibrosis in patients with chronic hepatitis C assessed by transient elastography: implications for determining the efficacy of antiviral therapy Evaluación de la fibrosis hepática en pacientes con hepatopatía crónica C mediante elastografía transitoria: implicaciones para determinar la eficacia del tratamiento antiviral

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J. Mendoza

2010-07-01

Full Text Available Background: the efficacy of combination therapy with peginterferon plus ribavirin to eradicate viral infection in patients with chronic hepatitis C (CHC is well established; moreover, it is able to arrest or even reverse liver fibrosis. Aims: to analyze the measurements of hepatic stiffness as an index of liver fibrosis using transient elastography (TE in patients who underwent a sustained virological response (SVR during long-term follow-up; comparing the changes in the severity of fibrosis with non-responders patients. Material and methods: after hepatic fibrosis was studied in three patients with CHC who underwent a SVR during long-term follow up, a prospective study was initiated in 24 patients with CHC who received combination therapy to compare the evolution of fibrosis in those with SVR and those who were non-responders. The genotype of hepatitis C virus (HCV and the degree of viremia were determined. METAVIR scoring system was used for liver fibrosis. Hepatic stiffness was measured by TE. Results: of the initial three patients pre-treatment liver biopsies revealed active disease and fibrosis (stage 3 in two and mild fibrosis (stage 1 in one. After several years of follow up serum AST/ALT levels were normal and HCV RNA was undetectable in each case; in contrast to the baseline histological assessments of fibrosis, values for hepatic stiffness (3.4-6.9 KPa were compatible with an absence of any appreciable hepatic fibrosis. In the prospective study, 8 patients underwent a SVR and 16 were non-responders. TE indicated that the severity of hepatic fibrosis in the SVR group improved in 7 (88% patients, whereas in the non-responder it improved in only 4 (25% (p < 0.05. The difference between development of severe fibrosis (F ≥ 3 in responders and non-responders was not significant (p = 0.23, possibly due to the small sample size. Conclusions: regression of hepatic fibrosis appears to be common in patients with CHC who undergo a SVR. TE is a

Glucose abnormalities in Asian patients with chronic hepatitis C

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Bo Q

2015-11-01

Full Text Available Qingyan Bo,1 Roberto Orsenigo,2 Junyi Wang,1 Louis Griffel,3 Clifford Brass3 1Beijing Novartis Pharma Co. Ltd., Shanghai, People’s Republic of China; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Many studies have demonstrated a potential association between type 2 diabetes (T2D and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D and their risk factors between Asian and non-Asian chronic hepatitis C (CHC patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries. This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025 as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%, and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08. Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had

Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria.

Science.gov (United States)

Tao, Jing; Li, Nana; Jia, Haitao; Liu, Zhen; Li, Xiaohong; Song, Jiaping; Deng, Ying; Jin, Xi; Zhu, Jun

2015-12-01

A growing body of research has suggested that tetrahydrobiopterin (BH4) responsive phenotype can be predicted by the phenylalanine hydroxylase (PAH) genotype in patients with phenylketonuria (PKU), but data concerning the association between genotype and BH4 responsiveness are scarce in China. A total of 165 PKU patients from China who had undergone a 24-h loading test with BH4 administration were recruited. Genotyping was performed by the next-generation sequencing (NGS) technique. Using the predicted residual PAH activity, we analyzed the association between genotype and BH4-responsiveness. Among the 165 patients, 40 patients (24.24%) responded to BH4. A total of 74 distinct mutations were observed, including 13 novel mutations. The mutation p.R241C was most frequently associated with response. Two known mutations (p.A322T and p.Q419R) and two novel mutations (p.L98V and IVS3-2A>T) were first reported as responsive to BH4. Residual PAH activity of at least 12.5% was needed for responsive genotypes. Genotype-based predictions of BH4-responsiveness are only for selecting potential responders. Accordingly, it is necessary to test potential responders with a long-term BH4 challenge.

High prevalence of ACE DD genotype among north Indian end stage renal disease patients

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Pandirikkal Baburajan Vinod

2006-10-01

Full Text Available Abstract Background The Renin-Angiotensin system (RAS is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1 is an important component of RAS which determines the vasoactive peptide Angiotensin-II. Methods In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8 and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR based DNA amplification using specific flanking primers Based on the method described elsewhere. Results The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95%CI = 1.54-8.07. The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95%CI limit = 3.4-8.5. However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, ~87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype Conclusion Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in

The Role of Cattell-Horn-Carroll (CHC) Cognitive Abilities in Predicting Writing Achievement during the School-Age Years

Science.gov (United States)

Cormier, Damien C.; Bulut, Okan; McGrew, Kevin S.; Frison, Jessica

2016-01-01

Writing is a complex academic task--it involves numerous mental processes. Given the necessity for developing writing skills from elementary to secondary school, this study aimed to investigate the role of broad cognitive abilities derived from the Cattell-Horn-Carroll (CHC) theory of intelligence in predicting skills associated with writing…

Epidemiological manifestations of hepatitis C virus genotypes and its association with potential risk factors among Libyan patients.

Science.gov (United States)

Elasifer, Hana A; Agnnyia, Yossif M; Al-Alagi, Basher A; Daw, Mohamed A

2010-11-13

The information on hepatitis C virus genotypes and subtypes among Libyan population and its association with various risk factors is not known. The objectives of this study were to determine the epidemiological manifestations of HCV genotypes among Libyan patients and their association with certain potential risk factors. A total of 1240 of HCV infected patients registered at Tripoli Medical Centre were studied in five years period from January 2005 to October 2009. The information were reviewed and the data were collected. A sample from each patient (785 male; 455 female) was analysed for genotyping and sub-typing using specific genotyping assay. The information was correlated with the risk factors studied and the statistical data were analyzed using SPSS version 11.5. Off the total patients studied, four different genotypes were reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest (35.7%), followed by genotype1 (32.6%). According to subtypes 28% were unclassified genotype 4, 14.6% were genotype 1b and some patients infected with more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c). Genotypes 1 was the commonest among males, while genotype 4 among females. According to the risk factors studied, Genotype1 and genotype 4 were found with most of the risk factors. Though they were particularly evident surgical intervention, dental procedures and blood transfusion while genotype 1 was only followed by genotype 3 mainly which mainly associated with certain risk groups such as intravenous drug abusers. Here in we report on a detailed description of HCV genotype among Libyans. The most common genotype was type 4 followed by genotype 1, other genotypes were also reported at a low rate. The distribution of such genotypes were also variable according to gender and age. The commonly prevalent genotypes found to be attributable to the medical -related transmission of HCV, such as blood, surgery and dental procedures when compared with other risk

Genotyping of Kell, Duffy, Kidd and RHD in patients with b Thalassemia

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Castilho Lilian

2000-01-01

Full Text Available Determination of Rh, Kell, Duffy and Kidd phenotypes in addition to ABO is used to prevent the alloimmunization to red blood cells (RBCs antigens and as part of the antibody identification process in patients with beta Thalassemia. However, phenotyping in these patients can be time consuming and difficult to interpret. In these situations, it would be valuable to have an alternative to hemagglutination tests to determine the patient's antigen profile. We used PCR-RFLP to genotype such patients. DNA was prepared from 50 patients with beta Thalassemia who had been phenotyped by routine hemagglutination, and tested for Kell, Kidd, Duffy/GATA mutation by PCR-RFLP. RHD/non-D was analysed by PCR product size associated to RHD gene sequence in intron 4 and exon 10/3'UTR. The genotyping assays were performed without knowledge of phenotype results. For RHD/non-D, 47 were RhD+ and RHD+/RHCE+, and 3 were RhD- and RHD-/RHCE+. For Kell, 48 kk were K2K2 and 2 Kk were K1K2. For Duffy, of 44 samples that had normal GATA box, 8 Fy(a+b- were FYA/FYA, 15 Fy(a+b+ were FYB/FYB, and 19 Fy(a+b+ were FYA/FYB; of the other 4 samples 3 were FYA/FYB and heterozygous GATA mutation, and 1 Fy(a-b- was FYB/FYB, homozygous GATA mutation. Two samples phenotyped as Fy(a+b- that had normal GATA , presented the 265T/298A mutations and two samples phenotyped as Fy(a-b+ were genotyped was FYA/FYB.. For Kidd , 15 Jk(a+b were JKA/JKA, 12 Jk(a-b+ were JKB/JKB, and 20 Jk(a+b+ were JKA/JKB. Three samples phenotyped as JK(a+b+ were genotyped as JKB/JKB. Genotype is more accurate than phenotype for determination of blood groups in polytransfused patients with betaThalassemia. Genotyping in these patients can be helpful to select antigen-negative RBCs for transfusion.

CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.

Science.gov (United States)

Stamer, Ulrike M; Zhang, Lan; Book, Malte; Lehmann, Lutz E; Stuber, Frank; Musshoff, Frank

2013-01-01

The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12(th) hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. In this postoperative setting, the number of functionally active CYP2D6 alleles had an impact

CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.

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Ulrike M Stamer

Full Text Available BACKGROUND: The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. METHODS: Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele, HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity, EM (extensive metabolizers, normal CYP2D6 activity and UM (ultrarapid metabolizers, increased CYP2D6 activity. Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. RESULTS: Metabolism differed between CYP2D6 genotypes. Mean (95%-CI oxymophone/oxycodone ratios were 0.10 (0.02/0.19, 0.13 (0.11/0.16, 0.18 (0.16/0.20 and 0.28 (0.07/0.49 in PM, HZ/IM, EM and UM, respectively (p = 0.005. Oxycodone consumption up to the 12(th hour was highest in PM (p = 0.005, resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8; EM and UM 2.2 (2.1/2.3; p<0.001. Pain scores did not differ between genotypes. CONCLUSIONS: In this postoperative setting, the number of

The study of correlation between HBV genotype and the response to transcatheter arterial chemoembolization therapy in hepatocellular carcinoma patients

International Nuclear Information System (INIS)

Huang Keyao; Yang Weizhu; Jiang Na; Zheng Qubing

2004-01-01

Objective: To evaluate the influence of hepatitis B virus(HBV) genotype on response to transcatheter arterial embolization therapy in patients with HBV-related HCC. Methods: Transcatheter arterial chemoem-bolization therapy was conducted in patients with HBV-related HCC and response to embolization therapy were observed according to the tumor necrosis rate, the HCC recurrence rate, the cumulative incidence of survival rate and the change of AFP. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. The response of HCC to embolization therapy was compared between patients who were infected with different genotypic HBV. Results: The tumor necrosis rate of genotype C patients was similar to that of genotype B patients (P=0.099). The HCC recurrence rate of genotype B was lower than that of genotype C patients (P=0.036). The cumulative incidence of survival rates of 2 and 3 years were significantly higher in the genotype B patients (P=0.036 and P=0.013). There was no difference between the two genotypes, patients in the change of AFP (P>0.05). Conclusions: HBV genotype B patients seem to have a better response to embolization therapy as compared to genotype C patients. Determination of HBV genotype may be useful in predicting the outcomes of TACE therapy in HBV-related HCC. (authors)

A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma.

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Tian, Meng-Xin; He, Wen-Jun; Liu, Wei-Ren; Yin, Jia-Cheng; Jin, Lei; Tang, Zheng; Jiang, Xi-Fei; Wang, Han; Zhou, Pei-Yun; Tao, Chen-Yang; Ding, Zhen-Bin; Peng, Yuan-Fei; Dai, Zhi; Qiu, Shuang-Jian; Zhou, Jian; Fan, Jia; Shi, Ying-Hong

2018-01-01

Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables ( P model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.

Hearing impairment in genotyped Wolfram syndrome patients.

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Plantinga, Rutger F; Pennings, Ronald J E; Huygen, Patrick L M; Bruno, Rocco; Eller, Philipp; Barrett, Timothy G; Vialettes, Bernard; Paquis-Fluklinger, Veronique; Lombardo, Fortunato; Cremers, Cor W R J

2008-07-01

Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment. Pure tone threshold data of 23 Wolfram syndrome patients were used for cross-sectional analysis in subgroups (age less than 16 years or between 19 and 25 years, gender, and origin). All subgroups, with 1 exception, showed a fairly similar type of hearing impairment with, on average, thresholds of about 25 dB (range, 0 to 65 dB) at 0.25 to 1 kHz, gently sloping downward to about 60 dB (range, 25 to 95 dB) at 8 kHz. The subgroup of Dutch women, which was excluded from the calculations of the average hearing thresholds, showed a higher degree of hearing impairment. Only the latter subgroup showed progression; however, contrary to the previous longitudinal analysis, progression was not significant in the present cross-sectional analysis, presumably because of the high degree of cross-subject variability. This unique collection of audiometric data from genotyped Wolfram syndrome patients shows no substantial progression in sensorineural hearing impairment with advancing age, no relation to the types of WFS1 mutations identified, and, with exclusion of the subgroup of Dutch female patients, no significant sex-related differences.

Epidemiological manifestations of hepatitis C virus genotypes and its association with potential risk factors among Libyan patients

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Daw Mohamed A

2010-11-01

Full Text Available Abstract Background The information on hepatitis C virus genotypes and subtypes among Libyan population and its association with various risk factors is not known. The objectives of this study were to determine the epidemiological manifestations of HCV genotypes among Libyan patients and their association with certain potential risk factors. Methods A total of 1240 of HCV infected patients registered at Tripoli Medical Centre were studied in five years period from January 2005 to October 2009. The information were reviewed and the data were collected. A sample from each patient (785 male; 455 female was analysed for genotyping and sub-typing using specific genotyping assay. The information was correlated with the risk factors studied and the statistical data were analyzed using SPSS version 11.5. Results Off the total patients studied, four different genotypes were reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest (35.7%, followed by genotype1 (32.6%. According to subtypes 28% were unclassified genotype 4, 14.6% were genotype 1b and some patients infected with more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c. Genotypes 1 was the commonest among males, while genotype 4 among females. According to the risk factors studied, Genotype1 and genotype 4 were found with most of the risk factors. Though they were particularly evident surgical intervention, dental procedures and blood transfusion while genotype 1 was only followed by genotype 3 mainly which mainly associated with certain risk groups such as intravenous drug abusers. Conclusion Here in we report on a detailed description of HCV genotype among Libyans. The most common genotype was type 4 followed by genotype 1, other genotypes were also reported at a low rate. The distribution of such genotypes were also variable according to gender and age. The commonly prevalent genotypes found to be attributable to the medical -related transmission of HCV, such as blood

Hepatitis B virus: molecular genotypes and HBeAg serological status among HBV-infected patients in the southeast of Brazil

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Gonçales Fernando L

2009-09-01

Full Text Available Abstract Background Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil and to correlate results with clinical and histopathological data. Methods One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 ± 14.5 years; range 7-80 years; 84% Caucasian and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche. Results HBV genotype A was the most prevalent (55%, while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76 were African descendents and, among the patients infected by genotype D, 11.3% (6/53 were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7 genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F. The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8 was significantly higher than the mean stage of fibrosis in genotype D patients (2.0 (P = 0.0179. Conclusion The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status

Haptoglobin 2-2 Genotype, Patient, and Graft Survival in Renal Transplant Recipients

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Dupont, Laust; Eide, Ivar Anders; Hartmann, Anders

2017-01-01

Background: Cardiovascular disease is the leading cause of death in renal transplant recipients. An association between haptoglobin genotype 2-2 and cardiovascular disease has been found in patients with diabetes mellitus and liver transplant recipients. To date, the role of haptoglobin genotype...... after renal transplantation has not been studied. Methods: In this single-center retrospective cohort study of 1975 adult Norwegian transplant recipients, who underwent transplantation between 1999 and 2011, we estimated the risk of all-cause and cardiovascular mortality and overall and death...... transplant recipients, we could not demonstrate any association between haptoglobin 2-2 genotype and patient or graft survival after renal transplantation....

Assessing risk of fibrosis progression and liver-related clinical outcomes among patients with both early stage and advanced chronic hepatitis C.

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Monica A Konerman

Full Text Available Assessing risk of adverse outcomes among patients with chronic liver disease has been challenging due to non-linear disease progression. We previously developed accurate prediction models for fibrosis progression and clinical outcomes among patients with advanced chronic hepatitis C (CHC. The primary aim of this study was to validate fibrosis progression and clinical outcomes models among a heterogeneous patient cohort.Adults with CHC with ≥3 years follow-up and without hepatic decompensation, hepatocellular carcinoma (HCC, liver transplant (LT, HBV or HIV co-infection at presentation were analyzed (N = 1007. Outcomes included: 1 fibrosis progression 2 hepatic decompensation 3 HCC and 4 LT-free survival. Predictors included longitudinal clinical and laboratory data. Machine learning methods were used to predict outcomes in 1 and 3 years.The external cohort had a median age of 49.4 years (IQR 44.3-54.3; 61% were male, 80% white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. Fibrosis progression occurred in 34% over a median of 4.9 years (IQR 3.2-7.6. Clinical outcomes occurred in 22% over a median of 4.4 years (IQR 3.2-7.6. Model performance for fibrosis progression was limited due to small sample size. The area under the receiver operating characteristic curve (AUROC for 1 and 3-year risk of clinical outcomes was 0.78 (95% CI 0.73-0.83 and 0.76 (95% CI 0.69-0.81.Accurate assessments for risk of clinical outcomes can be obtained using routinely collected data across a heterogeneous cohort of patients with CHC. These methods can be applied to predict risk of progression in other chronic liver diseases.

Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients

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Chia-Chi Wang

2015-10-01

Conclusion: FIB-4 could predict hepatic fibrosis in CHC patients. By adding two parameters (age and alanine aminotransferase, FIB-4 better predicts advanced fibrosis and cirrhosis than APRI in CHC patients.

Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection

International Nuclear Information System (INIS)

Bieche, Ivan; Asselah, Tarik; Laurendeau, Ingrid; Vidaud, Dominique; Degot, Claude; Paradis, Valerie; Bedossa, Pierre; Valla, Dominique-Charles; Marcellin, Patrick; Vidaud, Michel

2005-01-01

The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-α/β-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-γ-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-α/β-inducible genes (but not IFN-γ-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-α/β- and IFN-γ-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first

HFE mutations and hemochromatosis in Danish patients admitted for HFE genotyping

DEFF Research Database (Denmark)

Koefoed, P; Dalhoff, K; Dissing, J

2002-01-01

Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate the efficiency with which different hospitals and general practitioners select patients for HH genotype and to determine the distribution...... of HFE mutations in such patients. Nine hundred unrelated patients from Danish hospitals and general practitioners (group A) and 69 consecutive patients from a specialized liver unit (group B) were examined for HFE substitutions using multiplex real-time polymerase chain reaction. In group A we found 13...... in the H63D homozygotes or S65C heterozygotes. Moreover, 7 wild-type patients, 2 C282Y heterozygote patients and one H63D heterozygote patient fulfilled the criteria for HH. The significant enrichment of HH among associated genotype samples submitted for HFE testing indicates that the clinical selection...

Dlaczego Słowińcy nie chcą rozmawiać? O antropologicznym czytaniu historii

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Filip, Mariusz

2015-01-01

Celem eseju jest oswojenie czytelnika ze sposobem antropologicznej/etnologicznej lektury przeszłości. Nie będzie to czynione poprzez prezentowanie czy formułowanie jakiego teoretycznego programu, lecz przez spojrzenie, jak wygląda to w praktyce. Przykładem będzie intrygująca grypa Słowińców. Pretekstem dla mojego antropologicznego czytania historii, jest postawienie na pozór banalnego, lecz świadomego i przemyślanego pytania: „Dlaczego Słowińcy nie chcą rozmawiać”? To pytanie stało się najważ...

Genotyping of Hepatitis C virus isolated from hepatitis patients in Southeast of Iran by taqman realtime PCR

International Nuclear Information System (INIS)

Farivar, T.N.; Johari, P.

2011-01-01

Objectives: To check TaqMan Realtime PCR in detecting genotypes of hepatitis C virus in Iran. Methods: From July 2007 to April 2009, HCV genotyping was done on 52 patients who were referred to Research Centre for infectious Disease and Tropical Medicine, in Bou-Ali Hospital, Zahedan University of Medical Sciences. All these patients had proven hepatitis C infection. Results: Out of 52 anti HCV positive samples, 28(53.84%) had genotype 1, 2 cases (3.88 %) had genotype 2 , 12 (23.08 %) had genotype 3 and 7 (13.4 %) had genotype 4 . Mixed infection with genotypes 1 and 3 was seen in 3 cases (5.77 %). Conclusion: TaqMan probes for detecting genotyping of HCV were successful in picking genotyping of HCV infection especially those with mixed genotypes. (author)

Hepatitis virus genotyping by Polymerase Chain Reaction and DNA Enzyme immunoassay among Saudi patients in the Western Province, Saudi Arabia

International Nuclear Information System (INIS)

Osoba, A.O.; Ibrahim, M.; Abdelaal, M.A.; Al-Mowallad, A.; Al-Shareef, B.; Hussein, B.A.

2000-01-01

The distribution of hepatitis C virus (HCV) genotypes in the Western Province of Saudi Arabia is unknown. The purpose of our study was to determine the prevalent HCV genotypes among HCV seropositive Saudi patients in the Western Province and to study the relationship between types/subtypes, clinical status and liver histology. Serum samples were collected from 140 consecutive patients attending the Hematology Clinic with varying grades of liver diseases, high almandine transferees (ALT) for > 6 months, positive HCV, qualitative PCR and who had liver biopsy. HCV genotyping was determined on patients who had tested positive by both HCV enzyme immunoassay (EIA) and the recombinant immunoblot assay (RIBA). Of the 140 patients, 97 (69.2%) had genotype 4, 18 (12.8%) had genotype 1a, and 16 (11.4%) had genotype 1b. Genotype 2b and 5 were found in two patients (1.4%) each, while 5 patients (3.6%) had mixed infections with genotype 4 and 5. Of the 97 patients infected with genotype 4, 84 (86.6%) had chronic active hepatitis (CAH), two (2.1%) had CAH with active cirrhosis, 9(9.3%) had cirrhosis and two (2.1%) had normal liver histology (NLH). The most prevalent HCV genotype in the Western Province of Saudi Arabia was genotype 4 (69.2%). Genotype 1b was encountered in 16 (11.4%) patients. For the first time, genotype 5 was identified in the Western Province of Saudi Arabia. Genotype 1b and 4 were associated with different histological grades of liver disease. (author)

Global, Broad, or Specific Cognitive Differences? Using a MIMIC Model to Examine Differences in CHC Abilities in Children with Learning Disabilities

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Niileksela, Christopher R.; Reynolds, Matthew R.

2014-01-01

This study was designed to better understand the relations between learning disabilities and different levels of latent cognitive abilities, including general intelligence (g), broad cognitive abilities, and specific abilities based on the Cattell-Horn-Carroll theory of intelligence (CHC theory). Data from the "Differential Ability…

Relationships between Cattell-Horn-Carroll (CHC) Cognitive Abilities and Math Achievement within a Sample of College Students with Learning Disabilities

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Proctor, Briley

2012-01-01

This study examined the relationship between cognitive abilities and math achievement within a sample of college students with learning disabilities (LD). The cognitive abilities were seven areas identified by Stratum II of the Cattell-Horn-Carroll (CHC) theory of cognitive abilities, in addition to the eighth area of Working Memory. Math…

Hepatitis C genotypes /subtypes among chronic hepatitis patients in Saudi Arabia

International Nuclear Information System (INIS)

Shobokshi, Ossama A.; Serebour, Frank E.; Skakni, Leila L.

2003-01-01

To determine the molecular epidemiology of Hepatitis C virus (HCV) in K.S.A. 492 histological proven chronic HCV patients recruited from all regions of KSA,between November 1999 and March 2002 were genotyped and subtyped using amplified products of specific primers from the 5-UTR region in a reverse transcription polymerase chain reaction followed by a hybridization technique. 62% of Saudis were found to be genotype4. Other genotypes were 1(24.1%); 2(7.4%); 3(5.9%); 5(0.3%) add 10(0.3%).All regions showed similar distribution except except the Eastern region where subtype 2a/c emerged. 86% of Saudi chronic hepatitis C cases are due to genotypes 1 and 4.Since these are considered difficult to treat an aggressive approach to management using combination therapy of pegylated interferon plus ribavirin for 48 weeks should be considered for all cases of chronic hepatitis C until genotyping proves otherwise. (author)

Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome.

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Maas, S M; Lombardi, M P; van Essen, A J; Wakeling, E L; Castle, B; Temple, I K; Kumar, V K A; Writzl, K; Hennekam, Raoul C M

2009-10-01

Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative in Goltz-Gorlin syndrome. A series of 17 patients with Goltz-Gorlin syndrome is reported on, and their phenotype and genotype are described. In 14 patients (13 females and one male), a PORCN mutation was found. Mutations included nonsense (n = 5), frameshift (n = 2), aberrant splicing (n = 2) and missense (n = 5) mutations. No genotype-phenotype correlation was found. All patients with the classical features of the syndrome had a detectable mutation. In three females with atypical signs, no mutation was found. The male patient had classical features and showed mosaicism for a PORCN nonsense mutation in fibroblasts. Two affected sisters had a mutation not detectable in their parents, supporting germline mosaicism. Their father had undergone radiation for testicular cancer in the past. Two classically affected females had three severely affected female fetuses which all had midline thoracic and abdominal wall defects, resembling the pentalogy of Cantrell and the limb-body wall complex. Thoracic and abdominal wall defects were also present in two surviving patients. PORCN mutations can possibly cause pentalogy of Cantrell and limb-body wall complexes as well. Therefore, particularly in cases with limb defects, it seems useful to search for these. PORCN mutations can be found in all classically affected cases of Goltz-Gorlin syndrome, including males. Somatic and germline mosaicism occur. There is no evident genotype-phenotype correlation.

Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

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Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

2015-01-01

The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

Hepatitis C virus genotypes among multiply transfused hemoglobinopathy patients from Northern Iraq

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Adil A Othman

2014-01-01

Full Text Available Background and Aim: Owing to the scarcity of data on hepatitis C virus (HCV genotypes in Iraq and due to their epidemiological as well as therapy implications, this study was initiated aiming at determining these genotypes in Northern Iraq. Materials and Methods: A total of 70 HCV antibody positive multi transfused patients with hemoglobinopathies, who had detectable HCV ribonucleic acid, were recruited for genotyping using genotype-specific nested polymerase chain reaction. Results: The most frequent genotype detected was genotype 4 (52.9% followed by 3a (17.1%, 1b (12.9% and 1a (1.4%, while mixed genotypes (4 with either 3a or 1b were detected in 7.1%. Conclusion: The predominance of genotype 4 is similar to other studies from surrounding Eastern Mediterranean Arab countries and to the only earlier study from central Iraq, however the significant high proportion of 3a and scarcity of 1a, are in contrast to the latter study and may be explainable by the differing population interactions in this part of Iraq. This study complements previous studies from Eastern Mediterranean region and demonstrates relative heterogeneity of HCV genotype distribution within Iraq and should trigger further studies in other parts of the country.

Hepatitis C genotype distribution in patient and blood donor samples in South Africa for the period 2008-2012.

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Prabdial-Sing, N; Chirwa, T; Thaver, J; Smuts, H; Vermeulen, M; Suchard, M; Puren, A J

2016-11-01

There are limited molecular epidemiological studies of hepatitis C at a national level in South Africa. The introduction of newer treatment modalities for hepatitis C requires knowledge of the genotypes as these may have different prognostic and therapeutic implications. This retrospective study describes genotype distributions of patients attending specialist clinics and a blood donor group studied during the period 2008-2012 in South Africa. Residual samples from diagnostic viral load testing from specialist clinics in South Africa (n=941) and from the South African National Blood Service (n=294) were analysed quantitatively by real-time PCR and genotyped using the Versant line probe assay or sequencing. Genotype 1 was predominant in blood donors (34%), whilst genotype 5a was prevalent in patients (36%). In the blood donor group, genotype 4 was detected for the first time. Genotype 2 was rare in the patient group and not detected in blood donors. Genotype 1 was the predominant genotype in the younger age groups (less than 30 years), whereas genotype 5a was found at higher proportions in the older age groups for both the patient and blood donor groups, comprising more than 60% of genotypes in those older than 50 years. Genotypes 1 and 5 were at highest proportions across all provinces compared to other genotypes. In blood donors, genotype 1 was predominant among Caucasians (43%) and genotype 5a among Blacks (54%). Such information is required for planning the impact on the health sector with regard to newly emerging therapies for hepatitis C and burden of disease. © 2016 John Wiley & Sons Ltd.

The genotypes of Orientia tsutsugamushi, identified in scrub typhus patients in northern Vietnam.

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Nguyen, Hang L K; Pham, Hang T T; Nguyen, Tinh V; Hoang, Phuong Vm; Le, Mai T Q; Takemura, Taichiro; Hasebe, Futoshi; Hayasaka, Daisuke; Yamada, Akio; Hotta, Kozue

2017-03-01

There are an estimated one million patients with scrub typhus in the Asia-Pacific region. There are few reports describing the incidence of scrub typhus in Vietnam. Blood samples collected from 63 patients clinically diagnosed as having scrub typhus from July 2015 to September 2016 were subjected to genotyping of Orientia tsutsugamushi. Of these patients, 42 (67%) tested positive for O. tsutsugamushi, and the most common genotype was identified to be Karp (55%). Other genotypes, TA763, Gilliam type in Japan variant, and Kato were also found in 17%, 17% and 12% of patients, respectively. To better understand the epidemiological landscape of scrub typhus in Vietnam, a countrywide study is needed. LC110330-LC110333, LC110336-LC110351 and LC214804-LC214825. © The Author 2017. 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.

Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients.

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Jekic, Biljana; Lukovic, Ljiljana; Bunjevacki, Vera; Milic, Vera; Novakovic, Ivana; Damnjanovic, Tatjana; Milasin, Jelena; Popovic, Branka; Maksimovic, Nela; Damjanov, Nemanja; Radunovic, Goran; Kovacevic, Ljiljana; Krajinovic, Maja

2013-03-01

Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G > T and 452 C > T), CCND1 (870 A > G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as non-responders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p = 0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p = 0.003). No other significant association were observed. The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T > G polymorphism may have high predictive value for myelosuppression in RA patients.

Neurocognitive Problems in Children and Adolescents With Depression Using the CHC Theory and the WJ-III.

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Basnet, Pravesh; Noggle, Chad A; Dean, Raymond S

2015-01-01

Depression has been commonly associated with both subjective complaints and objectively measured problems in cognition. Most commonly discussed in relation to the adult population, growing evidence has supported the idea that children and adolescents experience cognitive problems in relation to depression. The purpose of this study was to further examine the negative influence of depression on the cognitive functioning of children and adolescents. Additionally, the present study evaluated the sensitivity of the Woodcock-Johnson III Test of Cognitive Abilities (WJ-III-COG) and, in turn, the Cattell-Horn-Carroll (CHC) theory in measuring cognitive problems related to depression in children and adolescents. Participants included 420 children and adolescents aged 8 to 18 years old (M = 13.09, SD = 2.95) with a clinical diagnosis of depression. Comparisons were made against the normative mean. All participants completed 11 subtests of the WJ-III-COG including Visual-Auditory Learning, Spatial Relations, Sound Blending, Concept Formations, Visual Matching, Numbers Reversed, Auditory-Working Memory, Picture Recognition, Analysis Synthesis, Decision Speed, and Memory for Words. Children and adolescents with depression demonstrated significantly lower performance on subtests related to learning and memory (long-term retrieval), attentional capacity, working memory, reasoning, and processing speed. No problems were noted on subtests related to visual-spatial thinking and auditory processing. Findings suggested sensitivity of the WJ-III-COG and CHC theory in identifying cognitive problems associated with depression in children and adolescents.

Molecular epidemiology and genotyping of hepatitis B virus of HBsAg-positive patients in Oman.

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Al Baqlani, Said Ali; Sy, Bui Tien; Ratsch, Boris A; Al Naamani, Khalid; Al Awaidy, Salah; Busaidy, Suleiman Al; Pauli, Georg; Bock, C-Thomas

2014-01-01

Hepatitis B virus (HBV) infection is a major global health burden with distinct geographic public health significance. Oman is a country with intermediate HBV carrier prevalence; however, little is known about the incidence of HBV variants in circulation. We investigated the HBV genotype distribution, the occurrence of antiviral resistance, and HBV surface antigen (HBsAg) escape mutations in HBsAg-positive patients in Oman. Serum samples were collected from 179 chronically HBV-infected patients enrolled in various gastroenterology clinics in Oman. HBV genotypes were determined by sequencing and phylogenetic analysis. Mutations in the HBV polymerase and the HBsAg gene were characterized by mutational analysis. HBV genotypes D (130/170; 76.47%) and A (32/170; 18.28%) are predominant in Oman. The HBV genotypes C and E were less frequent (each 1.18%), while the HBV genotypes B, G, F, and H were not detected. Four patients revealed HBV genotype mixtures (HBV-A/D and D/C). The analyses of vaccine escape mutations yield that 148/170 (87.06%) HBV sequences were wild type. 22/170 (12.94%) HBV sequences showed mutations in the "a" determinant of the HBsAg domain. Two patients showed the described HBV vaccine escape mutation sP120T. 8/146 (5.48%) HBV isolates harbored mutations in the HBV polymerase known to confer resistance against antiviral therapy. Especially the lamivudine resistance mutations rtL180M/rtM204V and rtM204I were detected. This study shows the distribution of HBV genotypes, therapy resistance, and vaccine escape mutations in HBV-infected patients in Oman. Our findings will have a major impact on therapy management and diagnostics of chronic HBV infections in Oman to control HBV infection in this intermediate HBV-endemic country.

32. Boop - experiência do serviço de pneumologia do C.H.C

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Ana Luisa Fonseca

2003-11-01

, embora a relação CD4/CD8 tenha sido pouco orientadora para o diagnóstico; a boa resposta à corticoterapia. : BOOP (Bronchiolitis Obliterans Organizing Pneumonia is a physiopathologic syndrome associating suggestive clinical and imaging features, together with histopathologic studies showing buds of connective tissue in the lumen of the distal pulmonary airspace. The aim of the study is a retrospective review of all patients with BOOP, diagnosed in the Pulmonology Ward of CHC, between June 2000 and June 2003.Nine cases were diagnosed. Six patients were female and three were male; average age was in 58,6 years; eight patients were non-smokers and one had quit smoking several years before; five patients had co-morbidities; mean duration of symptoms was 68,5 days; initial symptoms were dyspnoea (7 patients, cough (6 patients, fever (5 patients and weight loss (2 patients; the majority (8 of patients had been given multiple antibiotics before the diagnosis; crackles were heard in 6 patients, fever was detected in 2 patients, and cyanosis in 1; chest X-ray showed bilateral alveolar opacities in 6 cases, linear opacities in 1 and focal pneumonia in 3; lung function testing, performed in 5 patients, showed a reduction in the diffusion capacity (average DLCO/VA of 59%; the bronchoalveolar lavage (BAL was performed in 6 patients, and all revealed an increase in the percentage of lymphocytes, with CD4/CD8 of 1.6 in average; histopathologic studies of pulmonary biopsy were diagnostic in 8 cases, while the diagnosis in one patient was based on clinical evidence and imaging; all patients were given corticosteroids; resolution was favourable in all patients except one who died.Of the parameters we looked at we emphasize: the presence of symptoms during long periods before diagnosis and administration and failure of multiple systemic antibiotics; agreement between imaging and those published in the literature; the increase in lymphocytes in the BAL, although the ratio CD4/CD8 was

Pathological features of liver tissue in autoantibody-positive chronic hepatitis C patients after plasmaphoresis

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WU Huili

2018-02-01

Full Text Available ObjectiveTo investigate the detection rate and features of autoantibodies in chronic hepatitis C (CHC patients after plasmaphoresis, as well as the liver pathological features of autoantibody-positive CHC patients. MethodsA total of 120 patients who were infected with hepatitis C virus after plasmaphoresis in the Hospital of Dingxi County and Dingxi Hospital of Infectious Diseases from January 1992 to December 1995 were selected as test group; 11 healthy people from the same region were selected as control group. Autoantibody detection was performed for the 120 CHC patients, and liver pathological features were compared between the autoantibody-positive group(n=44 and autoantibody-negative group(n=76 of these patients. The t test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. ResultsOf all 120 CHC patients who underwent plasmaphoresis, 44 (36.7% were found to have serum autoantibodies, with antinuclear antibodies as the most common type (21.7%. Compared with the autoantibody-negative group, the autoantibody-positive group had significantly higher scores of focal necrosis inside the hepatic lobules (211±0.88 vs 164±0.88, t=2.349，P=0.021 and ductular reaction inside the portal area (1.86±0.71 vs 1.13±0.66, t=4.217，P＜0.001, as well as a significantly higher rate of interlobular bile duct injury (86.4% vs 55.3%, χ2=12.129，P=0.001. There were no significant differences between the two groups in the degree of liver fibrosis and hepatic steatosis (both P＞0.05. ConclusionAutoantibody-positive are common in CHC patients after plasmaphoresis, and autoantibody-positive patients tend to have more severe injuries of the liver.

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

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Jeannesson-Thivisol, Elise; Feillet, François; Chéry, Céline; Perrin, Pascal; Battaglia-Hsu, Shyue-Fang; Herbeth, Bernard; Cano, Aline; Barth, Magalie; Fouilhoux, Alain; Mention, Karine; Labarthe, François; Arnoux, Jean-Baptiste; Maillot, François; Lenaerts, Catherine; Dumesnil, Cécile; Wagner, Kathy; Terral, Daniel; Broué, Pierre; de Parscau, Loïc; Gay, Claire; Kuster, Alice; Bédu, Antoine; Besson, Gérard; Lamireau, Delphine; Odent, Sylvie; Masurel, Alice; Guéant, Jean-Louis; Namour, Fares

2015-12-15

Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes. We seek here to improve prediction of BH4-responsiveness through comparison of genotypes, BH4-loading test, predictions of responsiveness according to the literature and types and locations of mutations. A total of 364 French patients among which, 9 % had mild hyperphenylalaninemia, 17.7 % mild phenylketonuria and 73.1 % classical phenylketonuria, benefited from a 24-hour BH4-loading test and had the PAH gene sequenced and analyzed by Multiplex Ligation Probe Amplification. Overall, 31.6 % of patients were BH4-responsive. The number of different mutations found was 127, including 26 new mutations. The mutations c.434A > T, c.500A > T, c.529G > C, c.1045 T > G and c.1196 T > C were newly classified as being BH4-responsive. We identified 261 genotypes, among which 46 were newly recognized as being BH4-responsive. Even though patients carry 2 responsive alleles, BH4-responsiveness cannot be predicted with certainty unless they present mild hyperphenylalaninemia. BH4-responsiveness cannot be predicted in patients carrying one responsive mutation only. In general, the milder the phenotype is, the stronger the BH4-response is. Almost exclusively missense mutations, particularly in exons 12, 11 and 8, are associated with BH4-responsiveness and any other type of mutation predicts a negative response. This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

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Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

2016-08-01

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

Diagnosis, gB genotype distribution and viral load of symptomatic congenitally infected CMV patients in Cuba.

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Correa, C; Kourí, V; Pérez, L; Soto, Y; Limia, C

2016-10-01

Cytomegalovirus (CMV) is the leading cause of viral congenital infection. Some viral factors have been proposed to be CMV pathogenicity markers. The objective of this study was to investigate the frequency of congenital CMV infection in symptomatic patients and the possible association with the CMV glycoprotein B (gB) genotype and viral load. A total of 361 newborns (NB) and 158 pregnant women (PW) with clinically suspected CMV infection were enrolled. Studied samples included urine, saliva, serum, vaginal swabs and amniotic fluid. CMV infection was diagnosed by multiplex nested PCR. CMV gB genotyping was performed on infected samples, followed by viral load determination. Overall, 18.7% of the tested patients were positive for CMV infection, 19.7% of NB were congenitally infected and 16.5% of PW showed active CMV infection. gB-2 was the most prevalent genotype detected (39/97 patients). gB CMV mixed infections were detected in 12 patients. gB-2 was associated with mono-infections (PCMV load was statistically significant among patients presenting different clinical signs (P=0.04). This study showed that CMV is a frequent cause of congenital infection in symptomatic Cuban patients. Despite gB2 being the most frequently detected, gB-4 was the only genotype associated with clinical features (sepsis-like syndrome in NB). No other associations among specific genotypes and clinical characteristics were found. Further studies are needed to clarify the role that viral load and genotype play in the outcome of congenital infection.

Genotypic frequency of Caveolin-1 (CAV1 T29107A polymorphism in the Iranian patients with breast cancer

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Ahmad Hamta

2016-09-01

Full Text Available Introduction: Caveolin-1 (Cav-1 is a scaffolding protein found in special structures of plasma membrane, known as Caveolae. Cav-1 can regulate many intracellular processes, including signal transmission and cholesterol metabolism. This protein plays an important role in the growth and differentiation of breast tissue and acts as a tumor suppressor gene as well. The aim of this study was to determine the genotypic frequency of Cav-1 T29107A (rs7804372 polymorphism and its association with susceptibility to breast cancer among the female population in Kermanshah, Iran. Methods: A total of 120 patients with breast cancer and an equal number of non-cancer individuals (control group, matched for age and gender with the patients, were selected in this study. The paraffin tissues of the patients from 2006 to 2013 were collected from Imam Reza hospital, Kermanshah, and 2.5 cc blood sample was taken from non-cancer individuals. The genomic DNA was extracted from paraffin tissues and blood by salting out method. The genotype of samples was determined by RFLP-PCR method, and Sau3A1 enzyme was used for RFLP analysis. Results: The distribution of Cav-1 T29107A genotype was found to be significantly different between breast cancer patients and control group (p=0.004. Among the patients, 84 (70% samples had genotype TT, 29 (24.78% genotype AT and 7 (5.83% genotype AA. As for the control group, however, 59 (49.17% samples had genotype TT, 49 (40.83% genotype AT and 12 (10% genotype AA. Conclusion: The results of this study showed that genotype TT is associated with an increased risk of susceptibility to breast cancer.

The longitudinal impact of patient navigation on equity in colorectal cancer screening in a large primary care network.

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Percac-Lima, Sanja; López, Lenny; Ashburner, Jeffrey M; Green, Alexander R; Atlas, Steven J

2014-07-01

The long-term effects of interventions to improve colorectal (CRC) screening in vulnerable populations are uncertain. The authors evaluated the impact of patient navigation (PN) on the equity of CRC prevention over a 5-year period. A culturally tailored CRC screening PN program was implemented in 1 community health center (CHC) in 2007. In a primary care network, CRC screening rates from 2006 to 2010 among eligible patients from the CHC with PN were compared with the rates from other practices without PN. Multivariable logistic regression models for repeated measures were used to assess differences over time. Differences in CRC screening rates diminished among patients at the CHC with PN and at other practices between 2006 (49.2% vs 62.5%, respectively; P practices (5% vs 3.4% per year; P practices, lower CRC screening rates in 2006 (47.5% vs 52.1%, respectively; P = .02) were higher by 2010 (73.5% vs 67.3%, respectively; P practices in 2006 (44.3% vs 44.7%, respectively; P = .79) were higher at the CHC by 2010 (70.6% vs 58.6%, respectively; P practices (both P < .001). A PN program increased CRC screening rates in a CHC and improved equity in vulnerable patients. Long-term funding of PN programs has the potential to reduce cancer screening disparities. © 2014 American Cancer Society.

Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe

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Soriano, Vincent; Mocroft, Amanda; Peters, Lars

2010-01-01

Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce.......Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce....

Relationship between Helicobacter pylori vacA genotypes status and risk of peptic ulcer in Saudi patients

International Nuclear Information System (INIS)

Momenah, Aiman M.; Tayeb, Mohammad T.

2006-01-01

To determine if there is a significant correlation between different Helicobacter pylori (H. pylori) vacA genotypes strains and severe gastric clinical outcomes. A total of 1104 gastric biopsies from 368 patients who presented with symptoms suggestive of chronic gastritis or peptic ulcer were taken from the main hospitals in the western region of Saudi Arabia from July 2004 to July 2005. These samples were cultured for H. pylori, and a polymerase chain reaction (PCR) was carried out to determine vacA genotypes status. One hundred and three (28%) patients were positive for H. pylori using culture technique. The distribution of vacA genotypes was 13 for vacAs1m1, 47 for vacAs1m2 and 43 for vacAs2m2. None of the clinical isolates were vacAs2m1 positive. The study showed a significant correlation between the vacAs1m2 genotype and gastritis cases, and a significant correlation between vacAs1m1 genotype and ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacAs1m1 genotype H. pylori strains. (author)

Recent update of the 2017 Korean Association for the Study of the Liver (KASL) treatment guidelines of chronic hepatitis C: comparison of guidelines from other continents, 2017 AASLD/IDSA and 2016 EASL.

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Yeon, Jong Eun

2018-05-02

The paradigm for the treatment of chronic hepatitis C (CHC) has been changed due to the development of direct acting antivirals (DAAs) of hepatitis C virus (HCV). The high sustained virologic response rate and ease of administration makes the DAAs approach ideal to contribute to the complete eradication of HCV. Currently, treatment options for individual patients vary depending on the genotype or subtype of HCV, presence or absence of liver cirrhosis, previous experience of antiviral treatment or resistance associated substitutions. Because of drug avalilability, cost-effectiveness, preference, compliance and greater possibility of desirable effects and presumed patient-important outcomes may vary between countries, treatment options for individual patients are different. The review focuses on the comparing the current treatment options for CHC in other continents with the 2017 Korea Association for the Study of the Liver guidelines.

Hepatitis G virus infection and genotypes in Iraqi thalassemia patients

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Maryam S Ibrahim

2015-01-01

Conclusion: the prevalence rate of HGV RNA in β-thalassemia major patients is 18.2%, while the prevalence rate of anti-HGV (past infection is 10.4%. No one of thalassemia patients had HGV RNA and anti-HGV simultaneously. The Gene sequence analysis of PCR products identified HGV genotypes 2 and 5 with percentage of 91.7% and 8.3% respectively

Low Prevalence of Insulin Resistance among Iranian Patients with Chronic Hepatitis C Virus Infection: A Case-Control Study.

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Eshraghian, Kavous; Lankarani, Kamran B; Fattahi, Mohammad Reza; Esmailnejad, Atefeh; Peymani, Payam

2017-07-14

Association between chronic hepatitis C virus (CHC) infection and type 2 diabetes mellitus has been challenging in recent decades. Despite of extensive research in this area, there is no general agreement on the direct effect of HCV infection on insulin resistance. The study was performed in 52 CHC patients (mean age = 39.48) and 52 and sex‑matched healthy Iranian controls, referred to the Hepatitis Clinic, Department of Gastroenterohepatology, Shiraz University of medical sciences, Shiraz, Iran, from 2012 to 2015. Fasting blood glucose level, fasting insulin level and insulin resistance defined as a homeostasis model assessment of insulin resistance (HOMA-IR) index were determined and compared between two groups. Insulin resistance was present in 26.9% of CHC patients and 34.62% of healthy controls. Mean HOMA index was 1.93 in patients and 2.18 in controls. There were no statistically significant differences between patient and control groups with regard to fasting insulin level, fasting blood glucose, HOMA index and insulin resistance. HOMA index and fasting insulin level were significantly higher in IR CHC patients relative to IR controls. Fasting blood glucose was also significantly higher in controls younger than 40 years. Results obtained in this study showed that chronic hepatitis C cannot be considered as a risk factor for insulin resistance and diabetes in Iranian population. However, regular screening for insulin resistance is recommended in CHC patients with age ≥ 40 years and fasting blood glucose ≥ 100 mg/dl. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

DEFF Research Database (Denmark)

Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

2003-01-01

The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scand......The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...

Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease.

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Pais, Raluca; Rusu, Elena; Zilisteanu, Diana; Circiumaru, Alexandra; Micu, Laurentiu; Voiculescu, Mihai; Poynard, Thierry; Ratziu, Vlad

2015-01-01

The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB). To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD. Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest>0.38 as a surrogate for steatosis >5%), IR (HOMA-IR>2.7 as a surrogate for IR) and fibrosis (FibroTest>0.48 as a surrogate for significant fibrosis, ≥F2). HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p<0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p<0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p<0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p<0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p<0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p<0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC. Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Response to hepatitis A and B vaccination in patients with chronic hepatitis C: 8-year follow-up.

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Kalyoncu, Derya; Urganci, Nafiye

2012-08-01

In patients with chronic hepatitis C (CHC), superinfection with hepatitis A (HAV) or B (HAB) viruses is associated with increased morbidity and mortality. The seroconversion rate of these patients following vaccination is considered to be lower than in healthy subjects. To evaluate the response to HAV and HBV vaccination in children with CHC. Thirty patients with CHC aged from 7.3 to 18 years were compared with 50 healthy age-, gender- and body-mass-index-matched controls. Post-vaccination serological evaluation was performed 1 month after the last dose of primary vaccination, 1 month after the booster dose and once a year during follow-up. Twenty-two patients received hepatitis A vaccine and response rate was 95.4%. Thirty patients received hepatitis B vaccine and 80% responded (hepatitis Bs titres ≥10 mIU/ml). Thirty-five controls received hepatitis A vaccine and protective anti-HAV antibodies developed in all. All of the controls were vaccinated against hepatitis B virus and 90% responded. After the whole vaccination series, overall seroprotection rates were 86% in patients and 96% in controls. No significant reduction in antibody response was observed in patients or controls during 8-years follow-up. The rate of seroconversion to the HBV vaccine is lower in patients with CHC than in healthy controls but response to HAV is adequate.

Detection and genotyping of human papilloma virus in cervical cancer specimens from Saudi patients.

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Al-Badawi, Ismail A; Al-Suwaine, Abdulrahman; Al-Aker, Murad; Asaad, Lina; Alaidan, Alwaleed; Tulbah, Asma; Fe Bohol, Marie; Munkarah, Adnan R

2011-07-01

To determine the rates and types of human papilloma virus (HPV) infection in cervical cancer specimens from Saudi patients. One hundred specimens were randomly selected and retrieved from the achieved samples stored in the pathology department accessioned under the diagnosis of cervical cancer and carcinoma in situ between the years 1997 and 2007. Human papilloma virus in the clinical samples was detected using polymerase chain reaction amplification methods. Two primer systems are commonly used: the MY09-MY11 primers and the GP5+-GP6+ that amplify a wide range of HPV genotypes. Human papilloma virus isolates were genotyped using DNA sequencing and reverse line blot hybridization assay to identify the high-risk HPV genotypes. Ninety cases fulfilled the diagnostic criteria and were analyzed. The rate of HPV genotype detection among cervical cancer samples was 95.5%. The most common HPV genotype detected by both methods was HPV-16 (63.4%), followed by HPV-18 (11.1%), HPV-45 (4.5%), HPV-33 (3.3%), and HPV-31, HPV-52, HPV-53, HPV-58, HPV-59, and HPV-66 with 2.2% prevalence rate each. Prevalence of HPV genotypes among patients with cervical cancer in Saudi Arabia is comparable to the international rates. The use of the reverse line blot hybridization assay genotyping method could be useful for classifying oncogenic HPV-positive women. It is relatively inexpensive and reliable and can be performed in routine practice or epidemiological study compared with the available standard commercial kits.

Mycobacterium tuberculosis strains of the Beijing genotype are rarely observed in tuberculosis patients in South America.

Science.gov (United States)

Ritacco, Viviana; López, Beatriz; Cafrune, Patricia I; Ferrazoli, Lucilaine; Suffys, Philip N; Candia, Norma; Vásquez, Lucy; Realpe, Teresa; Fernández, Jorge; Lima, Karla V; Zurita, Jeannete; Robledo, Jaime; Rossetti, Maria L; Kritski, Afranio L; Telles, Maria A; Palomino, Juan C; Heersma, Herre; van Soolingen, Dick; Kremer, Kristin; Barrera, Lucía

2008-08-01

The frequency of the Beijing genotype of Mycobacterium tuberculosis as a cause of tuberculosis (TB) in South America was determined by analyzing genotypes of strains isolated from patients that had been diagnosed with the disease between 1997 and 2003 in seven countries of the subcontinent. In total, 19 of the 1,202 (1.6%) TB cases carried Beijing isolates, including 11 of the 185 patients from Peru (5.9%), five of the 512 patients from Argentina (1.0%), two of the 252 Brazilian cases (0.8%), one of the 166 patients from Paraguay (0.6%) and none of the samples obtained from Chile (35), Colombia (36) and Ecuador (16). Except for two patients that were East Asian immigrants, all cases with Beijing strains were native South Americans. No association was found between carrying a strain with the Beijing genotype and having drug or multi-drug resistant disease. Our data show that presently transmission of M. tuberculosis strains of the Beijing genotype is not frequent in Latin America. In addition, the lack of association of drug resistant TB and infection with M. tuberculosis of the Beijing genotype observed presently demands efforts to define better the contribution of the virulence and lack of response to treatment to the growing spread of Beijing strains observed in other parts of the world.

Mycobacterium tuberculosis strains of the Beijing genotype are rarely observed in tuberculosis patients in South America

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Viviana Ritacco

2008-08-01

Full Text Available The frequency of the Beijing genotype of Mycobacterium tuberculosis as a cause of tuberculosis (TB in South America was determined by analyzing genotypes of strains isolated from patients that had been diagnosed with the disease between 1997 and 2003 in seven countries of the subcontinent. In total, 19 of the 1,202 (1.6% TB cases carried Beijing isolates, including 11 of the 185 patients from Peru (5.9%, five of the 512 patients from Argentina (1.0%, two of the 252 Brazilian cases (0.8%, one of the 166 patients from Paraguay (0.6% and none of the samples obtained from Chile (35, Colombia (36 and Ecuador (16. Except for two patients that were East Asian immigrants, all cases with Beijing strains were native South Americans. No association was found between carrying a strain with the Beijing genotype and having drug or multi-drug resistant disease. Our data show that presently transmission of M. tuberculosis strains of the Beijing genotype is not frequent in Latin America. In addition, the lack of association of drug resistant TB and infection with M. tuberculosis of the Beijing genotype observed presently demands efforts to define better the contribution of the virulence and lack of response to treatment to the growing spread of Beijing strains observed in other parts of the world.

Blood genotyping for improved outcomes in chronic transfusion patients: current and future perspectives

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Kutner JM

2014-09-01

Full Text Available Jose Mauro Kutner,1 Mariza Mota,1 Fabiana Conti,1 Lilian Castilho1,2 1Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 2Hemocentro Unicamp, Campinas, SP, Brazil Abstract: Blood transfusions are life sustaining in chronically transfused patients. However, certain complications, such as alloimmunization to red blood cells, can create challenges in the management of those patients. Routine phenotyping of blood recipients and the use of phenotype-matched blood units for transfusion have been useful to lower the occurrence of red cell alloantibodies in chronically transfused individuals. Nevertheless, extensive phenotyping is expensive, laborious, and cannot be performed in certain situations. The molecular understanding of blood groups has enabled the design of assays that may be used to better guide matched red blood cell transfusions. This review summarizes key findings related to red cell alloimmunization, the already identified and potential future benefits of blood group genotyping, and how molecular typing is being incorporated in the blood bank's routine to improve clinical and long-term outcomes in chronically transfused patients. Keywords: blood group genotyping, chronically transfused patients, platelet genotyping, RBC alloimmunization

Identification of imaging predictors discriminating different primary liver tumours in patients with chronic liver disease on gadoxetic acid-enhanced MRI: a classification tree analysis

International Nuclear Information System (INIS)

Park, Hyun Jeong; Jang, Kyung Mi; Kang, Tae Wook; Song, Kyoung Doo; Kim, Seong Hyun; Kim, Young Kon; Cha, Dong Ik; Kim, Joungyoun; Goo, Juna

2016-01-01

To identify predictors for the discrimination of intrahepatic cholangiocarcinoma (IMCC) and combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) for primary liver cancers on gadoxetic acid-enhanced MRI among high-risk chronic liver disease (CLD) patients using classification tree analysis (CTA). A total of 152 patients with histopathologically proven IMCC (n = 40), CHC (n = 24) and HCC (n = 91) were enrolled. Tumour marker and MRI variables including morphologic features, signal intensity, and enhancement pattern were used to identify tumours suspicious for IMCC and CHC using CTA. On CTA, arterial rim enhancement (ARE) was the initial splitting predictor for assessing the probability of tumours being IMCC or CHC. Of 43 tumours that were classified in a subgroup on CTA based on the presence of ARE, non-intralesional fat, and non-globular shape, 41 (95.3 %) were IMCCs (n = 29) or CHCs (n = 12). All 24 tumours showing fat on MRI were HCCs. The CTA model demonstrated sensitivity of 84.4 %, specificity of 97.8 %, and accuracy of 92.3 % for discriminating IMCCs and CHCs from HCCs. We established a simple CTA model for classifying a high-risk group of CLD patients with IMCC and CHC. This model may be useful for guiding diagnosis for primary liver cancers in patients with CLD. (orig.)

Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients

International Nuclear Information System (INIS)

Wegman, Pia; Vainikka, Linda; Stål, Olle; Nordenskjöld, Bo; Skoog, Lambert; Rutqvist, Lars-Erik; Wingren, Sten

2005-01-01

Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. The patients were genotyped using PCR followed by cleavage with restriction enzymes. Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041). The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort

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.

Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

International Nuclear Information System (INIS)

Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Huei-Jean; Chao, Angel; Chang, Chee-Jen; Chang, Ting-Chang; Chou, Hung-Hsueh; Hong, Ji-Hong

2010-01-01

Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy. Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method. Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group. Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration.

Molecular identification of t4 and t5 genotypes in isolates from acanthamoeba keratitis patients.

Science.gov (United States)

Ledee, D R; Iovieno, A; Miller, D; Mandal, N; Diaz, M; Fell, J; Fini, M E; Alfonso, E C

2009-05-01

Acanthamoeba keratitis (AK) is a rare but sight-threatening ocular infection. Outbreaks have been associated with contaminated water and contact lens wear. The epidemiology and pathology may be associated with unique genotypes. We determined the Rns genotype for 37 clinical isolates from 23 patients presenting at the University of Miami Bascom Palmer Eye Institute with confirmed AK infections in 2006 to 2008. The genus-specific ASA.S1 amplicon allowed for rapid genotyping of the nonaxenic cultures. Of the 37 isolates, 36 were of the T4 genotype. Within this group, 13 unique diagnostic fragment 3 sequences were identified, 3 of which were not in GenBank. The 37th isolate was a T5, the first in the United States and second worldwide to be found in AK. For five patients with isolates from the cornea and contact lens/case, identical sequences within each patient cluster were observed, confirming the link between contact lens contamination and AK infection. Genotyping is an important tool in the epidemiological study of AK. In this study, it allowed for the detection of new strains and provided an etiological link between source and infection. Additionally, it can allow for accurate categorizing of physiological differences, such as strain virulence, between isolates and clades.

Childhood Pompe disease: clinical spectrum and genotype in 31 patients

NARCIS (Netherlands)

Capelle, C.I. van; Meijden, J.C. van der; Hout, J.M. van den; Jaeken, J.; Baethmann, M.; Voit, T.; Kroos, M.A.; Derks, T.G.; Rubio-Gozalbo, M.E.; Willemsen, M.A.A.P.; Lachmann, R.H.; Mengel, E.; Michelakakis, H.; Jongste, J.C. de; Reuser, A.J.; Ploeg, A.T. van der

2016-01-01

BACKGROUND: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the

Childhood Pompe disease: Clinical spectrum and genotype in 31 patients

NARCIS (Netherlands)

C.I. van Capelle (Carine); J.C. van der Meijden (Chris); J.M.P. van den Hout (Johanna); J. Jaeken; M. Baethmann; T. Voit; M.A. Kroos (Marian); T.G.J. Derks (Terry G J); M.E. Rubio-Gozalbo (Estela); M.A. Willemsen (Michél); R. Lachmann (Robin); E. Mengel; H. Michelakakis (Helen); J.C. de Jongste (Johan); A.J.J. Reuser (Arnold); A.T. van der Ploeg (Ans)

2016-01-01

textabstractBackground: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in

Childhood Pompe disease : clinical spectrum and genotype in 31 patients

NARCIS (Netherlands)

van Capelle, C I; van der Meijden, J C; van den Hout, J M P; Jaeken, J; Baethmann, M; Voit, T; Kroos, M A; Derks, T G J; Rubio-Gozalbo, M E; Willemsen, M A; Lachmann, R H; Mengel, E; Michelakakis, H; de Jongste, J C; Reuser, A J J; van der Ploeg, A T

2016-01-01

Background: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the

GST genotypes in head and neck cancer patients and its clinical ...

African Journals Online (AJOL)

STORAGESEVER

2008-11-05

Nov 5, 2008 ... carcinogens found in tobacco smoke, are relatively common in most populations. ... It is possible that the decreased activity of GST affects various ..... Difference in genotypes between patients and non-smoking controls.

Comparative study of patients with chronic hepatitis C virus infection due to genotypes 1 and 3 referred for treatment in southeast Brazil

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Gonçales Fernando L

2008-12-01

Full Text Available Abstract Background The progression of liver disease in patients with chronic hepatitis C virus (HCV infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literatute. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics. Methods Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms. Results A total of 283 patients were included; genotype 1 was idenfied in 163 (57.6% patients, genotype 3 in 112 (39.6%, genotype 2 in 7 (2.5%, and genotype 4 in 1 (0.35%. Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p Conclusion Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies.

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.

Nutritional status in patients with hepatitis C

International Nuclear Information System (INIS)

Ismail, F.W.; Khan, R.A.; Kamani, L.; Shah, H.A.; Jafri, W.

2012-01-01

To assess the nutritional status via the SGA (subjective global assessment) screening tool of patients at all stages of hepatitis C virus (HCV) liver disease. Study Design: Descriptive study. Place and Duration of Study: Out-patient Clinics of the Aga Khan University Hospital, Karachi, conducted from October 2009 to January 2011. Methodology: Patients with hepatitis C virus infection and their HCV-negative attendants were enrolled from the outpatient clinics, and categorized into 4 groups of 100 patients each: healthy controls (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). The validated subjective global assessment (SGA) tool was used to assess nutritional status. Results: A total of 400 patients were enrolled. Most of the patients in the HC group were class 'A' (best nutritional status). In contrast, the majority (64%) in the DC group were in the class 'C' (worst status). The compensated cirrhosis (CC) group showed that 90% of patients were malnourished, while 98% of all patients were malnourished in the DC group, predominantly class 'C'. Most importantly, 14% of patients with chronic hepatitis C (CHC) also scored a 'B' on the SGA; which when compared to HC was statistically significant (p=0.005). As the groups progressed in their disease from CHC to DC, the transition in nutritional status from 'A' to 'C' between groups was statistically significant. Conclusion: Malnutrition occurs early in the course of HCV, and progresses relentlessly throughout the spectrum of HCV disease. (author)

Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.

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Jannie Pedersen

Full Text Available The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23 or non-sustained virologic response (n = 16 were enrolled. Samples taken prior to treatment were tested for their ability to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1. The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer. We observed no genotype or subtype specific differences in NAb50-titers between patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However, NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400 against DH6/JFH1 compared to a mean NAb50-titer of 50 (range: <50-400 against all other included isolates. Subsequent studies demonstrated that the efficient neutralization of DH6/JFH1 could be linked to engineered adaptive mutations in the envelope-2 protein. In analysis of envelope 1 and 2 sequences of HCV, recovered from a subset of patients, we observed no apparent link between relatedness of patient sequences with culture viruses used and the corresponding neutralization results. In conclusion, pre-treatment levels of neutralizing antibodies against HCV genotype 1 isolates could not predict treatment outcome in patients with chronic HCV infection. High neutralization susceptibility of DH6/JFH1 could be correlated with adaptive envelope mutations previously highlighted as important for neutralization. Our

Genotype-phenotype correlation in patients suspected of having Sotos syndrome

NARCIS (Netherlands)

de Boer, Lonneke; Kant, Sarina G.; Karperien, Marcel; van Beers, Lotte; Tjon, Jennifer; Vink, Geraldine R.; van Tol, Dewy; Dauwerse, Hans; le Cessie, Saskia; Beemer, Frits A.; van der Burgt, Ineke; Hamel, Ben C. J.; Hennekam, Raoul C.; Kuhnle, Ursula; Mathijssen, Inge B.; Veenstra-Knol, Hermine E.; Stumpel, Connie T. Schrander; Breuning, Martijn H.; Wit, Jan M.

2004-01-01

Background: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. Methods:

Genotype-phenotype correlation in patients suspected of having sotos syndrome.

NARCIS (Netherlands)

Boer, L. de; Kant, S.; Karperien, M.; Beers, L. van; Tjon, J.; Vink, G.R.; Tol, D. van; Dauwerse, H.G.; Cessie, S. le; Beemer, F.A.; Burgt, C.J.A.M. van der; Hamel, B.C.J.; Hennekam, R.C.M.; Kuhnle, U.; Mathijssen, I.B.; Veenstra-Knol, H.E.; Stumpel, C.T.; Breuning, M.H.; Wit, J.M.

2004-01-01

BACKGROUND: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. METHODS:

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype.

Science.gov (United States)

de Heredia, Miguel López; Clèries, Ramón; Nunes, Virginia

2013-07-01

Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. (i) 15% of published patients do not fulfill the current -inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient's genotypic class; and (vi) disease progression rate might depend on genotypic class. New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome.

Science.gov (United States)

Zeuzem, Stefan; Mizokami, Masashi; Pianko, Stephen; Mangia, Alessandra; Han, Kwang-Hyub; Martin, Ross; Svarovskaia, Evguenia; Dvory-Sobol, Hadas; Doehle, Brian; Hedskog, Charlotte; Yun, Chohee; Brainard, Diana M; Knox, Steven; McHutchison, John G; Miller, Michael D; Mo, Hongmei; Chuang, Wan-Long; Jacobson, Ira; Dore, Gregory J; Sulkowski, Mark

2017-05-01

The efficacy of NS5A inhibitors for the treatment of patients chronically infected with hepatitis C virus (HCV) can be affected by the presence of NS5A resistance-associated substitutions (RASs). We analyzed data from 35 phase I, II, and III studies in 22 countries to determine the pretreatment prevalence of various NS5A RASs, and their effect on outcomes of treatment with ledipasvir-sofosbuvir in patients with genotype 1 HCV. NS5A gene deep sequencing analysis was performed on samples from 5397 patients in Gilead clinical trials. The effect of baseline RASs on sustained virologic response (SVR) rates was assessed in the 1765 patients treated with regimens containing ledipasvir-sofosbuvir. Using a 15% cut-off, pretreatment NS5A and ledipasvir-specific RASs were detected in 13% and 8% of genotype 1a patients, respectively, and in 18% and 16% of patients with genotype 1b. Among genotype 1a treatment-naïve patients, SVR rates were 91% (42/46) vs. 99% (539/546) for those with and without ledipasvir-specific RASs, respectively. Among treatment-experienced genotype 1a patients, SVR rates were 76% (22/29) vs. 97% (409/420) for those with and without ledipasvir-specific RASs, respectively. Among treatment-naïve genotype 1b patients, SVR rates were 99% for both those with and without ledipasvir-specific RASs (71/72 vs. 331/334), and among treatment-experienced genotype 1b patients, SVR rates were 89% (41/46) vs. 98% (267/272) for those with and without ledipasvir-specific RASs, respectively. Pretreatment ledipasvir-specific RASs that were present in 8-16% of patients have an impact on treatment outcome in some patient groups, particularly treatment-experienced patients with genotype 1a HCV. The efficacy of treatments using NS5A inhibitors for patients with chronic hepatitis C virus (HCV) infection can be affected by the presence of NS5A resistance-associated substitutions (RASs). We reviewed results from 35 clinical trials where patients with genotype 1 HCV infection

Using variants of CHC Algorithms in the Design of Radio Frequency Networks in Wireless Communications.

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Daniel Antonio Molina

2015-09-01

Full Text Available In this paper we apply to solve the Radio Network Design problem (RND a series  of the non-conventional genetic algorithms called Cross generational elitist selection Heterogeneous recombination Cataclysmic mutation (CHC. A set of genetic algorithms is used to perform a comparative performance of the proposed algorithms. An objective function based on signal coverage efficiency is used. Genetic variability of the population is used for both, as a parameter of convergence and detection of incest. Furthermore the variability of the best individual is proposed as a shaking mechanism. This allows generating dynamic populations according to the most promising solutions generating different search spaces. The results obtained by the proposed algorithms are satisfactory.

Hepatitis C virus genotypes in Bahawalpur

International Nuclear Information System (INIS)

Qazi, M.A.; Fayyaz, M.; Chaudhry, G.M.D.; Jamil, A.

2006-01-01

This study was conducted at Medical Unit-II Bahawal Victoria Hospital / Quaid-e-Azam Medical College Bahawalpur from May 1st , 2005 to December 31st 2005. The objective of this study was to determine hepatitis C virus (HCV) genotypes in Bahawalpur, Pakistan. In consecutive 105 anti-HCV (ELISA-3) positive patients, complete history and physical examination was performed. Liver function tests, complete blood counts and platelet count, blood sugar fasting and 2 hours after breakfast, prothrombin time, serum albumin, serum globulin and abdominal ultrasound were carried out in all the patients. Tru cut biopsy was performed on 17 patients. We studied HCV RNA in all these patients by Nested PCR method. HCV RNA was detected in 98 patients and geno typing assay was done by genotype specific PCR. Among total of 105 anti-HCV positive patients, HCV-RNA was detected in 98 patients. Out of these 98 patients there were 57 (58.2%) males and 41 (42.8%) females. Their age range was 18-75 years. The age 18-29 years 26 (26.5%), 30-39 years 35 (35.7%) and 40-75 37 (37.8%), while 10 (10.2%) patients were diabetics and 34 (34.7%) patients were obese. Liver cirrhosis was present in 10 (10.2%) patients. Forty two (43.9%) patients were symptomatic while 56 (57.1%) were asymptomatic. Out of 98 patients 11 (11.2%) were un type-able and 87 (88.8%) were type able. 70/98 (71.4%) were genotype 3; 10/98 (10.2%) were genotype 1; 03/98 (3.1%) were genotype 2; 03/98 (3.1%) were mixed genotype 2 and 3; 01/98 (1%) were mixed genotype 3a and 3b. Genotype 3 is the most common HCV virus in our area which shows that both virological and biochemical response will be better. Because HCV genotype 3 is more frequent among the drug users which points towards unsafe injection practices in our area. (author)

Cytomegalovirus glycoprotein B genotyping in ocular fluids and blood of AIDS patients with cytomegalovirus retinitis

NARCIS (Netherlands)

Peek, R.; Verbraak, F.; Bruinenberg, M.; van der Lelij, A.; van den Horn, G.; Kijlstra, A.

1998-01-01

To determine the frequency of cytomegalovirus glycoprotein B (gB) genotypes in clinical samples of ocular fluids of patients with acquired immune deficiency syndrome (AIDS) who have cytomegalovirus retinitis and to compare these with the cytomegalovirus gB genotype in paired peripheral blood

Is Period3 Genotype Associated With Sleep and Recovery in Patients With Disorders of Consciousness?

Science.gov (United States)

Bedini, Gloria; Bersano, Anna; Sebastiano, Davide Rossi; Sattin, Davide; Ciaraffa, Francesca; Tosetti, Valentina; Brenna, Greta; Franceschetti, Silvana; Ciusani, Emilio; Leonardi, Matilde; Vela-Gomez, Jesus; Boncoraglio, Giorgio B; Parati, Eugenio A

2016-06-01

Background Sleep evaluation is increasingly being used as prognostic tool in patients with disorders of consciousness, but, surprisingly, the role of Period3 (Per3) gene polymorphism has never been evaluated. Objective The aim of this study was to investigate the contribution of Per3 genotype on sleep quantity and consciousness recovery level in patients with disorders of consciousness (DOC). Methods In this observational study, we evaluated 71 patients with DOC classified as vegetative state/unresponsive wakefulness syndrome or minimally conscious state. Demographic and clinical data were collected and a standardised diagnostic workup, including a polysomnographic record, was applied. After informed consent provided by proxy, genomic DNA was obtained and Per3 polymorphism was analysed by polymerase chain reaction to identify 5/5, 4/5, or 4/4 genotype. Results Per3(5/5) genotype was found in 12.7% of our DOC patients. The median total Coma Recovery Scale-revised score in Per3(5/5) carriers was significantly higher than 4/4 genotype (10, range 5-16 vs 7, range 4-11; post hoc P = .036). Moreover, total sleep time seemed to be higher in 5/5 genotype (5/5, 221 minutes, range 88-515 minutes; 4/4, 151.5 minutes, range 36-477 minutes; and 4/5, 188 minutes, range 44-422 minutes). Conclusion For the first time we have shown a possible association between Per3 polymorphism and consciousness recovery level in DOC patients. Even though the exact molecular mechanism has not been defined, we speculate that its effect is mediated by higher total sleep time and slow wave sleep, which would improve the preservation of main cerebral connections. © The Author(s) 2015.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) genotypes in non-HIV-immunocompromised patients: a tertiary care reference health centre study.

Science.gov (United States)

Tyagi, A K; Mirdha, B R; Luthra, K; Guleria, R; Mohan, A; Singh, U B; Samantaray, J C; Dar, L; Iyer, V K; Sreenivas, V

2011-02-01

Studies on Pneumocystis jirovecii dihydropteroate synthase (DHPS) genotypes among non-HIV immunocompromised patients from developing countries are rare. In the present prospective investigation, 24 (11.8%) cases were found to be positive for Pneumocystis jirovecii out of 203 non-HIV patients with a clinical suspicion of Pneumocystis pneumonia (PCP). Dihydropteroate synthase (DHPS) genotype 1 (Thr55+Pro57) was noted in 95.8% P. jirovecii isolates in the present study in contrast to only 4.1% of patients with DHPS genotype 4 (Thr55Ala + Pro57Ser).

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

Science.gov (United States)

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

[Distribution of hepatitis C virus genotypes among patients with chronic hepatitis C infection in Akdeniz University Hospital, Antalya, Turkey: a five-year evaluation].

Science.gov (United States)

Sağlik, İmran; Mutlu, Derya; Öngut, Gözde; İnan, Dilara; Öğünç, Dilara; Can Sarinoğlu, Rabia; Özhak Baysan, Betil; Gültekin, Meral; Çolak, Dilek

2014-07-01

Hepatitis C virus (HCV) is one of the major causes of chronic hepatitis. It is important to know the genotypes of HCV in the decision of the HCV related chronic hepatitis therapy. The aim of this study was to evaluate the HCV genotypes determined at the Microbiology Laboratory of Akdeniz University Hospital, and to evaluate the changes in the distribution of the genotypes within the last five years. A total of 422 blood samples from HCV-RNA positive chronic hepatitis C patients (219 male, 203 female; age range: 8-79 yrs, mean age 46.3 ± 15.5 yrs) which were sent to our laboratory for genotyping between 2009-2013 period, were analyzed retrospectively. HCV-RNA extractions were performed in an automated system (EZ1 Virus Mini Kit v2.0, Qiagen, Germany), and a commercial reverse hybridization line probe-based assay (LIPA; GEN-C RT-PCR, Italy) was carried out for genotyping, For viral load determinations, a real-time PCR method (Cobas TaqMan HCV, Roche Diagnostics, Germany) was used. Demographic data of the patients were obtained from the hospital information systems and electronic patients' files. Out of the 422 patients, genotype 1b was detected in 63.3% (n= 267), genotype 1a in 14.7% (n= 62), genotype 3a in 11.1% (n= 47), genotype 2b in 0.9% (n= 4), genotype 4e in 0.2% (n= 1). The subtypes couldn't be determined for 5.4% (n= 23), 2.6% (n= 11) and 1.4% (n= 6) of the patients infected with genotype 1, 2 and 4, respectively. One (0.2%) patient, was coinfected with genotype 1 and 4. Of the patients, 40 were foreign-born (16 cases from Russia; 4 of each from Ukraine and Georgia; 3 of each from Turkmenistan, Kyrgyzstan, and Germany; one of each from Tajikistan, Azerbaijan, Uzbekistan, Chechnya, Moldova, Switzerland and Romania) and among these patients genotype 3a (19/40; 47.5%) was the most common genotype followed by genotype 1b (17/40; 42.5%). Median values of HCV viral load were 668.500 IU/ml (range: 2.000-9.630.000) in the whole group; while it was 732.000 IU

Identification of a natural intergenotypic recombinant hepatitis delta virus genotype 1 and 2 in Vietnamese HBsAg-positive patients.

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Sy, B T; Nguyen, H M; Toan, N L; Song, L H; Tong, H V; Wolboldt, C; Binh, V Q; Kremsner, P G; Velavan, T P; Bock, C-T

2015-01-01

Hepatitis D virus (HDV) infection is acquired as a co- /superinfection of Hepatitis B virus (HBV) and can modulate the pathophysiology of chronic hepatitis B and related liver diseases including hepatocellular carcinoma. Among the eight distinct HDV genotypes reported, relatively few studies have attempted to investigate the prevalence of HDV mixed genotypes and RNA recombination of HDV. With a recorded prevalence of 10-20% HBV infection in Vietnam, this study investigated the HDV variability, HDV genotypes and HDV recombination among twenty-one HDV isolates in Vietnamese HBsAg-positive patients. HDV subgenomic and full-length genome sequences were obtained using newly established HDV-specific RT-PCR techniques. The nucleotide homology was observed from 74.6% to 99.4% among the investigated full-length genome of the HDV isolates. We observed HDV genotype 1 and HDV genotype 2 in the investigated Vietnamese patients. Although no HDV genotype mixtures were observed, we report here a newly identified recombinant of HDV genotypes (HDV 1 and HDV 2). The identified recombinant HDV isolate C03 revealed sequence homology to both HDV genotype 1 (nt1 to nt907) and HDV genotype 2 (nt908 to nt1675; HDAg coding region) with a breakpoint at nt908. Our findings demonstrate the prevalence of intergenotypic recombination between HDV genotypes 1 and 2 in a Vietnamese HBsAg-positive patient. Extended investigation on the distribution and prevalence of HDV, HDV mixed genotypes and recombinant HDV genotypes in a larger Vietnamese population offers vital insights into understanding of the micro-epidemiology of HDV and subsequent pathophysiology in chronic HBV- /HDV-related liver diseases. © 2014 John Wiley & Sons Ltd.

Full-length genomic sequence of hepatitis B virus genotype C2 isolated from a native Brazilian patient

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Mónica Viviana Alvarado-Mora

2011-06-01

Full Text Available The hepatitis B virus (HBV is among the leading causes of chronic hepatitis, cirrhosis and hepatocellular carcinoma. In Brazil, genotype A is the most frequent, followed by genotypes D and F. Genotypes B and C are found in Brazil exclusively among Asian patients and their descendants. The aim of this study was to sequence the entire HBV genome of a Caucasian patient infected with HBV/C2 and to infer the origin of the virus based on sequencing analysis. The sequence of this Brazilian isolate was grouped with four other sequences described in China. The sequence of this patient is the first complete genome of HBV/C2 reported in Brazil.

Fc RIIA Genotypes and Its Association with Anti-C1q Autoantibodies in Lupus Nephritis (LN Patients from Western India

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Vandana Pradhan

2010-01-01

Full Text Available To identify Fc RIIA genotypes in Systemic Lupus Erythematosus (SLE patients and their association with anti-C1q antibodies. Methods. Fc RIIA genotyping was done in eighty Indian SLE patients and eighty healthy controls using allele-specific PCR. Anti-C1q antibodies were measured by ELISA. Results. LN patients showed higher SLEDAI (6–32 as compared to SLE patients without renal manifestations and had SLEDAI between 6–23. Fc RIIA polymorphic frequency in SLE patients was R131/H131 (67.5%, R131/R131 (20% and H131/ H131 (12.5% as against that of normal population (62.5%, 10%, and 27.5%, respectively. Sixty two patients (77.5% showed positivity for anti-C1q antibodies. LN patients showed elevated levels of anti-C1q antibodies (258.2u/ml±38.5U/mL as compared to SLE patients without nephritis (134.6±24.6 U/mL. Among anti-C1q positive patients, 71% had R131/H131 genotype, 22.6% had R131/R131 and remaining 6.4%, patients had H131/H131 genotype. All anti-C1q positive patients with R131/R131 genotype had elevated levels of anti-C1q antibodies (>100 U/ml, whereas among anti-C1q negative patients, none had R131/R131 genotype. Conclusion. This first report on Indian SLE patients supports the hypothesis that Fc RIIA R131 variant over expression may constitute a susceptibility factor for development of severe SLE manifestations in LN patients.

Maintenance of Chronic Fatigue Syndrome (CFS in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype.

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Benedicte Meyer

Full Text Available Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT may be important for the re-uptake of serotonin (5-HT in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S versus long (L 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS. All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years. Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI. Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

The prevalence of autoantibody and its relationship with genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection.

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Kirdar, Sevİn; Sener, Asli Gamze; Cengİz, Merve; Aydin, Nerİman

2016-11-01

The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti-HCV positive and 86 anti-HCV negative patients were included in the study. Anti-HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse-line blot hybridization. Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), Anti-mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti-HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Variations in cerebrospinal fluid viral loads among enterovirus genotypes in patients hospitalized with laboratory-confirmed meningitis due to enterovirus.

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Volle, Romain; Bailly, Jean-Luc; Mirand, Audrey; Pereira, Bruno; Marque-Juillet, Stéphanie; Chambon, Martine; Regagnon, Christel; Brebion, Amélie; Henquell, Cécile; Peigue-Lafeuille, Hélène; Archimbaud, Christine

2014-08-15

Acute enterovirus (EV) meningitis is a major cause of hospitalization among adults and children. It is caused by multiple EV genotypes assigned to 4 species (EV-A, EV-B, EV-C, and EV-D). We determined viral loads in the cerebrospinal fluid (CSF) of 156 patients of all ages with EV meningitis during a 5-year observational prospective study. The virus strains were genotyped, and their time origin was determined with Bayesian phylogenetic methods. The CSF viral loads ranged between 3.4 and 7.5 log10 copies/mL (median, 4.9 log10 copies/mL). They were higher in neonates than in infants and children (P = .02) but were comparable in adults. Viral loads were associated with EV genotypes (P < .001). The EV strains were identified in 152 of 156 patients and assigned to 23 genotypes within the EV-A and EV-B species. The most frequent genotypes, echoviruses 6 and 30, were associated with different viral loads (P < .001). The highest viral loads were in meningitis cases caused by coxsackievirus A9, B4, and B5 genotypes. Most patients infected by a same genotype were infected by a major virus variant of recent emergence. The variations in CSF viral loads in patients at the onset of EV meningitis are related to genotypic differences in the virus strains involved. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular characterization of rotavirus genotypes in immunosuppressed and non-immunosuppressed pediatric patients

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Luciane A. Pereira

2013-05-01

Conclusion: RVA infections can be associated with severe clinical manifestations, and the surveillance of genotypic variability of this virus is crucial to monitor the emergence of new strains and the impact of the immunization in these patients.

vacA genotypes of Helicobacter pylori in the oral cavity and stomach of patients with chronic gastritis and gastric ulcer.

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Román-Román, Adolfo; Giono-Cerezo, Silvia; Camorlinga-Ponce, Margarita; Martínez-Carrillo, Dinorah Nashely; Loaiza-Loeza, Salome; Fernández-Tilapa, Gloria

2013-03-01

Helicobacter pylori adheres to various components of the human saliva. Therefore, the objective of this research was to simultaneously detect H. pylori in saliva and in gastric biopsy, and to determine the agreement between the vacA genotypes in both saliva and gastric biopsy. A total of 162 patients with chronic gastritis and 34 with gastric ulcer were studied, and saliva and biopsy samples were collected from each patient. H. pylori DNA was detected by conventional PCR and nested PCR was used for vacA genotyping. In 24% of the patients (47/196) H. pylori DNA was found in saliva and in biopsy; 52.5% (103/196) were saliva(negative)/biopsy(positive) and 6.6% (13/196) were saliva(positive)/biopsy(negative). In either or both H. pylori vacAs1m1 or s1m2 genotypes were detected in saliva in 41.5% of the patients with chronic gastritis. Forty-seven percent had >1 genotype, and the s1m1/s1m2 combination was found in 36% of them. H. pylori vacAs1m1 and s1m2 were also found in the saliva and biopsy of patients with gastric ulcer. The genotypes found in saliva and biopsy of the same patient had 51.1% agreement. In 27.6% of the 47 patients saliva(positive)/biopsy(positive) two genotypes were found in saliva, and one or both in the stomach. The s1m1/s1m2 genotypes, alone or together, are found simultaneously in saliva and gastric biopsy of the same patient. These results suggest that H. pylori reaches the oral cavity by various ways, and that saliva can be the transmitting and re-infecting vector. Copyright © 2012 Elsevier España, S.L. 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. �

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.

IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α.

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Holmes, Jacinta A; Nguyen, Tin; Ratnam, Dilip; Heerasing, Neel M; Tehan, Jane V; Bonanzinga, Sara; Dev, Anouk; Bell, Sally; Pianko, Stephen; Chen, Robert; Visvanathan, Kumar; Hammond, Rachel; Iser, David; Rusli, Ferry; Sievert, William; Desmond, Paul V; Bowden, D Scott; Thompson, Alexander J

2013-05-01

IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort. This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA < 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA < 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed. IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype. In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

CYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia Patients.

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Barratt, Daniel T; Cox, Hannah K; Menelaou, Andrew; Yeung, David T; White, Deborah L; Hughes, Timothy P; Somogyi, Andrew A

2017-08-01

The aims of this study were to determine the effects of the CYP2C8*3 and *4 polymorphisms on imatinib metabolism and plasma imatinib concentrations in chronic myeloid leukaemia (CML) patients. We genotyped 210 CML patients from the TIDELII trial receiving imatinib 400-800 mg/day for CYP2C8*3 (rs11572080, rs10509681) and *4 (rs1058930). Steady-state trough total plasma N-desmethyl imatinib (major metabolite):imatinib concentration ratios (metabolic ratios) and trough total plasma imatinib concentrations were compared between genotypes (one-way ANOVA with Tukey post hoc). CYP2C8*3 (n = 34) and *4 (n = 15) carriers had significantly higher (P  50% higher for CYP2C8*1/*4 than for CYP2C8*1/*1 and CYP2C8*3 carriers (2.18 ± 0.66 vs. 1.45 ± 0.74 [P < 0.05] and 1.36 ± 0.98 μg/mL [P < 0.05], respectively). CYP2C8 genotype significantly alters imatinib metabolism in patients through gain- and loss-of-function mechanisms.

Genotype X/C recombinant (putative genotype I) of hepatitis B virus is rare in Hanoi, Vietnam--genotypes B4 and C1 predominate.

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Phung, Thi Bich Thuy; Alestig, Erik; Nguyen, Thanh Liem; Hannoun, Charles; Lindh, Magnus

2010-08-01

There are eight known genotypes of hepatitis B virus, A-H, and several subgenotypes, with rather well-defined geographic distributions. HBV genotypes were evaluated in 153 serum samples from Hanoi, Vietnam. Of the 87 samples that could be genotyped, genotype B was found in 67 (77%) and genotype C in 19 (22%). All genotype C strains were of subgenotype C1, and the majority of genotype B strains were B4, while a few were B2. The genotype X/C recombinant strain, identified previously in Swedish patients of indigenous Vietnamese origin, was found in one sample. This variant, proposed to be classified as genotype I, has been found recently also by others in Vietnam and Laos. The current study indicates that the genotype X/C recombinant may represent approximately 1% of the HBV strains circulating in Vietnam. (c) 2010 Wiley-Liss, Inc.

The Role of Ultrasound Imaging in the Definition of the Stage of Liver Fibrosis in Patients with Chronic Hepatitis C

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Dmitry Konstantinov

2014-09-01

Full Text Available The aim of this research was to develop a method for noninvasive staging of liver fibrosis (LF in patients with chronic hepatitis C (CHC based on ultrasound imaging (UI of the abdominal cavity. We examined 124 patients with CHC. The diagnosis was verified on the basis of clinical and epidemiological, serological and molecular biological data. Direct ultrasonic parameters of the structure and hemodynamics of liver and spleen were supplemented with estimated indicators: square of the expected cross-section of the lobes of the liver and spleen, as well as their ratio. On the basis of the discriminant analysis of the survey data of 82 patients, we developed an analytical model (with predictive value of 95.2% for interval estimation of the fibrosis degree in CHC patients. We have concluded that UI performed on modern equipment, including Doppler, is able to determine the degree of LF without resorting to histological verification.

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.

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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.

TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

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Özgür GÜNAL

2017-12-01

Full Text Available Objective: We aimed to review the influence of host genetic factors on the clinical course, treatment response as well as fibrosis progression in patients with viral hepatitis C genotype 1. Materials and Methods: Ninety-five patients with chronic hepatitis C virus (HCV infection and 97 controls were enrolled. The patients received pegylated interferon (Peg-IFN+ribavirin therapy for 48 weeks and were followed up for the next 48 weeks. Aspartat aminotransferase/platelet ratio (APRI was used to detect liver fibrosis DNA specimens were extracted from the peripheral blood mononuclear cells and the tumor necrosis factor-alpha (TNF-α 308 rs3091256 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Results: All patients included in the study were infected with HCV genotype 1. of the 95 HCV-positive patients, spontaneous viral clearence was observed in 25.5%, rapid viral response in 44.2%, early viral response in 91.8%, and sustained viral response was found in 73.3% of patients. The allele and genotype were not significant between patients and controls. There was no significant difference in virologic response as well. However, TNF-α-308 single nucleotide polymorphisms (SNP rs3091256 GG genotype was strongly associated with fibrosis and alanine aminotransferase (ALT levels (p=0.006 and p=0.017, respectively. Conclusion: TNF-α-308 polymorphisms may reveal different results among countries. Patients having SNP rs3091256 GG are prone to have higher ALT levels and fibrosis score but have better treatment outcome.

Genotype distribution and treatment response among incarcerated drug-dependent patients with chronic hepatitis C infection.

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Chun-Han Cheng

Full Text Available The prevalence of hepatitis C virus (HCV infection is disproportionately high among prisoners, especially among those who are drug-dependent. However, current screening and treatment recommendations are inconsistent for this population, and appropriate care is not reliably provided. To address these problems, the present study aimed to identify unique characteristics and clinical manifestations of incarcerated patients with HCV infection. We included incarcerated patients who received treatment with pegylated-interferon combined with ribavirin at Mackay Memorial Hospital in Taitung and were serving sentences at either the Taiyuan Skill Training Institute or the Yanwan Training Institute. HCV genotypes 1 (41.4%, 3 (25.9%, and 6 (24.1% were the most prevalent in the incarcerated patients. During the study period, we analyzed treatment response among 58 incarcerated patients and compared obtained results with treatment response among 52 patients who were living in the community. Higher sustained virological response rate was observed among patients with incarceration and HCV genotype other than 1. The odds ratios (corresponding 95% confidence intervals for incarceration and genotype 1 were 2.75 (1.06-7.11 and 0.37 (0.14-0.99, respectively. Better treatment compliance among incarcerated patients might partially explain these results. The results of this study suggest that treatment of prisoners with HCV infection is feasible and effective. More appropriate and timely methods are needed to prevent HCV transmission among injection drug users inside prisons.

Experimental investigation of HFC407C/HC290/HC600a mixture in a window air conditioner

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Jabaraj, D.B.; Avinash, P.; Lal, D. Mohan; Renganarayan, S.

2006-01-01

HCFC22, one of the widely used refrigerants in window air conditioners must be phased out soon as per the Montreal protocol. Presently, HFC407C is considered as a potential drop in substitute for HCFC22, but retrofitting HCFC22 systems with HFC407C with polyol ester oil (POE) is a major issue as HFC407C is immiscible with mineral oil. The miscibility issue of HFC407C with mineral oil was overcome with the addition of a HC blend to it. The above technoeconomic feasibility issues to retrofit the existing HCFC22 systems with an ozone friendly refrigerant and retain the energy efficiency of the system are challenges in the air conditioning sector. In this present work, an experimental analysis has been conducted in a window air conditioner retrofitted with eco-friendly refrigerant mixtures of HFC407C/HC290/HC600a without changing the mineral oil. Its performance, as well as energy consumption, was compared with the conventional one. It is observed that the mixtures demand lengthening of the condenser in order to maintain the discharge pressure within acceptable limits. This also resulted in better heat transfer at the condenser. Therefore, in this study, the condenser tube length was increased by 19% to suit the mixtures as compared to HCFC22. Compared to HCFC22, the refrigeration capacity of the new mixture was 9.54-12.76% higher than that of HCFC22, while the actual COP was found to be 11.91-13.24% higher than that of HCFC22. The overall performance has proved that the HFC407C/HC blend refrigerant mixture could be an eco-friendly substitute to phase out HCFC22

A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian subjects but not in patients with coronary heart disease.

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Sustar, A; Nikolac Perkovic, M; Nedic Erjavec, G; Svob Strac, D; Pivac, N

2016-08-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with an important role in the regulation of body weight, body mass index (BMI) and obesity. Increased BMI that leads to obesity is a substantial risk factor for coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265) has been associated with CHD, obesity and BMI. The aim of the study was to determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in patients with CHD and healthy control subjects. The study included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control subjects. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more

Genotype, Phenotype and Outcomes of Nine Patients with T-B+NK+ SCID

OpenAIRE

Yu, Grace P; Nadeau, Kari C; Berk, David R; de Saint Basile, Geneviève; Lambert, Nathalie; Knapnougel, Perrine; Roberts, Joseph; Kavanau, Kristina; Dunn, Elizabeth; Stiehm, E. Richard; Lewis, David B; Umetsu, Dale T; Puck, Jennifer M; Cowan, Morton J

2011-01-01

There are few reports of clinical presentation, genotype, and hematopoietic cell transplant (HCT) outcomes for T-B+NK+ SCID patients. Between 1981 and 2007, 8 of 84 SCID patients who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype. One additional T-B+NK+ SCID patient was identified as the sibling of a patient treated at UCSF. Chart reviews were performed. Molecular analyses of IL7R, IL2RG, JAK3 and the genes encoding the CD3 T-cell receptor components δ (CD3D), ε (CD...

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

Science.gov (United States)

Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

2018-01-30

Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein expression predicts disease severity in chronic hepatitis C patients

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Ching-I Huang

2017-08-01

Full Text Available Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP has recently been developed as a promising liver fibrosis glyco biomarker. We assessed its efficacy in evaluating liver disease severity in chronic hepatitis C (CHC in Taiwan. The association between WFA+-M2BP and histological features was evaluated among those CHC patients underwent liver biopsy. We also aimed to clarify the factors determining the performance of WFA+-M2BP in CHC. A total of 229 CHC patients were consecutively recruited. The mean value of WFA+-M2BP in patients from F0 to F4 was 1.68, 2.23, 3.45, 3.48, 3.77 respectively (linear trend P = 0.008. Linear regression analysis revealed that alanine aminotransferase (odds ratio [OR]: 0.03, 95% confidence intervals [CI]: 0.02–0.05, P < 0.001, AST (OR: −0.1, 95% CI: −0.02 to −0.01, P < 0.001, and liver fibrosis (OR: 0.30, 95% CI: 0.01–0.59, P = 0.043 were the independent factors correlated to serum WFA+-M2BP level. The optimal cutoff values of WFA+-M2BP for fibrosis stages F1, F2, F3, and F4 were 1.42, 1.61, 1.42, and 2.67, respectively. Multivariate analysis revealed that the platelet count (OR/CI: −0.009/0.986–0.996, P = <0.001, r-glutamyl transferase (OR/CI: 0.007/1.000–1.013, P = 0.036, and WFA+-M2BP (OR/CI: 0.187/1.057–1.374, P = 0.005. We concluded that WFA+-M2BP is a competent noninvasive marker for liver fibrosis assessment in CHC patients.

Genotyping of Toxoplasma gondii: DNA extraction from formalin-fixed paraffin-embedded autopsy tissues from AIDS patients who died by severe disseminated toxoplasmosis.

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Bastos da Silva, Inara; Batista, Tatiana Pimental de Andrade; Martines, Roosecelis Brasil; Kanamura, Cristina Takami; Ferreira, Isabelle Martins Ribeiro; Vidal, Jose Ernesto; Pereira-Chioccola, Vera Lucia

2016-06-01

This study investigated the genetic features of Toxoplasma gondii isolated directly in autopsies of HIV-infected patients who died with severe disseminated toxoplasmosis. This retrospective analysis was conducted in a cohort of 15 HIV-infected patients with clinical and laboratory data. They had previous cerebral toxoplasmosis at least 6 months before the disseminated toxoplasmosis episode. The hypothesis was that they were infected with highly virulent parasites due to the condition in which they died. T. gondii genotyping was done directly in DNA extracted from 30 autopsy brain and lung samples (2 per patient) and mutilocus PCR-RFLP genotyping was done using 12 molecular markers. The 30 clinical samples were genotyped successfully in 8 or more loci and six suggestive genotypes were identified. One of them was Toxo DB #11, previously identified in different domestic animals and virulent in experimental animals. The other five suggestive genotypes identified in 14 patients were not described. TgHuDis1 was the most frequent and was determined in 8 patients. TgHuDis3 and TgHuDis5 were identified in two patients each. TgHuDis2 and TgHuDis4 have been identified in one patient each. These suggestive genotypes could be considered as virulent, since they caused severe tissue damage and had similar characteristics as Toxo # DB 11. Copyright © 2016 Elsevier Inc. All rights reserved.

Study of general awareness, attitude, behavior, and practice study on dog bites and its management in the context of prevention of rabies among the victims of dog bite attending the opd services of chc muradnagar

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Piyush Jain

2014-01-01

Full Text Available Objectives: This is a recent study conducted during 15th September 2013 to 15th December 2013 at the community health centre (CHC, Muradnagar, distt Ghaziabad, among the victims of dog/animal bite attending the daily OPD services of CHC. To identify the level of general awareness and knowledge of wound management and rabies among the cases of dog bite and to study the awareness of people about antirabies vaccines and health service utilization. Methods: The study population composed of 250 victims of dog or animal bite, Patients were selected and approached after proper briefing, with well-prepared two page structured questionnaire designed in local language to assess their knowledge about the wound management, information about the epidemiology of dog bite. Results and conclusion: The result of the study reflect the very low level of awareness about the postdog bite management of wounds as well as about the disease rabies group of people questioned and also reveals serious gaps in understanding of wound severity ,classification and correct application of PEP with ARV vaccine and RIG. There is definitely a gap in people′s knowledge, attitude, and practices about dog bite and its management and there is need of taking serious measures for the control of stray dog population at the block level.

HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

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Andreia Silva Evangelista

2015-01-01

Full Text Available Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS > 45%, and serum ferritin (SF > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n=16 were the HFE hereditary hemochromatosis (HFE-HH group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n=92. Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population.

High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer.

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Yolanda López-Vidal

Full Text Available BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008, and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003. A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036. A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003. Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.

Frequency of HCV infection and its genotypes among patients attending a liver clinic and voluntary blood donors in a rural area of Pakistan

International Nuclear Information System (INIS)

Abbas, S.Z.; Ali, M.; Muhammad, A.H.; Shaw, S.; Abbas, S.Q.

2009-01-01

Objectives: To determine the frequency of Hepatitis C virus (HCV) infection and its genotypic distribution in a rural area of Sindh, Pakistan. Methodology: Retrospective study of patients attending the Free Liver Clinic (FLC), and investigated for detectable HCV antibodies (n=1638), and those screened for HCV infection prior to voluntary blood donation (n=804) at a teaching hospital, located in rural Sindh. All patients had HCV antibodies tested by ELISA. A total of 1022 patients, who tested 'reactive' to HCV antibodies, and who could financially afford to have HCV RNA tested by PCR, had their results analysed. A total of 200 patients also had their HCV genotyped and analysed. Results: Patients at FLC had a higher chance of being reactive for HCV antibodies, compared to voluntary blood donors (20% VS 14% - p = 0.004). HCV RNA was detectable in 904/1022 (88%) patients. Among type able genotypes, 125/166 (75%) had a single genotype, and 7 patients (4%) were infected with genotype 1, either alone (n=4) or in combination with 3a. Conclusions: One out of every five people tested in our FLC, and 14% of 'healthy' voluntary blood donors were seropositive for HCV antibodies. Genotype 1 is very rare in our region. (author)

Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

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Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

2003-01-01

OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

Limited protective effect of the CCR5Δ32/CCR5Δ32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

DEFF Research Database (Denmark)

Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn

2003-01-01

The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)–infected patients with hemophilia. One patient (0.6%) had the CCR5Δ32/CCR5Δ32 genotype (which occurs in ∼2% of the Scandinavian population...

Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.

Science.gov (United States)

Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

2015-03-01

The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.

Comparison of vitamin D deficiency and magnitude of severity of vitamin D deficiency in cirrhotic and non-cirrhotic patients with chronic hepatitis C in a tertiary care hospital Rawalpindi, Pakistan

International Nuclear Information System (INIS)

Hamid, S.; Faheem, M.; Ambreen, S.; Tirmizi, A.; Umar, M.

2017-01-01

Objective: To determine Vitamin D deficiency in both cirrhotic and non-cirrhotic patients with chronic hepatitis C (CHC). Methodology: We conducted a cross-sectional study at Centre for Liver and Digestive Diseases (CLD), Holy Family Hospital, Rawalpindi, Pakistan from August 2015 to February 2016 and included 120 Patients with CHC with or without cirrhosis. Two groups were formed and vitamin D levels were measured and level of severity was assessed. Results: Out of 120 patients, 94(78.3%) patients had Vitamin D deficiency. 63(100%) cirrhotic patients and 31 54.4%) non cirrhotic patients had Vitamin D deficiency. In cirrhotic patients, 26(41.3%) had mild and 36(58.7%) had moderate Vitamin D deficiency while in non-cirrhotic patients 25(43.9%) had mild and 6(10.5%) had moderate deficiency. No patient with severe Vitamin D deficiency was observed. Conclusion: Most of the patients infected with CHC suffer from vitamin D deficiency. This was observed more in cirrhotic patients than non-cirrhotic patients. Moreover, positive correlation was observed among vitamin D deficiency and stage of fibrosis. (author)

Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

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Seljeflot Ingebjørg

2008-06-01

Full Text Available Abstract Background Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA alone. Aims The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR. Methods Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC before PCR amplification (LightCycler and melting point analysis. Results The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation. Conclusion CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.

Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.

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Soh, Lip Min; Druce, Maralyn; Grossman, Ashley B; Differ, Ann-Marie; Rajput, Liala; Bitner-Glindzicz, Maria; Korbonits, Márta

2015-02-01

Patients with Pendred syndrome have genotypic and phenotypic variability, leading to challenges in definitive diagnosis. Deaf children with enlarged vestibular aqueducts are often subjected to repeated investigations when tests for mutations in SLC26A4 are abnormal. This study provides genotype and phenotype information from patients with suspected Pendred syndrome referred to a single clinical endocrinology unit. A retrospective analysis of 50 patients with suspected Pendred syndrome to investigate the correlation between genetic, perchlorate discharge test (PDT) and endocrine status. Eight patients with monoallelic SLC26A4 mutations had normal PDT. Of the 33 patients with biallelic mutations, ten of 12 patients with >30% discharge developed hypothyroidism. In our cohort, c.626G>T and c.3-2A>G result in milder clinical presentations with lower median perchlorate discharge of 9.3% (interquartile range 4-15%) compared with 40% (interquartile range 21-60%) for the remaining mutations. Eight novel mutations were detected. All patients with PDT 30% have a high risk of developing goitre and hypothyroidism, and should have lifelong monitoring. © 2015 European Society of Endocrinology.

Distribution of Hepatitis C Virus Genotypes in the South Marmara Region

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Harun Agca

2014-03-01

Full Text Available Aim: Hepatitis C virus (HCV is an important caustive agent of hepatitis, cirrhosis and hepatocellular carcinoma both in our country and the world. Prognosis and response to treatment is related with the genotype of HCV which has six genotypes and over a hundred quasispecies. Knowing the HCV genotype is also important for epidemiological data. In this study we aimed to investigate the HCV genotypes of samples sent to Uludag University Hospital Microbiology Laboratory which is the reference centre in the South Marmara Region. Material and Method: This study was done retrospectively to analyse the HCV patients%u2019 sera sent to our laboratory between July 2010and December 2012 for HCV genotyping. Artus HCV QS-RGQ PCR kit (Qiagene,Hilden, Germany was used in Rotor-Gene Q (Qiagene, Hilden Germany for detection of HCV RNA. HCV RNA positive samples of patients%u2019 sera were were used for genotyping by the Linear Array HCV genotyping test (Roche, NJ, USA.Results: 214 (92.6 % of total 231 patients included in the study were genotype 1, one (0.4 % was genotype 2, nine (3.9 % were genotype 3 and, seven (3.4 % were found genotype 4. Three of genotype 3 patients were of foreign nationality, two were born abroad and one of the genotype 4 patients were born abroad. Discussion: Concordant with our country data the most frequent genotype was 1, genotype 2 was seen in patients especially related with foreign countries and genotype 4 was seen rare. The importance of genotype 1, which is seen more frequent in our country and region is; resistance to antiviral treatment and prolonged treatment duration in chronic hepatitis C patients.

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

Science.gov (United States)

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.

IFN-Alpha receptor-1 upregulation in PBMC from HCV naïve patients carrying cc genotype. possible role of IFN-lambda.

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Eleonora Lalle

Full Text Available IL-28B gene polymorphisms predict better therapeutic response and spontaneous clearance of HCV. Moreover, higher expression of IFN-lambda has been reported in patients with the rs12979860 CC favourable genotype. The study aim was to establish possible relationships between IL-28B rs12979860 genotypes and expression of IFN-alpha receptor-1 (IFNAR-1 in naïve HCV patients, and to explore the possible role of IFN-lambda.IFNAR-1 mRNA levels were measured in PBMC from naïve patients with chronic hepatitis C with different IL-28 genotypes. The ability of IFN-lambda to up-regulate the expression of IFNAR-1 was established in PBMC from healthy donors carrying different IL-28B genotypes.Lower IFNAR-1 mRNA levels were observed in PBMC from HCV-infected naïve patients as compared to healthy donors. In healthy donors, IFNAR-1 mRNA levels were independent from IL-28B genotype, while in HCV patients, an increasing gradient was observed in TT vs CT vs CC carriers. In the latter group, a direct correlation between IFNAR-1 and endogenous IL-28B expression was observed. Moreover, IFN-lambda up-regulated IFNAR-1 expression in normal PBMC in a time-and dose-dependent manner, with a more effective response in CC vs TT carriers.Endogenous levels of IFN-lambda may be responsible for partial restoration of IFNAR-1 expression in HCV patients with favourable IL-28 genotype. This, in turn, may confer to CC carriers a response advantage to either endogenous or exogenous IFN-alpha, representing the biological basis for the observed association between CC genotype and favourable outcome of either natural infection (clearance vs chronicization or IFN therapy.

[Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

Science.gov (United States)

Zhang, Ming-xue; He, Wei; Gu, Ping

2010-08-01

To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

Cost Effectiveness of Genotype-Guided Warfarin Dosing in Patients with Mechanical Heart Valve Replacement Under the Fee-for-Service System.

Science.gov (United States)

Kim, Dong-Jin; Kim, Ho-Sook; Oh, Minkyung; Kim, Eun-Young; Shin, Jae-Gook

2017-10-01

Although studies assessing the cost effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation, deep vein thrombosis, and pulmonary embolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service (FFS) insurance system. The aim of this study was to evaluate the cost effectiveness of genotype-guided warfarin dosing in patients with MHVR under the FFS system from the Korea healthcare sector perspective. A decision-analytic Markov model was developed to evaluate the cost effectiveness of genotype-guided warfarin dosing compared with standard dosing. Estimates of clinical adverse event rates and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs than standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8) (year 2016 values). The ICER was US$1356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant compared with standard dosing, and a 99.8% probability that it was cost effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost effective in MHVR patients under the FFS insurance system.

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.

Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C.

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Vergniol, Julien; Boursier, Jérôme; Coutzac, Clélia; Bertrais, Sandrine; Foucher, Juliette; Angel, Camille; Chermak, Faiza; Hubert, Isabelle Fouchard; Merrouche, Wassil; Oberti, Frédéric; de Lédinghen, Victor; Calès, Paul

2014-07-01

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM 0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. © 2014 by the American Association for the Study of Liver Diseases.

Association of Angiotensin-Converting Enzyme Genotype, Insertion/Deletion Polymorphism and Saphenous Vein Graft Atherosclerosis in Iranian Patients

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Neda Zeinali

2015-10-01

Full Text Available ABSTRACT OBJECTIVE: The aim of this study was to evaluate possible interactions among Angiotensin-I converting enzyme genotype, insertion/deletion polymorphism and atherosclerosis of vein grafts in Iranian patients, and characterize their clinical and demographic profile. METHODS: In this cross-sectional study, patients who underwent coronary artery bypass graft surgery more than five years ago, were included for angiographic analysis. Atherosclerosis was determined by quantitative angiography and adjusted Gensini score. The gene angiotensin converting enzyme I/D polymorphism was detected by polymerase chain reaction. RESULTS: A total of 102 patients participated in this study. Eighty-four patients were male. The frequency distribution of DD, ID and II polymorphism were 23.6%, 62.7% and 13.7% respectively. There were no differences among genotypic groups in age, sex, number of risk factors, number of vein grafts and months since bypass surgery. According to adjusted Gensini score [0.18±0.12 (II vs. 0.11±0.09 (ID and 0.1±0.09 (DD P=0.021] the II genotype was associated with severity of vein graft atherosclerosis. CONCLUSION: Although there are conflicting results about gene angiotensin converting enzyme I/D polymorphism and the degree of venous bypass graft degeneration, this study suggests an association between ACE genotype II and atherosclerosis of saphenous vein grafts, however, large samples considering clinical, demographic and ethnic profile are necessary to confirm these results.

(Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I

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Sano, Shinichiro; Nakamura, Akie; Matsubara, Keiko; Nagasaki, Keisuke; Fukami, Maki; Kagami, Masayo

2018-01-01

Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting

Aspartate aminotransferase-to-platelet ratio index for fibrosis and cirrhosis prediction in chronic hepatitis C patients

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Roberto Gomes da Silva Junior

Full Text Available In chronic hepatitis C (CHC, liver biopsy is the gold standard method for assessing liver histology, however it is invasive and can have complications. Non-invasive markers have been proposed and aspartate aminotransferase (AST-to-platelet ratio index (APRI has been shown as an easy and inexpensive marker of liver fibrosis. This study evaluated the diagnostic performance of APRI for significant fibrosis and cirrhosis prediction in CHC patients. This study included treatment-naive CHC patients who had undergone liver biopsy from January 2000 to August 2006. All histological slides were reviewed according to the METAVIR system. APRI was calculated based on laboratory results performed within four months from the biopsy. Twenty-eight (56% patients had significant fibrosis (F2-F4 and 13 (26% had cirrhosis (F4. The area under ROC curves of APRI for predicting significant fibrosis and cirrhosis were 0.92 (0.83-1.00 and 0.92 (0.85-1.00, respectively. Using cut-off values recommended by prior studies, significant fibrosis could be identified, in accordance with liver biopsy, in 44% and cirrhosis in 66% of patients. APRI could identify significant fibrosis and cirrhosis at a high degree of accuracy in studied patients.

MATHEMATICAL MODELS PREDICTING LEUKOPENIA AND NEUTROPENIA IN PATIENTS WITH CHRONIC HEPATITIS C IN THE BACKGROUND INTERFERONCONTAINING SCHEMES

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I. G. Bakulin

2016-01-01

Full Text Available Currently in the Russian Federation or chronic hepatitis C (CHC are still relevant Interferon-based regimens. The purpose of this study is to investigate the influence of baseline characteristics and prognosis of the patient HCV genotype 1 for the development  of leukopenia (LP and neutropenia  (NP. We investigated  factors such as sex, age, body mass index (BMI, viral load, genotype  of Interleukin-28 B (IL-28B,  the initial level of leukocytes and neutrophils,  alanine aminotransferase (ALT, fibrosis, duration  of infection, presence  of previous therapy.  Absolute values of leukocytes  and neutrophils  were analyzed on 4, 12, 24, 48 weeks of therapy,  and at 4, 12, 24 weeks after antiviral treatment with protease  inhibitors (PI 1 and 2 generation. Prognostic criteria were identified, indicating the possible development  of the LP and NP expressed during treatment with interferon: female  gender,  low initial load, TT-genotype of IL-28B, the  initial level of white  blood cells and neutrophils  below 5,7×109/L and 3,4×109/L, respectively. Mathematical  models predicting the onset of LP and NP, formalized in the form of decision trees were also constructed. These models have shown the greatest potential for practical use in view of highest accuracy and reliability.

Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials.

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Tara L Kieffer

Full Text Available In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR in combination with peginterferon and ribavirin (PR significantly increased sustained virologic response (SVR rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR.Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment.Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm, 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms. NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients.A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment.

Community health centers and primary care access and quality for chronically-ill patients - a case-comparison study of urban Guangdong Province, China.

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Shi, Leiyu; Lee, De-Chih; Liang, Hailun; Zhang, Luwen; Makinen, Marty; Blanchet, Nathan; Kidane, Ruth; Lindelow, Magnus; Wang, Hong; Wu, Shaolong

2015-11-30

Reform of the health care system in urban areas of China has prompted concerns about the utilization of Community Health Centers (CHC). This study examined which of the dominant primary care delivery models, i.e., the public CHC model, the 'gate-keeper' CHC model, or the hospital-owned CHC models, was most effective in enhancing access to and quality of care for patients with chronic illness. The case-comparison design was used to study nine health care organizations in Guangzhou, Dongguan, and Shenzhen cities within Guangdong province, China. 560 patients aged 50 or over with hypertension or diabetes who visited either CHCs or hospitals in these three cities were surveyed by using face-to-face interviews. Bivariate analyses were performed to compare quality and value of care indicators among subjects from the three cities. Multivariate analyses were used to assess the association between type of primary care delivery and quality as well as value of chronic care after controlling for patients' demographic and health status characteristics. Patients from all three cities chose their current health care providers primarily out of concern for quality of care (both provider expertise and adequate medical equipment), patient-centered care, and insurance plan requirement. Compared with patients from Guangzhou, those from Dongguan performed significantly better on most quality and value of care indicators. Most of these indicators remained significantly better even after controlling for patients' demographic and health status characteristics. The Shenzhen model (hospital-owned and -managed CHC) was generally effective in enhancing accessibility and continuity. However, coordination suffered due to seemingly duplicating primary care outpatients at the hospital setting. Significant associations between types of health care facilities and quality of care were also observed such that patients from CHCs were more likely to be satisfied with traveling time and follow-up care by

HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: A nationwide cohort study

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Krarup, Henrik; Andersen, Stig; Madsen, Poul Henning

2011-01-01

To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: a nationwide cohort study

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Krarup, Henrik Bygum; Andersen, Stig; Madsen, Poul Henning

2011-01-01

To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

Genotypes of Mycobacterium tuberculosis in patients at risk of drug resistance in Bolivia.

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Monteserin, Johana; Camacho, Mirtha; Barrera, Lucía; Palomino, Juan Carlos; Ritacco, Viviana; Martin, Anandi

2013-07-01

Bolivia ranks among the 10 Latin American countries with the highest rates of tuberculosis (TB) and multidrug resistant (MDR) TB. In view of this, and of the lacking information on the population structure of Mycobacterium tuberculosis in the country, we explored genotype associations with drug resistance and clustering by analyzing isolates collected in 2010 from 100 consecutive TB patients at risk of drug resistance in seven of the nine departments in which Bolivia is divided. Fourteen isolates were MDR, 29 had other drug resistance profiles, and 57 were pansusceptible. Spoligotype family distribution was: Haarlem 39.4%, LAM 26.3%, T 22.2%, S 2.0%, X 1.0%, orphan 9.1%, with very low intra-family diversity and absence of Beijing genotypes. We found 66 different MIRU-VNTR patterns; the most frequent corresponded to Multiple Locus Variable Analysis (MLVA) MtbC15 patterns 860, 372 and 873. Twelve clusters, each with identical MIRU-VNTR and spoligotypes, gathered 35 patients. We found no association of genotype with drug resistant or MDR-TB. Clustering associated with SIT 50 and the H3 subfamily to which it belongs (pBolivia. However, results should be taken cautiously because the sample is small and includes a particular subset of M. tuberculosis population. Copyright © 2013 Elsevier B.V. All rights reserved.

High-producing MBL2 genotypes increase the risk of acute and chronic carditis in patients with history of rheumatic fever

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Schafranski, Marcelo Derbli; Pereira Ferrari, Lílian; Scherner, Daniela

2008-01-01

with a history of RF. Polymorphisms in exon 1 and in the X/Y promoter region of the MBL2 gene were determined by PCR-SSP in 149 patients with a history of RF and 147 controls. Genotypes associated with the high production of MBL (YA/YA and YA/XA) were more frequent in the patients with acute (26/35, 74...... patients presenting MBL2 genotypes related to the low production of MBL (10/14, 71% vs. 10/28, 36%; p=0.048, OR 0.22, 95% CI 0.05-0.89). We concluded that MBL2 genotypes associated with the high production of MBL seem to be involved in the pathogenesis of rheumatic carditis and its progression to CRHD....

Common genotypes of hepatitis B virus

International Nuclear Information System (INIS)

Idrees, M.; Khan, S.; Riazuddin, S.

2004-01-01

Objective: To find out the frequency of common genotypes of hepatitis-B virus (HBV). Subjects and Methods: HBV genotypes were determined in 112 HBV DNA positive sera by a simple and precise molecular genotyping system base on PCR using type-specific primers for the determination of genotypes of HBV A through H. Results: Four genotypes (A,B,C and D) out of total eight reported genotypes so far were identified. Genotypes A, B and C were predominant. HBV genotype C was the most predominant in this collection, appearing in 46 samples (41.7%). However, the genotypes of a total of 5 (4.46%) samples could not be determined with the present genotyping system. Mixed genotypes were seen in 8(7.14% HBV) isolates. Five of these were infected with genotypes A/D whereas two were with genotypes C/D. One patient was infected with 4 genotypes (A/B/C/D). Genotype A (68%) was predominant in Sindh genotype C was most predominant in North West Frontier Province (NWFP) (68.96) whereas genotype C and B were dominant in Punjab (39.65% and 25.86% respectively). Conclusion: All the four common genotypes of HBV found worldwide (A,B,C and D) were isolated. Genotype C is the predominant Genotypes B and C are predominant in Punjab and N.W.F.P. whereas genotype A is predominant in Sindh. (author)

Major components of metabolic syndrome and nutritional intakes in different genotype of UCP2 -866G/A gene polymorphisms in patients with NAFLD.

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Abbasalizad Farhangi, Mahdieh; Mohseni, Fatemeh; Farajnia, Safar; Jafarabadi, Mohammad-Asghari

2016-06-14

It has been suggested that dietary modifications in combination with genetic predisposition play an important role in the pathogenesis of NAFLD. In the current study we aimed to investigate the major components of metabolic syndrome in patients with non-alcoholic fatty liver disease (NAFLD) and nutritional intakes according to different genotype of uncoupling protein-2 (UCP2) -866G/A gene polymorphism in these patients. In this study 151 participants including 75 patients with NAFLD and 76 healthy individuals were enrolled. Dietary intakes were assessed using a semi-quantitative food-frequency questionnaire. Physical activity was obtained by metabolic equivalent questionnaire. Anthropometric assessments were conducted by a trained researcher and body mass index and waist to hip ratio were calculated. Body composition was measured by bioelectrical impedance analysis and biochemical assays including fasting serum glucose, liver enzymes and lipid profiles were measured. Polymorphisms of -866G/A UCP2 gene was determined using polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride concentrations in 53.3 % of NAFLD patients compared with 35.5 % of control group was more than 150 mg/dl (P = 0.034). A significantly higher prevalence of low serum high density lipoprotein cholesterol concentrations was also observed in female NAFLD patients (P  0.05). However, according to genotypes patients with AG genotype had significantly higher protein consumption compared with control group (P < 0.05). Significantly higher consumption of dietary iron and copper in NAFLD patients with AG genotype was only observed among patients with NAFLD. However, the comparison of macro and micronutrient intakes in control group sound for stronger differences for AA genotype although these differences did not achieve significant threshold. A high prevalence of metabolic abnormalities was reported among NAFLD patients. Additionally, among NAFLD group

Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania

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Stavrum, Ruth; PrayGod, George; Range, Nyagosya

2014-01-01

a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages. METHODS: Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were......BACKGROUND: There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from....... tuberculosis lineage of the infectious agent for each patient. RESULTS: The most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST's out of 248...

Core Gene Expression and Association of Genotypes with Viral ...

African Journals Online (AJOL)

Purpose: To determine genotypic distribution, ribonucleic acid (RNA) RNA viral load and express core gene from Hepatitis C Virus (HCV) infected patients in Punjab, Pakistan. Methods: A total of 1690 HCV RNA positive patients were included in the study. HCV genotyping was tested by type-specific genotyping assay, viral ...

Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing.

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Tafazoli, Alireza; Eshraghi, Peyman; Pantaleoni, Francesca; Vakili, Rahim; Moghaddassian, Morteza; Ghahraman, Martha; Muto, Valentina; Paolacci, Stefano; Golyan, Fatemeh Fardi; Abbaszadegan, Mohammad Reza

2018-03-01

Noonan Syndrome (NS) is an autosomal dominant disorder with many variable and heterogeneous conditions. The genetic basis for 20-30% of cases is still unknown. This study evaluates Iranian Noonan patients both clinically and genetically for the first time. Mutational analysis of PTPN11 gene was performed in 15 Iranian patients, using PCR and Sanger sequencing at phase one. Then, as phase two, Next Generation Sequencing (NGS) in the form of targeted resequencing was utilized for analysis of exons from other related genes. Homology modelling for the novel founded mutations was performed as well. The genotype, phenotype correlation was done according to the molecular findings and clinical features. Previously reported mutation (p.N308D) in some patients and a novel mutation (p.D155N) in one of the patients were identified in phase one. After applying NGS methods, known and new variants were found in four patients in other genes, including: CBL (p. V904I), KRAS (p. L53W), SOS1 (p. I1302V), and SOS1 (p. R552G). Structural studies of two deduced novel mutations in related genes revealed deficiencies in the mutated proteins. Following genotype, phenotype correlation, a new pattern of the presence of intellectual disability in two patients was registered. NS shows strong variable expressivity along the high genetic heterogeneity especially in distinct populations and ethnic groups. Also possibly unknown other causative genes may be exist. Obviously, more comprehensive and new technologies like NGS methods are the best choice for detection of molecular defects in patients for genotype, phenotype correlation and disease management. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Liver enzymes and psychological well-being response to aerobic exercise training in patients with chronic hepatitis C.

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Abd El-Kader, Shehab M; Al-Jiffri, Osama H; Al-Shreef, Fadwa M

2014-06-01

Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person's physical and psychological health. The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic exercise training in patients with CHC. Fifty CHC patients were included in two equal groups. The first group (A) received aerobic exercise training in addition to their regular medical treatment. The second group (B) received no training and only has their regular medical treatment. The program consisted of three sessions per week for three months. There was a significant decrease in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT), Beck Depression Inventory (BDI ) & Profile of Mood States(POMS) and increase in Rosenberg Self-Esteem Scale (RSES) in group (A) after treatments, but the changes in group (B) were not significant. Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Aerobic exercise training improves hepatic enzymes and psychological well-being in patients with chronic hepatitis C.

Prevalence of genotype D in chronic liver disease patients with occult HBV infection in northern region of India

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Meher Rizvi

2014-01-01

Full Text Available Background: Etiology of nearly 30% cases of chronic viral hepatitis remains undetected. Occult HBV infection (OBI has emerged as an important clinical entity in this scenario. Apart from prevalence and clinical outcome of OBI patients genotype was determined in northern region of India. Materials and Methods: A total of 847 patients with chronic liver disease (CLD were screened for common viral etiologies and others serological markers of HBV. Amplification of surface, precore and polymerase genes of HBV was performed in patients negative for other etiologies. Genotyping and sequencing of the precore region was performed for OBI cases. Results: Twenty-nine (7.61% cases of OBI were identifiedof which 9 had chronic liver disease (CHD, 11 liver cirrhosis (LC and 9 hepatocellular carcinoma (HCC. Majority of OBI cases were detected by amplification of surface gene 26 (89.6%, followed by pre-core gene 12 (41.3%. Their liver functions tests were significantly deranged in comparison to overt HBV cases. IgG anti HBc was present in 8 (27.6% OBI cases. Mutation was observed in 8 (32% in pre-core region at nt. 1896 of overt HBV cases. Genotype D was the predominant genotype. In conclusion: OBI in our study was characterized by predominance of genotype D and more severe clinical and biochemical profile in comparison to overt HBV. IgG anti HBc positivity could be utilized as a marker of OBI. We recommend use of sensitive nested PCR for diagnosis of OBI, amplifying at least surface and precore gene.

Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer.

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Martínez-Carrillo, D N; Atrisco-Morales, J; Hernández-Pando, R; Reyes-Navarrete, S; Betancourt-Linares, R; Cruz-del Carmen, I; Illades Aguiar, B; Román-Román, A; Fernández-Tilapa, G

2014-01-01

Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.

Detection of Aggregatibacter actinomycetemcomitans leukotoxin and fimbria-associated protein gene genotypes among periodontitis patients and healthy controls: A case–control study

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Mahalakshmi, Krishnan; Krishnan, Padma; Chandrasekaran, S. C.

2018-01-01

Background: Aggregatibacter actinomycetemcomitans has been reported in higher proportions in subgingival microbiota of individuals with aggressive periodontitis (AgP) compared with those with chronic periodontitis (ChP) and healthy controls. The major virulence factors are the ones that help in colonization and evasion of host's defenses. Hence, this study was aimed to assess the prevalence of A. actinomycetemcomitans 16S rRNA and its virulent genotypes (leukotoxin [lktA] and fimbria-associated protein [fap]). Materials and Methods: In this case– control study We performed periodontal examination and measured probing depth and clinical attachment level (CAL). Subgingival plaque samples from 200 (ChP: n = 128 and AgP: n = 72) periodontitis patients and 200 healthy controls were screened for the presence of A. actinomycetemcomitans 16S rRNA, lktA, and fap genotypes by polymerase chain reaction. The prevalence of genotypes between periodontitis patients and healthy controls was compared with Pearson's Chi-square test. P periodontitis patients, while A. actinomycetemcomitans fap genotype showed 31.8% prevalence. The prevalence of these genotypes was insignificant in healthy controls. Conclusion: The high odds ratio for A. actinomycetemcomitans prevalence suggests its strong link to periodontitis. Detection of A. actinomycetemcomitans lktA + genotype may be a useful marker for AgP as its prevalence was found to be high in AgP. PMID:29922337

Isolation and characterization of new Leptospira genotypes from patients in Mayotte (Indian Ocean.

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Pascale Bourhy

Full Text Available BACKGROUND: Leptospirosis has been implicated as a severe and fatal form of disease in Mayotte, a French-administrated territory located in the Comoros archipelago (southwestern Indian Ocean. To date, Leptospira isolates have never been isolated in this endemic region. METHODS AND FINDINGS: Leptospires were isolated from blood samples from 22 patients with febrile illness during a 17-month period after a PCR-based screening test was positive. Strains were typed using hyper-immune antisera raised against the major Leptospira serogroups: 20 of 22 clinical isolates were assigned to serogroup Mini; the other two strains belonged to serogroups Grippotyphosa and Pyrogenes, respectively. These isolates were further characterized using partial sequencing of 16S rRNA and ligB gene, Multi Locus VNTR Analysis (MLVA, and pulsed field gel electrophoresis (PFGE. Of the 22 isolates, 14 were L. borgpetersenii strains, 7 L. kirschneri strains, and 1, belonging to serogoup Pyrogenes, was L. interrogans. Results of the genotyping methods were consistent. MLVA defined five genotypes, whereas PFGE allowed the recognition of additional subgroups within the genotypes. PFGE fingerprint patterns of clinical strains did not match any of the patterns in the reference strains belonging to the same serogroup, suggesting that the strains were novel serovars. CONCLUSIONS: Preliminary PCR screening of blood specimen allowed a high isolation frequency of leptospires among patients with febrile illness. Typing of leptospiral isolates showed that causative agents of leptospirosis in Mayotte have unique molecular features.

Deep sequencing analysis of HBV genotype shift and correlation with antiviral efficiency during adefovir dipivoxil therapy.

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Yuwei Wang

Full Text Available Viral genotype shift in chronic hepatitis B (CHB patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38% increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.

Clinical validation and applicability of different tipranavir/ritonavir genotypic scores in HIV-1 protease inhibitor-experienced patients.

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Saracino, Annalisa; Monno, Laura; Tartaglia, Alessandra; Tinelli, Carmine; Seminari, Elena; Maggiolo, Franco; Bonora, Stefano; Rusconi, Stefano; Micheli, Valeria; Lo Caputo, Sergio; Lazzaroni, Laura; Ferrara, Sergio; Ladisa, Nicoletta; Nasta, Paola; Parruti, Giustino; Bellagamba, Rita; Forbici, Federica; Angarano, Gioacchino

2009-07-01

Tipranavir, a non-peptidic protease inhibitor which shows in vitro efficacy against some HIV-1-resistant strains, can be used in salvage therapies for multi-experienced HIV patients due to its peculiar resistance profile including 21 mutations at 16 protease positions according to International AIDS Society (IAS). Other genotypic scores, however, which attribute a different weight to single amino-acid substitutions, have been recently proposed. To validate the clinical utility of four different genotypic scores for selecting tipranavir responders, the baseline resistance pattern of 176 HIV heavily experienced patients was correlated with virological success (HIV-RNA42.5% of patients. With univariate analysis, genotypic scores were all associated with outcome but showed a low accuracy with ROC analysis, with the weighted score (WS) by Scherer et al. demonstrating the best performance with an AUC of 68%. Only 52% of patients classified as susceptible (WSIAS mutations: L33F, I54AMV, Q58E, and non-IAS mutation: N37DES. On the contrary, the use of T20 in T20-naïve patients and the V82AFSI and F53LY non-IAS mutations were associated with virological success. The study suggests that even if the "weighted" scores are able to interpret correctly the antiretroviral resistance profile of multi-experienced patients, it is difficult to individuate a cut-off which can be easily applied to this population for discriminating responders.

Detection of HCV genotypes using molecular and radio-isotopic methods

International Nuclear Information System (INIS)

Ahmad, N.; Baig, S.M.; Shah, W.A.; Khattak, K.F.; Khan, B.; Qureshi, J.A.

2004-01-01

Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B liver diseases. Persistent HCV infection may lead to liver cirrhosis and hepatocellular carcinoma. Six major HCV genotypes have been recognized. Infection with different genotypes results in different clinical pictures and responses to antiviral therapy. In the area of Faisalabad (Punjab province of Pakistan), the prevalence and molecular epidemiology of Hepatitis C virus infection had never been investigated before. In this study, we have made an attempt to determine the prevalence, distribution and clinical significance of HCV infection in 1100 suspected patients of liver disease by nested reverse transcriptase polymerase chain reaction (RTPCR) over a period of four years. HCV genotypes of isolates were determined by dot-blot hybridization with genotype specific radiolabeled probes in 337 subjects. The proportion of patients with HCV genotypes 1,2,3 and 4 were 37.38%, 1.86%, 16.16% and 0.29% respectively. Mixed infection of HCV genotype was detected in 120 (35.6%) patients, whereas 31 (9.1%) samples remained unclassified. This study revealed changing epidemiology of hepatitis C virus genotype 1 and 3 in the patients. Multiple infection of HCV genotype in the same patient may be of great clinical and pathological importance and interest. (author)

Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

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Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

2008-01-01

OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

[Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients].

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Cifuentes, Celia; Mancebo-Hernández, María; Pérez-Navarro, Elisabet; Recio, Eva; Monje-Agudo, Patricia; Valiente, Adoración; Pineda, Juan A

2015-02-01

The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=<.001), and for the HCV-RNA was 255 (49%) vs. 240 (37%) (P=<.001). In both periods, the HCV genotype distribution was: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (P=.881). The prevalence of HCV infection in HIV-infected patients has decreased in our area, including overall exposure to HCV virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The association of complex liver disorders with HBV genotypes prevalent in Pakistan

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Qureshi Huma

2007-11-01

Full Text Available Abstract Background Genotyping of HBV is generally used for determining the epidemiological relationship between various virus strains and origin of infection mostly in research studies. The utility of genotyping for clinical applications is only beginning to gain importance. Whether HBV genotyping will constitute part of the clinical evaluation of Hepatitis B patients depends largely on the availability of the relevance of the evidence based information. Since Pakistan has a HBV genotype distribution which has been considered less virulent as investigated by earlier studies from south East Asian countries, a study on correlation between HBV genotypes and risk of progression to further complex hepatic infection was much needed Methods A total of 295 patients with HBsAg positive were selected from the Pakistan Medical Research Council's (PMRC out patient clinics. Two hundred and twenty six (77% were males, sixty nine (23% were females (M to F ratio 3.3:1. Results Out of 295 patients, 156 (53.2% had Acute(CAH, 71 (24.2% were HBV Carriers, 54 (18.4% had Chronic liver disease (CLD Hepatitis. 14 (4.7% were Cirrhosis and HCC patients. Genotype D was the most prevalent genotype in all categories of HBV patients, Acute (108, Chronic (39, and Carrier (53. Cirrhosis/HCC (7 were HBV/D positive. Genotype A was the second most prevalent with 28 (13% in acute cases, 12 (22.2% in chronics, 14 (19.7% in carriers and 5 (41.7 in Cirrhosis/HCC patients. Mixed genotype (A/D was found in 20 (12.8% of Acute patients, 3 (5.6% of Chronic and 4 (5.6% of carriers, none in case of severe liver conditions. Conclusion Mixed HBV genotypes A, D and A/D combination were present in all categories of patients except that no A/D combination was detected in severe conditions. Genotype D was the dominant genotype. However, genotype A was found to be more strongly associated with severe liver disease. Mixed genotype (A/D did not significantly appear to influence the clinical outcome.

Combinations of SNP genotypes from the Wellcome Trust Case Control Study of bipolar patients

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Mellerup, Erling; Jørgensen, Martin Balslev; Dam, Henrik

2018-01-01

Objectives: Combinations of genetic variants are the basis for polygenic disorders. We examined combinations of SNP genotypes taken from the 446 729 SNPs in The Wellcome Trust Case Control Study of bipolar patients. Methods: Parallel computing by graphics processing units, cloud computing, and data...

Barriers and enablers to the delivery of psychological care in the management of patients with type 2 diabetes mellitus in China: a qualitative study using the theoretical domains framework.

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Chapman, Anna; Yang, Hui; Thomas, Shane A; Searle, Kendall; Browning, Colette

2016-03-29

China has the largest number of type 2 diabetes mellitus (T2DM) cases globally and individuals with T2DM have an increased risk of developing mental health disorders and functional problems. Despite guidelines recommending that psychological care be delivered in conjunction with standard T2DM care; psychological care is not routinely delivered in China. Community Health Centre (CHC) doctors play a key role in the management of patients with T2DM in China. Understanding the behavioural determinants of CHC doctors in the implementation of psychological care recommendations allows for the design of targeted and culturally appropriate interventions. As such, this study aimed to examine barriers and enablers to the delivery of psychological care to patients with T2DM from the perspective of CHC doctors in China. Two focus groups were conducted with 23 CHC doctors from Shenzhen, China. The discussion guide applied the Theoretical Domains Framework (TDF) that examines current practice and identifies key barriers and enablers perceived to influence practice. Focus groups were conducted with an interpreter, and were digitally recorded and transcribed. Two researchers independently coded transcripts into pre-defined themes using deductive thematic analysis. Barriers and enablers perceived by doctors as being relevant to the delivery of psychological care for patients with T2DM were primarily categorised within eight TDF domains. Key barriers included: CHC doctors' knowledge and skills; time constraints; and absence of financial incentives. Other barriers included: societal perception that treating psychological aspects of health is less important than physical health; lack of opinion leaders; doctors' intentional disregard of psychological care; and doubts regarding the efficacy of psychological care. In contrast, perceived enablers included: training of CHC doctors in psychological skills; identification of afternoon/evening clinic times when recommendations could be

Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection

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Lieveld, Faydra I.; Swaans, Niels; Newsum, Astrid M.; Ho, Cynthia K. Y.; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T. M.; Arends, Joop E.; Hoepelman, Andy I. M.; Wensing, Anne M. J.; Siersema, Peter D.; van Erpecum, Karel J.; Boland, Greet J.

2016-01-01

Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

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R. Focaccia

Full Text Available Hepatitis C virus (HCV infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62% and white patients (80%. The analysis of HCV-infecting strains showed a predominance of genotype 1 (64% over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

Distribution of genotypes C825T polymorphism G-protein β3-subunit gene in patients with hypertension depending on body mass index

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Prystupa L.N.

2015-09-01

Full Text Available The aim of the study was to investigate the frequency of genotypes of C825T polymorphism G-protein β3-subunit gene (GNB3 in patients with arterial hypertension (AH, depending on body mass index (BMI. The study involved 155 patients with verified diagnosis of AH (study group and 50 healthy individuals (control group. The patients of the main group were divided into 3 groups according to BMI: I - 35 patients with normal body weight, II - 38 patients with overweight, III - 82 patients with obesity. We used general clinical, anthropometric, instrumental, molecular-genetic and statistical methods. Probability of differences in the frequency of alleles and genotypes was determined using χ² criteria. Pairwise comparison of groups was made using nonparametric Mann-Whitney test. The difference was considered statistically significant at p <0,05. Investigation of the distribution of genotypes C825T polymorphism GNB3 in patients with AH according to BMI showed statistically significant increase in the frequency of genotypes C / T and T / T and T allele in patients with overweight and obesity as compared with patients with normal body weight (χ² = 26 8; p <0.001. The risk of weight increase in AH patients with T allele carriers is 2,2 times higher than in C allele carriers. Association of C825T polymorphism of GNB3 with a tendency to obesity and overweight in patients with AH was proved.

Molecular Characterization of Echinococcus granulosus Cysts in North Indian Patients: Identification of G1, G3, G5 and G6 Genotypes

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Sharma, Monika; Sehgal, Rakesh; Fomda, Bashir Ahmad; Malhotra, Anil; Malla, Nancy

2013-01-01

Background Cystic echinococcosis (CE) caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s) of the parasite responsible for human hydatidosis in North India. Methodology/Principal Findings To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE) patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1) sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype. Conclusions/Significance These findings demonstrate the zoonotic potential of G1 (sheep strain) and G3 (buffalo strain) genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain) in an Asian country and presence of G6 genotype (camel strain) in India. The results may have important implications in the planning of control strategies for human hydatidosis. PMID:23785531

Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

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Santen, Gijs W E; Aten, Emmelien; Vulto-van Silfhout, Anneke T; Pottinger, Caroline; van Bon, Bregje W M; van Minderhout, Ivonne J H M; Snowdowne, Ronelle; van der Lans, Christian A C; Boogaard, Merel; Linssen, Margot M L; Vijfhuizen, Linda; van der Wielen, Michiel J R; Vollebregt, M J Ellen; Breuning, Martijn H; Kriek, Marjolein; van Haeringen, Arie; den Dunnen, Johan T; Hoischen, Alexander; Clayton-Smith, Jill; de Vries, Bert B A; Hennekam, Raoul C M; van Belzen, Martine J

2013-11-01

De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation. © 2013 WILEY PERIODICALS, INC.

Correlation of oxidative stress in patients with HBV-induced liver disease with HBV genotypes and drug resistance mutations.

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Xianyu, Jianbo; Feng, Jiafu; Yang, Yuwei; Tang, Jie; Xie, Gang; Fan, Lingying

2018-05-01

This study aims to explore the correlation of oxidative stress (OxS) in patients with chronic hepatitis B (CHB) and the disease severity with HBV genotypes and drug resistance mutations. A total of 296 patients with CHB were enrolled into the study. PCR-reverse dot-blot hybridization was used to detect the HBV genotypes (B, C, and D) and the drug resistance-causing HBV mutant genes. In addition, the total oxidative stress (TOS) and total antioxidant status (TAS) were determined, and oxidative stress index (OSI) was calculated and compared. Serum levels of TOS and OSI, the B/C ratio, and drug resistance mutation rate were increased along with the elevated disease severity degree (CHBHBV mutation had higher serum TOS and OSI levels, while lower serum TAS levels (P HBV-induced liver disease, and the damage degree is correlated with the HBV genotype and drug resistance mutation. Oxidative stress might be a useful indicator of the progression of HBV-induced liver disease in patients. Copyright © 2018. Published by Elsevier Inc.

Enterovirus genotypes among patients with severe acute respiratory illness, influenza-like illness, and asymptomatic individuals in South Africa, 2012-2014.

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Hellferscee, Orienka; Tempia, Stefano; Walaza, Sibongile; Variava, Ebrahim; Dawood, Halima; Wolter, Nicole; Madhi, Shabir A; du Plessis, Mignon; Cohen, Cheryl; Treurnicht, Florette K

2017-10-01

Enteroviruses can cause outbreaks of severe acute respiratory illness (SARI) and EV-A, -B, -C, and -D species have different pathogenic profiles and circulation patterns. We aimed to characterize and determine the prevalence of enterovirus genotypes among South African patients with respiratory illness and controls during June 2012 to July 2014. Syndromic SARI and influenza-like illness (ILI) surveillance was performed at two sentinel sites. At each site nasopharyngeal/oropharyngeal specimens were collected from SARI and ILI patients as well as controls. Specimens were tested for enterovirus by real-time PCR. Positive specimens were further genotyped by sequencing a region of the VP1 gene. The prevalence of enterovirus was 5.8% (87/1494), 3.4% (103/3079), and 3.4% (46/1367) among SARI, ILI, and controls, respectively (SARI/controls, P = 0.002 and ILI/control, P = 0.973). Among the 101/236 (42.8%) enterovirus-positive specimens that could be genotyped, we observed a high diversity of circulating enterovirus genotypes (a total of 33 genotypes) from all four human enterovirus species with high prevalence of Enterovirus-B (60.4%; 61/101) and Enterovirus-A (21.8%; 22/101) compared to Enterovirus-C (10.9%; 11/101) and Enterovirus-D (6.9%; 7/101) (P = 0.477). Of the enterovirus genotypes identified, Echovirus 30 (9.9%, 10/101), Coxsackie virus B5 (7.9%, 8/101) and Enterovirus-D68 (6.9%, 7/101) were most prevalent. There was no difference in disease severity (SARI or ILI compared to controls) between the different enterovirus species (P = 0.167). We observed a high number of enterovirus genotypes in patients with respiratory illness and in controls from South Africa with no disease association of EV species with disease severity. © 2017 Wiley Periodicals, Inc.

Prevalence and clinical utility of human papilloma virus genotyping in patients with cervical lesions.

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Kaur, Parminder; Aggarwal, Aruna; Nagpal, Madhu; Oberoi, Loveena; Sharma, Swati

2014-08-01

Cervical cancer is the commonest cancer among Indian women. High-risk human papilloma virus (HPV) detection holds the potential to be used as a tool to identify women, at risk of subsequent development of cervical cancer. There is a pressing need to identify prevalence of asymptomatic cervical HPV infection in local population. In our study, we explored the prevalence of HPV genotypes and their distribution in women with cervical lesions. Scrape specimens were obtained from 100 women (study group) with cervical abnormalities. HPV was detected with amplicor HPV tests, and the individual genotypes in these specimens were identified by Hybribio Genoarray test kit. Fifty specimens were also collected from females with healthy cervix (control group). The present study also aimed to determine the status of HPV prevalence and its association with different sociodemographic factors. Out of the total number of 100 samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens collected from patients with healthy cervix were not infected with any of the HPV genotype. Our study generates data of HPV prevalence in patients with cervical lesions visiting tertiary care institute. The data generated will be useful for laying guidelines for mass screening of HPV detection, treatment, and prophylaxis.

KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.

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Alessandro Soria

Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

Colonization of patients, healthcare workers, and the environment with healthcare-associated Staphylococcus epidermidis genotypes in an intensive care unit: a prospective observational cohort study.

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Widerström, Micael; Wiström, Johan; Edebro, Helén; Marklund, Elisabeth; Backman, Mattias; Lindqvist, Per; Monsen, Tor

2016-12-09

During the last decades, healthcare-associated genotypes of methicillin-resistant Staphylococcus epidermidis (HA-MRSE) have been established as important opportunistic pathogens. However, data on potential reservoirs on HA-MRSE is limited. The aim of the present study was to investigate the dynamics and to which extent HA-MRSE genotypes colonize patients, healthcare workers (HCWs) and the environment in an intensive care unit (ICU). Over 12 months in 2006-2007, swab samples were obtained from patients admitted directly from the community to the ICU and patients transferred from a referral hospital, as well as from HCWs, and the ICU environment. Patients were sampled every third day during hospitalization. Antibiotic susceptibility testing was performed according to EUCAST guidelines. Pulsed-field gel electrophoresis and multilocus sequence typing were used to determine the genetic relatedness of a subset of MRSE isolates. We identified 620 MRSE isolates from 570 cultures obtained from 37 HCWs, 14 patients, and 14 environmental surfaces in the ICU. HA-MRSE genotypes were identified at admission in only one of the nine patients admitted directly from the community, of which the majority subsequently were colonized by HA-MRSE genotypes within 3 days during hospitalization. Almost all (89%) of HCWs were nasal carriers of HA-MRSE genotypes. Similarly, a significant proportion of patients transferred from the referral hospital and fomites in the ICU were widely colonized with HA-MRSE genotypes. Patients transferred from a referral hospital, HCWs, and the hospital environment serve as important reservoirs for HA-MRSE. These observations highlight the need for implementation of effective infection prevention and control measures aiming at reducing HA-MRSE transmission in the healthcare setting.

Porphyromonas gingivalis Fim-A genotype distribution among Colombians

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Jaramillo, Adriana; Parra, Beatriz; Botero, Javier Enrique; Contreras, Adolfo

2015-01-01

Introduction: Porphyromonas gingivalis is associated with periodontitis and exhibit a wide array of virulence factors, including fimbriae which is encoded by the FimA gene representing six known genotypes. Objetive: To identify FimA genotypes of P. gingivalis in subjects from Cali-Colombia, including the co-infection with Aggregatibacter actinomycetemcomitans, Treponema denticola, and Tannerella forsythia. Methods: Subgingival samples were collected from 151 people exhibiting diverse periodontal condition. The occurrence of P. gingivalis, FimA genotypes and other bacteria was determined by PCR. Results: P. gingivalis was positive in 85 patients. Genotype FimA II was more prevalent without reach significant differences among study groups (54.3%), FimA IV was also prevalent in gingivitis (13.0%). A high correlation (p= 0.000) was found among P. gingivalis, T. denticola, and T. forsythia co-infection. The FimA II genotype correlated with concomitant detection of T. denticola and T. forsythia. Conclusions: Porphyromonas gingivalis was high even in the healthy group at the study population. A trend toward a greater frequency of FimA II genotype in patients with moderate and severe periodontitis was determined. The FimA II genotype was also associated with increased pocket depth, greater loss of attachment level, and patients co-infected with T. denticola and T. forsythia. PMID:26600627

Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes.

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Monika Sharma

Full Text Available BACKGROUND: Cystic echinococcosis (CE caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s of the parasite responsible for human hydatidosis in North India. METHODOLOGY/PRINCIPAL FINDINGS: To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1 sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32 were found to be infected with hydatid cyst of either G3 (53.1% or G1 (40.62% genotype and one each of G5 (cattle strain and G6 (camel strain genotype. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate the zoonotic potential of G1 (sheep strain and G3 (buffalo strain genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain in an Asian country and presence of G6 genotype (camel strain in India. The results may have important implications in the planning of control strategies for human hydatidosis.

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....

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.

Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

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Dandan Tan

Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

Haptoglobin genotype and risk markers of cardiovascular disease in patients with chronic kidney disease

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Strandhave, Charlotte; Svensson, My; Krarup, Henrik

2013-01-01

-5 were included. Hp genotype was determined by high-performance liquid chromatography. HRV was analysed from the 24 h Holter recordings. Hs-CRP was measured using an immunoturbidimetric assay. The results show that the HRV indices SDNN and SDANN were significantly lower in the Hp 2-2 patients (P = 0...

PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

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Salvatore Petta

Full Text Available BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT, IMT thickening(IMT≥1 mm and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02 were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively. These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12-7.71, p = 0.02, and OR4.11;95%C.I. 1.69-9.96, p = 0.002, respectively, although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36-29, p = 0.01, and to IMT progression (p = 0.05 in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.

QOL in caregivers of Japanese patients with Prader-Willi syndrome with reference to age and genotype.

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Ihara, Hiroshi; Ogata, Hiroyuki; Sayama, Masayuki; Kato, Aya; Gito, Masao; Murakami, Nobuyuki; Kido, Yasuhiro; Nagai, Toshiro

2014-09-01

This study aimed to measure quality of life (QOL) of the primary family caregivers for patients with Prader-Willi syndrome (PWS). Comparisons were made between caregivers' QOL in regard to their dependents' genotype and age group. The participants with PWS consisted of 22 children (aged from 6 to 12 years) and 23 adolescents (aged from 13 to 19 years), including 6 children and 7 adolescents with maternal uniparental disomy (mUPD) and 16 children and 16 adolescents with deletion (DEL). The QOL of the primary family caregiver for each patient was assessed using the Japanese version of the WHOQOL-BREF. To examine the effect that age (children vs. adolescents) and genotype (DEL vs. mUPD) have on the QOL of caregivers, a two-way ANOVA was conducted, followed by the Bonferroni procedure to test the simple main effects. The two age groups and the two genotypes of PWS were used as independent variables and the total QOL of caregivers as a dependent variable. The two-way ANOVA (F(1, 41) = 6.98, P caregivers of DEL adolescents showed little difference from that with DEL children, but the QOL of caregivers for mUPD adolescents was shown to be lower than that with mUPD children along with that of caregivers with DEL adolescents. There is hence a growing tendency for the deterioration in the QOL of caregivers to manifest itself later in the patients' adolescence, found mainly with mUPD patients. © 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Spleen Stiffness Correlates with the Presence of Ascites but Not Esophageal Varices in Chronic Hepatitis C Patients

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Kazuyo Mori

2013-01-01

Full Text Available Although spleen stiffness has recently been identified as potential surrogate marker for portal hypertension, the relationship between spleen stiffness and portal hypertension has not been fully elucidated. We attempted to determine the relationship between the liver or spleen stiffness and the presence of ascites or esophageal varices by acoustic radiation force impulse (ARFI imaging. A total of 33 chronic hepatitis C (CHC patients (median age 68; range 51–84 were enrolled. We evaluated the relationship between the liver or spleen stiffness and indicators of portal hypertension as well as clinical and biochemical parameters. Fourteen healthy volunteers were used for validating the accuracy of AFRI imaging. The liver and spleen stiffness increased significantly with progression of liver disease. A significant positive correlation was observed between the liver and spleen stiffness. However, spleen stiffness, but not liver stiffness, was significantly associated with the presence of ascites (, while there was no significant association between the spleen stiffness and spleen index/presence of esophageal varices in CHC patients. The area under the receiver operating characteristic curve based on the spleen stiffness was 0.80. In conclusion, spleen stiffness significantly correlates with the presence of ascites but not esophageal varices in CHC patients.

Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

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Lee, Bolyun; Yu, Hee Joon; Kang, Eun-Suk; Lee, Munhyang; Lee, Jeehun

2014-08-01

Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

Enterovirus genotypes among patients with severe acute respiratory illness, influenza-like illness, and asymptomatic individuals in South Africa, 2012–2014

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Hellferscee, Orienka; Tempia, Stefano; Walaza, Sibongile; Variava, Ebrahim; Dawood, Halima; Wolter, Nicole; Madhi, Shabir A.; du Plessis, Mignon; Cohen, Cheryl; Treurnicht, Florette K.

2017-01-01

Enteroviruses can cause outbreaks of severe acute respiratory illness (SARI) and EV-A, -B, -C, and -D species have different pathogenic profiles and circulation patterns. We aimed to characterize and determine the prevalence of enterovirus genotypes among South African patients with respiratory illness and controls during June 2012 to July 2014. Syndromic SARI and influenza-like illness (ILI) surveillance was performed at two sentinel sites. At each site nasopharyngeal/oropharyngeal specimens were collected from SARI and ILI patients as well as controls. Specimens were tested for enterovirus by real-time PCR. Positive specimenswere further genotyped by sequencing a region of theVP1 gene. The prevalence of enterovirus was 5.8% (87/1494), 3.4% (103/3079), and 3.4% (46/1367) among SARI, ILI, and controls, respectively (SARI/controls, P=0.002 and ILI/control, P = 0.973). Among the 101/236 (42.8%) enterovirus-positive specimens that could be genotyped, we observed a high diversity of circulating enterovirus genotypes (a total of 33 genotypes) from all four human enterovirus species with high prevalence of Enterovirus-B (60.4%; 61/101) and Enterovirus-A (21.8%; 22/101) compared to Enterovirus-C (10.9%; 11/101) and Enterovirus-D (6.9%; 7/101) (P = 0.477). Of the enterovirus genotypes identified, Echovirus 30 (9.9%, 10/101), Coxsackie virus B5 (7.9%, 8/101) and Enterovirus-D68 (6.9%, 7/101) were most prevalent. There was no difference in disease severity (SARI or ILI compared to controls) between the different enterovirus species (P = 0.167).We observed a high number of enterovirus genotypes in patients with respiratory illness and in controls from South Africa with no disease association of EV species with disease severity. PMID:28574589

Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia.

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Ho, Shiaw-Hooi; Ng, Kee-Peng; Kaur, Harvinder; Goh, Khean-Lee

2015-06-01

Genotypes of hepatitis C virus (HCV) are distributed differently across the world. There is a paucity of such data in a multi-ethnic Asian population like Malaysia. The objectives of this study were to determine the distribution of HCV genotypes between major ethnic groups and to ascertain their association with basic demographic variables like age and gender. This was a cross-sectional prospective study conducted from September 2007 to September 2013. Consecutive patients who were detected to have anti-HCV antibodies in the University of Malaya Medical Centre were included and tested for the presence of HCV RNA using Roche Cobas Amplicor Analyzer and HCV genotype using Roche single Linear Array HCV Genotyping strip. Five hundred and ninety-six subjects were found to have positive anti-HCV antibodies during this period of time. However, only 396 (66.4%) were HCV RNA positive and included in the final analysis. Our results showed that HCV genotype 3 was the predominant genotype with overall frequency of 61.9% followed by genotypes 1 (35.9%), 2 (1.8%) and 6 (0.5%). There was a slightly higher prevalence of HCV genotype 3 among the Malays when compared to the Chinese (P=0.043). No other statistical significant differences were observed in the distribution of HCV genotypes among the major ethnic groups. There was also no association between the predominant genotypes and basic demographic variables. In a multi-ethnic Asian society in Malaysia, genotype 3 is the predominant genotype among all the major ethnic groups with genotype 1 as the second commonest genotype. Both genotypes 2 and 6 are uncommon. Neither genotype 4 nor 5 was detected. There is no identification of HCV genotype according to ethnic origin, age and gender.

Hepatitis C virus genotypes: A plausible association with viral loads

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Salma Ghulam Nabi

2013-01-01

Full Text Available Background and Aim: The basic aim of this study was to find out the association of genotypes with host age, gender and viral load. Material and Methods: The present study was conducted at Social Security Hospital, Pakistan. This study included 320 patients with chronic hepatitis C virus (HCV infection who were referred to the hospital between November 2011 and July 2012. HCV viral detection and genotyping was performed and the association was seen between genotypes and host age, gender and viral load. Results : The analysis revealed the presence of genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b + 3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV ribonucleic acid (RNA positive patients. The genotype 3a was observed in 124 (82.12% patients, 3b was found in 21 (13.91%, 1a was seen in 2 (1.32%, 1b in 1 (0.66%, mixed infection with 1b + 3a in 1 (0.66%, 1b + 3b in 1 (0.66% and 3a + 3b was also found in 1 (0.66% patient. Viral load quantification was carried out in all 151 HCV RNA positive patients and was compared between the various genotypes. The mean viral load in patients infected with genotype 1a was 2.75 × 10 6 , 1b 3.9 × 10 6 , 3a 2.65 × 10 6 , 3b 2.51 × 10 6 , 1b + 3a 3.4 × 106, 1b + 3b 2.7 × 106 and 3a + 3b 3.5 × 10 6 . An association between different types of genotypes and viral load was observed. Conclusion : Further studies should be carried out to determine the association of viral load with different genotypes so that sufficient data is available and can be used to determine the type and duration of therapy needed and predict disease outcome.

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer.

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Vreuls, C P H; Olde Damink, S W M; Koek, G H; Winstanley, A; Wisse, E; Cloots, R H E; van den Broek, M A J; Dejong, C H C; Bosman, F T; Driessen, A

2013-02-19

Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin. In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR. Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026). The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.

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.

The AA genotype of the regulatory BCL2 promoter polymorphism ( 938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients.

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Bachmann, Hagen S; Otterbach, Friedrich; Callies, Rainer; Nückel, Holger; Bau, Maja; Schmid, Kurt W; Siffert, Winfried; Kimmig, Rainer

2007-10-01

Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node-negative breast cancer patients, whereas no genotype effect could be observed in lymph node-positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer-related death in lymph node-negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node-positive but not of lymph node-negative breast cancer patients. In lymph node-negative cases, the (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2-expressing carcinomas (P = 0.006). These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node-negative breast cancer.

Helicobacter pylori cagA and iceA genotypes status and risk of peptic ulcer in Saudi patients

International Nuclear Information System (INIS)

Momenah, Aiman M.; Tayeb, Mohammad T.

2007-01-01

Objective was to determine the prevalence of cagA+ and iceA genotypes among Helicobacter pylori (H. pylori) isolates from a group of Saudi patients with gastric complaints, and to find out any significant correlation between these strains and severe gastric clinical outcomes such as peptic ulcer and gastric cancer in Saudi population. A total of 1104 gastric biopsies from 368 patients who presented with symptoms suggestive of chronic gastritis, peptic ulcer disease, or gastric carcinoma were taken from the main hospitals in the Western region of Saudi Arabia from July 2004 to July 2005. We cultured the samples for H. pylori and a polymerase chain reaction was carried out to check for the presence or absence of cagA gene and the status of iceA genotypes. Among the 368 suspected patients to be infected with H. pylori by means of clinical features and endoscopic findings; 103 (28%) were positive using culture technique. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (p=0.0001). Furthermore, this study revealed that 100% of ulcer cases were infected with iceA1 with a statistically significant correlation (p=0.0001), while 94.6% of gastritis and 90.9% of normal were infected with iceA2 (p=0.0001). Moreover cagA+/iceA1 combined genotypes was statistically correlated with peptic ulcer (100%) but not cagA-/iceA1 (0%; p=0.0001).Certain H. pylori genotypes were more virulent than others. Multiple clinical implications based on these finding might be studied further.(author)

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype

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A. Hannemann

2015-11-01

Full Text Available Sickle cell disease (SCD in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

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Renzhi Wang

2016-09-01

Full Text Available Adrenocorticotrophin (ACTH-secreting pituitary adenoma, also known as Cushing disease (CD, is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT. We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1, collagen type I α 1 chain (COL1A1, 5′-nucleotidase ecto (NT5E, HtrA serine peptidase 1 (HTRA1 and angiopoietin 1 (ANGPT1 and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

Lessons learned obtaining informed consent in research with vulnerable populations in community health center settings

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Riden Heather E

2012-11-01

Full Text Available Abstract Background To improve equity in access to medical research, successful strategies are needed to recruit diverse populations. Here, we examine experiences of community health center (CHC staff who guided an informed consent process to overcome recruitment barriers in a medical record review study. Methods We conducted ten semi-structured interviews with CHC staff members. Interviews were audiotaped, transcribed, and structurally and thematically coded. We used NVivo, an ethnographic data management software program, to analyze themes related to recruitment challenges. Results CHC interviewees reported that a key challenge to recruitment included the difficult balance between institutional review board (IRB requirements for informed consent, and conveying an appropriate level of risk to patients. CHC staff perceived that the requirements of IRB certification itself posed a barrier to allowing diverse staff to participate in recruitment efforts. A key barrier to recruitment also included the lack of updated contact information on CHC patients. CHC interviewees reported that the successes they experienced reflected an alignment between study aims and CHC goals, and trusted relationships between CHCs and staff and the patients they recruited. Conclusions Making IRB training more accessible to CHC-based staff, improving consent form clarity for participants, and developing processes for routinely updating patient information would greatly lower recruitment barriers for diverse populations in health services research.

Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China.

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Li, Xiaodong; Liu, Yan; Xin, Shaojie; Ji, Dong; You, Shaoli; Hu, Jinhua; Zhao, Jun; Wu, Jingjing; Liao, Hao; Zhang, Xin-Xin; Xu, Dongping

2017-06-01

The study aimed to investigate the association of prevalent genotypes in China (HBV/C and HBV/B) with HBV drug-resistant mutations. A total of 13,847 nucleos(t)ide analogue (NA)-treated patients with chronic HBV infection from North China were enrolled. HBV genotypes and resistant mutations were determined by direct sequencing and confirmed by clonal sequencing if necessary. HBV/B, HBV/C, and HBV/D occupied 14.3%, 84.9%, and 0.8% across the study population, respectively. NA usage had no significant difference between HBV/B- and HBV/C-infected patients. Lamivudine-resistant mutations were more frequently detected in HBV/C-infected patients, compared with HBV/B-infected patients (31.67% vs. 25.26%, p M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01). Multidrug-resistant mutations (defined as coexistence of mutation to nucleoside and nucleotide analogues) were detected in 104 patients. HBV/C-infected patients had a higher detection rate of multidrug-resistant mutation than HBV/B-infected patients (0.83% vs. 0.35%, p < 0.05). The study for the first time clarified that HBV/C-infected patients had a higher risk to develop multidrug-resistant mutations, compared with HBV/B-infected patients; and HBV/C- and HBV/B-infected patients had different inclinations in the ETV-resistant mutational pattern.

Hepatitis B virus prevalence, risk factors and genotype distribution in HIV infected patients from West Java, Indonesia.

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Fibriani, Azzania; Wisaksana, Rudi; Alisjahbana, Bachti; Indrati, Agnes; Schutten, Martin; van Crevel, Reinout; van der Ven, Andre; Boucher, Charles A B

2014-04-01

Indonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden. The objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia. A cross sectional study was conducted among a cohort of HIV infected patients in 2008. Demographic and disease related variables were compared between HBV negative and positive patients. Logistic regression was applied to determine risk factors for HBV co-infection. HBV and HIV genotyping was performed in co-infected patients. Of 636 HIV-infected patients, the rate of HBV co-infection was 7%. The proportion of males was higher in HBV/HIV co-infected patients than in HIV mono-infected patients (93% vs. 72%, P=0.001). A history of injecting drug use (IDU), but not tattooing, was associated with HBV co-infection [P=0.035 OR 2.41 (95% CI 1.06-5.47)]. In the HIV and HBV treatment naive patients, CD4 cells counts Java. However, an increased prevalence was observed in men with a history of IDU, underlining the need for routine HBV screening and monitoring. Copyright © 2014 Elsevier B.V. All rights reserved.

5′ UTR and NS5B-based genotyping of hepatitis C virus in patients from Damietta governorate, Egypt

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Radwa R. El-Tahan

2018-03-01

Full Text Available Chronic hepatitis C virus (HCV infection is a main health problem in Egypt causing high rates of mortalities. Egypt has the highest HCV prevalence in the world, with specific HCV subtypes epidemic and circulating extensively in the country. Different antiviral therapy protocols have been implemented for treating Egyptian HCV patients. Due to the limited data about HCV in Egypt, this study aimed to genotype HCV strains circulating in the Nile Delta Damietta governorate and to investigate the variation in the nonstructural 5B (NS5B region targeted by the newly approved antiviral drugs. Thirty HCV samples from treatment-naïve patients were genotyped by restriction fragment length polymorphism. Some samples were genotyped by direct sequencing of their 5′ untranslated region (UTR and NS5B regions. Phylogenetic analysis was also performed on the sequences of their NS5B regions. Fourteen new sequences have been deposited in the GenBank database. Results showed that subtype 4a was prevalent in addition to subtype 1g. None of the previously reported NS5B substitutions were detected in the sequenced isolates from treatment-naïve patients, which may be a good predictor for efficient treatment of HCV Egyptian patients with Sofosbuvir. Further studies on Sofosbuvir treated-HCV Egyptian patients are required to investigate whether any NS5B substitutions can confer resistance to treatment.

Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis

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Sperl J

2017-06-01

Full Text Available Jan Sperl,1 Sona Frankova,1 Miluse Kreidlova,2 Dusan Merta,3 Monika Tothova,4 Julius Spicak1 1Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 2Institute of Medical Biochemistry and Laboratory Medicine, General University Hospital, Charles University, 3Department of Anesthesiology, Resuscitation and Intensive Care, Institute for Clinical and Experimental Medicine, 4Dialysis Center Motol, Fresenius Medical Care, Prague, Czech Republic Abstract: Chronic hepatitis C virus infection (HCV has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF and daclatasvir (DCV represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25–53 years with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100% achieved sustained virological response, including two with cirrhosis and two with HCV RNA >6,000,000 IU

[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.

The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction

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Christoffersen, Dorte J; Damkier, Per; Feddersen, Søren

2016-01-01

Sudden death due to acute intoxication occurs frequently in patients with opioid addiction (OA). In order to examine if certain genotypes were associated with this, we examined the frequencies of 29 SNPs located in candidate genes related to opioid pharmacology: ABCB1, OPRM1, UGT2B7, CYP3A5, CYP2B6...... and fatal poisoning in OA is confirmed, then it may be possible at least in theory to personalize prevention of sudden death in this patient group. This article is protected by copyright. All rights reserved....

ENDOTHELIUM LESION MARKERS AND THROMBOCYTE AGGREGATION IN CHRONIC HEPATITIS AND HEPATIC CIRRHOSIS

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A. P. Shchekotova

2012-01-01

Full Text Available Aim — to estimate endothelium lesion, quantity and thrombocyte aggregation function correlation in viral chronic hepatitis C (CHC and hepatic cirrhosis (HC.Materials and methods. 50 CHC patients and 28 HC patients were examined. Using IFA method the total nitric oxide, endothelin‑1, vasculoendothelial growth factor levels, Willebrand factor (vWF activity were investigated, blood plasma desquamated endotheliocyte (DEC number was calculated with Hladovec method, 1978, thrombocyte aggregation (TA with ADP, collagen, ristocetine was determined.Results. DEC and vWF demonstrated correlation in CHC (p = 0.014 and HC (p = 0.000004. In HC patients reliable correlation of all the investigated indices of endothelium lesion with the thrombocyte number and TA was detected, but in CHC patients no correlations were revealed. Thus, significant elevation of TA with ristocetine was noted only in CHC. Decrease in thrombocyte amount among CHC patients and,especially in HC, and heightened vWF activity could change true TA indices. The corrected TA, whose indices in hepatic diseases significantlyincreased, was calculated taking into account the correction factor vWF / thrombocytes that in CHC did not differ from that of healthy patients and in HC was essentially higher.Conclusion. Endothelium dysfunction markers in CH and HC demonstrate correlation with thrombocyte reduction and TA elevation. Determinationof corrected TA permits to reveal disturbances of thrombocyte hemostasis in the form of elevated aggregation in all CHC and HC patients.

Insulin Resistance and Hyperinsulinemia in Patients with Chronic Liver Disease and Hepatocellular Carcinoma

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Valter Donadon

2009-01-01

Full Text Available Objectives To investigate the role of insulin resistance (IR and insulin plasma levels (IRI in patients with chronic liver disease (CLD and hepatocellular carcinoma (HCC. Methods We recruited the following patients: 125 with HCC, 128 with liver cirrhosis (LC and 133 with chronic hepatitis C (CHC. IR was assessed by the HOMA-IR method. To define IR and hyperinsulinemia we selected as a cut-off level, the value of the 80th percentile for HOMA-IR (2.72 and IRI (11.18 in 113 healthy subjects. Results The mean levels of HOMA-IR and IRI increase progressively among CHC (2.7 ± 2.9 and 11.5 ± 10.5, respectively, LC (5.4 ± 4.5 and 17.6 ± 11.2 and HCC (6.4 ± 9.8 and 18.2 ± 18.8. In the upper quintiles for HOMA-IR and IRI, the frequency of patients in the LC and HCC groups was twice as much in CHC cases. HCC with DM2 have the greatest percentage above the 80th percentile of HOMA-IR, their quintiles distribution is inverted and HOMA-IR mean values are significantly higher in comparison with HCC without DM2 cases. Discussion Our study shows that the association between IR and CLD begins in the early stages of liver fibrosis. DM2 increases HOMA-IR and IRI mean levels in HCC patients and these metabolic factors could play a major role in the link between diabetes mellitus and hepatocarcinoma.

Patients with chronic hepatitis type C and interferon-alpha-induced hyperthyroidism in two-years clinical follow-up.

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Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Magorzata; Wasko, Ryszard; Czepczynski, Rafal; Szczepanek-Parulska, Ewelina; Waligorska-Stachura, Joanna; Kurdybacha, Peter; Bereszynska, Iwona; Florek, Ewa; Stangierski, Adam; Zdanowska, Joanna; Nikisch, Elżbieta; Sowinski, Jerzy; Ruchala, Marek

2013-01-01

Interferon-α (IFN-α) is a gold standard in the therapy of viral chronic hepatitis type C (CHC). However, such treatment might lead to thyroid dysfunction. Patients usually present hypothyroidism, but rarely also hyperthyroidism may develop. The aim of the study is to present two-year clinical follow-up of patients with CHC and IFN-α-induced hyperthyroidism (IIH), with special regard to the methods and efficacy of the therapy. A group of 106 patients with CHC and IIH were analyzed. Subjects were divided into two groups according to etiology: group 1, with Graves' disease (GD) and group 2, with Hashitoxicosis (HT). The diagnosis of GD and HT was based on: clinical signs of hyperthyroidism, hormonal profile (TSH, fT4, fT3), level of thyroid autoantibodies (Tg-Abs, TPO-Abs, TSHRAbs). Treatment of hyperthyroidism was monitored by repeated clinical assessment and laboratory tests. RESULST: 28 patients (26 with GD of which 5 exhibited mild orbitopathy and 2 with HT) were treated with radioiodine [the average dose of was 17 mCi [668 MBq]. In adition 78 out of 80 patients with HT mostly β-blocker therapy was successful (transient hyperthyroidism). At the end of the observation period, in group 1 remission was achieved in 17 (65.4%) cases, 6 (23.1%) patients showed hypothyroidism and 3 (11.5%) presented recurrence of hyperthyroidism. Most patients with IIH present Hashitoxicosis, while a minority of them develop Graves' disease. In a majority of patients with HT spontaneous remission of disease occurs. In patients with long-term hyperthyroidism, radioiodine therapy is an effective and well-tolerated.

 Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection.

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Lieveld, Faydra I; Swaans, Niels; Newsum, Astrid M; Ho, Cynthia K Y; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T M; Arends, Joop E; Hoepelman, Andy I M; Wensing, Anne M J; Siersema, Peter D; van Erpecum, Karel J; Boland, Greet J

2016-01-01

 Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses. In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.

Hepatitis C virus genotypes in Myanmar.

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Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi

2016-07-21

Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined.

Phylogenetic analysis reveals two genotypes of the emerging fungus Mucor indicus, an opportunistic human pathogen in immunocompromised patients.

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Taj-Aldeen, Saad J; Almaslamani, Muna; Theelen, Bart; Boekhout, Teun

2017-07-12

Mucormycosis is a rare fungal infection caused by Mucor indicus. Phylogenetic analysis of many M. indicus isolates, mainly sampled from different clinical and environmental specimens collected worldwide, revealed two genotypes, I and II, based on ITS and D1/D2 LSU rDNA sequences. A retrospective review of the literature revealed 13 cases. Eight (76.9%) patients had disseminated infections, and the overall mortality rate was 30.7%. A pulmonary infection caused by M. indicus genotype I in a liver transplant recipient was disseminated to include the skin and was successfully treated with liposomal amphotericin B and aggressive surgery. M. indicus can infect a wide variety of patients with no real preference for the site of infection. We concluded that M. indicus has emerged as a significant cause of invasive mycosis in severely immunocompromised patients worldwide. Early diagnosis and initiation of appropriate therapy could enhance survival in these immunocompromised patient populations.

Long-term hormonal contraceptive use is associated with a reversible suppression of antral follicle count and a break from hormonal contraception may improve oocyte yield.

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Letourneau, Joseph M; Cakmak, Hakan; Quinn, Molly; Sinha, Nikita; I Cedars, Marcelle; Rosen, Mitchell P

2017-09-01

Unlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC). This is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used. Seven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P women present for FP on CHC, AFC may be suppressed. A CHC break of several months is associated with an increase in AFC and a potential improvement in overall egg yield.

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

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Gage, Brian F; Bass, Anne R; Lin, Hannah; Woller, Scott C; Stevens, Scott M; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J Philip; McMillin, Gwendolyn A; Pendleton, Robert C; Jaffer, Amir K; King, Cristi R; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M; Hyun, Gina; Anderson, Jeffrey L; Hollomon, Wesley; Barrack, Robert L; Nunley, Ryan M; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S

2017-09-26

Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. To determine whether genotype-guided dosing improves the safety of warfarin initiation. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0

Frequency and genotype of human parvovirus B19 among Iranian patients infected with HIV.

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Azadmanesh, Kayhan; Mohraz, Minoo; Kazemimanesh, Monireh; Aghakhani, Arezoo; Foroughi, Maryam; Banifazl, Mohammad; Eslamifar, Ali; Ramezani, Amitis

2015-07-01

The human parvovirus B19 (B19) usually causes a subclinical infection in immunocompetent individuals. Whereas immunocompromised individuals such as patients infected with HIV are at risk of persistent anemia due to B19 infection. Only few studies have been carried out on distribution and molecular epidemiology of B19 in Iran. We aimed to determine the frequency and genotype of B19 among Iranian patients infected with HIV. We conducted a survey on 99 HIV patients and 64 healthy controls. IgG and IgM antibodies against B19 were detected by ELISA and B19 DNA was assessed by nested PCR. PCR products were subjected to direct sequencing and classified after phylogenetic analysis. The prevalence of B19 immunoglobulin was 11.1% for IgG and 1% for IgM. B19 DNA was detected in 13.1% of cases. The prevalence of B19 IgG, IgM, and DNA in control group was 25%, 1.6%, and 9.4%, respectively. B19 IgG was significantly lower in HIV group than in normal controls. There was no significant difference regarding anemia between cases and controls. All sequenced B19 isolates belonged to genotype 1A with low genetic diversity. Our findings indicated that in the HAART era, the importance of B19 infections in HIV patients may be limited whereas persistent B19 viremia in the circulation of healthy controls raises a potential concern in blood donations. © 2015 Wiley Periodicals, Inc.

NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B.

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Morsica, Giulia; Andolina, Andrea; Merli, Marco; Messina, Emanuela; Hasson, Hamid; Lazzarin, Adriano; Uberti-Foppa, Caterina; Bagaglio, Sabrina

2017-08-01

The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.

Risk of new tumors in von Hippel-Lindau patients depends on age and genotype

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Binderup, Marie Louise Mølgaard; Budtz-Jørgensen, Esben; Bisgaard, Søs Marie Luise

2016-01-01

PURPOSE: The von Hippel-Lindau (vHL) phenotype is variable, which complicates genetic counseling and surveillance. We describe how the rate of new tumor development varies through the lifetimes of vHL patients and how it is influenced by age and genotype. METHODS: In a national cohort study, we i...... 02 April 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.44....

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections

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Dalgard, Olav; Weiland, Ola; Noraberg, Geir

2017-01-01

BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting...... in Scandinavia. METHODS: Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography...... was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). CONCLUSION: We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver...

A new trend of genotype distribution of hepatitis B virus infection in southeast China (Fujian), 2006-2013.

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Wei, D H; Liu, H Z; Huang, A M; Liu, X L; Liu, J F

2015-10-01

HBV genotypes have specific geographical distributions and can serve as epidemiological markers. Accumulated data have shown that the major HBV genotypes in China are B and C. Here, the HBV genotypes were examined from 6817 blood samples, which were collected from patients with chronic HBV infection in Fujian Province during 2006-2013; genotype B was identified in 3384 patients (49·6%), while genotype C was identified in 3430 patients (50·3%). The percentage of patients infected with genotype C gradually increased with age from 39·5% (patients aged 50 years), reaching a peak of 67·3% in the 45-50 years age group. These results clearly demonstrate that the genotype distribution of HBV in Fujian Province has significantly changed in recent years with almost equal numbers of genotype B and genotype C infections existing in the entire patient population, while higher incidence of genotype C infection exists in older patients, but genotype B is no longer dominant in the Fujian area as previously reported.

NOD2/CARD15 Gene Polymorphisms in Crohn's Disease: A Genotype-Phenotype Analysis in Danish and Portuguese Patients and Controls

DEFF Research Database (Denmark)

Vind, Ida; Vieira, A; Hougs, L

2005-01-01

to a healthy background population and to compare genotype-phenotype relations in the two countries. METHODS: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were...... recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. RESULTS: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates...... in Danish patients were significantly different (p=0.02) compared with Danish controls, no difference (p=0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p=0.03) using...

Molecular diversity in irregular or refugee immigrant patients with HBV-genotype-E infection living in the metropolitan area of Naples.

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Sagnelli, Caterina; Ciccozzi, Massimo; Coppola, Nicola; Minichini, Carmine; Lo Presti, Alessandra; Starace, Mario; Alessio, Loredana; Macera, Margherita; Cella, Eleonora; Gualdieri, Luciano; Caprio, Nunzio; Pasquale, Giuseppe; Sagnelli, Evangelista

2017-06-01

In a recent testing in the metropolitan area of Naples, Italy, on 945 irregular immigrants or refugees, 87 HBsAg chronic carriers were identified, 53 of whom were infected by HBV-genotype E. The aim of the present study was to identify the genetic diversity of HBV-genotype E in these 53 immigrants. The 53 immigrant patients with HBV-genotype-E infection were born in Africa, central or eastern Asia, eastern Europe or Latin America. These patients had been seen for a clinical consultation at one of the four first-level units from January 2012 to 2013. The first dataset contained 53 HBV-S gene isolates plus 128 genotype/subgenotype specific reference sequences downloaded from the National Center for Biotechnology Information. The second dataset, comprising the 53 HBV-S gene isolates, previously classified as HBV-genotype E, was used to perform the time-scaled phylogeny reconstruction using a Bayesian approach. Phylogenetic analysis showed that all 53 HBV-S isolates belonged to HBV-genotype E. Bayes factor analysis showed that the relaxed clock exponential growth model fitted the data significantly better than the other models. The time-scaled Bayesian phylogenetic tree of the second dataset showed that the root of the tree dated back to the year 1990 (95% HPD:1984-2000). Four statistically supported clusters were identified. Cluster A dated back to 2012 (95% HPD:1997-2012); cluster B dated back to 2008 (95% HPD:2001-2015); cluster C to 2006 (95% HPD:1999-2013); cluster D to 2004 (95% HPD:1998-2011). This study disclosed the genetic evolution and phylogenesis in a group of HBV-genotype-E-infected immigrants. J. Med. Virol. 89:1015-1024, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Impact of HBV genotype and mutations on HBV DNA and qHBsAg levels in patients with HBeAg-negative chronic HBV infection.

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Kuhnhenn, L; Jiang, B; Kubesch, A; Vermehren, J; Knop, V; Susser, S; Dietz, J; Carra, G; Finkelmeier, F; Grammatikos, G; Zeuzem, S; Sarrazin, C; Hildt, E; Peiffer, K-H

2018-04-10

HBV DNA and quantitative (q)HBsAg levels as prognostic markers for HBV-related disease are mostly validated in Asia and their significance in Western populations is uncertain. To analyse the impact of the HBV genotype and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV DNA and qHBsAg levels. HBV DNA and qHBsAg serum levels of 465 patients with HBeAg-negative chronic HBV infection were correlated with the HBV genotype and mutations in PC, BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HBsAg release in cell culture. While no impact of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to 1.4 log among the genotypes (P HBV DNA levels (P HBV genome harbouring a preS deletion. In contrast, a perinuclear HBsAg accumulation was detected for the PC and BCP-variants, reflecting an impaired HBsAg release. qHBsAg serum levels depend on the HBV genotype and together with HBV DNA levels on frequent mutations in PC, BCP and preS in HBeAg-negative patients. qHBsAg cut-offs when used as prognostic markers require genotype-dependent validation. © 2018 John Wiley & Sons Ltd.

Prevalence of fimA genotypes of Porphyromonas gingivalis in adolescent orthodontic patients.

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Shuang Pan

Full Text Available The placement of fixed orthodontic appliances may alter the composition of oral microbiota and has the potential risk of periodontal complication. Porphyromonas gingivalis fimbriae play a critical role in colonization of P. gingivalis in subgingival regions. In this study, we investigated the association between the prevalence of P. gingivalis-specific fimA genotypes and periodontal health status in adolescent orthodontic patients, to identify the pathogencity of P. gingivalis during orthodontic therapy.Sixty-one adolescent orthodontic patients were enrolled in the case group, while the control group consisted of 56 periodontally healthy adolescents. At baseline (T0, clinical parameter (gingival index was tested, and subgingival plaque samples were obtained from the lower incisors. The incidences of P. gingivalis and fimA genotypes were detected by polymerase chain reaction. All parameters were reassessed after 1 month (T1, 2 months (T2, 3 months (T3, and 6 months (T4 in the case group and then compared with those of the controls.Both microbiological and clinical parameters from orthodontic patients started to increase after placement of fixed appliances. Maximum values were reached at 3 months after placement and followed by their decreases at six months. However, the microbiological and clinical parameters in the case group were significantly higher than those of the control group. The GI of fimA II, IV-positive samples was significantly higher than that of negative samples.P. gingivalis carrying fimA II or IV was closely related to orthodontic gingivitis. In addition, proper oral hygiene control could lead to little increase in dental plaque accumulation, and exert a beneficial effect to periodontal tissues.

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.

Nonresponse to 18-month Lamivudine Monotherapy in Chronic Hepatitis B Patients with Dual Genotype B and C Infection and Acute Exacerbation

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Ming-Jen Sheu

2006-01-01

Full Text Available Molecular epidemiologic studies have indicated the possible existence of mixed infection of different hepatitis B virus (HBV genotypes in chronic hepatitis B (CH-B carriers, but the effect of dual HBV genotype B and C infection on the efficacy of lamivudine therapy remains unclear. We report four CH-B patients with dual HBV genotype B and C infection and acute exacerbation who received lamivudine monotherapy for about 18 months. None of them had achieved a sustained response at the end of the 18-month trial of treatment.

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 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.

A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients.

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Lee, S-Y; Masaoka, T; Han, H S; Matsuzaki, J; Hong, M J; Fukuhara, S; Choi, H S; Suzuki, H

2016-09-01

Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness. © 2016 John Wiley & Sons Ltd.

Prevalence of Porphyromonas gingivalis Four rag Locus Genotypes in Patients of Orthodontic Gingivitis and Periodontitis

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Liu, Yi; Zhang, Yujie; Wang, Lili; Guo, Yang; Xiao, Shuiqing

2013-01-01

Porphyromonas gingivalis is considered as a major etiological agent in periodontal diseases and implied to result in gingival inflammation under orthodontic appliance. rag locus is a pathogenicity island found in Porphyromonas gingivalis. Four rag locus variants are different in pathogenicity of Porphyromonas gingivalis. Moreover, there are different racial and geographic differences in distribution of rag locus genotypes. In this study, we assessed the prevalence of Porphyromonas gingivalis and rag locus genotypes in 102 gingival crevicular fluid samples from 57 cases of gingivitis patients with orthodontic appliances, 25 cases of periodontitis patients and 20 cases of periodontally healthy people through a 16S rRNA-based PCR and a multiplex PCR. The correlations between Porphyromona.gingivalis/rag locus and clinical indices were analyzed. The prevalence of Porphyromonas gingivalis and rag locus genes in periodontitis group was the highest among three groups and higher in orthodontic gingivitis than healthy people (porthodontic gingivitis and mild-to-moderate periodontitis in Shandong. Porphyromonas.gingivalis carrying rag-1 has the strong virulence and could be associated with severe periodontitis. PMID:23593379

Therapeutic effects and adverse drug reactions are affected by icotinib exposure and CYP2C19 and EGFR genotypes in Chinese non-small cell lung cancer patients.

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Chen, Jia; Zheng, Xin; Liu, Dong-Yang; Zhao, Qian; Wu, Yi-Wen; Tan, Fen-Lai; Wang, Yin-Xiang; Jiang, Ji; Hu, Pei

2014-01-01

The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. 274 NSCLC patients who accepted 125 mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in 672 nd (4th week) and 1,680 th hours (10th week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

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Cheng Jun

2012-09-01

Full Text Available Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC. Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV infection. Level of low density lipoprotein receptor (LDL-R and activity of peroxisome proliferator-activated receptor (PPAR α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP, and formation of very low density lipoprotein (VLDL have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN, HMG CoA reductase (HMGCR, liver X receptor (LXR, acetyl-CoA carboxylase 1 (ACC1, hepatic CB (1 receptors, retinoid X receptor (RXR α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

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Steiger, S; Capodeanu-Nägler, A; Gershman, S N; Weddle, C B; Rapkin, J; Sakaluk, S K; Hunt, J

2015-12-01

Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

rs11613352 polymorphism (TT genotype) associates with a decrease of triglycerides and an increase of HDL in familial hypercholesterolemia patients.

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Aledo, Rosa; Padró, Teresa; Mata, Pedro; Alonso, Rodrigo; Badimon, Lina

2015-04-01

Recent genome-wide association studies have identified a locus on chromosome 12q13.3 associated with plasma levels of triglyceride and high-density lipoprotein cholesterol, with rs11613352 being the lead single nucleotide polymorphism in this genome-wide association study locus. The aim of the study is to investigate the involvement of rs11613352 in a population with high cardiovascular risk due to familial hypercholesterolemia. The single nucleotide polymorphism was genotyped by Taqman(®) assay in a cohort of 601 unrelated familial hypercholesterolemia patients and its association with plasma triglyceride and high-density lipoprotein cholesterol levels was analyzed by multivariate methods based on linear regression. Minimal allele frequency was 0.17 and genotype frequencies were 0.69, 0.27, and 0.04 for CC, CT, and TT genotypes, respectively. The polymorphism is associated in a recessive manner (TT genotype) with a decrease in triglyceride levels (P=.002) and with an increase in high-density lipoprotein cholesterol levels (P=.021) after adjusting by age and sex. The polymorphism rs11613352 may contribute to modulate the cardiovascular risk by modifying plasma lipid levels in familial hypercholesterolemia patients. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

High Risk Human Papilloma Virus Genotypes in Kurdistan Region in Patients with Vaginal Discharge.

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Hussein, Nawfal R; Balatay, Amer A; Assafi, Mahde S; AlMufty, Tamara Abdulezel

2016-01-01

The human papilloma virus (HPV) is considered as the major risk factor for the development of cervical cancer. This virus is of different genotypes and generally can be classified into high and low risk types. To determine the rate of high risk HPV genotypes in women with vaginal discharge and lower abdominal pain in Kurdistan region, Iraq. Cervical swabs were taken from 104 women. DNA was extracted and the polymerase chain reaction (PCR) technique was used to determine the presence of high risk genotypes. It was found that 13/104 (12.5%) of the samples were positive for high risk HPV genotypes. Amongst those who were positive, 4/13 (30.7%) were typed as genotype 16 and 7/13 (53.8%) showed mixed genotyping. On the other hand, genotypes 53 and 56 were found in only one sample each. High risk HPV genotypes are not uncommon and further community based study is needed to determine the prevalence of HPV and its genotypes and plan for prevention of infection.

Genotyping panel for assessing response to cancer chemotherapy

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Hampel Heather

2008-06-01

Full Text Available Abstract Background Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc, and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis. The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes. Methods We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs in 160 candidate genes implicated in response to anticancer chemotherapy. Results The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94% produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TAnTAA repeat polymorphism. Conclusion This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.

New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients

Institute of Scientific and Technical Information of China (English)

Feng Lin; Zhi-Qiang Wang; Min-Ting Lin; Shen-Xing Murong; Ning Wang

2015-01-01

Background:Facioscapulohumeral muscular dystrophy (FSHD),a common autosomal dominant muscular disorder,is caused by contraction of the D4Z4 repeats on 4q35.The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject.We aimed to refine this correlation in order to provide new information for genetic counseling.Methods:Here,a cohort of 136 Chinese families including 178 affected individuals and 137 unaffected members were investigated.Genetic analyses were performed using the pl3E-11,4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting.A 10-grade FSHD clinical severity scale was adopted for clinical assessment.The genotype-phenotype correlation was established by linear regression analyses.Results:We observed a roughly inversed correlation between the short EcoRI fragment size and age-corrected clinical severity score in 154 symptomatic patients (P ＜ 0.05).Compared to male patients,a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment.A high incidence (19/42,45.2％) of asymptomatic (or minimally affected) carriers was found in familial members.Conclusions:Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation,a majority of phenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat,especial in female cases.Our results suggest that there are multi-factors synergistically modulating the phenotypic expression.

Frequency and Genotype of Human Parvovirus B19 among Iranian Hemodialysis and Peritoneal Dialysis Patients.

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Sharif, Alireza; Aghakhani, Arezoo; Velayati, Ali Akbar; Banifazl, Mohammad; Sharif, Mohammad Reza; Razeghi, Effat; Kheirkhah, Davood; Kazemimanesh, Monireh; Bavand, Anahita; Ramezani, Amitis

2016-01-01

The aim of this study was to evaluate the frequency and genotype of human parvovirus B19 and its relation with anemia among Iranian patients under dialysis. Fifty hemodialysis (HD) and 33 peritoneal dialysis (PD) patients were enrolled. B19 IgG and IgM antibodies were assessed by ELISA, and the presence of B19 DNA was evaluated by nested PCR. PCR products were sequenced directly and phylogenetic analysis was performed. In the HD group, the prevalence of B19 antibodies was 54% for IgG and 4% for IgM. B19 DNA was detected in 10% of the cases, and 10% showed B19 IgG and viremia simultaneously. In the PD group, the prevalence of B19 IgG and IgM was 57.6 and 0% respectively, whereas B19 DNA was found in 12.1% of the group. A total of 9.1% showed B19 IgG and viremia concurrently. There was no significant difference regarding anemia and B19 infection in either group. All B19 isolates were clustered in genotype 1A. Our findings indicate that B19 infection plays no role in leading chronic anemia in dialysis patients. However, persistent B19 viremia and the circulation of the same strains in dialysis patients may indicate a potential risk for the contamination of dialysis equipment and nosocomial spread of B19 infection within dialysis units. © 2017 S. Karger AG, Basel.

Beijing/W genotype Mycobacterium tuberculosis and drug resistance.

NARCIS (Netherlands)

Glynn, Judith R; Kremer, Kristin; Borgdorff, Martien W; Rodriguez, Mar Pujades; Soolingen, Dick van

2006-01-01

Beijing/W genotype Mycobacterium tuberculosis is widespread, may be increasing, and may have a predilection for drug resistance. Individual-level data on >29,000 patients from 49 studies in 35 countries were combined to assess the Beijing genotype's prevalence worldwide, trends over time and with

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

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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

Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

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Sibille, A.; Eng, C.M.; Kim, S.J.; Pastores, G. (Mount Sinai School of Medicine, New York, NY (United States)); Grabowski, G.A. (Mount Sinai School of Medicine, New York, NY (United States) Univ. of Cincinnati, OH (United States))

1993-06-01

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, and severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.

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

The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes

Science.gov (United States)

Piroozmand, Ahmad; Mostafavi Zadeh, Seyed Mostafa; Madani, Azita; Soleimani, Reza; Nedaeinia, Reza; Niakan, Mohammad; Avan, Amir; Manian, Mostafa; Moradi, Mohammad; Eftekhar, Zahra

2016-01-01

Background Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. Objectives The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. Materials and Methods Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. Results The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. Conclusions Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID:27279992

Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3.

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Abenavoli, Ludovico; Masarone, Mario; Peta, Valentina; Milic, Natasa; Kobyliak, Nazarii; Rouabhia, Samir; Persico, Marcello

2014-11-07

Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide. Non-alcoholic fatty liver disease and insulin resistance (IR) are the major determinants of fibrosis progression and response to antiviral therapy. The pathogenetic link between IR and chronic HCV infection is complex, and is associated with HCV genotype. Liver steatosis is the most common in the patients infected with genotype 3 virus, possibly due to direct effects of genotype 3 viral proteins. To the contrary, hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism, involving IR. In HCV genotype 3, liver steatosis correlates with viral load, reverts after reaching the sustained virologic response and reoccurs in the relapsers. A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

Anticipated outcomes from introduction of 5-HTTLPR genotyping for depressed patients

DEFF Research Database (Denmark)

Østergaard, Svetlana; Møldrup, C

2010-01-01

rates with genotyping at first sight do not appear to be superior to existing practice, i.e. without genotyping. It is anticipated that a combination of 5-HTTLPR testing with other genomic variables, which have yet to be determined, and compliance measurements can improve clinical outcomes in the future...

Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994-2009, a registry study.

Science.gov (United States)

Mundal, Liv; Veierød, Marit B; Halvorsen, Thomas; Holven, Kirsten B; Ose, Leiv; Iversen, Per Ole; Tell, Grethe S; Leren, Trond P; Retterstøl, Kjetil

2016-12-01

Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre-eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994-2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low.

Establishment of a novel two-probe real-time PCR for simultaneously quantification of hepatitis B virus DNA and distinguishing genotype B from non-B genotypes.

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Wang, Wei; Liang, Hongpin; Zeng, Yongbin; Lin, Jinpiao; Liu, Can; Jiang, Ling; Yang, Bin; Ou, Qishui

2014-11-01

Establishment of a simple, rapid and economical method for quantification and genotyping of hepatitis B virus (HBV) is of great importance for clinical diagnosis and treatment of chronic hepatitis B patients. We hereby aim to develop a novel two-probe real-time PCR for simultaneous quantification of HBV viral concentration and distinguishing genotype B from non-B genotypes. Conserved primers and TaqMan probes for genotype B and non-B genotypes were designed. The linear range, detection sensitivity, specificity and repeatability of the method were assessed. 539 serum samples from HBV-infected patients were assayed, and the results were compared with commercial HBV quantification and HBV genotyping kits. The detection sensitivity of the two-probe real-time PCR was 500IU/ml; the linear range was 10(3)-10(9)IU/ml, and the intra-assay CVs and inter-assay CVs were between 0.84% and 2.80%. No cross-reaction was observed between genotypes B and non-B. Of the 539 detected samples, 509 samples were HBV DNA positive. The results showed that 54.0% (275/509) of the samples were genotype B, 39.5% (201/509) were genotype non-B and 6.5% (33/509) were mixed genotype. The coincidence rate between the method and a commercial HBV DNA genotyping kit was 95.9% (488/509, kappa=0.923, PDNA qPCR kit were achieved. A novel two-probe real-time PCR method for simultaneous quantification of HBV viral concentration and distinguishing genotype B from non-B genotypes was established. The assay was sensitive, specific and reproducible which can be applied to areas prevalent with HBV genotypes B and C, especially in China. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden.

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Lindström, Ida; Kjellin, Midori; Palanisamy, Navaneethan; Bondeson, Kåre; Wesslén, Lars; Lannergard, Anders; Lennerstrand, Johan

2015-08-01

The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naïve patients and such baseline resistance will potentially complicate future treatment strategies. A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naïve patients of HCV genotypes 1a, 1b, 2b and 3a. The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50,000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient. Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

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Amalia Lamana

Full Text Available BACKGROUND: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS: We studied 640 patients with early arthritis (76% women; median age, 52 years, recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28 as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044. Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162. After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS: Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

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Lamana, Amalia; Balsa, Alejandro; Rueda, Blanca; Ortiz, Ana M; Nuño, Laura; Miranda-Carus, Maria Eugenia; Gonzalez-Escribano, Maria F; Lopez-Nevot, Miguel A; Pascual-Salcedo, Dora; Martin, Javier; González-Álvaro, Isidoro

2012-01-01

The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA

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Tapiero-Rodriguez SM

2018-04-01

Full Text Available Sandra M Tapiero-Rodriguez,1 Johanna C Acosta Guio,1 Gloria Liliana Porras-Hurtado,2 Natalia García,3 Martha Solano,4 Harry Pachajoa,5 Harvy M Velasco1 1Universidad Nacional de Colombia, Departamento de morfología, Maestría de genética humana, Bogotá, 2Family Compensation Fund of Risaralda, Pereira, 3Faculty of Medicine, Manizales University, Manizales, 4Department of Neuropediatrics, Cardioinfantil Foundation, Bogotá, 5Centro de Investigaciones en Anomalías Congénitas y Enfermedades Raras, Universidad ICESI y Fundación Valle del Lili, Cali, Colombia Background: As mucopolysaccharidosis IVA (MPS IVA is the most frequent MPS in Colombia, this paper aims to describe its clinical and mutational characteristics in 32 diagnosed patients included in this study. Methods: Genotyping was completed by amplification and Sanger sequencing of the GALNS gene. The SWISS-model platform was used for bioinformatic analysis, and mutant proteins were generated by homology from the wild-type GALNS code 4FDI template from the Protein Data Bank (PDB database. Docking was performed using the GalNAc6S ligand (PubChem CID: 193456 by AutoDock Vina 1.0 and visualized in PyMOL and LigPlot+. Results: Eleven variants were identified, and one new pathogenic variant was described in the heterozygous state, which is consistent with genotype c. 319 G>T or p.Ala107Ser. The pathogenic variant c.901G>T or p.Gly301Cys was the most frequent mutation with 51.6% of alleles. Docking revealed affinity energy of −5.9 Kcal/mol between wild-type GALNS and the G6S ligand. Some changes were evidenced at the intermolecular interaction level, and affinity energy for each mutant decreased. Conclusion: Clinical variables and genotypic analysis were similar to those reported for other world populations. Genotypic data showed greater allelic heterogeneity than those previously reported. Bioinformatics tools showed differences in the binding interactions of mutant proteins with the G6S

Interaction of IFNL3 with insulin resistance, steatosis and lipid metabolism in chronic hepatitis C virus infection.

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Eslam, Mohammed; Booth, David R; George, Jacob; Ahlenstiel, Golo

2013-11-07

Metabolic changes are inextricably linked to chronic hepatitis C (CHC). Recently polymorphisms in the IFNL3 (IL28B) region have been shown to be strongly associated with spontaneous and treatment induced recovery from hepatitis C virus (HCV) infection. Further, circumstantial evidence suggests a link between IFNL3 single nucleotide polymorphisms and lipid metabolism, steatosis and insulin resistance in CHC. The emerging picture suggests that the responder genotypes of IFNL3 polymorphisms are associated with a higher serum lipid profile, and less frequent steatosis and insulin resistance. This review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression.

CC genotype of anti-apoptotic gene BCL-2 (-938 C/A) is an independent prognostic marker of unfavorable clinical outcome in patients with non-small-cell lung cancer.

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Javid, J; Mir, R; Mirza, M; Imtiyaz, A; Prasant, Y; Mariyam, Z; Julka, P K; Mohan, A; Lone, M; Ray, P C; Saxena, A

2015-04-01

B cell lymphoma 2 (BCL-2) gene is a well-known regulator of apoptosis and a key element in cancer development and progression. A regulatory (-938C>A, rs2279115) single-nucleotide polymorphism in the inhibitory P2 BCL-2 gene promoter generates significantly different BCL-2 promoter activities and has been associated with different clinical outcomes in various malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on the risk and survival of Indian patients suffering from NSCLC. A hospital-based case-control study of 155 age- and sex-matched patients diagnosed with NSCLC and 155 cancer-free controls was conducted and genotyped by performing PIRA-PCR to elucidate the putative association between clinical outcome and genotypes of BCL-2 (-938C>A, rs2279115). The association of the polymorphism with the survival of NSCLC patients was analyzed by Kaplan-Meier curves. In Indian NSCLC, patients increased risk of developing NSCLC was found to be associated with BCL-2 (-938) CC genotype, [OR 3.68 (1.92-6.79), RR 1.87 (1.35-2.57) and RD 31.03 (16.79-45.27) p 0.00006 for CC and OR 2.08 (1.18-3.66), RR 1.36 (1.08-1.71) and RD 17.74 (4.68-30.81) p 0.01 for AC genotype]. Patients homozygous for C allele exhibited a significant poor overall survival compared with patients displaying AC + CC or AC or AA genotype [median survival (months) 8 vs. 11 vs. 14 vs. 35.5 (p A) polymorphism. Genetic polymorphism in the inhibitory P2 promoter region of anti-apoptotic BCL-2 genes contributes to the risk of developing non-small-cell lung cancer in Indian population. BCL-2 (-938CC) genotype was an independent adverse prognostic factor for patients with NSCLC.

Neuregulin-1 genotypes and eye movements in schizophrenia

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Haraldsson, H.M.; Ettinger, U.; Magnusdottir, B.B.

2010-01-01

Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain...... dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls. Patients (N = 113) and controls (N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms...... findings of impaired AS and SPEM performance in schizophrenia patients (all P

Comparison of lipoprotein electrophoresis and apolipoprotein e genotyping in investigating dysbetalipoproteinemia

International Nuclear Information System (INIS)

Ahmed, F.; Kadiki, A.E.

2017-01-01

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia. (author)

Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.

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Ahmed, Farhan; El-Kadiki, Alia; Gibbons, Stephen

2017-06-01

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.

Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of Cerebrotendinous xanthomatosis.

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Taboada, María; Martínez, Diego; Pilo, Belén; Jiménez-Escrig, Adriano; Robinson, Peter N; Sobrido, María J

2012-07-31

Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms

Chronic hepatitis C presenting with a diagnosis of hepatocellular carcinoma

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Hallager, Sofie; Weis, Nina

2014-01-01

Chronic hepatitis C (CHC) affects around 16,000 individuals in Denmark of whom about 50% are diagnosed. In the presence of CHC and cirrhosis the annual risk of hepatocellular carcinoma (HCC) is 1-5%. We report on two patients who presented with disseminated HCC at the time of CHC diagnosis...

Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population.

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Auger, Julie; Baptiste, Amandine; Benabbad, Imane; Thierry, Gaëlle; Costa, Jean-Marc; Amouyal, Mélanie; Kottler, Marie-Laure; Leheup, Bruno; Touraine, Renaud; Schmitt, Sébastien; Lebrun, Marine; Cormier Daire, Valérie; Bonnefont, Jean-Paul; de Roux, Nicolas; Elie, Caroline; Rosilio, Myriam

2016-01-01

The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions. © 2016 S. Karger AG, Basel.

The presence of PAI-1 4G/5G and ACE DD genotypes increases the risk of early-stage AVF thrombosis in hemodialysis patients.

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Güngör, Yahya; Kayataş, Mansur; Yıldız, Gürsel; Özdemir, Öztürk; Candan, Ferhan

2011-01-01

In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, β-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x(2) = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

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.

Major Components of Metabolic Parameters and Nutritional Intakes in Different Genotypes of Adiponectin +276 G>T Gene Polymorphism in Non-Diabetes and Non-Alcoholic Iranian Fatty Liver Patients.

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Mohseni, Fatemeh; Moghbelinejad, Sahar; Najafipour, Reza

2017-01-01

Genetic and environmental factors are both involved in the etiology of Non-Alcoholic Fatty Liver Disease (NAFLD). Among the genetic factors, certain polymorphisms of adiponectin gene are associated with NAFLD. In the current study, we investigated the association between metabolic parameters with different genotypes of adiponectin +276 G>T polymorphism among the Iranian NAFLD patients, and the effect of nutritional intake with development of NAFLD. In this study, 75 patients with NAFLD and 76 healthy individuals were enrolled. Dietary intakes were assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Body Mass Index (BMI) and Waist to Hip Ratio (WHR) were calculated. Biochemical assays including FSG (Fasting Serum Glucose), liver enzymes, lipid profiles, Malondialdehyde, insulin resistance and Total Antioxidant Capacity (TAC) were measured after 12 hr fasting. Gene polymorphism study was done by using of sequencing method. Although, T allele frequency was more prevalent in patients with NAFLD than control, adiponectin +276 G>T polymorphism was not associated with risk of NAFLD. Among the metabolic parameters, TAC in TT genotype was significantly lower 1.44(0.69 to 2.81) p>0.05, AST in GT, GG genotypes, and ALT in all three genotypes were higher in NAFLD patients in compared to healthy subjects (pconsumption and vitamin E intake as compared to control group with the same genotype (pstudy, we showed the association of different genotypes of +276 G>T polymorphism in adiponectin gene with some metabolic parameters.

A case report of a patient carrying CYP2C9*3/4 genotype with extremely low warfarin dose requirement.

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Lee, Soo Youn; Nam, Myung Hyun; Kim, June Soo; Kim, Jong Won

2007-06-01

We report a case of intolerance to warfarin dosing due to impaired drug metabolism in a patient with CYP2C9*3/*4. A 73-yr-old woman with atrial fibrilation was taking warfarin. She attained a high prothrombin time international normalized ratio (INR) at the standard doses during the induction of anticoagulation and extremely low dose of warfarin (6.5 mg/week) was finally chosen to reach the target INR. Genotyping for CYP2C9 revealed that this patient had a genotype CYP2C9*3/*4. This is the first Korean compound heterozygote for CYP2C9*3 and *4. This case suggests the clinical usefulness of pharmacogenetic testing for individualized dosage adjustments of warfarin.

Risk factors for congenital hydrocephalus

DEFF Research Database (Denmark)

Munch, Tina Noergaard; Rasmussen, Marie-Louise Hee; Wohlfahrt, Jan

2014-01-01

. Furthermore, to identify the risk factors unique for isolated CHC as compared to syndromic CHC. METHODS: We established a cohort of all children born in Denmark between 1978 and 2008. Information on CHC and maternal medical diseases were obtained from the National Patient Discharge Register, maternal intake...... increased risk of isolated CHC compared to unexposed children (RR 2.52, 95% CI 1.47 to 4.29) (1.5/1000 born children). Risk factors also found for syndromic CHC were: Male gender, multiples and maternal diabetes. CONCLUSIONS: The higher risk for isolated CHC in first-born children as well as behavioural......-born children, we observed 1193 cases of isolated CHC (0.062/1000) born children. First-borns had an increased risk of isolated CHC compared to later-borns (1.32 95% CI 1.17 to 1.49) (0.72/1000 born children). First trimester exposure to maternal use of antidepressants was associated with a significantly...

The Hepatitis C treatment experience: Patients' perceptions of the facilitators of and barriers to uptake, adherence and completion.

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Sublette, Victoria A; Smith, Sian K; George, Jacob; McCaffery, Kirsten; Douglas, Mark W

2015-01-01

This study explores the perceptions of patients receiving treatment for Hepatitis C to determine what factors influence their decision to commence treatment, ability to maintain adherence and complete their treatment program. Semi-structured interview techniques were used in a qualitative study of 20 patients undergoing treatment for Chronic Hepatitis C (CHC). To explore patients' perceived barriers and facilitators of Hepatitis C treatment adherence and completion. Analysis of patient interviews identified four key themes: (1) motivations for commencing CHC treatment - fear of death and ridding themselves of stigma and shame; (2) the influential role of provider communication - patients reported that information and feedback that was personalised to their needs and lifestyles was the most effective for improving adherence to treatment; (3) facilitators of treatment adherence and completion - social, emotional and practical support improved adherence and completion, as did temporarily ceasing employment; (4) barriers to treatment adherence and completion - these included side effects, stigma, a complicated dosing schedule and limitations of the public healthcare system. To increase treatment adherence and completion rates, a patient-centred approach is required that addresses patients' social, practical, and emotional support needs and adaptive coping strategies.

Associated Factors for Metabolic Syndrome in the Older Adults with Chronic Virus Hepatitis in the Community.

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Yuan-Hung Kuo

Full Text Available This study was to evaluate the association between metabolic syndrome (MetS and chronic virus hepatitis elders in the community. Those subjects with positive hepatitis B surface antigen (HBsAg and/or anti-hepatitis C virus (anti-HCV screened in the community before were invited to this study and 451 responded. All participants underwent anthropometric measurements, blood tests, ultrasound and fibroscan examinations. The cut-off of liver stiffness measurement-liver cirrhosis (LSM-LC was 10 kPa for chronic hepatitis B (CHB patients and 12 kPa for chronic hepatitis C (CHC patients, respectively. Among 451 responders, 56 were excluded due to negative HBsAg or anti-HCV. Three hundreds and ninety-five subjects included 228 CHB patients, 156 CHC patients and 11 dual hepatitis patients, had a mean age of 62±12.6 years. Fifty-four (23.7% CHB patients coexisted with MetS whereas 40 (25.6% CHC patients also had MetS. Those patients with MetS had more LSM-LC cases than those without (20.4% vs 9.8%, p = 0.04 in CHB patients; 28.2% vs 13.5%, p = 0.037 in CHC patients, respectively. In multivariate logistic analysis, detectable viremia was reversely associated with MetS in CHB patients after adjustment for age, gender and body mass index (odds ratio (OR: 0.42; 95% confidence interval (CI: 0.18-0.99; p = 0.047. Regarding CHC patients, higher LSM level was the only factor contributed to MetS (OR: 1.1; 95% CI: 1.02-1.19; p = 0.012. In conclusion, elder CHB patients coexisted with MetS might experience an inactive virus replication but have an advanced liver fibrosis. In elder CHC patients, only higher LSM level was associated with MetS.

Plasminogen activator inhibitor-1 5G/5G genotype is associated with early spontaneous recanalization of the infarct-related artery in patients presenting with acute ST-elevation myocardial infarction.

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Cagliyan, Caglar E; Yuregir, Ozge O; Balli, Mehmet; Tekin, Kamuran; Akilli, Rabia E; Bozdogan, Sevcan T; Turkmen, Serdar; Deniz, Ali; Baykan, Oytun A; Aslan, Huseyin; Cayli, Murat

2013-05-01

We aimed to examine the association between plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism and early spontaneous recanalization in patients presenting with acute ST-elevation myocardial infarction. Patients admitted to our emergency department with ST-elevation myocardial infarction in the first 6 h of symptom onset were included. An immediate primary percutaneous coronary intervention was performed. Patients were grouped according to the initial patency of the infarct-related artery (IRA) as follows: total occlusion (TO) group [Thrombolysis in Myocardial Infarction (TIMI) 0-1 flow in the IRA], partial recanalization group (TIMI 2 flow in the IRA), and complete recanalization (CR) group (TIMI 3 flow in the IRA). PAI-1 4G/5G polymorphism was detected using the real-time PCR method. There were 107 patients in the TO group, 30 patients in the partial recanalization group, and 45 patients in the CR group. When we evaluated degrees of patency according to the PAI-1 genotype, TO of the IRA was the highest in patients with the PAI 4G/4G genotype (PAI-1 4G/4G: 66.7%, PAI-1 4G/5G: 65.9%, PAI-1 5G/5G: 40.4%) and CR of the IRA was the highest in patients with the PAI 5G/5G genotype (PAI-1 5G/5G: 38.5%, PAI-1 4G/5G: 19.8%, PAI-1 4G/4G: 17.9%). The distribution of genotypes in different degrees of patency of IRA was statistically significant (P=0.029). In logistic regression analysis, the PAI-1 5G/5G genotype was associated independently with the spontaneous CR of the IRA (odds ratio: 2.875, 95% confidence interval [1.059-7.086], P=0.038). Patients with the PAI-1 5G/5G genotype seem to be luckier than others in terms of early spontaneous recanalization of the IRA. Further prospective studies with large patient populations are required for more precise results.

HLA-G 14-bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

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Genre, J; Reginaldo, F P Santos; Andrade, J Marco de Leon; Lima, F P; da Camara, A V Coutinho; Donadi, E A; Crispim, J C

2016-01-01

H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection. © 2015 The Foundation for the Scandinavian Journal of Immunology.

Association between pre‐sarcopenia, sarcopenia, and bone mineral density in patients with chronic hepatitis C

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Bering, Tatiana; Diniz, Kiara G.D.; Coelho, Marta Paula P.; Vieira, Diego A.; Soares, Maria Marta S.; Kakehasi, Adriana M.; Correia, Maria Isabel T.D.; Teixeira, Rosângela; Queiroz, Dulciene M.M.; Rocha, Gifone A.

2018-01-01

Abstract Background Preserved skeletal muscle is essential for the maintenance of healthy bone. Loss of bone mineral density (BMD) and muscle strength, considered a predictor of BMD, have been demonstrated in patients with cirrhosis, but they are poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to evaluate the prevalence of low BMD and its association with body composition, muscle strength, and nutritional status in CHC. Methods One hundred and four subjects [mean age, 50.5 ± 11.3 years; 75.0% males; 67.3% non‐cirrhotic; and 32.7% with compensated cirrhosis] with CHC, prospectively, underwent scanning of the lean tissue, appendicular skeletal muscle mass (ASM), fat mass, lumbar spine, hip, femoral neck, and whole‐body BMD by dual‐energy X‐ray absorptiometry. Muscle strength was assessed by dynamometry. Sarcopenia was defined by the presence of both low, ASM/height2 (ASMI) and low muscle strength according to the European Working Group on Sarcopenia in Older People criteria. The cut‐off points for low ASMI and low muscle strength, for women and men, were  50 years, the T‐score of osteopenia is between −1.0 and −2.49 standard deviation (SD) below the young average value and of osteoporosis is ≥−2.5 SD below the young normal mean for men, and the Z‐score of low bone mass is ≤−2.0 SD below the expected range in men aged < 50 years and women in the menacme. Nutritional status evaluation was based on the Controlling Nutritional Status score. Results Low BMD, low muscle strength, pre‐sarcopenia, sarcopenia, and sarcopenic obesity were observed in 34.6% (36/104), 27.9% (29/104), 14.4% (15/104), 8.7% (9/104), and 3.8% (4/104) of the patients, respectively. ASMI was an independent predictor of BMD (P < 0.001). Sarcopenia was independently associated with bone mineral content (P = 0.02) and malnutrition (P = 0.01). In 88.9% of the sarcopenic patients and in all with sarcopenic obesity, BMI was normal

Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants.

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Lin, Chih-Lin; Kao, Jia-Horng

2017-06-01

Molecular epidemiologic studies reveal remarkable differences in the geographical distribution of hepatitis B virus (HBV) genotypes. The frequency of mutants among HBV genotypes also varies. The role of HBV genotypes/mutants in the pathogenesis of HBV infection and natural history of HBV infection has been extensively investigated. The distribution of HBV genotypes in acute hepatitis B patients reflects the predominant genotypes in a given geographic area. In chronic hepatitis B patients, genotype C and D have a higher frequency of basal core promoter A1762T/G1764A mutations than genotype A and B. HBV genotypes C, D and F carry a higher lifetime risk of cirrhosis and HCC development than genotype A and B. HBV pre-S/S gene mutations were associated with immune escape of hepatitis B immunoglobulin or vaccine-induced immunity. Mutations in the pre-S, core promoter and X regions correlate with an increased risk of cirrhosis and HCC. In summary, HBV genotypes and mutants are associated with the disease progression and long-term outcome of HBV infection. They may serve as viral genetic markers for risk stratification of chronic hepatitis B patients in clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

The preproghrelin 3056 TT genotype is associated with the feeling of hunger and low acylated ghrelin levels in Japanese patients with Helicobacter pylori-negative functional dyspepsia.

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Futagami, Seiji; Shimpuku, Mayumi; Kawagoe, Tetsuro; Izumi, Nikki; Ohishi, Noriko; Yamawaki, Hiroshi; Shindo, Tomotaka; Nagoya, Hiroyuki; Horie, Akane; Kodaka, Yasuhiro; Gudis, Katya; Itoh, Takashi; Sakamoto, Choitsu

2013-01-01

An impairment of gastric motility is strongly associated with the pathophysiology of functional dyspepsia (FD). Plasma ghrelin is one of the key molecules linked to gastric motility. Therefore, this study aimed to evaluate whether ghrelin (GHRL) gene polymorphisms are associated with clinical symptoms, the plasma ghrelin levels and gastric emptying in patients with FD as defined by the Rome III classification. We enrolled 74 Helicobacter pylori-negative patients presenting with typical symptoms of FD (epigastric pain syndrome (EPS), n=23; postprandial distress syndrome (PDS), n=51) and 102 healthy volunteers. Gastric motility was evaluated according to the Tmax value and T1/2 using the (13)C-acetate breath test. We used the Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine the depression status. The Arg51Gln(346G->A), preproghrelin3056T->C, Leu72Met(408C->A) and Gln90Leu(3412T->A) polymorphisms were analyzed in DNA in blood samples obtained from the enrolled subjects. Genotyping was performed using polymerase chain reaction. There was a significant relationship (p=0.048) between the preproghrelin 3056TT genotype and the serum levels of acylated ghrelin in the H. pylori-negative FD patients. The preproghrelin 3056TT genotype was significantly (p=0.047) associated with the feeling of hunger in the H. pylori-negative FD patients. The preproghrelin 3056TT genotype is significantly associated with the acylated ghrelin levels and the feeling of hunger in H. pylori-negative FD patients. Further studies are needed to clarify the association between the preproghrelin 3056TT genotype and lower plasma acylated ghrelin levels and the impact of this relationship on the feeling of hunger in H. pylori-negative FD patients.

The influence of 5-HTTLPR genotype on the association between the plasma concentration and therapeutic effect of paroxetine in patients with major depressive disorder.

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Tetsu Tomita

Full Text Available The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD can differ depending on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR genotype, and the effects of varying plasma concentrations of drugs can also vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes.Fifty-one patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale (MADRS was used to evaluate patients at 0, 1, 2, 4, and 6 weeks. The patients' paroxetine plasma concentrations at week 6 were measured using high-performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms (alleles S and L were analyzed using a polymerase chain reaction with specific primers. We divided the participants into two groups based on their L haplotype: the SS group and the SL and LL group. We performed single and multiple regression analyses to investigate the associations between MADRS improvement and paroxetine plasma concentrations or other covariates for each group.There were no significant differences between the two groups with regard to demographic or clinical data. In the SS group, the paroxetine plasma concentration was significantly negatively correlated with improvement in MADRS at week 6. In the SL and LL group, the paroxetine plasma concentration was significantly positively correlated with improvement in MADRS at week 6 according to the results of the single regression analysis; however, it was not significantly correlated with improvement in MADRS at week 6 according to the results of the multiple regression analysis.Among patients with MDD who do not respond to paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might be more effective in those with the SS genotype, and a higher plasma concentration might be more effective in those with the SL or LL

Direct Molecular Detection and Genotyping of Borrelia burgdorferi from Whole Blood of Patients with Early Lyme Disease

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Eshoo, Mark W.; Crowder, Christopher C.; Rebman, Alison W.; Rounds, Megan A.; Matthews, Heather E.; Picuri, John M.; Soloski, Mark J.; Ecker, David J.; Schutzer, Steven E.; Aucott, John N.

2012-01-01

Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of early Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in early Lyme disease directly from whole blood specimens prior to seroconversion. PMID:22590620

Long QT syndrome genotyping by electrocardiography: fact, fiction, or something in between?

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Kanters, Jørgen K.; Graff, Claus; Andersen, Mads Peter

2006-01-01

Diagnosis of long QT syndrome (LQTS) is difficult. A prolonged QT interval is easily overlooked, and in 10% of all patients with LQTS, the QT interval is normal. Genotyping is unfortunately not able to detect all patients and healthy subjects correctly. Although QT prolongation is the most used r...... evaluation can serve as a guide for genotyping and can reduce the costs by suggesting which gene to start sequencing, but it is fiction that the ECG can replace genotyping....

Relationship between ureB Sequence Diversity, Urease Activity and Genotypic Variations of Different Helicobacter pylori Strains in Patients with Gastric Disorders.

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Ghalehnoei, Hossein; Ahmadzadeh, Alireza; Farzi, Nastaran; Alebouyeh, Masoud; Aghdaei, Hamid Asadzadeh; Azimzadeh, Pendram; Molaei, Mahsa; Zali, Mohammad Reza

2016-01-01

Association of the severity of Helicobacter pylori induced diseases with virulence entity of the colonized strains was proven in some studies. Urease has been demonstrated as a potent virulence factor for H. pylori. The main aim of this study was investigation of the relationships of ureB sequence diversity, urease activity and virulence genotypes of different H. pylori strains with histopathological changes of gastric tissue in infected patients suffering from different gastric disorders. Analysis of the virulence genotypes in the isolated strains indicated significant associations between the presence of severe active gastritis and cagA+ (P = 0.039) or cagA/iceA1 genotypes (P = 0.026), and intestinal metaplasia and vacA m1 (P = 0.008) or vacA s1/m2 (P = 0.001) genotypes. Our results showed a 2.4-fold increased risk of peptic ulcer (95% CI: 0.483-11.93), compared with gastritis, in the infected patients who had dupA positive strains; however this association was not statistically significant. The results of urease activity showed a significant mean difference between the isolated strains from patients with PUD and NUD (P = 0.034). This activity was relatively higher among patients with intestinal metaplasia. Also a significant association was found between the lack of cagA and increased urease activity among the isolated strains (P = 0.036). While the greatest sequence variation of ureB was detected in a strain from a patient with intestinal metaplasia, the sole determined amino acid change in UreB sequence (Ala201Thr, 30%), showed no influence on urease activity. In conclusion, the supposed role of H. pylori urease to form peptic ulcer and advancing of intestinal metaplasia was postulated in this study. Higher urease activity in the colonizing H. pylori strains that present specific virulence factors was indicated as a risk factor for promotion of histopathological changes of gastric tissue that advance gastric malignancy.

Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

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Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen

2008-01-01

BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4...

NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection.

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Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona

2016-01-15

Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Hepatitis C Genotypes in Libya: Correlation with Patients’ Characteristics, Level of Viremia, and Degree of Liver Fibrosis

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Abdel-Naser Elzuoki

2017-09-01

Full Text Available Objectives: Our study sought to determine the distribution of hepatitis C virus (HCV-genotypes among patients attending two tertiary care hospitals in Benghazi and Tripoli, Libya, and correlate this with patient’s characteristics, viral load, and degree of fibrosis. Methods: We conducted a retrospective study of 286 HCV-RNA positive Libyan patients referred from different health care facilities in east and west Libya for specific HCV treatment. HCV genotyping was carried out by gene amplification. Liver histology was graded by Metavir score according to the stage of fibrosis. Results: HCV genotypes 1, 2, 3, and 4 were found in 24.1%, 10.8%, 3.4%, and 61.5% of the patients, respectively. Genotype 4 was detected more frequently in patients from east Libya (Benghazi compared to west Libya (Tripoli (75.9% vs. 41.6%, p = 0.245. Genotype 1 was more frequent in patients from west Libya compared to east Libya (34.1% vs. 16.8%, p = 0.657. There was a significant correlation between HCV genotype distribution and viral load. Patients with genotype 4 exhibited a higher degree of liver fibrosis (p < 0.001. Conclusions: HCV genotype 4 is the predominant genotype in Libya followed by genotype 1. However, as we go from the east to the west of the country, genotype 1 increases. Genotype 4 was associated with higher level of viremia and higher stage of liver fibrosis. It is important to note that both genotypes 1 and 4 are associated with a poor response to pegylated interferon and ribavirin combination therapy. The findings emphasize the need to develop improved strategies in Libya for the successful treatment of HCV infection with novel newly available antiviral drugs.

Liver stiffness becomes stable in patients with chronic hepatitis C three months after ALT normalization due to antiviral therapy

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CHEN Feikai

2013-10-01

Full Text Available ObjectiveTo investigate the time for liver stiffness measurement (LSM to become stable in chronic hepatitis C (CHC patients with elevated alanine aminotransferase (ALT levels after ALT normalization due to antiviral therapy. MethodsCHC patients who sought initial treatment at Peking University People′s Hospital were screened for elevated ALT levels from May 2011. Liver stiffness was determined by FibroScan. A total of 29 patients had been included in the study by September 2012, who were followed up regularly after antiviral treatment. ALT tests were repeated every four weeks and LSM every eight weeks until their medians did not change significantly. Comparisons of matched data at two adjacent time points were made with the non-parametric Wilcoxon test, while multiple comparisons of repeated measurements were performed using Bonferroni correction. Correlation between two variables was analyzed with the Spearman rank test. ResultsPatients were followed up until 24 weeks after antiviral treatment, and 24 patients were included in analysis. The median ALT levels were 64, 26, 21, 20, and 22 U/L at baseline and 4, 8, 12, and 24 weeks, respectively (P= 0.000, 0.006, 0.337, and 0.109 for comparisons between two adjacent values. ALT decreased significantly below 1 ULN at 4 weeks after antiviral therapy and stabilized at 8 weeks. The median LSM values were 8.7, 7.8, 6.8, and 6.7 kPa at baseline and 8, 16, and 24 weeks, respectively (P= 0.009, 0.001, and 0188 for comparisons between two adjacent values. LSM decreased significantly within 16 weeks after antiviral therapy and stabilized afterwards. LSM stabilized 12 weeks after ALT normalization. ConclusionLSM becomes stable in CHC patients with elevated ALT levels three months after ALT normalization due to antiviral therapy.

Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

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Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Jiang, Xia; Miyamura, Tatsuo; Nakatani, Sueli M.; Ono, Suzane Kioko; Takahashi-Nakaguchi, Azusa; Gonoi, Tohru; Yokosuka, Osamu

2013-01-01

Background Hepatitis C virus (HCV) subgenotypes 1a and 1b have different impacts on the treatment response to peginterferon plus ribavirin with direct-acting antivirals (DAAs) against patients infected with HCV genotype 1, as the emergence rates of resistance mutations are different between these two subgenotypes. In Japan, almost all of HCV genotype 1 belongs to subgenotype 1b. Methods and Findings To determine HCV subgenotype 1a or 1b in Japanese patients infected with HCV genotype 1, real-time PCR-based method and Sanger method were used for the HCV NS5B region. HCV subgenotypes were determined in 90% by real-time PCR-based method. We also analyzed the specific probe regions for HCV subgenotypes 1a and 1b using ultra-deep sequencing, and uncovered mutations that could not be revealed using direct-sequencing by Sanger method. We estimated the prevalence of HCV subgenotype 1a as 1.2-2.5% of HCV genotype 1 patients in Japan. Conclusions Although real-time PCR-based HCV subgenotyping method seems fair for differentiating HCV subgenotypes 1a and 1b, it may not be sufficient for clinical practice. Ultra-deep sequencing is useful for revealing the resistant strain(s) of HCV before DAA treatment as well as mixed infection with different genotypes or subgenotypes of HCV. PMID:24069214

BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

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Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme

2018-01-02

BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.

Phenotypes in defined genotypes including siblings with Usher syndrome.

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Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

2011-06-01

To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

Late complications of clinical clostridium histolyticum collagenase use in Dupuytren's disease.

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Warren M Rozen

Full Text Available INTRODUCTION: While Dupuytren's disease can cause disabling contractures requiring open surgery, a less-invasive option using Clostridium Histolyticum collagenase (CHC via percutaneous injection was recently reported. A recent prospective, randomized trial demonstrated few complications during 90 days follow-up, however did not assess any longer term follow-up for these patients. Long-term outcomes in this setting have not been adequately reported, and the current manuscript aims to identify late complications from the clinical use of percutaneous CHC. METHODS: The current manuscript reports an extended 12-month follow-up for a cohort of twelve of patients enrolled in the original prospective, randomized trial, treated at a single institution. An analysis of complications requiring surgical intervention was undertaken. RESULTS: Two of twelve patients reported debilitating pain and triggering requiring surgical intervention. Extensive deep-tissue scarring and adhesions were identified, providing the first visual and qualitative analysis of the pathologic effects of CHC. CONCLUSION: Late complications from CHC use can and have occurred, outside the follow-up period of the initial phase III trials. Longer term follow-up of such patients is thus essential, and further investigation and characterization of the late effects of CHC use is warranted.

[Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients].

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Li, Ya-xin; Yang, Yan-jia; Yang, Mei; Chen, Li-yu; Lu, Jia-jie; Ma, Yuan-ji; Liu, Kai; Lei, Xue-zhong; Tang, Hong

2013-05-01

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.

Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C.

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Rodríguez-Muñoz, Y; Martín-Vílchez, S; López-Rodríguez, R; Hernández-Bartolomé, A; Trapero-Marugán, M; Borque, M J; Moreno-Otero, R; Sanz-Cameno, P

2011-10-01

Hepatitis C virus infection evolves into chronic progressive liver disease in a significant percentage of patients. Monocytes constitute a diverse group of myeloid cells that mediate innate and adaptive immune response. In addition to proinflammatory CD16+ monocytes, a Tie-2+ subgroup - Tie-2 expressing monocytes (TEMs) - that has robust proangiogenic potential has been recently defined. To study the heterogeneity of peripheral blood monocytes in chronic hepatitis C (CHC) patients and to examine their proposed pathophysiological roles on disease progression and response to antiviral therapy. We studied CD16+ and Tie-2+ peripheral monocyte subpopulations in 21 healthy subjects and 39 CHC patients in various stages of disease and responses to antiviral treatment using flow cytometry. Expression profiles of proangiogenic and tissue remodelling factors in monocyte supernatants were measured using ELISA and protein arrays. Intrahepatic expression of CD14, CD31 and Tie-2 was analysed using immunofluorescence. Increases of certain peripheral monocyte subsets were observed in the blood of CHC patients, wherein those cells with proinflammatory (CD16+) or proangiogenic (TEMs) potential expanded (P TEMs were significantly increased in nonresponders, particularly those with lower CD16 expression. In addition, many angiogenic factors were differentially expressed by peripheral monocytes from control or CHC patients, such as angiopoietin-1 and angiogenin (P TEMs were distinguished within portal infiltrates of CHC patients. These findings suggest for the first time the relevance of peripheral monocytes phenotypes for the achievement of response to treatment. Hence, the study of monocyte subset regulation might effect improved CHC prognoses and adjuvant therapies. © 2011 Blackwell Publishing Ltd.

Late-onset Tay-Sachs disease: phenotypic characterization and genotypic correlations in 21 affected patients.

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Neudorfer, Orit; Pastores, Gregory M; Zeng, Bai J; Gianutsos, John; Zaroff, Charles M; Kolodny, Edwin H

2005-02-01

The purpose of this study was to describe the phenotype (and corresponding genotype) of adult patients with late-onset Tay-Sachs disease, a clinical variant of the GM2-gangliosidoses. A comprehensive physical examination, including neurological assessments, was performed to establish the current disease pattern and severity. In addition, the patients' past medical histories were reviewed. The patients' alpha-subunit mutations (beta-Hexosaminidase A genotype) were determined and correlated with their corresponding clinical findings and disease course. Twenty-one patients (current mean age: 27.0 years; range: 14-47 years) were identified. The pedigree revealed a relative with the "classic" infantile or late-onset form of Tay-Sachs disease in four (out of 18) unrelated families. The patients were predominantly male (15/21 individuals) and of Ashkenazi Jewish ancestry (15/18 families). Mean age at onset was 18.1 years; balance problems and difficulty climbing stairs were the most frequent presenting complaints. In several cases, the diagnosis was delayed (mean age at diagnosis: 27.0 years). Analysis of the beta-hex A gene revealed the G269S mutation as the most common disease allele; found in homozygosity (N = 1) or heterozygosity (N = 18; including 2 sib pairs). Disease onset (age 36 years) was delayed and progression relatively slower in the homozygous G269S patient. Two siblings (ages 28 and 31 years), of non-Jewish ancestry, were compound heterozygotes (TATC1278/W474C); their clinical course is dominated by psychiatric problems. Brain imaging studies revealed marked cerebellar atrophy in all patients (N = 18) tested, regardless of disease stage. Late-onset Tay-Sachs disease is an infrequent disorder and the diagnosis is often missed or delayed (by approximately 8 years). Early on, the majority of patients develop signs of either cerebellar or anterior motor neuron involvement. Affected individuals may also develop psychotic episodes. In most cases, the later

Methylenetetrahydrofolate reductase (MTHFR) genotype, smoking habit, metastasis and oral cancer in Taiwan.

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Tsai, Chia-Wen; Hsu, Chia-Fang; Tsai, Ming-Hsui; Tsou, Yung-An; Hua, Chun-Hung; Chang, Wen-Shin; Lin, Cheng-Chieh; Bau, Da-Tian

2011-06-01

The aim of this study was to evaluate the association and interaction of genotypic polymorphism in methylenetetrahydrofolate reductase (MTHFR) with smoking habits and oral cancer in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed in association with oral cancer risk, and their joint effects with individual smoking habits on oral cancer risk are discussed. In total, 620 oral cancer patients and 620 non-cancer controls in central Taiwan were recruited and genotyped. The MTHFR C677T genotype, but not the A1298C, was differently distributed between the oral cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in oral cancer patients. Joint effects of smoking and MTHFR C677T genotype significantly affected oral cancer susceptibility. The MTHFR C677T CT and TT genotypes in association with smoking conferred lower odds ratios of 0.66 and 0.54 (95% confidence interval=0.49-0.82 and 0.39-0.86), respectively. Those patients with MTHFR C677T CT and TT genotypes also had a lower risk of oral cancer metastasis. MTHFR C677T genotype may have joint effects with smoking on oral carcinogenesis, and may be a useful biomarker for prediction and prognosis of oral cancer.

Novel HBV recombinants between genotypes B and C in 3'-terminal reverse transcriptase (RT) sequences are associated with enhanced viral DNA load, higher RT point mutation rates and place of birth among Chinese patients.

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Liu, Baoming; Yang, Jing-Xian; Yan, Ling; Zhuang, Hui; Li, Tong

2018-01-01

As one of the major global public health concerns, hepatitis B virus (HBV) can be divided into at least eight genotypes, which may be related to disease severity and treatment response. We previously demonstrated that genotypes B and C HBV, with distinct geographical distribution in China, had divergent genotype-dependent amino acid polymorphisms and variations in reverse transcriptase (RT) gene region, a target of antiviral therapy using nucleos(t)ide analogues. Recently recombination between HBV genotypes B and C was reported to occur in the RT region. However, their frequency and clinical significance is poorly understood. Here full-length HBV RT sequences from 201 Chinese chronic hepatitis B (CHB) patients were amplified and sequenced, among which 31.34% (63/201) were genotype B whereas 68.66% (138/201) genotype C. Although no intergenotypic recombination was detected among C-genotype HBV, 38.10% (24/63) of B-genotype HBV had recombination with genotype C in the 3'-terminal RT sequences. The patients with B/C intergenotypic recombinants had significantly (Pdistribution feature in China. Our findings provide novel insight into the virological, clinical and epidemiological features of new HBV B/C intergenotypic recombinants at the 3' end of RT sequences among Chinese CHB patients. The highly complex genetic background of the novel recombinant HBV carrying new mutations affecting RT protein may contribute to an enhanced heterogeneity in treatment response or prognosis among CHB patients. Published by Elsevier B.V.

Mutation frequency and genotype/phenotype correlation among phenylketonuria patients from Georgia

Energy Technology Data Exchange (ETDEWEB)

Woo, S.L.C.; Martinez, D.; Kuozmine, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). To determine the molecular basis of PKU in the state of Georgia, thirty-five Georgian PKU patients representing sixty independent alleles were examined by a combination of DGGE and direct sequence analysis. At present, this approach has led to the identification of 55/60 or about 92% of all mutant alleles. The relatively high frequencies of mutations common to the British Isles (R408W, I65T and L348V) are compatible with 1990 census data showing that 34% of the general Georgian population claim Irish, English or Scottish ancestors. Three new mutations, E76A (1/60), R241L (2/60), and R400R (2/60), were also detected in this study. Although the nucleotide substitution in codon 400 (AGG{r_arrow}CGG) did not change the amino acid sequence, it was the only base change detected in a scan of all 13 exons of two independent alleles. Since codon 400 is split between exons 11 and 12, this change may exert some effect on splicing, as has previously been seen in the PAH gene for the silent mutation Q304Q and the nonsense mutation Y356X, each of which effect codons immediately adjacent to splicing signals. This hypothesis remains to be tested by expression analysis or studies of ectopic transcripts. The remaining 19 characterized alleles contained one of 15 previously identified mutations. Twenty-five of the thirty non-related patients examined in this study were completely genotyped, and there was a strong correlation between mutant PAH genotype, PAH activity predicted from in vitro expression studies where known, and PKU or HPA phenotype. For mutations not yet studied by expression analysis, this correlation suggests that L213P, R241L, Y277D may drastically reduce residual PAH activity while F39L and E76A may retain significant amounts of PAH activity.

Representativeness of Tuberculosis Genotyping Surveillance in the United States, 2009-2010.

Science.gov (United States)

Shak, Emma B; France, Anne Marie; Cowan, Lauren; Starks, Angela M; Grant, Juliana

2015-01-01

Genotyping of Mycobacterium tuberculosis isolates contributes to tuberculosis (TB) control through detection of possible outbreaks. However, 20% of U.S. cases do not have an isolate for testing, and 10% of cases with isolates do not have a genotype reported. TB outbreaks in populations with incomplete genotyping data might be missed by genotyping-based outbreak detection. Therefore, we assessed the representativeness of TB genotyping data by comparing characteristics of cases reported during January 1, 2009-December 31, 2010, that had a genotype result with those cases that did not. Of 22,476 cases, 14,922 (66%) had a genotype result. Cases without genotype results were more likely to be patients <19 years of age, with unknown HIV status, of female sex, U.S.-born, and with no recent history of homelessness or substance abuse. Although cases with a genotype result are largely representative of all reported U.S. TB cases, outbreak detection methods that rely solely on genotyping data may underestimate TB transmission among certain groups.

Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai.

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Cai, Xun; Cao, Weiguo; Ding, Honghua; Liu, Tianshu; Zhou, Xinli; Wang, Mei; Zhong, Ming; Zhao, Ziyi; Xu, Qing; Wang, Liwei

2013-09-01

The UGT1A1*28 polymorphism, although closely linked with CPT-11-related adverse effects, cannot be used alone to guide individualized treatment decisions. However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics. Our study is designed to investigate whether there is a relationship between SN-38 peak or valley concentrations and efficacy or adverse effects of CPT-11-based chemotherapy. We retrospectively studied 98 patients treated with advanced colorectal cancer in various UGT1A1*28 genotype groups (mainly (TA)6/(TA)6 and (TA)6/(TA)7 genotypes) treated with CPT-11 as first-line chemotherapy in Shanghai. One hundred and sixty-four advanced colorectal cancer patients were enrolled. To understand differences in genotype expression, the frequency of UGT1A1*28 thymine-adenine (TA) repeats in TATA box arrangement was assessed by PCR with genomic DNA extracted from peripheral blood. For ninety-eight cases with the (TA)6/(TA)6 and (TA)6/(TA)7 genotypes treated with CPT-11 as first-line chemotherapy, the plasma concentration of SN-38 was detected by HPLC 1.5 and 49 h after CPT-11 infusion. Efficacy and adverse effects were observed subsequently, and the relationship between SN-38 plasma concentration and efficacy or adverse effects within genotype groups, as well as differences in efficacy and adverse effects between (TA)6/(TA)6 and (TA)6/(TA)7 genotypes were analyzed statistically. One hundred and fourteen patients (69.51 %) were identified with the (TA)6/(TA)6 genotype, forty-eight patients (29.27 %) with the (TA)6/(TA)7 genotype, and two patients (1.22 %) with the (TA)7/(TA)7 genotype. The average peak and valley concentrations of SN-38 after CPT-11 infusion and plasma bilirubin average levels before and after CPT-11 treatment in the (TA)6/(TA)7 genotype group were all higher than those in (TA)6/(TA)6 group, and the difference was statistically significant (p = 0.00). Stepwise regression analysis showed that SN-38 peak and valley

Early-onset stargardt disease: phenotypic and genotypic characteristics

NARCIS (Netherlands)

Lambertus, S.; Huet, R.A.C. van; Bax, N.M.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

2015-01-01

OBJECTIVE: To describe the phenotype and genotype of patients with early-onset Stargardt disease. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-one Stargardt patients with age at onset patient medical records for age at onset, medical history, initial

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.

Detection and genotyping of enteroviruses in cerebrospinal fluid in patients in Victoria, Australia, 2007-2013.

Science.gov (United States)

Papadakis, Georgina; Chibo, Doris; Druce, Julian; Catton, Michael; Birch, Chris

2014-09-01

Genotyping by VP1 fragment polymerase chain reaction (PCR) and nucleic acid sequencing to detect enterovirus (EV) genotypes was performed directly on 729 EV PCR positive cerebrospinal fluid (CSF) samples collected between 2007 and 2012 from Victorian hospital inpatients. The overall genotype identification rate from CSF-positive material was 43%. The four most common genotypes identified were Echovirus 6 (24%), Echovirus 30 (17%), Echovirus 25 (10%), and Coxsackievirus A9 (10%), together comprising 61% of all EVs typed. The seasonal distribution of all EVs identified followed the recognized pattern of mainly summer epidemics. Three of the four predominant genotypes were present in each of the 6 years in which the study was conducted, with 20 other EV genotypes also detected, often in only a single year. Genotyping of EVs directly in CSF is faster, simpler and more sensitive than traditional virus neutralization assays performed on EV positive samples. © 2014 Wiley Periodicals, Inc.

Hepatitis E Virus Genotype 3 in Sewage and Genotype 1 in Acute Hepatitis Cases, Israel

Science.gov (United States)

Ram, Daniela; Manor, Yossi; Gozlan, Yael; Schwartz, Eli; Ben-Ari, Ziv; Mendelson, Ella; Mor, Orna

2016-01-01

Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to monitor its spread. PMID:27246446

HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients.

Science.gov (United States)

Grasso, Alessandro; Malfatti, Federica; Andraghetti, Gabriella; Marenco, Simona; Mazzucchelli, Chiara; Labanca, Sara; Cordera, Renzo; Testa, Roberto; Picciotto, Antonino

2015-01-01

Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P = 0.033 and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

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Alessandro Grasso

2015-01-01

Full Text Available Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033 and 0.048, resp. in patients who achieved an early viral load decay (EVR, a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

Use of alternative product in patients with chronic viral hepatitis

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Mahmut Dulger

2014-09-01

Full Text Available Objectives: Some of the patients with chronic hepatitis use both alternative product and/or antiviral treatment. These herbal products sometimes lead to clinical deterioration. In this study we aimed to determine the purpose of alternative product utilization and rate among the chronic hepatitis B (CHB and C (CHC patients. Methods: This prospective cohort study included 200 consecutive adult patients with chronic hepatitis B and C at the Department of Infectious Diseases, Ondokuz Mayis University, between 1 March 2012 and 30 July 2012. At enrollment, clinical information, demographics, laboratory variables and knowledge about alternative products were recorded. Results: Of the patients 150 had CHB, 50 had CHC. 54% of patients were male. Use of alternative products was 26%. Antiviral treatment rate was 48.5% for all patients. The most used alternative products were artichoke extract and honey. 67.3% of patients were using single alternative product whereas the others were using two or more alternative products. 46.2% of patients who use alternative product provided information about the alternative product usage, but the others did not. Conclusions: Majority of patients used alternative products. More than half of these patients did not give information to their physicians about their use of alternative medicine. Use of alternative product should be asked in all patients with chronic hepatitis. Herbal product usage was detected in majority of patients and also approximately half of these patients did not give information to their doctors about taking alternative medicine. In conclusion, it is necessary to take detailed information about herbal product usage in patients with chronic hepatitis. J Microbiol Infect Dis 2014; 4(3: 102-106

Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis.

Science.gov (United States)

Nishioka, M; Morshed, S A; Parveen, S; Kono, K; Matsuoka, H; Manns, M P

1997-12-01

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.

Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life

Institute of Scientific and Technical Information of China (English)

Tatsuji Maeshiro; Tomofumi Nakayoshi; Tomokuni Nakayoshi; Masashi Mizokami; Jiro Fujita; Hiroshi Sakugawa; Shingo Arakaki; Takako Watanabe; Hajime Aoyama; Joji Shiroma; Tsuyoshi Yamashiro; Tetsuo Hirata; Akira Hokama; Fukunori Kinjo

2007-01-01

AIM: To investigate the different impact of genotypes B and C on the development of liver cirrhosis (LC) among different age groups of patients with chronic hepatitis B (CH-B).METHODS: We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS: In patients ＜ 30 years old, there were no significant predictors for development of LC. However,in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis (7 patients were positive for HBeAg). In the genotype B group, 4 of 8patients who developed LC were ≥ 50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION: The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at ＜ 30 years old. However,CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.

Hypertension care at a Cape Town community health centre | Lunt ...

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