WorldWideScience

Sample records for acute-on-chronic liver failure

  1. Acute-on-chronic Liver Failure.

    Science.gov (United States)

    Sarin, Shiv Kumar; Choudhury, Ashok

    2016-12-01

    Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.

  2. Predisposing Factors in Acute-on-Chronic Liver Failure

    DEFF Research Database (Denmark)

    Trebicka, J.

    2016-01-01

    Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality in patients with chronic liver disease. The definition of ACLF has been addressed recently in many publications, and despite regional differences the number and severity of organ failures are decisive for the prese......Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality in patients with chronic liver disease. The definition of ACLF has been addressed recently in many publications, and despite regional differences the number and severity of organ failures are decisive...... hypertension might predispose for the development of ACLF after proper injury and response. © 2016 by Thieme Medical Publishers, Inc....

  3. Update on acute-on-chronic liver failure.

    Science.gov (United States)

    Solé, Cristina; Solà, Elsa

    2018-01-01

    Acute-on-chronic liver failure (ACLF) is a recently defined syndrome characterised by acute decompensation of chronic liver disease, associated with organ failures and high mortality. ACLF is a common condition and may affect up to 30% of patients admitted to hospital for cirrhosis complications. Bacterial infections, alcoholism and reactivation of viral hepatitis are the most common precipitating factors in ACLF, although in up to 40% of patients no precipitating factor can be identified. Although the pathophysiology of ACLF is not completely understood, the presence of an excessive inflammatory response appears to play a key role. There is no specific treatment for patients with ACLF and management is based on organ support and liver transplantation. New treatment strategies based on liver support systems and immunomodulatory treatments are being evaluated but existing data are still limited. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  4. Research progress in prognostic markers of acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    ZHANG Yuling

    2014-10-01

    Full Text Available Acute-on-chronic liver failure (ACLF is a clinical entity encompassing an acute deterioration of liver function and failure of one or more organs, which results in high short-term mortality rate. In recent years, a number of novel prognostic markers of ACLF have emerged and provided a basis for the treatment and prognostic evaluation of ACLF. Researches on both commonly used and novel makers for prognosis of ACLF are reviewed in order to improve the existing prognostic evaluation system and to provide a basis for the treatment and prognostic evaluation of ACLF.

  5. Reviewing the diagnostic criteria for acute-on-chronic liver failure.

    Science.gov (United States)

    Jindal, Ankur; Rastogi, Archana; Sarin, Shiv Kumar

    2016-12-01

    For over 20 years, acute-on-chronic liver failure (ACLF) has taken multiple definitions and/or classifications. The definition outlines the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific time frame. Early and accurate diagnosis is essential as this inflammation of the liver may tilt the balance of liver destruction and regeneration adversely. Various factors such as superadded systemic sepsis, liver reserve, cause of primary chronic liver disease, state of immune system or the state of gut microbial flora might determine the ultimate prognosis. Areas covered: To date, there has been no universally accepted definition of ACLF. In this review, we discuss the strengths and weaknesses, controversies and basis for early identification and accurate diagnosis of ACLF. PubMed and Google scholar database searches were conducted, search terms included 'acute on chronic liver failure,' 'ACLF,' and 'diagnostic criteria.' Expert commentary: With recent advances in the management of advanced cirrhosis, research will gradually shift towards ACLF in the near future, focusing on the pathogenesis, new treatment options and improving survival. Once we improve understanding of this syndrome, newer definitions will evolve, thereby enabling earlier diagnosis and novel therapeutic avenues.

  6. Prognostic factors for patients with hepatitis B virus-related acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    LI Ying

    2017-03-01

    Full Text Available ObjectiveTo investigate the prognostic factors for patients with hepatitis B virus-related acute-on-chronic liver failure, and to provide a basis for clinical diagnosis and treatment. MethodsA total of 172 patients with hepatitis B virus (HBV-related acute-on-chronic liver failure who were admitted to The First Hospital of Jilin University from January 1, 2006 to January 1, 2016 and had complete medical records and follow-up data were enrolled, and a retrospective analysis was performed for their clinical data and laboratory markers to determine prognostic factors. The independent-samples t test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and a multivariate logistic regression analysis was performed for the indices determined to be statistically significant by the univariate analysis to screen out independent risk factors for the prognosis of patients with HBV-related acute-on-chronic liver failure. ResultsThe multivariate logistic regression analysis was performed for the indices determined to be statistically significant by the univariate analysis, and the results showed that the prognostic factors were total bilirubin (TBil, prothrombin time activity (PTA, Na+, total cholesterol (TC, Child-Turcotte-Pugh (CTP score, age ≥50 years, the presence of liver cirrhosis, bilirubin-enzyme separation, and complications. The multivariate regression analysis was performed for the complications determined to affect prognosis by the univariate analysis, and the results showed that the complications as risk factors were hepatic encephalopathy, hepatorenal syndrome, and infection. ConclusionTBil, PTA, Na+, TC, CTP score, age ≥50 years, the presence of liver cirrhosis, bilirubin-enzyme separation, and complications are independent risk factors for the prognosis of patients with HBV-related acute-on-chronic liver failure. Liver failure patients with hepatic

  7. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Bañares, Rafael; Nevens, Frederik; Larsen, Fin Stolze

    2013-01-01

    Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189...... sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event...

  8. Incidence, predictors and outcomes of acute-on-chronic liver failure in outpatients with cirrhosis.

    Science.gov (United States)

    Piano, Salvatore; Tonon, Marta; Vettore, Elia; Stanco, Marialuisa; Pilutti, Chiara; Romano, Antonietta; Mareso, Sara; Gambino, Carmine; Brocca, Alessandra; Sticca, Antonietta; Fasolato, Silvano; Angeli, Paolo

    2017-12-01

    Acute-on-chronic liver failure (ACLF) is the most life-threatening complication of cirrhosis. Prevalence and outcomes of ACLF have recently been described in hospitalized patients with cirrhosis. However, no data is currently available on the prevalence and the risk factors of ACLF in outpatients with cirrhosis. The aim of this study was to evaluate incidence, predictors and outcomes of ACLF in a large cohort of outpatients with cirrhosis. A total of 466 patients with cirrhosis consecutively evaluated in the outpatient clinic of a tertiary hospital were included and followed up until death and/or liver transplantation for a mean of 45±44months. Data on development of hepatic and extrahepatic organ failures were collected during this period. ACLF was defined and graded according to the EASL-CLIF Consortium definition. During the follow-up, 118 patients (25%) developed ACLF: 57 grade-1, 33 grade-2 and 28 grade-3. The probability of developing ACLF was 14%, 29%, and 41% at 1year, 5years, and 10years, respectively. In the multivariate analysis, baseline mean arterial pressure (hazard ratio [HR] 0.96; p=0.012), ascites (HR 2.53; p=0.019), model of end-stage liver disease score (HR 1.26; p<0.001) and baseline hemoglobin (HR 0.07; p=0.012) were found to be independent predictors of the development of ACLF at one year. As expected, ACLF was associated with a poor prognosis, with a 3-month probability of transplant-free survival of 56%. Outpatients with cirrhosis have a high risk of developing ACLF. The degree of liver failure and circulatory dysfunction are associated with the development of ACLF, as well as low values of hemoglobin. These simple variables may help to identify patients at a high risk of developing ACLF and to plan a program of close surveillance and prevention in these patients. There is a need to identify predictors of acute-on-chronic liver failure (ACLF) in patients with cirrhosis in order to identify patients at high risk of developing ACLF and to

  9. Characterization of Cerebral Edema in Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Gupta, Tarana; Dhiman, Radha K; Ahuja, Chirag K; Agrawal, Swastik; Chopra, Madhu; Kalra, Naveen; Duseja, Ajay; Taneja, Sunil; Khandelwal, Niranjan; Chawla, Yogesh

    2017-09-01

    The nature of cerebral edema in acute-on-chronic liver failure (ACLF) is not well studied. We aimed to characterize cerebral edema in ACLF using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Forty-six patients with cirrhosis and acute decompensation were included. Patients were divided into groups A (no cerebral failure, n  = 39) and B (cerebral failure, n  = 7). Group A was subdivided into no-ACLF ( n  = 11), grade 1 ( n  = 10), grade 2 ( n  = 9) and grade 3 ( n  = 9) ACLF as per CANONIC study. MRI brain and plasma TNF-alpha, IL-1beta and IL-6 were measured at baseline and 7-10 days after admission. Ten age- and sex-matched healthy controls were also included. Mean diffusivity (MD) values, an MRI marker of water content, progressively increased from controls to no-ACLF to ACLF grade 1, 2 and 3 in group A in frontal white matter (FWM) and basal ganglia ( P  8 × 10 -9  M 2 /s) in FWM were independent predictors of 90-day mortality. There was no significant difference in clinical and MRI parameters between group A and B. Cerebral edema increases with severity of ACLF. Correlation between MD values and IL-6 levels suggests pathogenic role of inflammation in cerebral edema. Patients with grade 3 ACLF have cerebral edema irrespective of presence of clinically evident cerebral failure. MELD score and cerebral edema have prognostic significance in ACLF.

  10. Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF)

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Rødgaard-Hansen, Sidsel; Aagaard, Niels Kristian

    2016-01-01

    BACKGROUND & AIMS: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose receptor......-III, respectively. The patients' clinical course was registered and their MELD, CLIF-C Acute Decompensation (AD), and CLIF-C ACLF-scores computed at inclusion. RESULTS: We found a stepwise increase (p....80 (0.76-0.85)). CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform...

  11. An analysis of predictive factors for concurrent acute-on-chronic liver failure and hepatorenal syndrome

    Directory of Open Access Journals (Sweden)

    CHEN Yanfang

    2015-09-01

    Full Text Available ObjectiveTo learn the clinical characteristics of concurrent acute-on-chronic liver failure (ACLF and hepatorenal syndrome (HRS, and to investigate the predictive factors for HRS in patients with ACLF. MethodsA total of 806 patients with ACLF who were admitted to our hospital from January 2012 to May 2014 were selected and divided into two groups according to the incidence of concurrent HRS. Clinical indices and laboratory test results were analyzed in the two groups, and the multivariate logistic regression analysis was used to figure out independent indices for the prediction of HRS in patients with ACLF. A prediction model was established and the receiver operating characteristic curve was drawn to evaluate the accuracy of the prediction model. Comparison of continuous data between the two groups was made by t test, and comparison of categorical data between the two groups was made by χ2 test. ResultsIn all patients with ACLF, 229 had HRS and 577 had no HRS. The univariate logistic regression analysis showed that hepatic encephalopathy, peritonitis, infection, age, cystatin C (Cys-C, serum creatinine (SCr, blood urea nitrogen, albumin, prealbumin, total bilirubin, direct bilirubin, total cholesterol, K+, Na+, phosphorus, Ca2+, prothrombin time, prothrombin activity, international normalized ratio, and hematocrit were significant predictive factors for HRS. The multivariate logistic regression analysis showed that concurrent peritonitis, Cys-C, SCr, and HCO3- were independent predictive factors for HRS in patients with ACLF (OR=3.155, P<0.01; OR=30.773, P<0.01; OR=1062, P<0.01; OR=0.915, P<0.05. The model was proved of great value in prediction. ConclusionConcurrent peritonitis, Cys-C, SCr, and HCO3- are effective predictive factors for HRS in patients with ACLF.

  12. Artificial liver support system combined with liver transplantation in the treatment of patients with acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    Full Text Available BACKGROUND: The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS combined with liver transplantation (LT in the treatment of ACLF. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group and the other 56 received emergency LT (LT group. The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2-226 days from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%. CONCLUSIONS/SIGNIFICANCE: Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.

  13. Pediatric Acute-on-Chronic Liver Failure in a Specialized Liver Unit: Prevalence, Profile, Outcome, and Predictive Factors.

    Science.gov (United States)

    Alam, Seema; Lal, Bikrant B; Sood, Vikrant; Rawat, Dinesh

    2016-10-01

    The aim of the study was to assess the prevalence, profile, outcome, and predictive factors of pediatric acute-on-chronic liver failure (ACLF). All children 3 months to 18 years satisfying the Asia Pacific Association for the Study of Liver Diseases definition of ACLF were included. Data were both extracted from records (January 2011 to December 2014) and prospectively collected (January to October 2015). Successful outcome was defined as survival with native liver at 90 days, whereas poor outcome included those who died or received liver transplantation. Of the 499 children with chronic liver disease (CLD), 56 (11.2%) presented as ACLF, with a mean age of 9.35 (±4.39) years. Wilson disease and autoimmune hepatitis were the commonest underlying CLDs accounting for 24 (42.8%) and 18 (32.1%) cases, respectively. The most frequent events precipitating ACLF were a flare up of the underlying disease in 27 (48.2%) and acute viral hepatitis in 17 (30%). Poor outcome occurred in 22 (39.3%) children: 17 (30.4%) died and 5 (8.9%) received liver transplantation. Poor outcome was associated with grades 3 to 4 hepatic encephalopathy, bilirubin ≥17.5, international normalized ratio ≥3.5, and presence of 2 or more organ failures. On multivariate analysis, a Chronic Liver Failure-Sequential Organ Failure Assessment score ≥10 best predicted mortality (odds ratio 20.45, 95% confidence interval 3.9-106.7). ACLF is present in 11.2% of childhood CLD, with a 90-day native liver survival of 61%. A Chronic Liver Failure-Sequential Organ Failure Assessment score of ≥10 best predicts mortality at day 90.

  14. Validation of prognostic scores to predict short-term mortality in patients with acute-on-chronic liver failure.

    Science.gov (United States)

    Song, Do Seon; Kim, Tae Yeob; Kim, Dong Joon; Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Jang, Jae Young; Kim, Hyoung Su; Kim, Sang Gyune; Yang, Jin Mo; Sohn, Joo Hyun; Choi, Eun Hee; Cho, Hyun Chin; Jeong, Soung Won; Kim, Moon Young

    2018-04-01

    The aim of this study was to validate the chronic liver failure-sequential organ failure assessment score (CLIF-SOFAs), CLIF consortium organ failure score (CLIF-C OFs), CLIF-C acute-on-chronic liver failure score (CLIF-C ACLFs), and CLIF-C acute decompensation score in Korean chronic liver disease patients with acute deterioration. Acute-on-chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF-C criteria. The diagnostic performances for short-term mortality were compared by the area under the receiver operating characteristic curve. Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF-C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs were significantly higher than those of the Child-Pugh, model for end-stage liver disease, and model for end-stage liver disease-Na scores in ACLF patients according to the CLIF-C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF-C definition, but not in ACLF patients according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF-C definition, but not the AARC definition. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  15. Experience of combined liver-kidney transplantation for acute-on-chronic liver failure patients with renal dysfunction.

    Science.gov (United States)

    Xing, T; Zhong, L; Chen, D; Peng, Z

    2013-01-01

    The aim of this study was to evaluate the outcomes of orthotopic liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for acute-on-chronic liver failure (ACLF) patients with renal dysfunction. From January 2001 to December 2009, 133 patients underwent OLT for ACLF at our center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients, 12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined according to the Asian Pacific Association for the Study of Liver Consensus Meeting. Clinical data were reviewed for survival outcomes. The median model for end-stage liver disease score (MELD) of patients with ACLF was 28. Among the 133 patients, all of whom received deceased donor liver grafts, 12 also got the kidney grafts from the same deceased donor. The hospital mortality rate was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for patients without renal dysfunction and 70% for patients with renal dysfunction. The results of patients with ESRD who underwent CLKT were better than those of subjects without renal dysfunction or patients with HRS1 who underwent OLT alone. OLT alone improved renal function in most patients with HRS1, including those requiring short-term hemodialysis. Simultaneous liver-kidney transplantation was an excellent strategy for patients with both ACLF and ESRD. It provided protection to the kidney allograft for liver-based metabolic diseases affecting the kidney. The rate of acute rejection episodes in kidneys was low. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV-related acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    YOU Shaoli

    2013-09-01

    Full Text Available ObjectiveTo construct a hybrid bioartificial liver support system and to investigate its safety and efficacy in patients with hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF. MethodsA hollow fiber bioreactor was constructed using cultured HepG2 cells transfected with human augmenter of liver regeneration gene. Patients with HBV-related ACLF who were hospitalized in our hospital from May 2009 to August 2011 were randomly divided into treatment group (n=10 and control group (n=10. The treatment group was treated using the hybrid bioartificial liver support system, while the control group was treated with conventional plasma exchange. Comparison of means between the two groups was made by independent-samples t test, and comparison of variables before and after treatment was made by paired t test. ResultsOf the 10 patients in treatment group, 7 had improvement in clinical symptoms and were discharged, 1 died of hepatic encephalopathy, 1 died of hepatorenal syndrome, and 1 died of liver failure after discharge. Of the 10 patients in control group, 5 survived, 1 underwent liver transplantation, and 4 died of liver failure. Before treatment, the treatment group and control group had model for end-stage liver disease (MELD scores of 24.26±2.54 and 24.71±2.79, respectively, without significant difference between the two groups (t=1.971, P=0.064. The treatment group had MELD scores of 21.71±2.92, 22.10±4.46, and 19.90±5.43 after 3 days, 1 week, and 4 weeks, respectively, of treatment. At the end of one-year follow-up, the mean serum alpha-fetoprotein levels were 14.24 ng/ml in treatment group and 11.32 ng/ml in control group, and no space-occupying lesions in the liver were found through abdominal ultrasound. ConclusionThe constructed hybrid bioartificial liver support system is effective and safe in the treatment of HBV-related ACLF.

  17. Economic evaluation of the artificial liver support system MARS in patients with acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    Hessel Franz P

    2006-10-01

    Full Text Available Abstract Background Acute-on-chronic liver failure (ACLF is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS. Methods In a clinical cohort trial with a prospective follow-up of 3 years 33 ACLF-patients treated with MARS were compared to 46 controls. Survival, health-related quality of life as well as direct medical costs for in- and outpatient treatment from a health care system perspective were determined. Based on the differences in outcome and indirect costs the cost-effectiveness of MARS expressed as incremental costs per life year gained and incremental costs per QALY gained was estimated. Results The average initial intervention costs for MARS were 14600 EUR per patient treated. Direct medical costs over 3 years follow up were overall 40000 EUR per patient treated with MARS respectively 12700 EUR in controls. The 3 year survival rate after MARS was 52% compared to 17% in controls. Kaplan-Meier analysis of cumulated survival probability showed a highly significant difference in favour of MARS. Incremental costs per life-year gained were 31400 EUR; incremental costs per QALY gained were 47200 EUR. Conclusion The results after 3 years follow-up of the first economic evaluation study of MARS based on empirical patient data are presented. Although high initial treatment costs for MARS occur the significantly better survival seen in this study led to reasonable costs per live year gained. Further randomized controlled trials investigating the medical efficacy and the cost-effectiveness are recommended.

  18. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise

    2016-01-01

    BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF) is char......BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF...

  19. Clinical features of HBV-associated acute-on-chronic liver failure induced by discontinuation of nucleoside analogues

    Directory of Open Access Journals (Sweden)

    LIU Xiaoyan

    2016-09-01

    Full Text Available Objective To investigate the clinical features of patients with HBV-associated acute-on-chronic liver failure (HBV-ACLF induced by the discontinuation of necleos(tide analogues. Methods A retrospective analysis was performed for 698 patients with a definite diagnosis of HBV-ACLF in The 302 Hospital of PLA from January 2014 to April 2016, and among these patients, 150 (discontinuation group had acute-on-chronic liver failure (ACLF induced by discontinuation, 396 (previously untreated group had not received antiviral therapy when they developed this disease for the first time, and the other 152 patients with ACLF caused by other reasons were enrolled as controls. The causative factors, underlying diseases, family history, serum hepatitis B markers, prognosis, and initial onset were summarized, and the drugs used and discontinuation time were recorded for patients who stopped taking necleos(tide analogues. The chi-square test was used for the comparison of categorical data between groups. Results Among the 698 patients, 355(50.86% had a family history of chronic hepatitis B (CHB, and 93 patients (62.00% in the discontinuation group had a family history of CHB. Among the 150 patients in the discontinuation group, 27 (18.00% had an underlying disease of chronic hepatitis, among whom 12 (44.44% had a family history of CHB, which was significantly lower than the overall level (χ2=2.57, P=0.07; 123 (82.00% had an underlying disease of liver cirrhosis (compensated, among whom 81 (65.85% had a family history of CHB, which was significantly higher than the overall level (χ2=48.77, P<0.001. Of all the patients in the discontinuation group, 77.33% (116/150 developed the disease within 1 year after discontinuation, and 21.33% (32/150developed the disease during the second year after discontinuation. The HBeAg-negative patients accounted for 47.33% (71/150. In the discontinuation group and previously untreated group, the patients with an underlying disease

  20. Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

    Science.gov (United States)

    Gerth, Hans U; Pohlen, Michele; Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Hüsing-Kabar, Anna; Wilms, Christian; Maschmeier, Miriam; Kabar, Iyad; Torner, Josep; Pavesi, Marco; Arroyo, Vicente; Banares, Rafael; Schmidt, Hartmut H J

    2017-10-01

    Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Medical Departments of University Hospital Muenster (Germany). This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1-3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Standard medical treatment and molecular adsorbent recirculating system. Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2-3). Concerning the

  1. NACSELD Acute-on-Chronic Liver Failure (NACSELD-ACLF) Score Predicts 30-Day Survival in Hospitalized Patients with Cirrhosis.

    Science.gov (United States)

    O'Leary, Jacqueline G; Reddy, K Rajender; Garcia-Tsao, Guadalupe; Biggins, Scott W; Wong, Florence; Fallon, Michael B; Subramanian, Ram M; Kamath, Patrick S; Thuluvath, Paul; Vargas, Hugo E; Maliakkal, Benedict; Tandon, Puneeta; Lai, Jennifer; Thacker, Leroy R; Bajaj, Jasmohan S

    2018-01-08

    NACSELD (North American Consortium for the Study of End-Stage Liver Disease) definition of acute-on-chronic liver failure (NACSELD-ACLF) as ≥2 extra-hepatic organ failures has been proposed as a simple bedside tool to assess risk of mortality in hospitalized patients with cirrhosis. We validated NACSELD-ACLF's ability to predict 30-day survival (defined as in-hospital death or hospice discharge) in a separate multicenter prospectively enrolled cohort of both infected and uninfected hospitalized patients with cirrhosis. We utilized the NACSELD database of 14 tertiary care hepatology centers that prospectively enrolled non-elective hospitalized patients with cirrhosis (N=2675). The cohort was randomly split 60%/40% into training (N=1605) and testing (N=1070) groups. Organ failures assessed were: 1) shock, 2) hepatic encephalopathy (grade III/IV), 3) renal (need for dialysis), and 4) respiratory (mechanical ventilation). Patients were most commonly Caucasian (79%) men (62%) with a mean age of 57 years with a diagnosis of alcohol-induced cirrhosis (45%). 1079 patients had an infection during hospitalization. Mean Model for End-Stage Liver Disease (MELD) was 19 and median Child score was 10. No demographic differences were present between the 2 split groups. Multivariable modeling revealed NACSELD-ACLF score, as determined by number of organ failures, was the strongest predictor of decreased survival after controlling for admission age, white blood cell count, serum albumin, MELD score, and presence of infection. The c-statistic for the training set was 0.8073 and was 0.8532 for the validation set. Although infection status remains an important predictor of death, NACSELD-ACLF was independently validated in a separate large multinational prospective cohort as a simple reliable bed-side tool to predict 30-day survival in both infected and uninfected patients hospitalized with a diagnosis of cirrhosis. This article is protected by copyright. All rights reserved. © 2018

  2. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Liu, Jianping; Als-Nielsen, Bodil

    2003-01-01

    Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation.......Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation....

  3. Characteristics of infection and its impact on short-term outcome in patients with acute-on-chronic liver failure.

    Science.gov (United States)

    Cai, Junjun; Zhang, Mengchen; Han, Tao; Jiang, Hui-Qing

    2017-09-01

    Bacterial infections are an important cause of mortality in liver failure. However, the type of infection, predictors of infection, and their impact on outcomes in patients with acute-on-chronic liver failure (ACLF) are limited.A total of 389 patients with ACLF were admitted in this retrospective, corhort study. Once admitted, clinical data including first infection site, type (community-acquired, healthcare-associated, or nosocomial), and second infection occurrence during hospitalization were collected. The outcome was mortality within 90 days. Multivariable logistic regression models were preformed to predict second infection development and 90-day mortality. Survival probability curves were calculated by the Kaplan-Meier method.Among 389 patients, 316 (81.2%) patients had infection. The 90-day mortality of patients with and without infection was 52.2% and 16.4%, respectively (P infection was healthcare associated (51.3%), followed by nosocomial (30.1%) and community-acquired infections (18.7%). Respiratory tract infection, spontaneous bacterial peritonitis, and urinary tract infection were most prevalent. Gram-positive organism was more frequently seen than gram-negative organisms. Of note, fungi accounted for 15.9% of the total infection cases. During hospitalization, 26.6% patients developed second infections. The 90-day mortality of patients developed or did not develop a second infection were 67.9% and 46.6%, respectively (P infected patients with ACLF were age, white blood cell (WBC) count, model for end-stage liver disease (MELD) score, hepatic encephalopathy (HE), and second infection.Infections (regardless of first or second infection) can increase the 90-day mortality significantly in patients with ACLF. And age, WBC count, MELD score, HE, and the presence of second infection are independent risk factors affecting 90-day mortality in patients with ACLF showing infection.

  4. Prognostic factors of the short-term outcomes of patients with hepatitis B virus-associated acute-on-chronic liver failure.

    Science.gov (United States)

    Lei, Qing; Ao, Kangjian; Zhang, Yinhua; Ma, Deqiang; Ding, Deping; Ke, Changzheng; Chen, Yue; Luo, Jie; Meng, Zhongji

    2017-11-01

    To investigate the impact of the baseline status of patients with hepatitis B virus-associated acute-on-chronic liver failure on short-term outcomes. A retrospective study was conducted that included a total of 138 patients with hepatitis B virus-associated acute-on-chronic liver failure admitted to the Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, from November 2013 to October 2016. The patients were divided into a poor prognosis group (74 patients) and a good prognosis group (64 patients) based on the disease outcome. General information, clinical indicators and prognostic scores of the patients' baseline status were analyzed, and a prediction model was established accordingly. Elder age, treatment with artificial liver support systems and the frequency of such treatments, high levels of white blood cells, neutrophils, neutrophil count/lymphocyte count ratio, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, urea, and prognostic scores as well as low levels of albumin and sodium were all significantly associated with the short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure. The predictive model showed that logit (p) = 3.068 + 1.003 × neutrophil count/lymphocyte count ratio - 0.892 × gamma-glutamyl transferase - 1.138 × albumin - 1.364 × sodium + 1.651 × artificial liver support therapy. The neutrophil count/lymphocyte count ratio and serum levels of gamma-glutamyl transferase, albumin and sodium were independent risk factors predicting short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure, and the administration of multiple treatments with artificial liver support therapy during the early stage is conducive to improved short-term outcomes.

  5. Logistic regression analysis of prognostic factors in 106 acute-on-chronic liver failure patients with hepatic encephalopathy

    Directory of Open Access Journals (Sweden)

    CUI Yanping

    2014-10-01

    Full Text Available ObjectiveTo analyze the prognostic factors in acute-on-chronic liver failure (ACLF patients with hepatic encephalopathy (HE and to explore the risk factors for prognosis. MethodsA retrospective analysis was performed on 106 ACLF patients with HE who were hospitalized in our hospital from January 2010 to July 2013. The patients were divided into improved group and deteriorated group. The univariate indicators including age, sex, laboratory indicators [total bilirubin (TBil, albumin (Alb, alanine aminotransferase (ALT, aspartate amino-transferase (AST, and prothrombin time activity (PTA], the stage of HE, complications [persistent hyponatremia, digestive tract bleeding, hepatorenal syndrome (HRS, ascites, infection, and spontaneous bacterial peritonitis (SBP], and plasma exchange were analyzed by chi-square test or t-test. Indicators with statistical significance were subsequently analyzed by binary logistic regression. ResultsUnivariate analysis showed that ALT (P=0.009, PTA (P=0.043, the stage of HE (P=0.000, and HRS (P=0.003 were significantly different between the two groups, whereas differences in age, sex, TBil, Alb, AST, persistent hyponatremia, digestive tract bleeding, ascites, infection, SBP, and plasma exchange were not statistically significant (P>0.05. Binary logistic regression demonstrated that PTA (b=-0097, P=0.025, OR=0.908, HRS (b=2.279, P=0.007, OR=9.764, and the stage of HE (b=1873, P=0.000, OR=6.510 were prognostic factors in ACLF patients with HE. ConclusionThe stage of HE, HRS, and PTA are independent influential factors for the prognosis in ACLF patients with HE. Reduced PTA, advanced HE stage, and the presence of HRS indicate worse prognosis.

  6. Association Between Grade of Acute on Chronic Liver Failure and Response to Terlipressin and Albumin in Patients With Hepatorenal Syndrome.

    Science.gov (United States)

    Piano, Salvatore; Schmidt, Hartmut H; Ariza, Xavier; Amoros, Alex; Romano, Antonietta; Hüsing-Kabar, Anna; Solà, Elsa; Gerbes, Alexander; Bernardi, Mauro; Alessandria, Carlo; Scheiner, Bernhard; Tonon, Marta; Maschmeier, Miriam; Solè, Cristina; Trebicka, Jonel; Gustot, Thierry; Nevens, Frederik; Arroyo, Vicente; Gines, Pere; Angeli, Paolo

    2018-01-31

    Type 1 hepatorenal syndrome (HRS) is the most high-risk type of renal failure in patients with cirrhosis. Terlipressin and albumin are effective treatments for type 1 HRS. However, the effects of acute on chronic liver failure (ACLF) grade on response to treatment are not clear. We aimed to identify factors associated with response to treatment with terlipressin and albumin in patients with type 1 HRS (reduction in serum level of creatinine to below 1.5 mg/dL at the end of treatment) and factors associated with death within 90 days of HRS diagnosis (90-day mortality). We performed a retrospective analysis of 4 different cohorts of consecutive patients with HRS treated with terlipressin and albumin from February 2007 through January 2016 at medical centers in Europe (total, 298 patients). We analyzed demographic, clinical, and laboratory data collected before and during treatment; patients were followed until death, liver transplantation, or 90 days after HRS diagnosis. Response to treatment was observed in 53% of patients. Of patients with grade 1 ACLF, 60% responded to treatment; among those with grade 2 ACLF, 48% responded, and among those with grade 3 ACLF, 29% responded (P < .001 for comparison between grades). In multivariate analysis, baseline serum level of creatinine (odds ratio, 0.23; P = .001) and ACLF grade (odds ratio, 0.63; P = .01) were independently associated with response to treatment. Patient age (hazard ratio [HR], 1.05; P < .001), white blood cell count (HR, 1.51; P = .006), ACLF grade (HR, 2.06; P < .001), and no response to treatment (HR, 0.41; P < .001) associated with 90-day mortality. In a retrospective analysis of data from 4 cohorts of patients treated for type 1 HRS, we found ACLF grade to be the largest determinant of response to terlipressin and albumin. ACLF grade affects survival independently of response to treatment. New therapeutic strategies should be developed for patients with type 1 HRS and extrarenal organ failure

  7. Risk factors associated with prognosis of progressive stages of acute-on-chronic hepatitis B liver failure

    Directory of Open Access Journals (Sweden)

    YE Peiyan

    2013-04-01

    Full Text Available ObjectiveTo identify the risk factors associated with progression of acute-on-chronic liver failure (ACLF occurring in patients with chronic hepatitis B virus (HBV infection (CHB. MethodsThe clinical, demographic, treatment and outcome data of 180 ACLF patients with concomitant CHB managed in our hospital between June 2009 and September 2012 were retrospectively reviewed. Clinical data, taken at baseline, included markers of inflammation/infection (white blood cell (WBC count, coagulation (prothrombin time (PT and prothrombin activity (PTA, and liver function (alanine aminotransferase (ALT, aspartate aminotransferase (AST, total bilirubin (TBil, direct bilirubin (DBil, choninesterase (CHE, albumin (Alb, globulin (Glb, total cholesterol (TC, and ammonia. In-hospital treatments included supplementation with traditional Chinese medicine-based therapies, such as Tuihuang decoction and detoxification enema. The primary outcome was survival during hospitalization. The patients were grouped for analysis according to ACLF stage (early, n=93; mid, n=61; late, n=26 and the risk factors associated with each stage were identified by using univariate (log-rank test and multivariate (Cox’s test regression analyses. The association of risk factors with patient survival was assessed by Kaplan-Meier curve analysis. ResultsThe three ACLF groups showed significantly different amounts of leukocytes, with the late ACLF group showing the highest WBC. The late ACLF group also showed significantly lower Glb and TC. There was a trend in reduced cumulative survival rate and shorter time to death that significantly corresponded to progressive stages of ACLF (early ACLF>mid ACLF>late ACLF; all P<0.001. One-hundred-and-twenty-six (70.0% of the patients died during their hospitalization, and multivariate regression analysis of this entire patient population identified absence of colonic enema, presence of hepatic encephalopathy, presence of hepatorenal syndrome, PTA

  8. Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Praktiknjo, Michael; Book, Marius; Luetkens, Julian

    2018-01-01

    in the sarcopenia group but resolved in the non-sarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure (ACLF). FFMA was an independent predictor of survival in these patients. CONCLUSION: This study......BACKGROUND: Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cut-off values are missing and most studies used computed tomography (CT). This study evaluated fat-free muscle area as a marker...

  9. Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure.

    Science.gov (United States)

    Laleman, Wim; Wilmer, Alexander; Evenepoel, Pieter; Elst, Ingrid Vander; Zeegers, Marcel; Zaman, Zahur; Verslype, Chris; Fevery, Johan; Nevens, Frederik

    2006-01-01

    Patients with acute-on-chronic liver failure show an aggravated hyperdynamic circulation. We evaluated, in a controlled manner, potential changes in systemic haemodynamics induced by the molecular adsorbent recirculating system (MARS) and the Prometheus system liver detoxification devices in a group of patients with acute-on-chronic liver failure. Eighteen patients (51.2 +/- 2.3 years old; Child-Pugh score, 12.5 +/- 0.2; Maddrey score, 63.1 +/- 5.0; hepatic venous pressure gradient, 17.6 +/- 0.9 mmHg) with biopsy-proven alcoholic cirrhosis and superimposed alcoholic hepatitis were either treated with standard medical therapy (SMT) combined with MARS (n = 6) or Prometheus (n = 6) or were treated with SMT alone (n = 6) on three consecutive days (6 hours/session). Liver tests, systemic haemodynamics and vasoactive substances were determined before and after each session. Groups were comparable for baseline haemodynamics and levels of vasoactive substances. Both MARS and Prometheus decreased serum bilirubin levels (P Prometheus device being more effective than MARS (P = 0.002). Only MARS showed significant improvement in the mean arterial pressure (Deltachange, +9 +/- 2.4 mmHg versus -0.3 +/- 2.4 mmHg with Prometheus and -5.2 +/- 2.1 mmHg with SMT, P Prometheus and -30.7 +/- 32.5 dyne x s/cm5/m2 with SMT; P Prometheus device, significantly attenuates the hyperdynamic circulation in acute-on-chronic liver failure, presumably by a difference in removal rate of certain vasoactive substances. These findings suggest conspicuous conceptual differences among the albumin dialysis devices.

  10. Clinical effect of plasma perfusion combined with plasma exchange in treatment of patients with acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    ZHOU Jian

    2017-04-01

    Full Text Available ObjectiveTo investigate the clinical effect of plasma perfusion (PP combined with plasma exchange (PE in the treatment of acute-on-chronic liver failure (ACLF. MethodsA total of 72 patients with ACLF who were admitted to The Second People’s Hospital of Lanzhou from January 2014 to December 2015 were enrolled. In addition to internal medication, all the patients were treated with the artificial liver support system (once every 3-4 days based on the patients’ conditions, 1-3 times on average for each patient. According to the difference in therapies, the patients were divided into combination group with 40 patients (PP combined with PE and a total of 107 case times and control group with 32 patients (PE alone and a total of 85 case times. Total bilirubin (TBil, alanine aminotransferase (ALT, and prothrombin time were recorded before treatment, after surgery, and at 72 hours after surgery. Clinical outcome was evaluated after 4 weeks of treatment. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe overall response rate of all patients was 63.89% (46/72. At 72 hours after surgery, there was a significant difference in the level of ALT between the combination group and the control group (319.54±86.23 U/L vs 354.75±100.76 U/L, t=2.60, P<0.05. Both groups had significant reductions in TBil and ALT after surgery (combination group: t=6.69 and 15.84, P<0.05; control group: t=5.34 and 14.38, P<0.05 and at 72 hours after surgery (combination group: t=3.24 and 8.83, P<0.05; control group: t=2.40 and 4.61, P<0.05. Both groups had significant changes in prothrombin time activity after surgery (t=4.83 and 5.01, both P<0.05. There were no significant differences in the incidence rates of pruritus and rash between the two groups, while there was a significant difference in the incidence rate of perioral or limb numbness between the

  11. Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis.

    Science.gov (United States)

    Markwardt, Daniel; Holdt, Lesca; Steib, Christian; Benesic, Andreas; Bendtsen, Flemming; Bernardi, Mauro; Moreau, Richard; Teupser, Daniel; Wendon, Julia; Nevens, Frederik; Trebicka, Jonel; Garcia, Elisabet; Pavesi, Marco; Arroyo, Vicente; Gerbes, Alexander L

    2017-10-01

    The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. We investigated whether cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality. We determined the plasma levels of CysC and NGAL in 429 patients hospitalized for acute decompensation of cirrhosis in the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study. The patients were followed for 90 days. Patients without RD or ACLF at inclusion but with development of either had significantly higher baseline concentrations of CysC and NGAL compared to patients without. CysC, but not NGAL, was found to be predictive of RD (odds ratio, 9.4; 95% confidence interval [CI], 1.8-49.7), HRS (odds ratio, 4.2; 95% CI, 1.2-14.8), and ACLF (odds ratio, 5.9; 95% CI, 1.3-25.9). CysC at day 3 was not found to be a better predictor than baseline CysC. CysC and NGAL were both predictive of 90-day mortality, with hazard ratios for CysC of 3.1 (95% CI, 2.1-4.7) and for NGAL of 1.9 (95% CI, 1.5-2.4). Baseline CysC is a biomarker of RD, HRS, and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis, though determining CysC at day 3 did not provide any benefit; while NGAL is also associated with short-term mortality, it fails to predict development of RD, HRS, and ACLF. Baseline CysC may help to identify patients at risk earlier and improve clinical management. (Hepatology 2017;66:1232-1241). © 2017 by the American Association for the Study of Liver Diseases.

  12. Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis

    DEFF Research Database (Denmark)

    Markwardt, Daniel; Holdt, Lesca; Steib, Christian

    2017-01-01

    C) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality. We determined the plasma levels of CysC and NGAL in 429 patients hospitalized for acute decompensation of cirrhosis in the EASL-CLIF Acute-on-Chronic Liver...

  13. Evaluation of the therapeutic efficacy of lamivudine combined with plasma exchange for treating acute-on-chronic hepatitis B liver failure

    Directory of Open Access Journals (Sweden)

    HU Qijiang

    2013-02-01

    Full Text Available ObjectiveTo observe the clinical effects of lamivudine antiviral therapy combined with plasma exchange in patients with acute-on-chronic hepatitis B liver failure. MethodsForty-seven patients (treatment group were administered lamivudine and underwent plasma exchange. An additional forty-five patients (control group were administered lamivudine but no plasma exchange. Otherwise, all patients received the same basic medical treatment. The two groups were further divided into three sub-groups according to the model for end-stage liver disease (MELD score: <30, 30-39, and ≥40. The significance of differences in survival rates between the groups and sub-groups was determined by the χ2 test. ResultsThe overall survival rate was significantly better in the treatment group (63.82% vs. control group: 44.44%; χ2=4.31, P<0.05. Within the treatment group, the survival rates were highest in the 30-39 MELD score sub-group (71.42%, which was significantly different from survival rate in the same sub-group of the controls (vs. 38.10%; χ2=4.71, P<005. The other two MELD score sub-groups showed no significant differences between the treatment and control groups (all P>0.05. ConclusionCombined therapy consisting of lamivudine treatment and plasma exchange can improve the survival rate of patients with acute-on-chronic hepatitis B liver failure who have MELD scores between 30 and 39.

  14. Dietary intake of selenium and serum selenium in patients with chronic hepatitis B, liver cirrhosis and acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    ZHAO Juan

    2015-07-01

    Full Text Available Objective To analyse dietary intake of selenium and serum selenium levels in patients with different types of chronic liver diseases, and to explore the relationship between selenium and severity of liver diseases. Methods Seventy-four patients admitted to Beijing YouAn Hospital from August 2008 to October 2014, as well as 16 healthy persons as healthy control (HC group, were recruited in this study. Based on liver disease types, these patients were divided into chronic hepatitis (CH group (n=23, liver cirrhosis (LC group (n=27, and acute-on-chronic liver failure (ACLF group (n=24. Dietary intake of selenium was calculated on admission by dietary assessment software, and serum selenium levels were measured by inductively coupled plasma-atomic emission spectroscopy. Comparison of continuous data between groups was made by one-way ANOVA; comparison of categorical data between groups was made by χ2 test; the correlation between variables was determined by Pearson correlation analysis. Results The dietary selenium intake in the HC group was 4545±18.10 μg. Compared with the HC group, the CH group, LC group, and ACLF group had insufficient dietary intake of selenium (37.69±11.30 μg, 32.65±13.55 μg, and 28.95±13.30 μg, respectively. Dietary selenium intake gradually decreased with the progression of liver disease. Compared with the HC group, the LC group and ACLF group had significantly lower dietary selenium intake (P=0.004 and 0.000, respectively. Serum selenium in the HC group was 0.17±0.04 μg/ml. Compared with the HC group, the CH group, LC group, and ACLF group had significantly lower serum selenium levels (0.12±0.05 μg/ml, P=0.007; 0.11±0.06 μg/ml, P=0.000; 0.13±0.05 μg/ml, P=0.015. Serum selenium in the LC group was reduced most among these groups. Furthermore, serum selenium was significantly associated with prealbumin level, white blood cell count, and platelet count (r=0.229, P=0.030; r=0.213, P=0.044; r=0.255, P=0

  15. Effect of extracorporeal liver support by molecular adsorbents recirculating system and Prometheus on redox state of albumin in acute-on-chronic liver failure.

    Science.gov (United States)

    Oettl, Karl; Stadlbauer, Vanessa; Krisper, Peter; Stauber, Rudolf E

    2009-10-01

    Oxidative stress is believed to play an important role in acute-on-chronic liver failure (AoCLF). Albumin, an important transport vehicle, was found to be severely oxidized in AoCLF patients. Extracorporeal liver support systems may exert beneficial effects in AoCLF via removal of albumin-bound toxins. At present, two systems are commercially available, the molecular adsorbents recirculating system (MARS) and fractionated plasma separation, adsorption and dialysis (FPAD, also known as Prometheus). The aim of this study was to compare the effect of MARS and Prometheus treatments on the redox state of human serum albumin. Eight patients with AoCLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Sixteen treatments (eight MARS and eight Prometheus) were available for analysis. The fraction of human mercaptalbumin (HMA), human nonmercaptalbumin-1 (HNA1), and human nonmercaptalbumin-2 (HNA2) were measured before and after single MARS and Prometheus treatments and during follow-up. In AoCLF patients the oxidized fractions of albumin, HNA1, and HNA2 were markedly increased. Both MARS and Prometheus treatments resulted in a shift of HNA1 to HMA, while HNA2 was not significantly affected. This shift in albumin fractions was transient and disappeared within 24 h after treatment. There were no significant differences between MARS and Prometheus treatments with respect to the redox state of albumin. Both MARS and Prometheus treatments lead to transient improvements of the redox state of albumin, which could be beneficial in the treatment of AoCLF.

  16. Performance of scoring systems to predict mortality of patients with acute-on-chronic liver failure: A systematic review and meta-analysis.

    Science.gov (United States)

    Zheng, Yi-Xiang; Zhong, Xiao; Li, Ya-Jun; Fan, Xue-Gong

    2017-10-01

    Acute-on-chronic liver failure (ACLF) has characteristic feature of multisystem organ failure, rapid progression, and low early transplant-free survival. We performed a meta-analysis to determine the accuracy of five scoring systems in predicting mortality of ACLF patients. A systematic database search was performed, and retrieved articles were graded according to methodological quality. Collated data was meta-analyzed by hierarchical summarized receiver operating characteristic model and bivariate model to evaluate the diagnostic accuracy of scoring systems. Of 4223 studies identified, 26 studies involving 4732 ACLF patients were included. The model of end-stage liver disease (MELD) score was found to have largest the area under summarized receiver operating characteristic (AUROC) (0.82) compared with other estimated scoring systems, especially for 3-month mortality. MELD serum sodium (MELD-Na) score showed homologous high accuracy, with the AUROC was 0.81. However, meta-analyses of 16 studies showed that Child-Pugh-Turcotte score had least AUROC (0.71). Sequential organ failure assessment (SOFA) score presented moderately lower diagnostic accuracy, with AUROC being 0.73. Moreover, chronic liver failure-SOFA score presented excellent accuracy of prognostication with highest diagnostic odds ratios. This review demonstrated that MELD had moderate diagnostic accuracy to predict mortality of ACLF patients. Considering the expectative diagnostic value, chronic liver failure-SOFA could be regarded as a promising replacement of MELD. To improve the predictive power of scoring systems, multicenter prospective studies of large sample sizes with long-term follow-up are needed. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  17. Gamma-glutamyl transpeptidase-to-platelet ratio predicts the prognosis in HBV-associated acute-on-chronic liver failure.

    Science.gov (United States)

    Liu, Longgen; Lan, Qing; Lin, Lin; Lu, Jianchun; Ye, Chunyan; Tao, Qian; Cui, Manman; Zheng, Shuqin; Zhang, Xiujun; Xue, Yuan

    2018-01-01

    The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new noninvasive marker for assessing liver fibrosis. We aimed to evaluate the performance of GPR for prediction of 90-day mortality in patients with acute-on-chronic liver failure (ACLF). A total of 355 patients with HBV-associated ACLF were enrolled from two clinical centers and divided into training group (n=210) and validation group (n=145). Potential risk factors for 90-day mortality were analyzed. Age, MELD score and GPR were independent risk factors associated with ACLF prognosis. A new scoring system (MELD-GPR) was developed. MELD-GPR=9.211-0.029×age-0.290×MELD-0.460×GPR. For ACLF patients with liver cirrhosis, the area under the receiver operating characteristic curve (AUROC) of MELD-GPR was 0.788, which was significantly higher than that of MELD and MELD-Na (0.706 and 0.666, respectively). Patients were stratified into three groups according to MELD-GPR scores (high risk: 0.95), and the high-risk group (MELD-GPRGPRGPR into MELD may provide more accurate survival prediction in patients with HBV-ACLF. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The effect of plasma exchange on entecavir-treated chronic hepatitis B patients with hepatic de-compensation and acute-on-chronic liver failure.

    Science.gov (United States)

    Yue-Meng, Wan; Yang, Li-Hong; Yang, Jin-Hui; Xu, Ying; Yang, Jing; Song, Gui-Bo

    2016-05-01

    Various studies showed that entecavir (ETV) failed to improve the short-term survival in chronic hepatitis B (CHB) patients with severe acute exacerbation (SAE) and hepatic de-compensation or acute-on-chronic liver failure (ACLF). One study concluded that plasma exchange (PE) significantly decreased the short-term mortality of CHB patients with ACLF who were treated with lamivudine (LAM). Our study was designed to examine the effect of PE on CHB patients with ACLF who were treated with ETV. From August 2010 to January 2015, 38 (PE group) and 120 (control group) consecutive CHB-naïve patients with hepatic de-compensation and ACLF treated with PE plus ETV and ETV, respectively, were recruited. The primary endpoint was liver-related mortality at week 12. Biochemical and virological responses were also studied. At baseline, the PE group had higher serum alanine aminotransferase (ALT) levels and model for end-stage liver disease (MELD) scores, and had lower albumin levels than the control group. The cumulative survival rate at week 4 and week 12 in the PE group and control group were, respectively, 37 and 18 %, and 29 and 14 % (p  0.05). Univariate analysis showed that the control group had a higher liver-related mortality (p = 0.038) at week 12 than the PE group. Multivariate analysis showed that hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12. PE significantly improved the short-term survival of CHB patients with hepatic de-compensation and ACLF who were treated with ETV. Hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12.

  19. Complement Factor 3 Could Be an Independent Risk Factor for Mortality in Patients with HBV Related Acute-on-Chronic Liver Failure

    Directory of Open Access Journals (Sweden)

    Geng-lin Zhang

    2016-01-01

    Full Text Available The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF remains unclear. Serum levels of the third and fourth complement components (C3, C4 and complement function (CH50 were examined in this prospective, observational study. Associations between their expression and disease activity were analyzed. Survival was analyzed by Kaplan-Meier curves. Predictors of clinical outcome were determined by Cox regression analysis. C3, C4, and CH50 levels were significantly lower in HBV-ACLF patients compared to controls. C3, C4, and CH50 levels were negatively correlated with Tbil levels but positively associated with PTA levels. C3 levels were negatively associated with MELD-Na. C3 levels were significantly lower in HBV-ACLF patients who died compared to patients who survived. In a median hospital stay of 39 days, mortality occurred in 41 patients with a progressive increase based on C3 grade (P=0.008. The actuarial probability of developing mortality was significantly higher in patients with low C3 grade compared to those with high C3 grade (P<0.001. Multivariate Cox regression analysis showed that C3 levels were an independent predictor of mortality. Complement played a pathogenic role in HBV-ACLF patients and C3 was an independent predictor of mortality.

  20. Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

    Science.gov (United States)

    Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

    2017-01-01

    Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

  1. Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus-infected acute-on-chronic liver failure treated by entercavir: A prospective study.

    Science.gov (United States)

    Wan, Yue-Meng; Li, Yu-Hua; Xu, Zhi-Yuan; Yang, Jing; Yang, Li-Hong; Xu, Ying; Yang, Jin-Hui

    2017-12-01

    Therapeutic plasma exchange (TPE) and double plasma molecular absorption system (DPMAS) were two extracorporeal liver support systems. Few studies compared their efficacy profile. This study was to compare the efficacy of TPE and DPMAS on acute-on-chronic liver failure (ACLF) caused by hepatitis B virus (HBV-ACLF). 60 HBV-ACLF patients were enrolled and prospectively studied. All patients received entecavir therapy, and were assigned to TPE group (n = 33) and DPMAS group (n = 27). Primary end-points were the effects of TPE and DPMAS on liver function and serum inflammatory markers. Serum procalcitonin, interleukin (IL)-6, and high sensitive C-reactive protein (hsCRP) were significantly elevated in patients with HBV-ACLF. TPE achieved significantly higher removal rates of total bilirubin (TBIL, P = .002), direct bilirubin (DBIL, P = .006), and hsCRP (P = .010) than DPMAS, but DPMAS displayed lower loss rate of albumin (P = .000). TPE and DPMAS resulted in similarly increased serum IL-6 levels and comparable 12-week survivals (P > .05). Multivariate analysis showed that hospital stay (Relative Risk [RR]: 1.062, 95% Confidence Interval [CI]: 1.011-1.115, P = .016), prothrombin time (RR: 1.346, 95% CI: 1.077-1.726, P = .010), and international normalized ratio (RR: 0.013, 95% CI: 0.006-0.788, P = .041) were independent predictors for 12-week survival. Both TPE and DPMAS treatments were well-tolerated. Compared to DPMAS, TPE was more efficient in eliminating TBIL, DBIL, and hsCRP, but it was associated with higher loss rate of albumin. TPE and DPMAS were similar in improving 12-week survivals in HBV-ACLF. © 2017 Wiley Periodicals, Inc.

  2. Combining serum cystatin C with total bilirubin improves short-term mortality prediction in patients with HBV-related acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Zhihong Wan

    Full Text Available HBV-related acute-on-chronic liver failure (HBV-ACLF is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF.Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC was used to evaluate the efficacy of the variates for early predicting mortality.Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7% during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC and total bilirubin (TBil were independent factors significantly (P < 0.01 associated with survival. Our results further showed that new prognostic index (PI combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr. The survival rate in low risk group (PI < 3.91 was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91 (17.4%, P < 0.001.We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.

  3. TLR2 Expression in Peripheral CD4+ T Cells Promotes Th17 Response and Is Associated with Disease Aggravation of Hepatitis B Virus-Related Acute-On-Chronic Liver Failure

    Directory of Open Access Journals (Sweden)

    Chunli Xu

    2017-11-01

    Full Text Available Th17 responses have been shown to play crucial roles in the pathogenesis of hepatitis B virus (HBV-associated acute-on-chronic liver failure (ACLF. The mechanism underlying the enhanced Th17 responses in these patients remains largely unclear. Here we investigated toll-like receptors (TLRs expression in peripheral T cells and their roles in Th17 cell differentiation and disease aggravation in ACLF patients. 18 healthy subjects (HS, 20 chronic HBV-infected (CHB patients, and 26 ACLF patients were enrolled and examined for TLRs expression in peripheral blood mononuclear cells (PBMCs. The correlations of T cell TLR2 expression with the antigen non-specific Th17 responses and disease aggravation, as well as the Th17 response to TLR2 ligand stimulation were evaluated in ACLF patients. Compared to HS and CHB patients, ACLF patients showed a distinct TLRs expression pattern in PBMCs. Significantly increased TLR2 expression in T cells was observed in ACLF patients. The TLR2 expression in CD4+ T cells was correlated with the Th17 responses and the clinical markers for disease aggravation in ACLF patients. Moreover, TLR2 ligands stimulation promoted Th17 cell differentiation and response in PBMCs of ACLF patients. These findings implicate that TLR2 signaling plays critical roles in Th17 cell differentiation and disease aggravation of HBV-related ACLF.

  4. Urinary biomarkers for the prediction of reversibility in acute-on-chronic renal failure.

    Science.gov (United States)

    Luk, Cathy Choi-Wan; Chow, Kai-Ming; Kwok, Jeffrey Sung-Shing; Kwan, Bonnie Ching-Ha; Chan, Michael Ho-Ming; Lai, Ka-Bik; Lai, Fernand Mac-Moune; Wang, Gang; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

    2013-01-01

    There is no reliable clinical test to predict the reversibility of acute-on-chronic renal failure. We study whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal failure. We studied 39 adult patients with pre-existing chronic renal impairment presenting to us with acute-on-chronic renal failure. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level was measured. The mRNA of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), alpha-1-microglobulin (α1M), sodium/hydrogen exchanger-3 (NHE3), beta-2 microglobulin (β2M), and N-acetyl-β-D-glucosaminidase (NAG) in urinary sediment were quantified. Urinary NGAL level significantly correlated with the serum creatinine at presentation (r=0.762, pacute tubular necrosis than other causes of acute kidney injury (prenal function (r=0.387, p=0.026), as well as the estimated GFR 6 months later (r=0.386, p=0.027). In patients with acute-on-chronic renal failure, urinary NGAL level correlates with the severity of renal failure, while urinary α1M expression correlates with the degree of renal function recovery. Quantification of urinary α1M mRNA may be developed as an non-invasive tool for risk stratification of this group of patients.

  5. Immune mediated liver failure

    OpenAIRE

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  6. Analysis of TCM deficiency and excess attributes in patients with HBV-related acute-on-chronic liver failure based on phenotype of dendritic cells and function of T lymphocytes

    Directory of Open Access Journals (Sweden)

    YIN Sihan

    2016-04-01

    Full Text Available ObjectiveTo summarize the traditional Chinese medicine (TCM deficiency and excess attributes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF, and to analyze its association with the phenotype of dendritic cells (DCs and T lymphocyte subsets. MethodsThe basic information, stages, and TCM syndromes of 30 patients who were diagnosed with HBV-ACLF in The First Affiliated Hospital of Hunan University of Chinese Medicine from March to November, 2012 were collected, and according to their deficiency and excess attributes, they were divided into excess group and deficiency group. Ten healthy volunteers were enrolled as the control group. Flow cytometry was used to measure the percentage of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood and the expression rate of CD4+CD25highCD127low cells, as well as the expression rates of DCs with phenotypes of CD1α, HLA-DR, CD80, CD83, and CD86 which were isolated from peripheral blood mononucleated cells, induced, and cultured in vitro, and its association with TCM deficiency and excess attributes. The t-test was used for comparison of normally distributed continuous data between groups, the Wilcoxon rank sum test was used for comparison of continuous data which were not normally distributed between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsCompared with the healthy control group, the HBV-ACLF patients showed significant reductions in the percentages of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood and the expression rates of DCs with phenotypes of CD1α, HLA-DR, CD80, CD83, and CD86, as well as a significant increase in the expression rate of CD4+CD25highCD127lowcells (all P<0.01. Compared with the excess group, the deficiency group showed significant reductions in the percentages of CD3+ and CD4+ T lymphocytes and the expression rate of CD4+CD25highCD127low cells (all P<0.05. Compared with the deficiency group, the

  7. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, J P; Gluud, L L; Als-Nielsen, B

    2004-01-01

    Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery.......Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery....

  8. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, Jianping; Kjaergard, Lise Lotte; Als-Nielsen, Bodil

    2002-01-01

    Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure....

  9. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  10. Acute liver failure and acute kidney injury: Definitions, prognosis, and outcome

    NARCIS (Netherlands)

    Włodzimirow, K.A.

    2013-01-01

    The objective of this thesis was to investigate definitions, prognostic indicators and their association with adverse events, mainly mortality for acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute kidney injury (AKI).

  11. Iron lung vs mask ventilation in the treatment of acute on chronic respiratory failure in COPD patients: a multicenter study.

    Science.gov (United States)

    Corrado, Antonio; Confalonieri, Marco; Marchese, Santino; Mollica, Corrado; Villella, Giuseppe; Gorini, Massimo; Della Porta, Rossana

    2002-01-01

    Evaluation of the effectiveness of negative-pressure ventilation (NPV) with the use of the iron lung vs noninvasive positive-pressure ventilation (NIPPV) in the treatment of COPD patients with acute on chronic respiratory failure. A retrospective case-control study. Four Italian respiratory intermediate ICUs. Of a total of 393 COPD patients admitted to the ICU in 1996, 53 pairs were treated with the iron lung (NPV group). Patients treated with NIPPV (NIPPV group) were matched according to mean (+/- SD) age (70.3 +/- 7.1 vs 70.3 +/- 6.9 years, respectively), sex, causes of acute respiratory failure (ARF), APACHE (acute physiology and chronic health evaluation) II score (22.4 +/- 5.3 vs 22.1 +/- 4.6, respectively), pH (7.26 +/- 0.05 vs 7.27 +/- 0.04, respectively), and PaCO(2) (88.1 +/- 11.5 vs 85.1 +/- 13.5 mm Hg, respectively) on admission to the ICU. The effectiveness of matching was 98.4%. Five patients from the NPV group (9.4%) and seven patients from the NIPPV group (13.2%) needed endotracheal intubation (EI). The treatment failure rate (ie, death and/or need of EI) was 20.7% in the NPV group and 24.5% in the NIPPV group (difference was not significant). The mean duration of mechanical ventilation (29.6 +/- 28.6 vs 62.3 +/- 35.7 h, respectively) and length of hospital stay (10.4 +/- 4.3 vs 15 +/- 5.2 d, respectively) among the 35 concordant surviving pairs were significantly lower in the NPV group than in the NIPPV group (p = 0.001 and p = 0.001, respectively). These data suggest that both ventilatory techniques are equally effective in avoiding EI and death in COPD patients with ARF. Prospective trials are needed to confirm these preliminary results.

  12. Plasma Glutamine Concentrations in Liver Failure.

    Directory of Open Access Journals (Sweden)

    Gunnel Helling

    Full Text Available Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations.Four different groups of patients were studies; chronic liver failure (n = 40, acute on chronic liver failure (n = 20, acute fulminant liver failure (n = 20, and post-hepatectomy liver failure (n = 20. Child-Pugh and Model for End-stage Liver Disease (MELD scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion.All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100, severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong.Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

  13. Acute Liver Failure

    Science.gov (United States)

    ... begins in or spreads to your liver can cause your liver to fail. Shock. Overwhelming infection (sepsis) and shock can severely impair blood flow to the liver, causing liver failure. Many cases of acute liver failure have no apparent ... liver failure often causes complications, including: ...

  14. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  15. Acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Lee, William M; Wendon, Julia

    2015-01-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

  16. Acute Liver Failure.

    Science.gov (United States)

    Newland, Catherine D

    2016-12-01

    Pediatric acute liver failure (ALF) is a complex and rapidly progressive syndrome that results from a variety of age-dependent etiologies. It is defined by the acute onset of liver disease with no evidence of chronic liver disease. There must be biochemical or clinical evidence of severe liver dysfunction as defined by an international normalized ratio (INR) ≥2. If hepatic encephalopathy is present, INR should be ≥1.5. Unfortunately, due to the rarity of ALF in pediatric patients, there is a paucity of diagnostic and management algorithms and each patient must have an individualized approach. [Pediatr Ann. 2016;45(12):e433-e438.]. Copyright 2016, SLACK Incorporated.

  17. Allocation of patients with liver cirrhosis and organ failure to intensive care

    DEFF Research Database (Denmark)

    Prier Lindvig, Katrine; Søgaard Teisner, Ane; Kjeldsen, Jens

    2015-01-01

    patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature...... on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score. CONCLUSION......AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized...

  18. Improving lives through a bioartificial liver support system

    CSIR Research Space (South Africa)

    Naidoo, K

    2008-11-01

    Full Text Available requiring treatment to prevent acute liver failure in progressive chronic liver disease. Typically, BALSS will address its defined markets through the following applications: • Bridging patients with acute liver failure to transplantation • Bridging... patients with acute liver failure to recovery • Bridging/support of patients with acute-on-chronic liver failure • Post liver transplantation support • Support/treatment of patients with chronic liver disease • Support of patients with chronic...

  19. Extracorporeal liver support therapy with Prometheus in patients with liver failure in the intensive care unit.

    Science.gov (United States)

    Oppert, Michael; Rademacher, Sibylle; Petrasch, Kathrin; Jörres, Achim

    2009-10-01

    Acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water-soluble and water-insoluble, protein-bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water-soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5-6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P Prometheus therapy was well tolerated without relevant side-effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.

  20. Prometheus system: a technological support in liver failure.

    Science.gov (United States)

    Santoro, A; Faenza, S; Mancini, E; Ferramosca, E; Grammatico, F; Zucchelli, A; Facchini, M G; Pinna, A D

    2006-05-01

    The Prometheus system is a plasma filtration treatment coupling adsorption and hemodialysis (FPSA) aimed to blood purification in liver failure. After separation through an albumin-permeable membrane, plasma enters a secondary circuit where protein-bound toxic substances are removed by two adsorbers; p01, a neutral resin, and p02, an anion exchanger. Plasma is then returned to the venous line, where a high-flux hemodialyzer removes water-soluble substances. We used the Prometheus system in 12 patients with acute or acute-on-chronic liver insufficiency: eight cirrhosis, one posttransplant dysfunction, and three secondary liver insult (two cardiogenic shock and one rhabdomyolysis). All patients were severely hyperbilirubinemic, hypercholemic, and hyperammonemic. Twenty-eight sessions each lasting 340 +/- 40 minutes were performed (2.5/patient). The mean total bilirubin decreased from 33.6 +/- 20 to 22.2 +/- 13.6 mg/dL (P Prometheus, based on FPSA, produced high clearance for protein-bound and water soluble markers, which resulted in high treatment efficacy.

  1. Nonacetaminophen Drug-Induced Acute Liver Failure.

    Science.gov (United States)

    Thomas, Arul M; Lewis, James H

    2018-05-01

    Acute liver failure of all causes is diagnosed in between 2000 and 2500 patients annually in the United States. Drug-induced acute liver failure is the leading cause of acute liver failure, accounting for more than 50% of cases. Nonacetaminophen drug injury represents 11% of all cases in the latest registry from the US Acute Liver Failure Study Group. Although rare, acute liver failure is clinically dramatic when it occurs, and requires a multidisciplinary approach to management. In contrast with acetaminophen-induced acute liver failure, non-acetaminophen-induced acute liver failure has a more ominous prognosis with a lower liver transplant-free survival. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. MARS treatment in posthepatectomy liver failure

    NARCIS (Netherlands)

    van de Kerkhove, Maarten-Paul; de Jong, Koert P.; Rijken, Arjen M.; de Pont, Anne-Cornélie J. M.; van Gulik, Thomas M.

    2003-01-01

    Posthepatactomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver

  3. Prometheus--a new extracorporeal system for the treatment of liver failure.

    Science.gov (United States)

    Rifai, Kinan; Ernst, Thomas; Kretschmer, Ulrich; Bahr, Matthias J; Schneider, Andrea; Hafer, Carsten; Haller, Hermann; Manns, Michael P; Fliser, Danilo

    2003-12-01

    Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus, a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus system. Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus on 2 consecutive days for >4 h. Prometheus treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis. Prometheus is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus system are necessary to evaluate hard clinical end-points.

  4. Valproic Acid-Associated Liver Failure

    OpenAIRE

    J Gordon Millichap

    2011-01-01

    Researchers at the University of Maryland School of Medicine, Baltimore, and other centers analyzed the records of 17 children undergoing liver transplantation (LT) for valproic acid-associated liver failure (VPA-ALF) and 98 with ALF caused by other drugs (non-VPA-drug-induced acute liver failure [DIALF].

  5. Acute liver failure : Spontaneous recovery or transplantation?

    NARCIS (Netherlands)

    Meerman, L; Zijlstra, JG; Schweizer, JJ; Verwer, R; Slooff, MJH; Haagsma, EB

    1997-01-01

    Background: Decision-making in acute liver failure. Acute liver failure is a disease with multiple organ involvement and a high mortality rate. Conservative management alone will only partly influence the outcome. The option of emergency liver transplantation has greatly improved survival rates, but

  6. Mesenchymal Stem Cell Transplantation for Liver Cell Failure: A New Direction and Option

    Directory of Open Access Journals (Sweden)

    Yantian Cao

    2018-01-01

    Full Text Available Background and Aims. Mesenchymal stem cell transplantation (MSCT became available with liver failure (LF, while the advantages of MSCs remain controversial. We aimed to assess clinical advantages of MSCT in patients with LF. Methods. Clinical researches reporting MSCT in LF patients were searched and included. Results. Nine articles (n=476 related with LF patients were enrolled. After MSCT, alanine aminotransferase (ALT baseline decreased largely at half a month (P<0.05; total bilirubin (TBIL baseline declined to a certain stable level of 78.57 μmol/L at 2 and 3 months (P<0.05. Notably, the decreased value (D value of Model for End-Stage Liver Disease score (MELD of acute-on-chronic liver failure (ACLF group was higher than that of chronic liver failure (CLF group (14.93 ± 1.24 versus 4.6 ± 5.66, P<0.05. Moreover, MELD baseline of ≥20 group was a higher D value of MELD than MELD baseline of <20 group with a significant statistical difference after MSCT (P=0.003. Conclusion. The early assessment of the efficacy of MSCT could be based on variations of ALT at half a month and TBIL at 2 and 3 months. And it had beneficial effects for patients with LF, especially in ACLF based on the D value of MELD.

  7. Timing of glucocorticoid therapy for liver failure

    Directory of Open Access Journals (Sweden)

    MENG Qinghua

    2017-09-01

    Full Text Available There are still controversies over the use of glucocorticoids in the treatment of liver failure, and current guidelines for liver failure recommend that glucocorticoids should be used with great caution. However, some latest studies have shown that the use of glucocorticoid therapy in the early stage of liver failure can bring more benefits to patients. Age, disease progression rate and severity, and complications of liver failure may affect the treatment outcome. Further studies are still needed for the selection of right patients, drugs and dose, and treatment timing.

  8. The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management.

    Science.gov (United States)

    Rocen, M; Kieslichova, E; Merta, D; Uchytilova, E; Pavlova, Y; Cap, J; Trunecka, P

    2010-11-01

    Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α(1) fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α(1) fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Acute liver failure in children.

    Science.gov (United States)

    Squires, Robert H

    2008-05-01

    Acute liver failure (ALF) in children differs from that observed in adults in both the etiologic spectrum and the clinical picture. Children, particularly very young ones, do not demonstrate classical features of encephalopathy and the definition of ALF has been revised to include patients with advanced coagulopathy, regardless of mental status. A significant number of these children will go on to require transplant or die. Etiologies vary by age with metabolic and infectious diseases prominent in the first year of life and acetaminophen overdose and Wilson's disease occurring in adolescents. In almost 50% of cases, however, the child has an indeterminate cause for ALF. Management requires a multidisciplinary approach and is directed at establishing the etiology where possible and monitoring, anticipating, and managing the multisystem complications that occur in children with ALF. Overall, short-term outcomes are better in children than adults but are dependent upon the degree of encephalopathy and diagnosis.

  10. Acute liver failure and self-medication

    OpenAIRE

    OLIVEIRA, André Vitorio Câmara de; ROCHA, Frederico Theobaldo Ramos; ABREU, Sílvio Romero de Oliveira

    2014-01-01

    INTRODUCTION: Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. AIM: To warn about how the practice of self-medication can be responsible for acute liver failure. METHOD: Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute l...

  11. Therapeutic hypothermia for acute liver failure

    DEFF Research Database (Denmark)

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    Cerebral edema is a potentially life-threatening complication of acute liver failure, the syndrome of abrupt loss of liver function in a patient with a previously healthy liver. Although the prevalence of cerebral edema appears to be decreasing, patients with rapidly progressive (hyperacute) liver...... failure, such as after acetaminophen overdose, remain at highest risk. In severe cases of cerebral edema, intracranial hypertension develops and leads to brain death after brainstem herniation or to anoxic brain injury and permanent neurologic impairment. Intracranial hypertension in patients with acute...... liver failure often can be temporarily controlled by manipulating body position, increasing the degree of sedation, and increasing blood osmolarity through pharmacologic means. However, these maneuvers often postpone, but do not eliminate, the risk of brainstem herniation unless orthotopic liver...

  12. Acute liver failure and self-medication.

    Science.gov (United States)

    de Oliveira, André Vitorio Câmara; Rocha, Frederico Theobaldo Ramos; Abreu, Sílvio Romero de Oliveira

    2014-01-01

    Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. To warn about how the practice of self-medication can be responsible for acute liver failure. Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute liver failure [tiab] AND acetaminophen [tiab]; self-medication [tiab] AND acetaminophen [tiab]; acute liver failure [tiab] AND dietary supplements [tiab]; self-medication [tiab] AND liver failure [tiab] and self-medication [tiab] AND green tea [tiab]. In Lilacs and SciELO used the descriptor self medication in Portuguese and Spanish. From total surveyed were selected 27 articles and five sites specifically related to the purpose of this review. Legislation and supervision disabled and information inaccessible to people, favors the emergence of cases of liver failure drug in many countries. In the list of released drugs that deserve more attention and care, are some herbal medicines used for the purpose of weight loss, and acetaminophen. It is recommended that institutes of health intensify supervision and better orient their populations on drug seemingly harmless, limiting the sale of products or requiring a prescription for release them.

  13. EVALUATION OF LIVER FAILURE STAGE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    G. V. Volynets

    2013-01-01

    Full Text Available Aim: to develop a system of evaluation of liver failure stage in children based on the International classification of functioning, disability and health (ICF. Patients and methods: based on the retrospective analysis of 14 biochemical markers, characterizing hepatic role in proteins, lipids and carbohydrates metabolism, of 115 children without liver diseases, 15 children who died of liver failure and 220 patients with various hepatic disorders, being followed-up in the SCCH of RAMS, a score system of evaluation of liver failure stage in children as an additional diagnostic tool was developed. Each of the biochemical markers was assessed according to the 5-point rating scale in dependence of its changes intensity. Results: the sum of points was considered to be a criterion of liver failure stage. According to the ICF recommendations, decrease of points on 0–4% (54–56 points corresponds with absence of liver failure; 5–24% (43–53 points — as mild dysfunction, 25–49% (29–42 points — as moderate; 50-95% (3–28 points — as severe; and 96–100% (0-2 points — as absolute failure. Conclusions: score system of evaluation of liver failure stage can be applied at any step of diagnostics and treatment of children of any age, due to independence of the used markers from the age. It can be used in assessment of the severity of disorder in dynamics, in determination of the prognosis and as criterion of indications to liver transplantation, as well as during medico-social examination.

  14. Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure

    Directory of Open Access Journals (Sweden)

    DING Yitao

    2017-09-01

    Full Text Available The main features of liver failure are extensive necrosis of hepatocytes, rapid disease progression, and poor prognosis, and at present, there are no effective drugs and methods for the treatment of liver failure. This article summarizes four treatment methods for liver failure, i.e., medical treatment, cell transplantation, liver transplantation, and artificial liver support therapy, and elaborates on the existing treatment methods. The current medical treatment regimen should be optimized; cell transplantation has not been used in clinical practice; liver transplantation is the most effective method, but it is limited by donor liver shortage and high costs; artificial liver can effectively remove toxic substances in human body. Therefore, this article puts forward artificial liver as a transition for liver transplantation; artificial liver can buy time for liver regeneration or liver transplantation and prolong patients′ survival time and thus has a promising future. The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

  15. Plasma osteopontin in acute liver failure

    DEFF Research Database (Denmark)

    Srungaram, Praveen; Rule, Jody A; Yuan, He Jun

    2015-01-01

    BACKGROUND: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function...... in the setting of massive hepatocyte injury. METHODS: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1...

  16. Liver function during extracorporeal whole liver perfusion in a pig model of acute ischemic liver failure.

    Science.gov (United States)

    Méchet, Isabelle; Lhuillier, Franck; Blanchet, Marie Cécile; Pouyet, Michel; Viale, Jean-Paul; Goudable, Joelle; Annat, Guy; Scoazec, Jean Yves; Boillot, Olivier; Liotard, Dominique; Merle, Eric; Delafosse, Bertrand

    2004-01-01

    The shortage of livers for transplant has renewed interest in the potential of temporary liver support such as extra corporeal whole liver perfusion. In an ischemic induced liver failure model we perfused an extra corporeal liver through only a portal vein and assessed the function of this ex vivo liver by using hepatic tests to estimate elimination as well as synthesis capacities. Acute liver failure was performed in five control pigs by a hepatic devascularization associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after this hepatic devascularization, animals were connected to an extra corporeal liver perfused via the portal vein with blood withdrawn from the ischemic liver animal from its portal vein. Devascularization of the liver induced an increase in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids to aromatic amino acids, and a decrease in blood urea and indocyanine green and galactose clearances. In treated animals, urea, amino acid ratio, and clearances increased after the ex vivo liver perfusion. In this group, mean bile production and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min, respectively. In an acute ischemic liver failure pig model, an extra corporeal whole liver perfusion demonstrated detoxification properties as well as synthesis capacities.

  17. Crizotinib-induced fatal fulminant liver failure

    NARCIS (Netherlands)

    van Geel, Robin M J M; Hendrikx, Jeroen J M A; Vahl, Jelmer E.; van Leerdam, Monique E.; van den Broek, Daan; Huitema, Alwin D R; Beijnen, Jos H.; Schellens, Jan H M; Burgers, Sjaak A.

    2016-01-01

    Herein we describe a case of a 62-year-old female in good clinical condition with non-small-cell lung cancer who was treated with crizotinib. After 24 days of crizotinib therapy she presented with acute liver failure. Serum aspartate aminotransferase and alanine aminotransferase levels had increased

  18. Acute Liver Failure Secondary to Niacin Toxicity

    Directory of Open Access Journals (Sweden)

    Marc A. Ellsworth

    2014-01-01

    Full Text Available A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

  19. Steroid use in acute liver failure

    DEFF Research Database (Denmark)

    Karkhanis, Jamuna; Verna, Elizabeth C; Chang, Matthew S

    2014-01-01

    UNLABELLED: Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug......-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS......% versus 66%, P = 0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P = 0...

  20. Prognostic modeling in pediatric acute liver failure.

    Science.gov (United States)

    Jain, Vandana; Dhawan, Anil

    2016-10-01

    Liver transplantation (LT) is the only proven treatment for pediatric acute liver failure (PALF). However, over a period of time, spontaneous native liver survival is increasingly reported, making us wonder if we are overtransplanting children with acute liver failure (ALF). An effective prognostic model for PALF would help direct appropriate organ allocation. Only patients who would die would undergo LT, and those who would spontaneously recover would avoid unnecessary LT. Deriving and validating such a model for PALF, however, encompasses numerous challenges. In particular, the heterogeneity of age and etiology in PALF, as well as a lack of understanding of the natural history of the disease, contributed by the availability of LT has led to difficulties in prognostic model development. Several prognostic laboratory variables have been identified, and the incorporation of these variables into scoring systems has been attempted. A reliable targeted prognostic model for ALF in Wilson's disease has been established and externally validated. The roles of physiological, immunological, and metabolomic parameters in prognosis are being investigated. This review discusses the challenges with prognostic modeling in PALF and describes predictive methods that are currently available and in development for the future. Liver Transplantation 22 1418-1430 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  1. Disease assessment and prognosis of liver failure

    Directory of Open Access Journals (Sweden)

    ZHANG Jing

    2016-09-01

    Full Text Available Liver failure has a high fatality rate and greatly threatens human health. Liver transplantation can effectively reduce the fatality rate. However, the problems such as donor shortage and allograft rejection limit the wide application of liver transplantation. An accurate early assessment helps to evaluate patients′ condition and optimize therapeutic strategies. At present, commonly used systems for prognostic evaluation include the King′s College Hospital, MELD, integrated MELD, Child-Pugh score, CLIF-SOFA, CLIF-C ACLFS, and D-MELD, and each system has its own advantages and disadvantages. Among these systems, the MELD scoring system is the most commonly used one, and the D-MELD scoring system is the most innovative one, which can be used for patients on the waiting list for liver transplantation. This article elaborates on the characteristics and predictive value of each scoring system in clinical practice.

  2. Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver

    NARCIS (Netherlands)

    van de Kerkhove, Maarten-Paul; di Florio, Ernesto; Scuderi, Vincenzo; Mancini, Antonio; Belli, Antonello; Bracco, Adele; Scala, Daniela; Scala, Simona; Zeuli, Laura; Di Nicuolo, Giuseppe; Amoroso, Pietro; Calise, Fulvio; Chamuleau, Robert A. F. M.

    2003-01-01

    Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 X 109 viable primary porcine hepatocytes isolated from a specified

  3. Acute liver failure complicating viral hepatitis A

    Directory of Open Access Journals (Sweden)

    Daniel Rui Diniz-Santos

    Full Text Available Hepatitis A is one of the most frequent infectious liver diseases affecting children worldwide. The disease is usually mild and self-limited, and complications are very rare. Nevertheless, hepatitis A can sometimes cause acute liver failure (ALF, a severe, life-threatening condition. Herein is reported a case of a child who presented ALF during a course of hepatitis A. The need for early identification of possible ALF cases among hepatitis A patients, and for effective ways of evaluating such a possibility, are discussed. We also emphasize the importance of prevention measures, especially vaccination.

  4. HEPATIC DIALYSIS IN NEONATES WITH ACUTE LIVER FAILURE

    OpenAIRE

    Stancu, Samantha Mc Kenzie; Cirstoveanu, Catalin Gabriel

    2016-01-01

    Hepatic dialysis is an artificial extracorporeal liver support device designed to filter out toxins accumulated in patients with acute liver failure. Although it is a rare entity encountered in neonates, acute liver failure is a highly fatal condition, with seventy percent resulting in mortality without liver transplantation. Scientific data on extracorporeal liver support concerning the pediatric population is scarce in literature. Artificial extracorporeal liver support devices in the form ...

  5. Etiology of pediatric acute liver failure

    OpenAIRE

    GUO Jing; SUN Mei

    2017-01-01

    Pediatric acute liver failure (PALF) is a complex syndrome with rapid progression, and the cause of PALF is age-dependent. This article analyzes the common causes of PALF in clinical practice, including infection factors, inherited metabolic factors, poisoning and drugs, abnormal perfusion, and autoimmune diseases, among which infection factors are the most common cause. With the improvement in diagnosis and treatment techniques, the diagnostic rate of PALF caused by inherited metabolic disea...

  6. "ACUTE LIVER FAILURE" : THE HEART MAY BE THE MATTER

    NARCIS (Netherlands)

    de Leeuw, K.; van der Horst, I. C. C.; van der Berg, A. P.; Ligtenberg, J. J. M.; Tulleken, J. E.; Zijlstra, J. G.; Meertens, John H. J. M.

    2011-01-01

    Hypoxic hepatitis secondary to heart failure is a known and treatable cause of liver failure. The diagnosis may be difficult, especially when symptoms of heart failure are absent. We present two patients who were transferred to our hospital with the diagnosis of acute liver failure to be screened

  7. Intensive Care Management of Pediatric Acute Liver Failure.

    Science.gov (United States)

    Lutfi, Riad; Abulebda, Kamal; Nitu, Mara E; Molleston, Jean P; Bozic, Molly A; Subbarao, Girish

    2017-05-01

    Pediatric acute liver failure is rare but life-threatening illness that occurs in children without preexisting liver disease. The rarity of the disease, along with its severity and heterogeneity, presents unique clinical challenges to the physicians providing care for pediatric patients with acute liver failure. In this review, practical clinical approaches to the care of critically ill children with acute liver failure are discussed with an organ system-specific approach. The underlying pathophysiological processes, major areas of uncertainty, and approaches to the critical care management of pediatric acute liver failure are also reviewed.

  8. Etiology of pediatric acute liver failure

    Directory of Open Access Journals (Sweden)

    GUO Jing

    2017-10-01

    Full Text Available Pediatric acute liver failure (PALF is a complex syndrome with rapid progression, and the cause of PALF is age-dependent. This article analyzes the common causes of PALF in clinical practice, including infection factors, inherited metabolic factors, poisoning and drugs, abnormal perfusion, and autoimmune diseases, among which infection factors are the most common cause. With the improvement in diagnosis and treatment techniques, the diagnostic rate of PALF caused by inherited metabolic diseases and autoimmune diseases keeps increasing. Due to the small number of PALF patients, there lacks experience in etiological diagnosis. This article summarizes related reports, in order to provide a reference for screening the causes of PALF.

  9. Babesiosis Presenting as Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Yousef Nassar

    2017-12-01

    Full Text Available Babesiosis is a zoonotic, tick-borne infection caused by the protozoan Babesia. It is transmitted by the Ixodes ticks which transmit the infection to humans. Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum are species that have been identified as being infectious to humans worldwide. The most common species causing infection to humans is B. microti which is endemic to the Northeast and Midwestern United States with most infections occurring between the months of May and October. We report a case of an elderly man with acute liver failure due to an infection with B. microti.

  10. Pediatric intestinal failure-associated liver disease.

    Science.gov (United States)

    Courtney, Cathleen M; Warner, Brad W

    2017-06-01

    The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients. Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined. IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.

  11. Several issues regarding evaluation of renal injury and renal insufficiency in patients with liver disease

    OpenAIRE

    HAO Kunyan; YU Yuecheng

    2016-01-01

    In patients with liver disease such as viral hepatitis and liver cirrhosis, renal injury and renal insufficiency can be generally classified as acute kidney injury (AKI), chronic kidney disease, and acute-on-chronic nephropathy. AKI can be classified as stage 1 (risk stage), stage 2 (injury stage), and stage 3 (failure stage). Traditionally hepatorenal syndrome is classified as types Ⅰ and Ⅱ, and in recent years, type Ⅲ hepatorenal syndrome with organic renal injury has been proposed. Hepator...

  12. Cerebral blood flow autoregulation in experimental liver failure

    DEFF Research Database (Denmark)

    Dethloff, T.J.; Larsen, F.S.; Knudsen, Gitte Moos

    2008-01-01

    Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes...... impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood...... edema/high ICP. Nor does portacaval shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis and reduced liver mass are associated with loss of CBF autoregulation Udgivelsesdato: 2008/5...

  13. Detoxifying capacity and kinetics of prometheus--a new extracorporeal system for the treatment of liver failure.

    Science.gov (United States)

    Evenepoel, Pieter; Laleman, Wim; Wilmer, Alexander; Claes, Kathleen; Maes, Bart; Kuypers, Dirk; Bammens, Bert; Nevens, Frederik; Vanrenterghem, Yves

    2005-01-01

    Extracorporeal liver support therapies have been used for several decades as a bridging therapy prior to liver transplantation or as an addendum to standard medical therapy. The Prometheus system represents a cell-free, extracorporeal, liver assist method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the removal capacity and selectivity of the different inbuilt dialyzers and adsorption columns during a single 6-hour treatment. Nine patients with acute on chronic liver failure were included (6 females, age 49+/- 4 years). Levels of endogenous toxins (urea nitrogen [UN, mg/dl], creatinine [Cr, mg/dl], total bilirubin [tB, mg/dl], and bile acids [BA, mumol/l]) and albumin [Alb, g/l] were monitored in blood sampled at different sites (arterial line, venous line and between the absorbers and the high-flux dialyzer) and at various time points (time 0, 30, 60, 120, 240, and 360 min). A significant decrease of the serum level of all toxins was observed (UN 108.7+/- 23.2 vs. 38.1+/- 14.9, Cr 2.4+/- 0.7 vs. 1.2+/- 0.3, tB 31.1+/- 4.1 vs. 17.0+/- 1.6, BA 155.7+/- 32.5 vs. 66.0+/- 15.4; mean+/- SEM, time 0 vs. time 360, signed rank rest, all pPrometheus system. Our data suggest that the rate and efficacy of removal of albumin-bound toxins is related to both the strength of the albumin binding and the saturation of the adsorption columns. Limited losses of albumin occur during treatment with the Prometheus system. Copyright (c) 2005 S. Karger AG, Basel.

  14. Acute renal failure in liver transplant patients: Indian study.

    Science.gov (United States)

    Naik, Pradeep; Premsagar, B; Mallikarjuna, M

    2015-01-01

    The acute renal failure is the frequent medical complication observed in liver transplant patients. The objective of this study was to determine the cause of acute renal failure in post liver transplant patients. A total of 70 patients who underwent (cadaveric 52, live 18) liver transplantation were categorized based on clinical presentation into two groups, namely hepatorenal failure (HRF, n = 29), and Hepatic failure (HF, n = 41). All the patients after the liver transplant had received tacrolimus, mycophenolate and steroids. We analyzed the modification of diet in renal disease, (MDRD) serum urea, creatinine and albumin before and after 5th and 30th day of liver transplant and data was categorized into survivors and non-survivors group. In HRF survivor group, serum creatinine, and urea levels were high and, albumin, MDRD were low in pre- transplant and reached to normal levels on 30th day of post transplant, and 79.3 % of patients in this group showed resumption of normal kidney function. On the contrary in HRF nonsurvivor group, we did not observed any significant difference and 20.7 % of patients showed irreversible changes after the liver transplant. In HF survivor group, 82.9 % of liver failure patients did not show any deviation in serum creatinine, urea, albumin and MDRD, whereas in HF non survivor group, 17.1 % of liver failure patients who had HCV positive before the transplant developed acute renal failure. The levels of creatinine, urea, albumin and MDRD were normal before the transplant and on day 30th, the levels of albumin and MDRD were significantly low whereas serum urea, creatinine levels were high. In conclusion, based on these observations, an diagnosis and treatment of Acute renal failure is important among the liver transplantation cases in the early postoperative period.

  15. Etiology and Outcome of Acute Liver Failure: Experience from a Liver Transplantation Centre in Montreal

    Directory of Open Access Journals (Sweden)

    Geneviève Tessier

    2002-01-01

    Full Text Available BACKGROUND: Acute liver failure is a rare condition in which massive liver injury is associated with the rapid development of hepatic encephalopathy. Although viral hepatitis and drug-induced liver injury are the most common causes, no specific etiology is found in a substantial proportion of cases reported from Europe and the United States.

  16. Systemic Mastocytosis Associated with Liver Failure in an Adult ...

    African Journals Online (AJOL)

    A 10-year–old German shepherd dog was presented with right fore limb oedema, ascites and hepatomegaly. A clinical diagnosis of ehrlichiosis and liver failure was made. Response to therapy was unfavorable and with the owner's consent, euthanasia was performed. Necropsy findings revealed a markedly enlarged liver ...

  17. Acute liver failure and transplantation in children | Horslen | South ...

    African Journals Online (AJOL)

    Acute liver failure (ALF) was relatively easy to recognise in the days before liver transplantation became available as rescue therapy, because the diagnosis was based on end-stage disease manifestations such as profound coagulopathy, jaundice, encephalopathy and cerebral oedema (in a patient with no history of ...

  18. Yogi Detox Tea: A Potential Cause of Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Keerthana Kesavarapu

    2017-01-01

    Full Text Available We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects.

  19. Advances in the treatment of acute liver failure

    Directory of Open Access Journals (Sweden)

    LUO Ling

    2018-02-01

    Full Text Available Acute liver failure (ALF is a rare life-threatening disease with rapid progression and a low survival rate and affects the function of multiple organ systems. Early identification of cause and protection of vital organs are critical for patients' survival. With the development in artificial liver, stem cell transplantation, and liver transplantation in recent years, the outcome of ALF has been greatly improved. This article elaborates on the treatment of ALF from the aspects of the etiology of ALF and major organ systems involved and introduces the latest advances in artificial liver and stem cell transplantation.

  20. Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation.

    Science.gov (United States)

    Ockner, S A; Brunt, E M; Cohn, S M; Krul, E S; Hanto, D W; Peters, M G

    1990-01-01

    A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.

  1. Clinical observation on the treatment of acute liver failure by combined non-biological artificial liver.

    Science.gov (United States)

    Li, Maoqin; Sun, Jingxi; Li, Jiaqiong; Shi, Zaixiang; Xu, Jiyuan; Lu, Bo; Cheng, Shuli; Xu, Yanjun; Wang, Xiaomeng; Zhang, Xianjiang

    2016-12-01

    The clinical efficacy and safety of different combinations of non-bio artificial liver in the treatment of acute liver failure was examined. A total of 61 cases were selected under blood purification treatment from the patients with severe acute liver failure admitted to the severe disease department of the hospital from December, 2010 to December, 2015. Three types of artificial liver combinations were observed, i.e., plasma exchange plus hemoperfusion plus continuous venovenous hemodiafiltration (PE+HP+CVVHDF), PE+CVVHDF and HP+CVVHDF. The heart rate (HR), mean arterial pressure (MAP), respiratory index (PaO 2 /FiO 2 ), liver and kidney function indicator, as well as platelet and coagulation function were compared. A comparison before and after the treatment using the three methods, showed improvement in the HRs, MAPs, PaO 2 /FiO 2 , total bilirubins (TBIL) and alanine aminotransferases (ALT) (Prate of 62.3% (38/61), and a viral survival rate of 35.0% (7/20); with the non-viral survival rate being 75.6% (31/41). In conclusion, following the treatment of three types of artificial livers, the function was improved to varying degrees, with the PE+HP+CVVHDF and the PE+CVVHDF method being better. By contrast, after the treatment of non-viral liver failure, the survival rate was significantly higher than the patients with viral liver failure.

  2. Outcome of acute liver failure in the elderly

    DEFF Research Database (Denmark)

    Schiødt, Frank V; Chung, Raymond T; Schilsky, Michael L

    2009-01-01

    Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age > or = 60 years, on outcomes in patients with ALF. One thousand one...... hundred twenty-six consecutive prospective patients from the US Acute Liver Failure Study Group registry were studied. The median age was 38 years (range, 15-81 years). One thousand sixteen patients (90.2%) were younger than 60 years (group 1), and 499 (49.1%) of these had acetaminophen-induced ALF...... and 48.2% in group 2 for non-acetaminophen patients (P liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P...

  3. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    A.C. Spósito

    1997-11-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

  4. Neonatal liver failure due to deoxyguanosine kinase deficiency

    Science.gov (United States)

    Nobre, Susana; Grazina, Manuela; Silva, Francisco; Pinto, Carla; Gonçalves, Isabel; Diogo, Luísa

    2012-01-01

    Deoxyguanosine kinase (dGK) deficiency, a rare severe cause of mitochondrial DNA (mtDNA) depletion, has two forms of presentation: hepatocerebral syndrome and isolated hepatic disease. The authors report three cases with neonatal liver failure due to dGK deficiency. Consanguinity was present in all patients. One patient had a brother who died with a probable diagnosis of neonatal haemochromatosis. All patients had progressive cholestatic liver failure, hypoglycaemia, hyperlactacidaemia, elevated ferritin levels and nystagmus, since first day of life. Liver tissue study revealed: cholestasis, iron deposits, microvesicular steatosis and fibrosis/cirrhosis. Only one patient was submitted to liver transplantation. The other two died, at 2 and 5 months of age. mtDNA quantification and DGUOK gene study should be considered in infants/neonates with acute liver failure and systematically performed in patients with hepatocerebral presentation. Differential diagnosis with neonatal haemochromatosis is needed. Liver transplantation might be a therapeutic option. Early diagnosis is important for genetic counselling. PMID:22602837

  5. Immunophenotype predicts outcome in pediatric acute liver failure.

    Science.gov (United States)

    Bucuvalas, John; Filipovich, Lisa; Yazigi, Nada; Narkewicz, Michael R; Ng, Vicky; Belle, Steven H; Zhang, Song; Squires, Robert H

    2013-03-01

    We sought to determine whether markers of T-cell immune activation, including soluble interleukin 2 receptor alpha (sIL2Rα) levels predict outcome in pediatric acute liver failure and may target potential candidates for immunomodulatory therapy. We analyzed markers of immune activation in 77 patients with pediatric acute liver failure enrolled in a multinational, multicenter study. The outcomes were survival with native liver, liver transplantation (LT), and death without transplantation within 21 days after enrollment. Adjusting for multiple comparisons, only normalized serum sIL2Rα level differed significantly among the 3 outcomes, and was significantly higher in patients who died (P=0.02) or underwent LT (P=0.01) compared with those who survived with their native liver. The 37 patients with normal sIL2Rα levels all lived, 30 with their native liver. Of the 15 subjects with markedly high sIL2Rα (≥5000 IU/mL), 5 survived with their native liver, 2 died, and 8 underwent LT. Evidence of immune activation is present in some patients who die or undergo LT. Patients with higher sIL2Rα levels were more likely to die or undergo LT within 21 days than those with lower levels. Identifying a subset of patients at risk for poor outcome may form the foundation for targeted clinical trials with immunomodulatory drugs.

  6. Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

    NARCIS (Netherlands)

    Stravitz, R. Todd; Ellerbe, Caitlyn; Durkalski, Valerie; Reuben, Adrian; Lisman, Ton; Lee, William M.

    BACKGROUND & AIMS: Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We

  7. Acute Liver Failure During Deferasirox Chelation: A Toxicity Worth Considering.

    Science.gov (United States)

    Menaker, Nathan; Halligan, Katharine; Shur, Natasha; Paige, John; Hickling, Matthew; Nepo, Anne; Weintraub, Lauren

    2017-04-01

    This case report details a unique case of acute, reversible liver failure in a 12-year-old male with sickle cell anemia on chronic transfusion protocol and deferasirox chelation. There is substantial literature documenting deferasirox-induced renal injury, including Fanconi syndrome, but less documentation of hepatic toxicity and few reports of hepatic failure. The case highlights the importance of close monitoring of ferritin, bilirubin, and transaminases for patients on deferasirox.

  8. A case of acute liver failure in dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Rama Biswas

    2013-07-01

    Full Text Available Dengue is an arboviral disease endemic in many parts of the world. The clinical presentation of dengue viral infection ranges from asymptomatic illness to fatal dengue shock syndrome. Although, it is known to cause hepatic involvement, it occasionally results in acute hepatic failure. We report a case of dengue hemorrhagic fever presenting with acute liver failure. The case recovered completely after treatment. Ibrahim Med. Coll. J. 2013; 7(2: 41-42

  9. Outcome of 200 Pediatric Living Donor Liver Transplantations in India.

    Science.gov (United States)

    Mohan, Neelam; Karkra, Sakshi; Rastogi, Amit; Dhaliwal, Maninder S; Raghunathan, Veena; Goyal, Deepak; Goja, Sanjay; Bhangui, Prashant; Vohra, Vijay; Piplani, Tarun; Sharma, Vivek; Gautam, Dheeraj; Baijal, S S; Soin, A S

    2017-11-15

    To describe our experience of pediatric living donor liver transplantation from India over a period of 12 years. A retrospective analysis of 200 living donor liver transplantation in children (18 years or younger) was done for demographic features, indications, donor and graft profile and outcome. Between September 2004 and July 2016, 200 liver transplants were performed on 197 children. Fifty transplants were done in initial 6 years and 150 in next 6 years. All donors (51% mothers) were discharged with a mean stay of 7 days. The leading indications of liver transplants were cholestatic liver disease (46%) followed by metabolic liver disease (33%) and acute liver failure/acute on chronic liver failure (28.5%). Biliary leakage (8.5%), biliary stricture (9%), hepatic artery thrombosis (4.5%) and portal vein thrombosis (4%) were the most common surgical complications; all could be managed by surgical or interventional radiological measures, except in one child who died. Sepsis, acute rejection and CMV hepatitis in first 6 months were seen in 14.5%, 25% and 17% cases, respectively. Post-transplant lymphoproliferative disease was seen in only 1.5%. Re-transplant rate was 1.5%. The overall 1 year survival rate was 94% and 5 year actuarial survival was 87% with no statistically significant difference between children weight 10 kg. Outcome in acute liver failure did not differ significantly between those with acute on chronic liver failure vs. those with chronic liver disease. Advances in medical and surgical techniques associated with multidisciplinary teams including skilled pediatric liver transplant surgeons, anesthetists, dedicated pediatric hepatologists, pediatric intensivists, interventional radiologists and pathologists resulted in an excellent outcome of living related liver transplants in children. Low age and weight of the baby does not seem to be a contraindication for liver transplantation as outcome were comparable in our experience.

  10. [The Importance of Early Referral in Pediatric Acute Liver Failure].

    Science.gov (United States)

    Jerónimo, Mónica; Moinho, Rita; Pinto, Carla; Carvalho, Leonor; Gonçalves, Isabel; Furtado, Emanuel; Farela Neves, José

    2015-01-01

    Acute liver failure is a rare disorder associated to high morbidity and mortality despite survival improvement through liver transplantation. The importance of a multidisciplinary approach and early referral to a pediatric liver transplantation center were important conclusions of a national meeting in 2008, from which resulted an actuation consensus. To characterize acute liver failure admissions in a Pediatric Intensive Care Unit of the portuguese pediatric livertransplantation center. To compare results before (A) and after (B) 2008. Observational, retrospective study during a 20 year period (1994-2014). age liver failure (INR ≥ 2 without vitamin K response and hepatocellular necrosis). Children with previous liver disease were excluded. Fifty children were included, with median age of 24.5 months. The most common etiology under 2 years old was metabolic (34.6%) and above that age was infectious (29.2%). Forty six percent were submitted to liver transplantation and 78% of them survived. Overall mortality was 34%. Median referral time was 7 days in period A (n = 35) and 2 days in period B (n = 15; p = 0.006). Pediatric risk of mortality's median was 14.7 in period A and 6.5 in B (p = 0.019). Mortality was 37% vs 26% in periods A and B, respectively (p = 0.474). Overall mortality was similar to the observed in other European centers. Liver transplantation is in fact the most effective therapeutic option. After 2008, there was a reduction in referral time and cases severity on admission; however, mortality has not reduced so far.

  11. Arterial ammonia levels in the management of fulminant liver failure

    Directory of Open Access Journals (Sweden)

    Curry S

    2011-06-01

    Full Text Available Previous studies have suggested that an arterial ammonia level greater than 150 mmol/L is highly sensitive for predicting subsequent development of cerebral edema in patients with fulminant liver failure. We performed a prospective cohort study to confirm this relationship. We enrolled 22 consecutive patients who presented to our transplant hepatology service with grade 3-4 encephalopathy associated with fulminant liver failure. All patients underwent placement of an intraparenchymal ICP monitor, and every 12 hourly arterial ammonia levels. The prevalence of intracranial hypertension (IHTN in our population was 95% (21/22 patients, with 82 discrete episodes recorded. The sensitivity of arterial ammonia levels to predict the onset of IHTN was 62% (95% CI: 40.8 to 79.3 at a cut point of 150 mmol/L. Arterial ammonia levels preceding the first intracranial hypertension event were less than 150 mmol/L in 8 of 21 patients (39%. Fifty nine of 82 episodes of IHTN (73% occurred when arterial ammonia levels were less than 150 mmol/L. We conclude that the arterial ammonia level is not useful in making decisions regarding management related to cerebral edema in patients with fulminant liver failure. In fact, since almost all our study patients with grade III or IV encephalopathy secondary to fulminant liver failure went on to develop intracranial hypertension, our study supports the contention that all such patients might benefit from ICP monitoring regardless of arterial ammonia levels.

  12. PREDICTION AND PREVENTION OF LIVER FAILURE AFTER MAJOR LIVER PRIMARY AND METASTATIC TUMORS RESECTION

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

    Full Text Available Abstract Purpose of the study. Improvement of results of treatment in patients with primary and metastatic liver cancer by decreasing the risk of post-resection liver failure on the basis of the evaluation of the functional reserves of the liver.Materials and Methods. The study included two independent samples of patients operated about primary or metastatic lesions of the liver at the Department of abdominal Oncology, P. A. Hertsen MORI. The first group included 53 patients who carried out 13C-breath test metallimovie and dynamic scintigraphy of the liver in the preoperative stage in addition to the standard algorithm of examination. Patients of the 2nd group (n=35 had a standard clinical and laboratory examination, the patients were not performed the preoperative evaluation of the functional reserve of the liver, the incidences of total bilirubin, albumin and prothrombin time did not reveal a reduction of liver function. Post-resection liver failure have been established on the basis of the 50/50 criterion in the evaluation on day 5 after surgery.Results. Analysis of operating characteristics of the functional tests showed the absolute methacin breath test sensitivity (SE≥100%, high specificity (SP≥67% of scintigraphy of the liver and the negative predictive value of outcome (VP≥100% at complex use of two diagnostic methods. The incidence of PROPS in the study group was significantly 2 times higher in the control group –15,1% and 26.8%, respectively (p<0.001.Conclusion. The combination of preoperative dynamic scintigraphy of the liver with carrying out 13C-breath methacin test allows you to conduct a comprehensive evaluation of the liver functional reserve and can significantly improve preoperative evaluation and postoperative results of anatomic resection in patients with primary and metastatic liver lesions.

  13. Prognostic indications of the failure to treat amoebic liver abscesses

    Science.gov (United States)

    Sánchez-Aguilar, Martín; Morán-Mendoza, Onofre; Herrera-Hernández, Miguel F; Hernández-Sierra, Juan Francisco; Mandeville, Peter B; Tapia-Pérez, J Humberto; Sánchez-Reyna, Martín; Sánchez-Rodríguez, José Juan; Gordillo-Moscoso, Antonio

    2012-01-01

    Objectives To identify the variables that predict the failure to treat amoebic liver abscesses. Methods We prospectively carried out a case–control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure. Results Of 40 patients with amoebic liver abscess, 24 (mean age: 36.7±11.2 years) responded to medical treatment and 16 (41.8±11.6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P99%) sensitivity and negative predictive value were observed for an abscess volume >500 ml and diameter >10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter. Conclusions The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy. PMID:23265424

  14. Acute liver failure after recommended doses of acetaminophen in patients with myopathies

    NARCIS (Netherlands)

    Ceelie, Ilse; James, Laura P.; Gijsen, Violette; Mathot, Ron A. A.; Ito, Shinya; Tesselaar, Coranne D.; Tibboel, Dick; Koren, Gideon; de Wildt, Saskia N.

    2011-01-01

    To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Retrospective analysis. Level III pediatric intensive care unit. Two pediatric patients with myopathies and acute liver failure. CLINICAL INVESTIGATIONS: We

  15. Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

    DEFF Research Database (Denmark)

    Jepsen, P; Schmidt, L E; Larsen, F S

    2010-01-01

    The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.......The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown....

  16. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in

  17. Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

    Science.gov (United States)

    Hoefer, Judith; Ulmer, Hanno; Kilo, Juliane; Margreiter, Raimund; Grimm, Michael; Mair, Peter; Ruttmann, Elfriede

    2017-06-01

    There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria. Clinical characteristics of heart failure together with hemodynamic and laboratory values were analyzed by logistic regression. A total of 45 patients (27.4%) with heart failure developed subsequent acute liver failure with a hospital mortality of 88.9%. Duration of heart failure, cause, cardiopulmonary resuscitation, use of vasopressors, central venous pressure, pulmonary capillary wedge pressure, pulmonary pulsatility index, cardiac index, and transaminases were not significantly associated with acute liver failure. Repeated decompensation, atrial fibrillation (P failure in univariate analysis only. In multivariable analysis, decreased antithrombin III was the strongest single measurement indicating acute liver failure (relative risk per %, 0.84; 95% confidence interval, 0.77-0.93; P = .001) and remained an independent predictor when adjustment for the Model for End-Stage Liver Disease score was performed (relative risk per %, 0.89; 95% confidence interval, 0.80-0.99; P = .031). Antithrombin III less than 59.5% was identified as a cutoff value to predict acute liver failure with a corresponding sensitivity of 81% and specificity of 87%. In addition to the Model for End-Stage Liver Disease score, decreased antithrombin III activity tends to be superior in predicting acute liver failure compared with traditionally thought predictors. Antithrombin III measurement may help to identify patients more precisely who are developing acute liver failure during mechanical

  18. Liver transplantation for acute liver failure accompanied by severe acute pancreatitis.

    Science.gov (United States)

    Kirino, Izumi; Fujimoto, Yasuhiro; Hata, Koichiro; Uemoto, Shinji

    2016-09-06

    The role of liver transplantation (LT) in acute liver failure (ALF) complicated by severe acute pancreatitis is still unclear. We here report a case of deceased-donor LT for idiopathic ALF accompanied by severe acute pancreatitis. A 58-year-old man with no history of liver disease presented with idiopathic ALF and acute pancreatitis. After careful consideration, he received a liver from a deceased donor. Following surgery, the patient's liver function rapidly reverted to normal level and the acute pancreatitis simultaneously subsided. The patient later developed a pancreatic pseudocyst, which was treated successfully with combination interventional radiology. LT can be considered for ALF associated with severe acute pancreatitis if there is no clinical evidence of an absolute contraindication for organ transplantation, such as systemic or local infection. Moreover, we recommend a close follow-up by ultrasonography to allow early detection and treatment of pancreatic pseudocysts following surgery. 2016 BMJ Publishing Group Ltd.

  19. A comprehensive method for predicting fatal liver failure of patients with liver cancer resection.

    Science.gov (United States)

    Li, Jiangfa; Lei, Biao; Nie, Xingju; Lin, Linku; Tahir, Syed Abdul; Shi, Wuxiang; Jin, Junfei; He, Songqing

    2015-05-01

    There are many methods to assess liver function, but none of them has been verified as fully effective. The purpose of this study is to establish a comprehensive method evaluating perioperative liver reserve function (LRF) in patients with primary liver cancer (PLC).In this study, 310 PLC patients who underwent liver resection were included. The cohort was divided into a training set (n = 235) and a validation set (n = 75). The factors affecting postoperative liver dysfunction (POLD) during preoperative, intraoperative, and postoperative periods were confirmed by logistic regression analysis. The equation for calculating the preoperative liver functional evaluation index (PLFEI) was established; the cutoff value of PLFEI determined through analysis by receiver-operating characteristic curve was used to predict postoperative liver function.The data showed that body mass index, international normalized ratio, indocyanine green (ICG) retention rate at 15 minutes (ICGR15), ICG elimination rate, standard remnant liver volume (SRLV), operative bleeding volume (OBV), blood transfusion volume, and operative time were statistically different (all P POLD. The relationship among PLFEI, ICGR15, OBV, and SRLV is expressed as an equation of "PLFEI = 0.181 × ICGR15 + 0.001 × OBV - 0.008 × SRLV." The cutoff value of PLFEI to predict POLD was -2.16 whose sensitivity and specificity were 90.3% and 73.5%, respectively. However, when predicting fatal liver failure (FLF), the cutoff value of PLFEI was switched to -1.97 whose sensitivity and specificity were 100% and 68.8%, respectively.PLFEI will be a more comprehensive, sensitive, and accurate index assessing perioperative LRF in liver cancer patients who receive liver resection. And keeping PLFEI <-1.97 is a safety margin for preventing FLF in PLC patients who underwent liver resection.

  20. Celiac artery trunk thrombosis presenting as acute liver failure

    International Nuclear Information System (INIS)

    Akbarian, M.A.; Kahrom, M.; Kahrom, H.

    2011-01-01

    Acute mesenteric ischemia is a life-threatening vascular emergency that requires early diagnosis and intervention to adequately restore mesenteric blood flow and to prevent bowel necrosis and patient death. While, almost always superior and inferior mesenteric arteries are involved, we report a 57-year-old male with an unusual celiac artery trunk thrombosis leading to gastero-duodenal and hepato-splenic infarction, and presenting an acute liver failure. (author)

  1. Liver perfusion in sepsis, septic shock, and multiorgan failure.

    Science.gov (United States)

    Spapen, Herbert

    2008-06-01

    Sepsis causes significant alterations in the hepatic macro- and microcirculation. Diverging views exist on global hepatic blood flow during experimental sepsis because of the large variety in animal and sepsis models. Fluid-resuscitated clinical sepsis is characterized by ongoing liver ischemia due to a defective oxygen extraction despite enhanced perfusion. The effects of vasoactive agents on the hepatosplanchnic circulation are variable, mostly anecdotal, and depend on baseline perfusion, time of drug administration, and use of concomitant medication. Microvascular blood flow disturbances are thought to play a pivotal role in the development of sepsis-induced multiorgan failure. Redistribution of intrahepatic blood flow in concert with a complex interplay between sinusoidal endothelial cells, liver macrophages, and passing leukocytes lead to a decreased perfusion and blood flow velocity in the liver sinusoids. Activation and dysfunction of the endothelial cell barrier with subsequent invasion of neutrophils and formation of microthrombi further enhance liver tissue ischemia and damage. Substances that regulate (micro)vascular tone, such as nitric oxide, endothelin-1, and carbon monoxide, are highly active during sepsis. Possible interactions between these mediators are not well understood, and their therapeutic manipulation produces equivocal or disappointing results. Whether and how standard resuscitation therapy influences the hepatic microvascular response to sepsis is unknown. Indirect evidence supports the concept that improving the microcirculation may prevent or ameliorate sepsis-induced organ failure.

  2. Successful living donor liver transplantation for acute liver failure after acetylsalicylic acid overdose.

    Science.gov (United States)

    Shirota, Tomoki; Ikegami, Toshihiko; Sugiyama, Satoshi; Kubota, Kouji; Shimizu, Akira; Ohno, Yasunari; Mita, Atsuyoshi; Urata, Koichi; Nakazawa, Yuichi; Kobayashi, Akira; Iwaya, Mai; Miyagawa, Shinichi

    2015-04-01

    A 20-year-old woman was admitted to an emergency hospital after ingesting 66 g of acetylsalicylic acid in a suicide attempt. Although she was treated with gastric lavage, oral activated charcoal, and intravenous hydration with sodium bicarbonate, her hepatic and renal function gradually deteriorated and serum amylase levels increased. Steroid pulse therapy, plasma exchange, and continuous hemodiafiltration did not yield any improvement in her hepatic or renal function, and she was transferred to our hospital for living donor liver transplantation. Nine days after drug ingestion, she developed hepatic encephalopathy: thus, we diagnosed the patient with acute liver failure with hepatic coma accompanied by acute pancreatitis due to the overdose of acetylsalicylic acid. Living donor liver transplantation was immediately performed using a left lobe graft from the patient's mother. Following transplantation, the patient's renal and hepatic function and consciousness improved, and she was discharged. In this report, we describe a rare case of acetylsalicylic acid-induced acute liver failure with acute hepatic coma and concomitant acute pancreatitis and acute renal failure, which were treated successfully with emergency living donor liver transplantation.

  3. Study on TCM syndromes of liver failure and yang-supporting therapy

    Directory of Open Access Journals (Sweden)

    MAO Dewen

    2015-01-01

    Full Text Available This paper reviews traditional Chinese medicine (TCM physicians′understanding of liver failure including its TCM causes, mechanisms, positions, and syndrome differentiation in various dynasties. The results suggest that modern researchers agree with ancient physicians on these aspects of liver failure. Based on achievements of ancient TCM physicians, modern researchers have further developed and improved their understanding of TCM causes, mechanisms, positions, and syndrome differentiation of liver failure. Moreover, this paper discusses the treatment of chronic liver failure with yang-supporting therapy, which provides a novel perspective and method for treating chronic liver failure.

  4. Acute Liver Failure Due to Regorafenib May Be Caused by Impaired Liver Blood Flow: A Case Report.

    Science.gov (United States)

    Akamine, Takaki; Ando, Koji; Oki, Eiji; Saeki, Hiroshi; Nakashima, Yuichiro; Imamura, Y U; Ohgaki, Kippei; Maehara, Yoshihiko

    2015-07-01

    Regorafenib has been approved for treatment of patients with unresectable or recurrent gastrointestinal stromal tumors resistant to imatinib or sunitinib. However, regorafenib has severe side-effects, including acute liver failure. We describe the case of a patient with multiple liver metastases of a small intestinal stromal tumor who experienced acute liver failure while being treated with regorafenib. A 50-year-old patient with an unresectable small intestinal stromal tumor resistant to prior treatment with imatinib and sunitinib was started on regorafenib, but experienced acute liver failure 10 days later. Plasma exchange and steroid pulse treatment improved her liver function. During liver failure, abdominal ultrasonography showed to-and-fro flow in the portal vein. Lactate dehydrogenase concentration was markedly elevated to 1633 U/l. These findings indicate that liver failure in this patient was due to impaired liver blood flow. Regorafenib may impair liver blood flow, inducing acute liver failure. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Acute liver failure: a critical appraisal of available animal models.

    Science.gov (United States)

    Bélanger, Mireille; Butterworth, Roger F

    2005-12-01

    The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

  6. Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group.

    Science.gov (United States)

    Davis, Brian C; Tillman, Holly; Chung, Raymond T; Stravitz, Richard T; Reddy, Rajender; Fontana, Robert J; McGuire, Brendan; Davern, Timothy; Lee, William M

    2017-04-01

    In the United States, nearly 1000 annual cases of heat stroke are reported but the frequency and outcome of severe liver injury in such patients is not well described. The aim of this study was to describe cases of acute liver injury (ALI) or failure (ALF) caused by heat stroke in a large ALF registry. Amongst 2675 consecutive subjects enrolled in a prospective observational cohort of patients with ALI or ALF between January 1998 and April 2015, there were eight subjects with heat stroke. Five patients had ALF and three had ALI. Seven patients developed acute kidney injury, all eight had lactic acidosis and rhabdomyolysis. Six patients underwent cooling treatments, three received N-acetyl cysteine (NAC), three required mechanical ventilation, three required renal replacement therapy, two received vasopressors, one underwent liver transplantation, and two patients died-both within 48 hours of presentation. All cases occurred between May and August, mainly in healthy young men because of excessive exertion. Management of ALI and ALF secondary to heat stroke should focus on cooling protocols and supportive care, with consideration of liver transplantation in refractory patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Endotoxin and interleukin-1 related hepatic inflammatory response promotes liver failure after partial hepatectomy

    NARCIS (Netherlands)

    Boermeester, M. A.; Straatsburg, I. H.; Houdijk, A. P.; Meyer, C.; Frederiks, W. M.; Wesdorp, R. I.; van Noorden, C. J.; van Leeuwen, P. A.

    1995-01-01

    Impairment of various functions of the liver and concomitantly increased levels of parameters of liver damage, a clinical entity termed liver failure, is commonly seen after partial hepatectomy. We investigated in a rat model whether damage of the remnant liver was due to local inflammatory

  8. Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

    Science.gov (United States)

    Tao, Ya-Chao; Wang, Meng-Lan; Chen, En-Qiang; Tang, Hong

    2018-02-23

    Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. S-100b and neuron-specific enolase in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Christiansen, Michael; Møller, Kirsten

    2001-01-01

    , the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery......Patients with fulminant hepatic failure (FHF) frequently develop cerebral edema and intracranial hypertension. The aim of this study was to evaluate circulating S-100b and neuron-specific enolase (NSE) levels as markers of neurological outcome in patients with FHF. In a subgroup of patients...

  10. Liver progenitor cell line HepaRG differentiated in a bioartificial liver effectively supplies liver support to rats with acute liver failure.

    Directory of Open Access Journals (Sweden)

    Geert A A Nibourg

    Full Text Available A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into hepatocytes and bile duct cells. Metabolism and synthesis of HepaRG monolayer cultures is relatively high and their drug metabolism can be enhanced upon treatment with 2% dimethyl sulfoxide (DMSO. However, their potential for bioartificial liver application has not been assessed so far. Therefore, HepaRG cells were cultured in the Academic Medical Center bioartificial liver (AMC-BAL with and without DMSO and assessed for their hepatic functionality in vitro and in a rat model of acute liver failure. HepaRG-AMC-BALs cultured without DMSO eliminated ammonia and lactate, and produced apolipoprotein A-1 at rates comparable to freshly isolated hepatocytes. Cytochrome P450 3A4 transcript levels and activity were high with 88% and 37%, respectively, of the level of hepatocytes. DMSO treatment of HepaRG-AMC-BALs reduced the cell population and the abovementioned functions drastically. Therefore, solely HepaRG-AMC-BALs cultured without DMSO were tested for efficacy in rats with acute liver failure (n = 6. HepaRG-AMC-BAL treatment increased survival time of acute liver failure rats ∼50% compared to acellular-BAL treatment. Moreover, HepaRG-AMC-BAL treatment decreased the progression of hepatic encephalopathy, kidney failure, and ammonia accumulation. These results demonstrate that the HepaRG-AMC-BAL is a promising bioartificial liver for clinical application.

  11. Pediatric acute liver failure of undetermined cause: A research workshop.

    Science.gov (United States)

    Alonso, Estella M; Horslen, Simon P; Behrens, Edward M; Doo, Edward

    2017-03-01

    Pediatric acute liver failure (PALF) is a potentially devastating condition that occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single-day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials. The clinical phenotype of indeterminate PALF shares important similarities to the hyperinflammatory state characteristic of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). A failure of cytotoxic T cells to limit or contract inflammatory responses may propagate injury and lead to a local and systemic milieu that does not support normal hepatic regeneration. Evidence was presented that bone marrow (BM)-derived Sinusoidal endothelial cell PROgenitor Cells (sprocs) play a vital role in hepatic regeneration. Overwhelming systemic inflammatory responses may suppress mobilization of BM sprocs and dampen hepatic recovery. Experience gained through treatment trials of HLH and MAS in childhood may inform study design for therapy of PALF. Successful approaches to limiting neuroinflammation through reduction of systemic inflammation and standardized neuroprotection protocols that limit glial injury could significantly improve intact survival. Finally, given that PALF is a rare disease, investigative efforts must include broad multicenter collaboration and careful stewardship of biorepository specimens. (Hepatology 2017;65:1026-1037). © 2016 by the American Association for the Study of Liver Diseases.

  12. Acute Liver Failure in Infants and Young Children in a Specialized Pediatric Liver Centre in India.

    Science.gov (United States)

    Alam, Seema; Lal, Bikrant Bihari; Khanna, Rajeev; Sood, Vikrant; Rawat, Dinesh

    2015-10-01

    To study the etiological spectrum of acute liver failure in infants and young children and to identify clinical and biochemical markers for metabolic liver disease (MLD). This study was conducted at Department of Pediatric Hepatology, in a tertiary care specialized centre for liver diseases. All children less than 3 y of age, with liver dysfunction and INR ≥2 were included in the study. They were managed as per the departmental protocol. Included children were divided based on the etiology into 2 groups: MLD and non MLD group. Comparison analysis (MLD vs. non MLD) of the clinical and biochemical parameters was done. There were 30 children under 3 y of age with acute liver failure (ALF) with median age of 12.5 mo. Fifteen children were less than 12 mo. MLD (33 %) and hemophagocytic lymphohistiocytosis (HLH) (17 %) together accounted for half of the cases of ALF in children below 3 y of age. The other common etiologies were drug induced liver injury and acute viral hepatitis A. Etiology remained indeterminate in 3 cases (10 %). Comparative analysis of the clinical and biochemical parameters between MLD and non MLD group showed significant difference between the two groups in the median values of age (p = 0.014), bilirubin (p = 0.017), jaundice to encephalopathy (JE) interval (p = 0.039) and blood sugar (p = 0.001). Suggestive family history (OR 3.73, 95 %CI 1.67-8.30), developmental delay (OR 4.4 95 %CI 2.03-9.51), presence of diarrhea/vomiting (OR 3.28, 95 %CI 1.32-8.13) in the history and presence of urinary non glucose reducing substance (NGRS) (OR 15.5, 95 %CI 2.26-106.87) were also significantly associated with MLD group. Only 40 % children survived with native liver. MLD and HLH account for majority of ALF in infants. About 10 % of cases remain indeterminate. Viral hepatitis is more common in young children. Apart from clinical indicators, young age, high bilirubin, synthetic dysfunction, low sugar and NGRS in urine indicate MLD

  13. The role of intestinal endotoxemia in liver failure and its complications

    Directory of Open Access Journals (Sweden)

    GAO Fangyuan

    2014-08-01

    Full Text Available Recent studies have found that endotoxin not only activates immune response, exacerbates liver injury, and induces liver failure, but also plays an important role in the development of hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, and other fatal complications. The recent progress in research on the pathogenesis of intestinal endotoxemia (IETM and its impact on the development and progression of liver failure is reviewed and summarized. It is suggested that seeking effective methods to prevent and control IETM holds promise as the key to treating severe liver disease and liver failure successfully.

  14. Pediatric liver failure: we came, we saw, but have we conquered?

    Science.gov (United States)

    Smith, Sara Kathryn; Rosenthal, Philip

    2017-01-01

    Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this article, we will discuss our current understanding of liver failure and updated management strategies in children with acute liver failure.

  15. Pediatric liver failure: we came, we saw, but have we conquered? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sara Kathryn Smith

    2017-08-01

    Full Text Available Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this article, we will discuss our current understanding of liver failure and updated management strategies in children with acute liver failure.

  16. DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

    Directory of Open Access Journals (Sweden)

    Valentín Roales-Gómez

    2014-08-01

    Full Text Available Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

  17. Successful Treatment of Acute on Chronic Mesenteric Ischaemia by Common Iliac to Inferior Mesenteric Artery Bypass

    Directory of Open Access Journals (Sweden)

    D. N. Coakley

    2015-01-01

    Full Text Available Chronic mesenteric ischaemia is a rare and potentially fatal condition most commonly due to atherosclerotic stenosis or occlusion of two or more mesenteric arteries. Multivessel revascularisation of both primary mesenteric vessels, the celiac artery and superior mesenteric artery (SMA, is the current mainstay of treatment; however, in a certain cohort of patients, revascularisation one or both vessels may not be possible. Arteries may be technically unreconstructable or the patient may be surgically unfit for the prolonged aortic cross clamping times required. Here we present a case involving a 72-year-old woman with acute on chronic mesenteric ischaemia. She was a high risk surgical patient with severe unreconstructable stenotic disease of the SMA and celiac arteries. She was successfully treated with single vessel revascularisation of the inferior mesenteric artery (IMA via a common iliac to IMA reversed vein bypass. At two-year follow-up, the graft remains patent and the patient continues to be symptom-free and is maintaining her weight.

  18. The relationship between preoperative creatinine clearance and outcomes for patients undergoing liver transplantation: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Wenger Urs

    2013-02-01

    Full Text Available Abstract Background Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients. Methods In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors. Results There was a significant difference in ICU mortality (p=.008, hospital mortality (p=.002 and cumulative survival (p Conclusion This study shows that in liver transplant recipient’s acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.

  19. Pediatric acute liver failure in Brazil: Is living donor liver transplantation the best choice for treatment?

    Science.gov (United States)

    Tannuri, Ana Cristina Aoun; Porta, Gilda; Kazue Miura, Irene; Santos, Maria Merces; Moreira, Daniel de Albuquerque Rangel; de Rezende, Nathassia Mancebo Avila; Miyatani, Helena Thie; Tannuri, Uenis

    2016-07-01

    Acute liver failure (ALF) in children is a life-threatening condition that often leads to urgent liver transplantation (LT). The aim of the present investigation was to describe the experience in Brazil in treating pediatric ALF, with an emphasis on the role of living donor liver transplantation (LDLT) in treating this condition. All children with ALF who fulfilled the criteria for an urgent LT were admitted to the intensive care unit. Patients were divided into 2 groups based on the moment of admission: before and after June 2007, when the LDLT program for ALF was started. Statistical analyses were performed to identify prognostic factors of patients with ALF. For the study, 115 children with ALF were admitted. All patients had some degree of encephalopathy. Among the patients, 26% of them required intracranial pressure monitoring (IPM), 12.8% of the patients required hemodialysis, and 79 patients underwent transplantation (50 deceased donors and 29 living donors) corresponding to 12.4% of all pediatric LTs. Only 9 children recovered without LT. The need for IPM and nonperformance of LT were related to a higher mortality. The mortality rate of patients who underwent LT was significantly lower than that of children with ALF who did not undergo a LT (48.1% versus 75%; P = 0.02). The incidences of primary nonfunction and mortality were statistically higher among deceased donor liver transplantations than LDLTs. Finally, it was verified that the overall survival rate of transplanted patients was increased after the introduction of LDLT (P = 0.02). In conclusion, ALF in children continues to be a severe and devastating condition, and a LT should be performed promptly. The introduction of LDLT could increase the survival rate of patients in Brazil. Liver Transplantation 22 1006-1013 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

  20. [A case of liver failure associated with liver damage due to mFOLFOX 6 after resection for multiple liver metastases from colorectal cancer].

    Science.gov (United States)

    Ishizaki, Tetsuo; Abe, Tomomi; Koyanagi, Yasuhisa; Katsumata, Kenji; Wada, Tatehiko; Tsuchida, Akihiko; Aoki, Tatsuya

    2007-06-01

    A case of colorectal cancer in a 60-year-old man became resectable after downstaging was achieved with mFOLFOX 6 for multiple liver metastases from colorectal cancer. The patient received 8 cycles of mFOLFOX 6 on the basis of a diagnosis of multiple liver metastases in the right and left lobes and a single metastasis in the right lung. After chemotherapy, the liver metastases showed partial response, and the lung metastasis stable disease. Because the lung metastasis was controlled and radical cure of the liver metastases was thought possible by resection, we performed right lobectomy of the liver. Postoperative progress was good, and we then planned a staged partial resection of the lung. However,on postoperative day 28, the patient was hospitalized again with liver dysfunction, which evolved into liver failure, in spite of conservative treatment. The patient died on postoperative day 95. The needle biopsy specimens of the liver taken on readmission showed bile duct occlusion, portal hypertension, and perisinusoidal fibrosis, and histopathology of the surgical non-tumoral liver specimen showed the same findings. We think that liver failure was triggered by resection of the liver which had been damaged by mFOLFOX 6. Recently, liver damage due to oxaliplatin was reported, and evaluation of liver injury is considered important before liver resection for colorectal liver metastases with neoadjuvant FOLFOX.

  1. Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation.

    Science.gov (United States)

    Cheong, Jaeyoun; Galanko, Joseph A; Arora, Sumant; Cabezas, Joaquin; Ndugga, Nambi J; Lucey, Michael R; Hayashi, Paul H; Barritt, Alfred Sidney; Bataller, Ramon

    2017-02-01

    Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P renal failure was less marked in patients with ALD (HR = 1.31, P renal failure had better long-term prognosis than non-ALD patients. Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Chronic acetaminophen exposure in pediatric acute liver failure.

    Science.gov (United States)

    Leonis, Mike A; Alonso, Estella M; Im, Kelly; Belle, Steven H; Squires, Robert H

    2013-03-01

    Acetaminophen (N-acetyl-p-aminophenol [APAP]) is a widely used medication that can cause hepatotoxicity. We examined characteristics and outcomes of children with chronic exposure (CE) to APAP in the multinational Pediatric Acute Liver Failure (PALF) Study. A total of 895 children enrolled from 2002 to 2009 were grouped by APAP exposure history as: CE (received multiple doses \\x{2265}2 days; n = 83), single dose exposure (SE; n = 85), and no exposure (NE; n = 498). CE was the reference group for pairwise comparisons. Median values are shown. Patients with CE compared with those with SE were younger (3.5 vs 15.2 years, P liver transplantation at 21 days was worse for CE than for SE (68% vs 92%, P = .0004) but better than for NE (49%, P = .008). Children in the PALF study with CE had lower bilirubin and higher alanine aminotransferase than those with NE. Outcomes with CE were worse than with SE but better than with NE. Potential reasons for this outcomes advantage over non-APAP-exposed subjects should be explored.

  3. Organ sharing in the management of acute liver failure.

    Science.gov (United States)

    Pezzati, D; Ghinolfi, D; De Simone, P; Tincani, G; Fiorenza, G; Filipponi, F

    2013-04-01

    Liver transplantation (OLT) for acute liver failure (ALF) is associated with high morbidity and mortality rates in the early posttransplant course. An efficient organ-sharing organization may grant favorable results. This is a retrospective analysis of prospectively collected data on patients wait listed for ALF at a single center. Patients were listed for OLT when matching King's College Criteria. Based on patients' clinical status, ABO-incompatible grafts were used. From January 2001 to December 2010, 37 patients were wait listed for ALF. Two patients were de-listed (5.4%) for improvement of their clinical conditions; two patients (5.4%) died on the list and 33 (89.2%) underwent OLT. Among these latter, 21 (63.6%) were Italian and 12 (36.4%) were foreign citizens, with four referred from their home country on the basis of international agreements on ALF management. Donors were procured in our region in 10 cases (30.3%), nationally in 22 (66.6%), and outside Italy in 1 (3.1%). Mean time from wait listing to OLT was 1 day (range 0-6), and seven patients received an ABO-incompatible graft. Graft and patient survivals at 1 month, 1 year, and 3 years were 78.8%, 72.7%, 66.5%, and 81.8%, 75.8%, and 72.7%, respectively. Five patients underwent retransplantation: two on postoperative day (POD) 2 for primary nonfunction of the liver graft, two on POD 8 and 95 for hepatic artery thrombosis, and one at 18 months for nonanastomotic biliary stenosis. Prompt referral to a OLT center and efficient organ-sharing system play a fundamental role in optimizing the outcome of the patient with ALF. Development of international organ exchange programs might further improve the results for this category of patients. In very selected cases, ABO-incompatible grafts may be a valuable resource. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

    Science.gov (United States)

    Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

  5. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

    NARCIS (Netherlands)

    Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

    . Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

  6. Clinical analysis and prognostic judgment of artificial extracorporeal liver support therapy for pediatric acute liver failure

    Directory of Open Access Journals (Sweden)

    ZHANG Zhen

    2015-08-01

    Full Text Available Objective To observe the clinical efficacy of artificial extracorporeal liver support therapy in the treatment of pediatric acute liver failure (PALF and to analyze the associated prognostic factors. Methods The clinical records of 23 patients with PALF treated from January 2012 to February 2015 in the Pediatric Intensive Care Unit of the First Hospital of Jilin University were analyzed retrospectively. After three-month follow-up, 15 patients survived (survival group, n=15, while 8 patients died (death group, n=8. The changes in biomarkers of liver function and coagulation function after treatment were evaluated within groups. At the same time, the above parameters and Model for End-Stage Liver Disease (MELD score before treatment were compared between the two groups. The efficacy of artificial extracorporeal liver support therapy was analyzed, and the prognostic factors were reviewed. The t test was applied in the comparison of continuous data. Results In the survival group, the levels of serum alanine aminotransferase (ALT, total bilirubin (TBil, ammonia, and lactic acid were significantly reduced after treatment (t=8.812, 6.243, 8.431, and 6.721, respectively; all P<0.01. However, in the death group, only ALT level was significantly reduced after treatment (t=2.532, P<0.05. Compared with the levels before treatment, the levels of prothrombin time (PT, prothrombin time activity (PTA, and international normalized ratio (INR were significantly improved after treatment (t=6.256, -2.738, and 6.711, respectively; all P<0.05. Before treatment, compared with the survival group, patients in the death group presented significantly lower level of ALT (t=6.283,P<0.01, significantly higher level of TBil (t=-3.938, P=0.001, significantly longer PT (t=-2.394, P=0.026, and significantly higher MELD score (t=-6.239, P<0.01. Conclusion Artificial extracorporeal liver support therapy is an effective way of treating PALF. Once patients with high ALT level

  7. What factors determine the severity of hepatitis A-related acute liver failure?

    Science.gov (United States)

    Ajmera, V.; Xia, G.; Vaughan, G.; Forbi, J. C.; Ganova-Raeva, L. M.; Khudyakov, Y.; Opio, C. K.; Taylor, R.; Restrepo, R.; Munoz, S.; Fontana, R. J.; Lee, W. M.

    2016-01-01

    SUMMARY The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were subgenotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare subgenotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. PMID:21143345

  8. What factors determine the severity of hepatitis A-related acute liver failure?

    Science.gov (United States)

    Ajmera, V; Xia, G; Vaughan, G; Forbi, J C; Ganova-Raeva, L M; Khudyakov, Y; Opio, C K; Taylor, R; Restrepo, R; Munoz, S; Fontana, R J; Lee, W M

    2011-07-01

    The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. © 2010 Blackwell Publishing Ltd.

  9. Adrenal Insufficiency as a Cause of Acute Liver Failure: A Case Report

    Directory of Open Access Journals (Sweden)

    Jamshid Vafaeimanesh

    2013-01-01

    Full Text Available Introduction. Many diseases and conditions can contribute to elevated liver enzymes. Common causes include viral and autoimmune hepatitis, fatty liver, and bile duct diseases, but, in uncommon cases like liver involvement in endocrine disorders, liver failure is also seen. Adrenal insufficiency is the rarest endocrine disorder complicating the liver. In the previously reported cases of adrenal insufficiency, mild liver enzymes elevation was seen but we report a case with severe elevated liver enzymes and liver failure due to adrenal insufficiency. Based on our knowledge, this is the first report in this field. Case Report. A 39-year-old woman was referred to emergency ward due to drowsiness and severe fatigue. Her laboratory tests revealed prothrombin time: 21 sec, alanine aminotransferase (ALT: 2339 IU/L, aspartate aminotransferase (AST: 2002 IU/L, and ALP: 90 IU/L. No common cause of liver involvement was discovered, and eventually, with diagnosis of adrenal insufficiency and corticosteroid therapy, liver enzymes and function became normal. Finally, the patient was discharged with good general condition. Conclusion. With this report, we emphasize adrenal insufficiency (primary or secondary as a reason of liver involvement in unexplainable cases and recommend that any increase in the liver enzymes, even liver failure, in these patients should be observed.

  10. Pyruvate dehydrogenase complex and lactate dehydrogenase as targets for therapy of acute liver failure.

    Science.gov (United States)

    Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola

    2018-03-23

    Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate in the nucleus to regulate histone acetylation and gene expression. Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-Ab, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by Gene Ontology Enrichment Analysis. Efficacy of histone acetyltransferase inhibitor garcinol and LDH inhibitor galloflavin at reducing liver damage was evaluated in mice with induced hepatotoxicity. Levels and activities of PDHC and LDH were increased in cytoplasmatic and nuclear fractions of livers of mice with acute liver failure. The increase of nuclear PDHC and LDH was associated with increased concentrations of acetyl-coA and lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression in livers of mice with acute liver failure suggested that increased histone H3 acetylation induces the expression of genes related to response to damage. Reduced histone acetylation by the histone acetyltransferase inhibitor garcinol decreased liver damage and improved survival in mice with acute liver failure. Knock-down of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus. Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC, reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines in mice with acute liver failure. Mice treated with galloflavin also showed a dose-response increase in survival. PDHC and LDH translocate to the nucleus and are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive and life-threatening deterioration of liver function resulting in high mortality and

  11. Causes of liver failure and impact analysis of prognostic risk factors

    Directory of Open Access Journals (Sweden)

    WU Xiaoqing

    2013-04-01

    Full Text Available ObjectiveTo perform a retrospective analysis of patients with liver failure to investigate the causative factors and related risk factors that may affect patient prognosis. MethodsThe clinical, demographic, and laboratory data of 79 consecutive patients diagnosed with liver failure and treated at our hospital between January 2010 and January 2012 (58 males and 21 females; age range: 16-74 years old were collected from the medical records. To identify risk factors of liver failure, the patient variables were assessed by Student’s t-test (continuous variables or Chi-squared test (categorical variables. Multivariate logistic regression analysis was used to investigate the relation between patient outcome and independent risk factors. ResultsThe 79 cases of liver failure were grouped according to disease severity: acute liver failure (n=6; 5 died, subacute liver failure (n=35; 19 died, and chronic liver failure (n=38; 28 died. The overall rate of death was 66%. The majority of cases (81% were related to hepatitis B virus infection. While the three groups of liver failure severity did not show significant differences in sex, mean age, occupation, presence of potassium disorder, total bilirubin (TBil or total cholesterol (CHO at admission, or lowest recorded level of CHO during hospitalization, there were significant intergroup differences in highest recorded TBil level, prothrombin activity (PTA at admission, and highest and lowest recorded PTA, and highest recorded level of CHO. Five independent risk factors were identified: the highest recorded TBil level during hospitalization, presence of infection, hepatorenal syndrome, gastrointestinal bleeding, and hepatic encephalopathy. ConclusionThe major cause of liver failure in this cohort of patients was hepatitis infection, and common biomarkers of liver function, such as TBil, CHO and PTA, may indicate patients with poor prognosis despite clinical intervention. Complications should be addressed as

  12. Hepatitis e and acute liver failure in pregnancy.

    Science.gov (United States)

    Shalimar; Acharya, Subrat K

    2013-09-01

    Hepatitis E virus is a positive strand RNA virus with three open reading frames which is transmitted predominantly through the fecal contamination of water and food. It is the most common cause of acute liver failure in endemic areas. Pregnant women especially from the Indian subcontinent and Africa are at increased risk of contracting acute HEV infection as well as developing severe complications including ALF. Transmission of HEV occurs from mother to unborn child. Both maternal and fetal complications may occur, including abortion, fetal demise, preterm labor and maternal or neonatal death. The precise reasons for increased susceptibility to HEV infection during pregnancy and associated severe disease are still an enigma. Management is supportive and termination of pregnancy is not recommended as a general rule. Prevention of infection is of vital importance, as availability of clean drinking water can reduce the burden of this disease in the community. There is a need for future research to focus on prevention of ALF in pregnancy and to study the disease pathogenesis, which is not explicitly understood at present. The availability of a vaccine may alter the natural course of the disease in this select population which is at risk.

  13. A Rare Case of Propofol-Induced Acute Liver Failure and Literature Review

    Directory of Open Access Journals (Sweden)

    G. Kneiseler

    2010-02-01

    Full Text Available The incidence of drug-induced acute liver failure is increasing. A number of drugs can inhibit mitochondrial functions, alter β-oxidation and cause accumulation of free fatty acids within the hepatocytes. This may result in hepatic steatosis, cell death and liver injury. In our case, propofol, an anesthetic drug commonly used in adults and children, is suspected to have induced disturbance of the mitochondrial respiratory chain, which in consequence led to insufficient energy supply and finally liver failure. We report the case of a 35-year-old Caucasian woman with acute liver failure after anesthesia for stripping of varicose veins. Liver histology, imaging and laboratory data indicate drug-induced acute liver failure, presumably due to propofol. Hepatocyte death and microvesicular fatty degeneration of 90% of the liver parenchyma were observed before treatment with steroids. Six months later, a second biopsy was performed, which revealed only minimal steatosis and minimal periportal hepatitis. We suggest that propofol led to impaired fatty acid oxidation possibly due to a genetic susceptibility. This caused free fatty acid accumulation within hepatocytes, which presented as hepatocellular fatty degeneration and cell death. Large scale hepatocyte death was followed by impaired liver function and, consecutively, progressed to acute liver failure.

  14. Acute liver failure in Japan: definition, classification, and prediction of the outcome.

    Science.gov (United States)

    Sugawara, Kayoko; Nakayama, Nobuaki; Mochida, Satoshi

    2012-08-01

    Acute liver failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to severe impairment of liver function caused by massive or submassive liver necrosis. Viral hepatitis is the most important and frequent cause of acute liver failure in Japan. The diagnostic criteria for fulminant hepatitis, including that caused by viral infections, autoimmune hepatitis, and drug allergy induced-liver damage, were first established in 1981. Considering the discrepancies between the definition of fulminant hepatitis in Japan and the definitions of acute liver failure in the United States and Europe, the Intractable Hepato-Biliary Disease Study Group established the diagnostic criteria for "acute liver failure" for Japan in 2011, and performed a nationwide survey of patients seen in 2010 to clarify the demographic and clinical features and outcomes of these patients. According to the survey, the survival rates of patients receiving medical treatment alone were low, especially in those with hepatic encephalopathy, despite artificial liver support, consisting of plasma exchange and hemodiafiltration, being provided to almost all patients in Japan. Thus, liver transplantation is inevitable to rescue most patients with hepatic encephalopathy. The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996. Recently, however, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients. Algorithms for outcome prediction have also been developed based on data-mining analyses. These novel guidelines need further evaluation to determine their usefulness.

  15. ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE.

    Science.gov (United States)

    Miguel, Fabiano Moraes; Schemitt, Elizângela Gonçalves; Colares, Josieli Raskopf; Hartmann, Renata Minuzzo; Morgan-Martins, Maria Isabel; Marroni, Norma Possa

    2017-01-01

    Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. To evaluate the antioxidant effect of vitamin E in this ALF model. We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P E, we observed a reduction in liver enzymes AST (U/L) (101.32±19.45 in 24 hours and 97.85±29.65 in 48 hours) related to the TAA group (469.56± 0.69 in 24 hours and 598.23±55.45 in 48 hours) and ALT (U/L) (76.59±8.56 in 24 hours and 68.47±6.49 in 48 hours) compared to the TAA group (312.21±10.23 in 24 hours and 359.15±17.58 in 48 hours). There was a reduction of LPO (nmol/mg Prot) in the TAA+Vit.E group (0

  16. Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting.

    Directory of Open Access Journals (Sweden)

    Clare Selden

    Full Text Available Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2 cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6 × 10(10cells, were transported from preparation-laboratory to point-of-use operating theatre (6000 miles under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL, and those connected to circuit containing alginate capsules without cells (Empty-bead BAL. Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without

  17. Presenting Features and Prognosis of Ischemic and Nonischemic Neonatal Liver Failure.

    Science.gov (United States)

    Zozaya Nieto, Carlos; Fernández Caamaño, Beatriz; Muñoz Bartolo, Gema; Menéndez Suso, Juan J; Frauca Remacha, Esteban; Valverde Núñez, Eva

    2017-05-01

    To describe the epidemiological features, clinical characteristics and outcomes of neonates diagnosed with liver failure, as well as determine prognostic factors. Cohort study conducted at a single tertiary referral and university-affiliated pediatric center. Hospital records of all neonates diagnosed with liver failure between January 2003 and December 2015 were retrospectively reviewed, and data on clinical and laboratory findings, treatment, and outcomes were collected. Survival analysis (Kaplan-Meier) and Cox regression were performed to identify prognostic factors at diagnosis. Liver failure diagnosis was established using the pediatric acute liver failure study group's diagnostic criteria for every patient with coagulopathy and biochemical pattern of liver disease. Forty-five patients were included. In our series, most cases were secondary to ischemia (28.9%). Other causes were neonatal hemochromatosis (17.8%), viral infections (13.3%), and inborn errors of metabolism (13.3%). A total 55.6% (25/45) of the patients died (median age: 16 days; range 1-235 days). Alanine aminotransferase (ALT) at diagnosis was associated with higher mortality or the need for liver transplantation on day 21 after diagnosis (P = .006). For every 500 IU/L increase in ALT serum levels, the mortality/liver transplantation rate increased 1.3 times (hazard ratio 95% confidence interval: 1.1-1.6). Although ischemic neonatal acute liver failure presents with higher ALT levels, these cases appear to have better outcomes. Higher international normalized ratio tended to increase mortality/transplantation (hazard ratio 1.02; 95% confidence interval 0.91-1.2). Neonatal liver failure should perhaps be considered in the differential diagnoses of any coagulopathy. ALT and international normalized ratio levels at diagnosis could predict prognosis in the short term. Ischemic liver failure appears to have a better prognosis.

  18. Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report.

    Science.gov (United States)

    Nacif, Lucas Souto; Waisberg, Daniel R; Pinheiro, Rafael Soares; Lima, Fabiana Roberto; Rocha-Santos, Vinicius; Andraus, Wellington; D'Albuquerque, Luiz Carneiro

    2018-03-10

    There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment. We report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases.

  19. Traditional Chinese medicine treatment of liver diseases

    Directory of Open Access Journals (Sweden)

    WANG Rongbing

    2015-01-01

    Full Text Available Traditional Chinese medicine (TCM treatment of liver diseases is derived from the regulation of liver function including storing blood and governing the free flow of qi, in which functional systems such as modern digestion, endocrine, and the gut-liver axis are involved, and is established on modern hepatic physiology, pathology, and etiology. To objectively reveal the characteristics and advantages of modern TCM treatment of liver diseases, we analyzed the clinical and research situation of TCM therapy for liver diseases in the last decade and collected major achievements that have been applied in clinical treatment of diseases, published in core journals, and confirmed by major scientific research programs. The results showed TCM combined with antiviral therapy can improve the clinical outcomes of chronic hepatitis B. TCM can help HBV carriers prevent disease progression. Integrated traditional Chinese and Western medicine therapy for acute-on-chronic liver failure can block the deterioration induced by endotoxin. TCM has been widely applied in protecting the liver through nonspecific anti-inflammation, alleviating hepatic fibrosis, and preventing non-alcoholic fatty liver. TCM plays an important role in treating some currently untreatable liver diseases. Therefore, it is our common responsibility to inherit and develop effective principle-method-recipe-medicines and create a better medical care system.

  20. Analysis of viral testing in nonacetaminophen pediatric acute liver failure.

    Science.gov (United States)

    Schwarz, Kathleen B; Dell Olio, Dominic; Lobritto, Steven J; Lopez, M James; Rodriguez-Baez, Norberto; Yazigi, Nada A; Belle, Steven H; Zhang, Song; Squires, Robert H

    2014-11-01

    Viral infections are often suspected to cause pediatric acute liver failure (PALF), but large-scale studies have not been performed. We analyzed the results of viral testing among nonacetaminophen PALF study participants. Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either causative viruses (CVs) or associated viruses (AVs). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included "viral," "indeterminate," and "other." Of 860 participants, 820 had at least 1 test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among "viral" (66/80 [82.5%]), "indeterminate" (52/420 [12.4%]), and "other" (48/320 [15.0%]) diagnoses. CVs accounted for 81/166 (48.8%) positive tests. Herpes simplex virus (HSV) was positive in 39/335 (11.6%) who were tested 26/103 (25.2%) and 13/232 (5.6%) among infants 0 to 6 and >6 months, respectively. HSV was not tested in 61.0% and 53% of the overall cohort and those 0 to 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Viral testing in PALF occurs frequently but is often incomplete. The evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation.

  1. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure

    DEFF Research Database (Denmark)

    Wendon,, Julia; Cordoba, Juan; Dhawan, Anil

    2017-01-01

    The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute...... abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately...

  2. Change of liver echogenicity in chronic renal failure: Correlation with serologic test and pathologic findings

    International Nuclear Information System (INIS)

    Eun, Hyo Won; Cho, Kyoung Sik; Kim, Jeong Kon; Kim, Jung Hoon

    2002-01-01

    To correlate serologic test and pathologic findings with change of hepatic parenchymal echogenicity on ultrasound (US) in patients with chronic renal failure. From January 1995 to April 2000, among eight hundred eighty four patients with kidney transplantation due to chronic renal failure, sixty seven patients who underwent US-guided liver biopsy were selected. Change of liver echogenicity on US was analyzed, and this change was compared with serologic test and pathologic findings. Among sixty seven patients, pathologic findings of thirty four patients with the normal liver echogenicity on US revealed normal in 15 patients (44%), viral hepatitis in 18 (53%), and liver cirrhosis in one patient (3%). Meanwhile, twenty seven patients with chronic liver disease on US were pathologically confirmed as normal in 13 patients (48%), viral hepatitis in 11 (40%), liver cirrhosis in four patients (11%); six patients with cirrhotic change on US, liver cirrhosis in four patients (67%) and viral hepatitis on two patients (33%). Serologic test of thirty four patients with the normal liver echogenicity on US showed positive HBs Ag in 17 patients (50%), positive anti-HCV Ab in 11 (32%), positive in both HBs Ag and anti-HCV Ab in one (3%), and normal result in five patients (15%). In patients with chronic renal failure, it is nor enough to determine the presence of liver disease only based on change of echogenicity on US. A careful correlation with serologic test and, if needed, pathologic confirmation are recommended for the accurate preoperative evaluation of the liver.

  3. TRANSPLANTATION OF CRYOPRESERVED FETAL LIVER CELLS SEEDED INTO MACROPOROUS ALGINATE-GELATIN SCAFFOLDS IN RATS WITH LIVER FAILURE

    Directory of Open Access Journals (Sweden)

    D. V. Grizay

    2015-01-01

    Full Text Available Aim. To study the therapeutic potential of cryopreserved fetal liver cells seeded into macroporous alginategelatin scaffolds after implantation to omentum of rats with hepatic failure.Materials and methods.Hepatic failure was simulated by administration of 2-acetyl aminofl uorene followed partial hepatectomy. Macroporous alginate-gelatin scaffolds, seeded with allogenic cryopreserved fetal liver cells (FLCs were implanted into rat omentum. To prevent from colonization of host cells scaffolds were coated with alginate gel shell. Serum transaminase activity, levels of albumin and bilirubin as markers of hepatic function were determined during 4 weeks after failure model formation and scaffold implantation. Morphology of liver and scaffolds after implantation were examined histologically. Results. Macroporous alginate-gelatin scaffolds after implantation to healthy rats were colonized by host cells. Additional formation of alginate gel shell around scaffolds prevented the colonization. Implantation of macroporous scaffolds seeded with cryopreserved rat FLCs and additionally coated with alginate gel shell into omentum of rats with hepatic failure resulted in signifi cant improvement of hepatospecifi c parameters of the blood serum and positive changes of liver morphology. The presence of cells with their extracellular matrix within the scaffolds was confi rmed after 4 weeks post implantation.Conclusion. The data above indicate that macroporous alginate-gelatin scaffolds coated with alginate gel shell are promising cell carriers for the development of bioengineered liver equivalents.

  4. Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure.

    Science.gov (United States)

    McKenzie, Rebecca B; Berquist, William E; Nadeau, Kari C; Louie, Christine Y; Chen, Sharon F; Sibley, Richard K; Glader, Bertil E; Wong, Wendy B; Hofmann, Lawrence V; Esquivel, Carlos O; Cox, Kenneth L

    2014-08-01

    In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Liver failure in a child receiving highly active antiretroviral therapy and voriconazole

    NARCIS (Netherlands)

    Scherpbier, Henriette J.; Hilhorst, Michaela I.; Kuijpers, Taco W.

    2003-01-01

    We describe a 10-year-old child with vertically transmitted acquired immunodeficiency syndrome who was receiving antiretroviral combination therapy and died of liver failure after beginning voriconazole therapy

  6. Acute liver failure after recommended doses of acetaminophen in patients with myopathies

    NARCIS (Netherlands)

    I. Ceelie (Ilse); L.P. James (Laura); V.M.G.J. Gijsen (Violette); R.A.A. Mathôt (Ron); S. Ito (Shinya); C.D. Tesselaar (Coranne); D. Tibboel (Dick); G. Koren (Gideon); S.N. de Wildt (Saskia)

    2011-01-01

    textabstractObjective: To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Design: Retrospective analysis. Setting: Level III pediatric intensive care unit. Patients: Two pediatric patients with myopathies and acute

  7. Changes in cerebral oxidative metabolism in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P N; Larsen, F S

    2013-01-01

    acid cycle, induces substrate depletion through marked glutamate utilization for glutamine synthesis and leads to mitochondrial dysfunction. In patients with acute liver failure cerebral microdialysis studies show a linear correlation between the lactate to pyruvate ratio and the glutamine...

  8. Fatal Acute Liver Failure With Intravenous Amiodarone: A Case Report and Literature Review

    Science.gov (United States)

    Gayam, Vijay; Khalid, Mazin; Dahal, Sumit; Garlapati, Pavani; Gill, Arshpal; Alex, Ragin; Mansour, Mohammad

    2018-01-01

    Amiodarone is a drug which frequently causes elevated transaminases. However, acute liver failure has been rarely reported. Here, we present a case of fatal acute liver failure following the administration of intravenous amiodarone. It is important to be aware of this rare but potentially fatal complication of intravenous amiodarone so that it can be withdrawn immediately at the first sign of hepatic impairment. PMID:29511409

  9. Pediatric liver failure: we came, we saw, but have we conquered?

    OpenAIRE

    Smith, Sara Kathryn; Rosenthal, Philip

    2017-01-01

    Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this art...

  10. Prometheus therapy for the treatment of acute liver failure in patients after cardiac surgery.

    Science.gov (United States)

    Komardina, Ekaterina; Yaroustovsky, Michael; Abramyan, Marina; Plyushch, Marina

    2017-12-01

    Acute liver failure usually develops in multiple organ dysfunction syndrome and significantly increases the mortality risk in patients after cardiac surgery. To assess the safety and efficacy of extracorporeal liver support in patients with acute liver failure after cardiac surgery. We studied 39 adult patients with multiple organ dysfunction syndrome and acute liver failure as postoperative complication, treated with Prometheus therapy. Inclusion criteria comprised clinical and laboratory signs of acute liver failure. Criteria to start Prometheus therapies were: serum bilirubin above 180 µmol/l (reference values: 3-17 µmol/l), hepatocyte cytolysis syndrome (at least 2-fold increase in aspartate aminotranspherase and alanine aminotranspherase concentrations; reference values 10-40 U/l) and decrease in plasma cholinesterase (reference values 4490-13 320 U/l). Extracorporeal therapy provided stabilization of hemodynamics, decrease in serum total bilirubin and unconjugated bilirubin levels, decrease in cytolysis syndrome severity and positive effect on the synthetic function of the liver. The 28-day survival rate in the group treated with Prometheus therapy was 23%. Prometheus procedures could be recommended as a part of combined intensive care in patients with acute liver failure after cardiac and major vessel surgery. The efficiency of this method could be improved by a multi-factor evaluation of patient condition in order to determine indications for its use.

  11. Abnormal Liver Function in Relation to Hemodynamic Profile in Heart Failure Patients

    NARCIS (Netherlands)

    Van Deursen, V. M.; Damman, K.; Hillege, H. L.; Van Beek, A. P.; Van Veldhuisen, D. J.; Voors, A. A.

    Background: We studied the relation between liver function abnormalities and hemodynamic profile in patients with heart failure (HF). Methods and Results: in 323 HF patients, liver function was determined by aspartate and alanine aminotransferase (AST, ALT), alkaline phosphatase, gamma-glutamyl

  12. Pediatric liver transplantation for fulminant hepatic failure secondary to intentional iron overdose.

    Science.gov (United States)

    Lai, Joanne; Chu, Jaime; Arnon, Ronen

    2017-09-01

    Acute iron poisoning may lead to life-threatening hepatotoxicity. We present the cases of two pediatric patients with hepatotoxicity following intentional iron ingestion that progressed rapidly to fulminant hepatic failure despite treatment with deferoxamine. Liver transplantation was lifesaving in both patients. These cases emphasize the need for a high index of suspicion for iron ingestion, close monitoring for liver toxicity, and timely consideration for liver transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Artificial liver support: a real step forward.

    Science.gov (United States)

    Saliba, F; Samuel, D

    2015-02-01

    Since the early 1960s, several authors reported on the use of some experimental artificial liver devices in order to support patients with either acute liver failure (ALF) or end-stage chronic liver disease. In the 1980s, liver transplantation became an established real treatment replacing the whole liver with a major survival benefit. In the 1990s, the concept of albumin dialysis appeared as a new revolution in the concept of dialysis with the great capacity of removal of toxins, drugs and molecules strongly bound to albumin. Currently, three artificial liver support devices are available: The MARS®, the Prometheus® and the SPAD®. The most widely studied and used system is the MARS® that uses albumin dialysis to replace the detoxification function of the liver. MARS has shown in several uncontrolled studies and few randomized studies an improvement in the patient condition in terms of clinical symptoms (hepatic encephalopathy, pruritus, jaundice) and in liver and kidney biological parameters bringing these patients safely to liver transplantation. MARS® has shown for some patients with ALF (mainly paracetamol intoxication) an improvement of spontaneous or transplant free survival. The use of MARS in acute on chronic liver failure (ACLF) require further studies based on strict definition of the syndrome. The use of albumin dialysis technique, require the performance of multiple sessions of treatment or even (in situations of ALF) a continuous treatment in order to improve spontaneous recovery or bridge these patients to liver transplantation. The performance of these systems would need further improvement. Large randomized trials are still needed in both patients with ALF and ACLF to establish the indications, the timing and the real place of liver support therapies. Meanwhile, early use of these devices in patients with ALF and ACLF could be considered as an additional tool among others in the management of these patients in specialized liver units.

  14. Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure.

    Directory of Open Access Journals (Sweden)

    Keila Rodriguez

    Full Text Available Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA was defined as total calcium (mg/dl /ionized calcium (mmol/L ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs defined as bleeding, hemodynamic instability, arrhythmias. Fifty-one patients (median age 3.5 (IQR 0.75-14.2 years received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29-74; 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention.

  15. Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure.

    Science.gov (United States)

    Rodriguez, Keila; Srivaths, Poyyapakkam R; Tal, Leyat; Watson, Mary N; Riley, Alyssa A; Himes, Ryan W; Desai, Moreshwar S; Braun, Michael C; Akcan Arikan, Ayse

    2017-01-01

    Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT) as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA) is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA) was defined as total calcium (mg/dl) /ionized calcium (mmol/L) ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs) defined as bleeding, hemodynamic instability, arrhythmias). Fifty-one patients (median age 3.5 (IQR 0.75-14.2) years) received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29-74); 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention.

  16. NBAS mutations cause acute liver failure: when acetaminophen is not a culprit.

    Science.gov (United States)

    Calvo, Pier Luigi; Tandoi, Francesco; Haak, Tobias B; Brunati, Andrea; Pinon, Michele; Olio, Dominic Dell; Romagnoli, Renato; Spada, Marco

    2017-09-25

    Pediatric acute-liver-failure due to acetaminophen (APAP) administration at therapeutic dosage is rare, while viral infections and metabolic defects are the prevalent causes. Yet, as acetaminophen is routinely used in febrile illnesses, it may be mistakenly held responsible for the acute liver damage. An 11 month old boy had been on acetaminophen for 10 days (total dose 720 mg = 72 mg/kg) when he developed acute-liver-failure with encephalopathy. As he rapidly improved on N-acetylcysteine (NAC) infusion, it was concluded that chronic acetaminophen administration in an infant had lead to acute-liver-failure even at therapeutic doses, that N-acetylcysteine infusion had been life-saving and should be immediately started in similar circumstances. The child, however, had two further episodes of acute liver damage over a 34-month period, without having been given acetaminophen, as the parents carefully avoided using it. His clinical, laboratory and radiological findings between the acute episodes were unremarkable. His features and skeletal surveys were not suggestive of a syndromic condition. He then went on to suffer another episode of acute-liver-failure with multi-organ failure, necessitating an urgent liver transplant. All efforts to come to a diagnosis for the causes of his recurrent episodes of liver failure had been unsuccessful, until a biallelic mutation in the NBAS gene was reported to be associated with recurrent acute-liver-failure in children. The boy's DNA analysis revealed compound heterozygous pathogenic mutations in the NBAS gene. Liver failure episodes in these patients are triggered and worsened by fever, most likely due to thermal susceptibility of hepatocytes, hence APAP, rather than being a culprit, is part of the supportive treatment. We suggest that, in acute-liver-failure with a history of acetaminophen exposure at therapeutic dosage, clinicians should not be contented with administering NAC, but should consider an alternative etiology

  17. The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Hansen, Bent Adel

    2008-01-01

    Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has...

  18. Development and validation of a dynamic outcome prediction model for paracetamol-induced acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Wang, Yanzhong; Maggs, James

    2016-01-01

    BACKGROUND: Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver...... transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death. METHODS: Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK...... normalised ratio (INR), and cardiovascular failure were used to derive an initial predictive model, with a second (day 2) model including additional changes in INR and lactate. FINDINGS: We developed and validated new high-performance statistical models to support decision making in patients with paracetamol...

  19. Reversal of intestinal failure-associated liver disease (IFALD)

    DEFF Research Database (Denmark)

    Hvas, Christian; Kodjabashia, Kamelia; Nixon, Emma

    2016-01-01

    in an adult patient with IF secondary to severe Crohn's disease and multiple small bowel resections. The patient developed liver dysfunction and pathology consistent with IFALD. Multiple causal factors were implicated, including nutrition-related factors, catheter sepsis and the use of hepatotoxic medications....... Multidisciplinary treatment in a tertiary IF referral centre included aggressive sepsis management, discontinuation of hepatotoxic medications and a reduction of parenteral nutrition dependency through optimisation of enteral nutrition via distal enteral tube feeding. Upon this, liver function tests normalised....

  20. Living donor liver transplantation for acute liver failure in pediatric patients caused by the ingestion of fireworks containing yellow phosphorus.

    Science.gov (United States)

    Ates, Mustafa; Dirican, Abuzer; Ozgor, Dincer; Aydin, Cemalettin; Isik, Burak; Ara, Cengiz; Yilmaz, Mehmet; Ayse Selimoglu, M; Kayaalp, Cuneyt; Yilmaz, Sezai

    2011-11-01

    Yellow phosphorus is a protoplasmic toxicant that targets the liver. The ingestion of fireworks containing yellow phosphorus, either by children who accidentally consume them or by adults who are attempting suicide, often results in death due to acute liver failure (ALF). We present the outcomes of 10 children who ingested fireworks containing yellow phosphorus. There were 6 boys and 4 girls, and their ages ranged from 21 to 60 months. One patient remained stable without liver complications and was discharged. Three patients died of hepatorenal failure and cardiovascular collapse, and living donor liver transplantation (LDLT) was performed for 6 patients. The patients had grade II or III encephalopathy, a mean alanine aminotransferase level of 1148.2 IU/L, a mean aspartate aminotransferase level of 1437.5 IU/L, a mean total bilirubin level of 6.9 mg/dL, a mean international normalized ratio of 6.6, a mean Pediatric End-Stage Liver Disease score of 33.7, and a mean Child-Pugh score of 11.3. Postoperatively, 2 patients had persistent encephalopathy and died on the second or third postoperative day, and 1 patient died of cardiac arrest on the first postoperative day despite a well-functioning graft. The other 3 patients were still alive at a mean of 204 days. In conclusion, the ingestion of fireworks containing yellow phosphorus causes ALF with a high mortality rate. When signs of irreversible ALF are detected, emergency LDLT should be considered as a lifesaving procedure; however, if yellow phosphorus toxicity affects both the brain and the heart in addition to the liver, the mortality rate remains very high despite liver transplantation. Copyright © 2011 American Association for the Study of Liver Diseases.

  1. Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute Liver Failure.

    Science.gov (United States)

    Deep, Akash; Stewart, Claire E; Dhawan, Anil; Douiri, Abdel

    2016-10-01

    To establish the effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. Retrospective cohort study. Sixteen-bed PICU in a university-affiliated tertiary care hospital and specialist liver centre. All children (0-18 yr) admitted to PICU with pediatric acute liver failure between January 2003 and December 2013. Children with pediatric acute liver failure were managed according to a set protocol. The guidelines for continuous renal replacement therapy in pediatric acute liver failure were changed in 2011 following preliminary results to indicate the earlier use of continuous renal replacement therapy for both renal dysfunction and detoxification. Of 165 children admitted with pediatric acute liver failure, 136 met the inclusion criteria and 45 of these received continuous renal replacement therapy prior to transplantation or recovery. Of the children managed with continuous renal replacement therapy, 26 (58%) survived: 19 were successfully bridged to liver transplantation and 7 spontaneously recovered. Cox proportional hazards regression model clearly showed reducing hyperammonemia by 48 hours after initiating continuous renal replacement therapy significantly improved survival (HR, 1.04; 95% CI, 1.013-1.073; p = 0.004). On average, for every 10% decrease in ammonia from baseline at 48 hours, the likelihood of survival increased by 50%. Time to initiate continuous renal replacement therapy from PICU admission was lower in survivors compared to nonsurvivors (HR, 0.96; 95% CI, 0.916-1.007; p = 0.095). Change in practice to initiate early and high-dose continuous renal replacement therapy led to increased survival with maximum effect being visible in the first 14 days (HR, 3; 95% CI, 1.0-10.3; p = 0.063). Among children with pediatric acute liver failure who did not receive a liver transplant, use of continuous renal replacement therapy significantly improved survival (HR, 4; 95% CI, 1.5-11.6; p = 0.006). Continuous renal replacement

  2. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Carolina Roos Mariano da Rocha

    2017-01-01

    Full Text Available Neonatal liver failure (NLF is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment.

  3. Human Parechovirus as a Cause of Isolated Pediatric Acute Liver Failure.

    Science.gov (United States)

    Bigelow, Amee M; Scott, John P; Hong, Johnny C; Cronin, David C; Vitola, Bernadette E; Fons, Roger A; Petersen, Tara L

    2016-11-01

    Among infants, almost half of acute liver failure cases are classified as indeterminate, whereas only a small number of cases show a documented viral infection. We present the first reported case of isolated acute hepatic failure in an infant in the setting of a human parechovirus (HPeV) infection. HPeV also may have been contributory to the posttransplant complication of 2 intussusceptions. This is a 10-month-old girl who presented with only symptoms of fussiness and was noted to have progressive decline in synthetic liver function as well as worsening coagulopathy requiring a liver transplant. The acute liver failure was in the setting of a positive serum RNA HPeV, subtype 3 (HPeV-3), after extensive diagnostic testing with genetic, autoimmune, and infectious causes otherwise negative. After liver transplantation, the postoperative course was complicated by both an ileal-ileal intussusception as well as a jejunal intussusception. Viral testing in pediatric acute liver failure is often performed, but the workup is frequently incomplete. This case report would support more extensive viral testing in this population of patients. In the setting of HPeV, clinicians could be alerted to the possibility of delayed gastrointestinal pathology in the posttransplant phase. Wider use of routine HPeV testing may more clearly define the variable clinical presentations and outcomes. Copyright © 2016 by the American Academy of Pediatrics.

  4. Predicting post-hepatectomy liver failure by combined volumetric, functional MR image and laboratory analysis.

    Science.gov (United States)

    Chuang, Yi-Hsuan; Ou, Hsin-You; Lazo, Marirose Z; Chen, Chao-Long; Chen, Meng-Hsiang; Weng, Ching-Chun; Cheng, Yu-Fan

    2017-10-07

    To assess the efficacy of functional MR image with volumetric, liver function test and indocyanine green clearance (ICG) in identifying the patients who are at risk of post-hepatectomy liver failure (PHLF). We retrospectively included 115 patients undergoing gadoxetic acid-enhanced MR imaging before hepatectomy at one medical centre from January 2013 to December 2015. Contrast enhancement ratio (CER) between transitional and hepatobiliary phases (3 and 30 minutes post-contrast) was calculated. Total liver volume (TLV) and spleen volume (Sp) were measured. Post-operatively, the histological Ishak fibrosis score was collected. Potential risk factors for liver failure were analysed, and the performance was examined by receiver operating characteristic curve. Post-hepatectomy liver failure (PHLF) occurred in 16 patients (13.9%). TLV/SLV, ADC value, CER HBP/TP and total liver contrast enhancement ratio (tCER) were associated with PHLF (P imaging with volumetric is a reliable method for evaluating functional liver volume and determining the risk of PHLF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. The use Prometheus FPSA system in the treatment of acute liver failure: preliminary results.

    Science.gov (United States)

    Skwarek, A; Grodzicki, M; Nyckowski, P; Kotulski, M; Zieniewicz, K; Michalowicz, B; Patkowski, W; Grzelak, I; Paczkowska, A; Giercuszkiewicz, D; Sańko-Resmer, J; Paczek, L; Krawczyk, M

    2006-01-01

    The preliminary outcomes of patients with acute liver failure treated with the Prometheus Fractionated Plasma Separation and Absorption (FPSA) system are presented herein. The procedures were performed in 13 patients (4, intoxication by Amanita phalloides; 4, unknown reason; 3, acetaminophen intoxication; 1, Wilson disease, and 1, liver insufficiency after hemihepatectomy owing to metastases of colon adenocarcinoma). The patients were qualified for the procedure according to the King's College Hospital criteria. The patients' general status was assessed on basic of GCS, UNOS, and the 4-grade encephalopathy classifications. The procedures were performed with the Prometheus 4008H Fresenius Medical Care unit. The 29 procedures were of mean duration 6.5 hours. There were statistically significant reductions in total bilirubin, ammonia, and aminotransferase levels. In addition, the procedures corrected water, mineral, and carbohydrate disorders. One patient did not require liver transplantation. Seven patients received liver transplants: three patients with positive outcomes; two died due to septicemia within 30 days perioperatively, one died at 6 months after OLT owing to respiratory failure; and one, owing to hemorrhagic diathesis. Four patients did not receive a liver transplant because of lack of a organ, no consent for the surgery, or neoplastic disease with metastases. The Prometheus FPSA-System was an effective detoxication method for patients with acute liver failure. The system was useful as a symptomatic treatment before liver transplantation allowing a longer wait for a graft.

  6. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease.

    Science.gov (United States)

    Jacobi, Johannes; Schnellhardt, Susanne; Opgenoorth, Mirian; Amann, Kerstin U; Küttner, Axel; Schmid, Axel; Eckardt, Kai-Uwe; Hilgers, Karl F

    2010-04-18

    Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.

  7. Value of serum PCT in early diagnosis of bacterial infection in patients with liver failure

    Directory of Open Access Journals (Sweden)

    WANG Chuanmin

    2017-06-01

    Full Text Available ObjectiveTo investigate the value of serum procalcitonin (PCT in early diagnosis of bacterial infection in patients with liver failure. MethodsA total of 463 patients with hepatitis B were selected from January to December, 2014, in the Department of Infectious Diseases, Taihe Hospital. According to the degree of liver injury, the patients were divided into four groups: mild liver injury group (n=120, moderate liver injury group (n=222, sever liver injury group (n=53, and liver failure group (n=68. Serum PCT was measured for all patients, and the white blood cell count (WBC and high-sensitivity C-reactive protein (hsCRP were measured for patients with liver failure. The clinical manifestations were observed and recorded. The t test was used for comparison of normally distributed continuous data, while the Kruskal-Wallis H test was used for non-normally distributed continuous data; the Mann-Whitney U test was used for pairwise comparison of continuous data. The chi-square test was used for comparison of categorical data. The receiver operating characteristic (ROC curve was used for the analysis of predictive value. ResultsThe liver failure group had a significantly higher PCT level than the severe liver injury group, moderate liver injury group, and mild liver injury group (0.81[0.34-2.15] vs 0.53[0.21-1.59], 0.35[010-1.18], and 0.17[0.10-0.60], χ2=25.091, P<0.05. The liver failure patients with PCT levels of <0.25 ng/ml (n=10, 0.25-0.5 ng/ml (n=10, and >0.5 ng/ml (n=48 had infection rates of 20%, 30%, and 66.7%, respectively, with a significant difference between the patients with a PCT level of >0.5 ng/ml and those with PCT levels of <0.25 ng/ml and 0.25-0.5 ng/ml (χ2=5631,4650,P=0018,0031. Among the liver failure patients, the infection cases had significantly higher PCT, WBC, and hsCRP than the non-infection cases (PCT: 3.72±1.33 ng/ml vs 0.34±0.12 ng/ml, t=-2.547, P=0.015; hsCRP: 16.70±7.03 mg

  8. Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

    Science.gov (United States)

    Kok, Beverley; Lester, Erica L W; Lee, William M; Hanje, A James; Stravitz, R Todd; Girgis, Safwat; Patel, Vaishali; Peck, Joshua R; Esber, Christopher; Karvellas, Constantine J

    2018-03-21

    Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

  9. Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Kazushige Nirei

    2013-01-01

    Full Text Available This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient’s jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.

  10. Pediatric acute liver failure: variations in referral timing are associated with disease subtypes.

    Science.gov (United States)

    Sturm, Ekkehard; Lexmond, Willem S; Verkade, Henkjan J

    2015-02-01

    In pediatric acute liver failure (PALF), rapid referral to a transplant center (TC) is advocated. Clinical variability of PALF may influence referral timing. We aimed to analyze early or late timing of referral in relation to clinical characteristics and outcome in PALF. We conducted a retrospective, single-center, comparative analysis of clinical and liver function parameters in two PALF cohorts (n = 23 per cohort): cohort 1 (early referral, duration of in-patient care before referral (DCR) liver failure (SLF >7 days between disease onset and development of encephalopathy) was independently associated with late referral (relative risk 9.48; 95 % CI 1.37-64.85, p liver function patterns. Early recognition of prognostic indicators and of SLF may help to improve referral timing and thus PALF management.

  11. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema) and an incre......1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema......) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  12. Management of Pediatric Acute Liver Failure in a Region With Insufficient Deceased Donor Support: A Single-Center Experience.

    Science.gov (United States)

    Yankol, Yucel; Ertugrul, Mustafa; Kanmaz, Turan; Mecit, Nesimi; Ocak, Ilhan; Durmaz, Ozlem; Acarli, Koray; Kalayoglu, Munci

    2016-10-01

    Acute liver failure is a rapidly progressive and life-threatening disease in children, whose clinical features differ from those of adults. This is a review of a single center's experience with pediatric acute liver failure in a region with insufficient deceased donor support. The study is a retrospective review and analysis of 22 pediatric patients with acute liver failure between January 2007 and May 2013. The cause of acute liver failure was indeterminate in 45.4% of cases. Listing for liver transplant was required in 72.7% of patients, whereas 27.3% developed spontaneous remission. In the patients placed on the liver transplant wait list, 75% underwent liver transplant and 25% died before undergoing liver transplant. The presence of ascites, high-grade encephalopathy, and laboratory findings including high lactate dehydrogenase and phosphorous levels and international normalized ratio were significant parameters in selecting patients needing liver transplants. All liver transplants were from living donors. One- and 3-year patient survival rates after liver transplant were 75% and 75%. No serious donor complications occurred. Living-donor liver transplant may be the only option to save the lives of pediatric patients with acute liver failure, especially in regions with insufficient deceased-donor support. Timely referral to a multidisciplinary transplant center, expedient evaluation of living donors, and appropriate timing of transplant are crucial for a successful outcome.

  13. Pre-operative risk factors predict post-operative respiratory failure after liver transplantation.

    Directory of Open Access Journals (Sweden)

    Ching-Tzu Huang

    Full Text Available OBJECTIVE: Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF after liver transplantation and the impact on short-term survival rates. DESIGN: The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not. MEASUREMENTS AND MAIN RESULTS: Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS use, source of organ transplantation, model for end-stage liver disease score (MELD and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05. Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001. CONCLUSIONS: The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation.

  14. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

    Directory of Open Access Journals (Sweden)

    Schmid Axel

    2010-04-01

    Full Text Available Abstract Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.

  15. Hepatitis A related acute liver failure by consumption of contaminated food.

    Science.gov (United States)

    Chi, Heng; Haagsma, Elizabeth B; Riezebos-Brilman, Annelies; van den Berg, Arie P; Metselaar, Herold J; de Knegt, Robert J

    2014-11-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. A study on risk factors and diagnostic efficiency of posthepatectomy liver failure in the nonobstructive jaundice.

    Science.gov (United States)

    Wang, He; Lu, Shi-Chun; He, Lei; Dong, Jia-Hong

    2018-02-01

    Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors.t test and χ test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes.Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

  17. Acute liver failure complication of brucellosis infection: a case report and review of the literature.

    Science.gov (United States)

    García Casallas, Julio César; Villalobos Monsalve, Walter; Arias Villate, Sara Consuelo; Fino Solano, Ingrid Marisol

    2018-03-09

    Brucellosis is one of the most widespread zoonoses worldwide. It can affect any organ system, particularly the gastrointestinal system, but there is no report of acute liver failure as a brucellosis complication. We present a case of acute liver failure secondary to brucellosis infection. A 75-year-old Hispanic man presented to a University Hospital in Chía, Colombia, with a complaint of 15 days of fatigue, weakness, decreased appetite, epigastric abdominal pain, jaundice, and 10 kg weight loss. On examination in an emergency room, abdomen palpation was normal with hepatosplenomegaly and the results of a liver function test were elevated. The diagnosis of brucellosis was confirmed by epidemiological contact and positive Rose Bengal agglutination with negative enzyme-linked immunosorbent assay immunoglobulin M for Brucella. He was then treated with doxycycline plus trimethoprim/sulfamethoxazole, with a favorable clinical outcome. The clinical presentation of brucellosis can be very imprecise because it can affect any organ system; however, there is no report of acute liver failure as a brucellosis complication. This is the first reported case in the Colombian literature of acute liver failure due to brucellosis. We found this case to be of interest because it could be taken into account for diagnosis in future appearances and we described adequate treatment and actions to be taken at presentation.

  18. Dengue hemorrhagic fever complicated with acute liver failure: a case report.

    Science.gov (United States)

    Dalugama, Chamara; Gawarammana, Indika Bandara

    2017-12-08

    Dengue is a common arboviral infection with a clinically diverse spectrum of presentations. Although hepatic dysfunction is commonly identified in patients will dengue illness, acute liver failure is rare. The etiopathogenesis of hepatic dysfunction is multifactorial and related to direct viral invasion of hepatocytes, immunological factors and hypoxia particularly in cases of shock in dengue hemorrhagic fever. Ideal management of dengue-related hepatic dysfunction and acute liver failure is still debated. We report a 53-year-old Sri Lankan Sinhalese male with serologically confirmed dengue fever presenting with evidence of plasma leakage developing acute liver failure evidenced by deranged liver functions, coagulopathy and altered sensorium. In addition to the 'standard care', the patient was managed with intravenous N-acetyl cysteine and blood transfusions even in the absence of bleeding or dropping packed cell volume (PCV), targeting a higher PCV in anticipation of better oxygenation at tissue level. He made a full recovery with no sequential infections. N-acetyl cysteine and packed cell transfusion aiming at a higher PCV to maintain adequate tissue perfusion during shock may be beneficial in acute liver failure due to dengue virus. Large randomized trials should be carried out to establish the efficacy of these treatment strategies to support these observations and change the current practice.

  19. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

    DEFF Research Database (Denmark)

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral

    2012-01-01

    The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.......The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....

  20. A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Murphy, Nicholas; Brown, Sarah

    2016-01-01

    BACKGROUND & AIMS: Animal models and human case series of acute liver failure (ALF) suggest moderate hypothermia (MH) to have protective effects against cerebral oedema (CO) development and intracranial hypertension (ICH). However, the optimum temperature for patient management is unknown...... above management at 36°C in prevention of ICH or in overall survival. This study did not confirm advantage of its prophylactic use. (ISRCTN registration number 74268282; no funding.) LAY SUMMARY: Studies in animals with acute liver failure (ALF) have suggested that cooling (hypothermia) could prevent...

  1. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema......) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  2. Acute Liver Failure: Outcome and Value of Pediatric End-Stage Liver Disease Score in Pediatric Cases.

    Science.gov (United States)

    Núñez-Ramos, Raquel; Montoro, Soledad; Bellusci, Marcello; Del Fresno-Valencia, María Rosa; Germán-Díaz, Marta; Urruzuno, Pedro; Medina, Enrique; Manzanares, Javier

    2016-09-30

    The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.

  3. Preoperative Cholangitis and Future Liver Remnant Volume Determine the Risk of Liver Failure in Patients Undergoing Resection for Hilar Cholangiocarcinoma

    Science.gov (United States)

    Aloia, Thomas A; Shindoh, Junichi; Fabio, Forchino; Amisano, Marco; Passot, Guillaume; Ferrero, Alessandro; Vauthey, Jean-Nicolas

    2016-01-01

    Background The highest mortality rates after liver surgery are reported in patients who undergo resection for hilar cholangiocarcinoma (HCCA). In these patients, postoperative death usually follows the development of hepatic insufficiency. We sought to determine the factors associated with postoperative hepatic insufficiency and death due to liver failure in patients undergoing hepatectomy for HCCA. Study Design This study included all consecutive patients who underwent hepatectomy with curative intent for HCCA at two centers from 1996 through 2013. Preoperative clinical and operative data were analyzed to identify independent determinants of i) hepatic insufficiency and ii) liver failure–related death. Results The study included 133 patients with right or left major (n=67) or extended (n=66) hepatectomy. Preoperative biliary drainage was performed in 98 patients and was complicated by cholangitis in 40 cases. In all these patients, cholangitis was controlled before surgery. Major (Dindo III-IV) postoperative complications occurred in 73 patients (55%), with 29 suffering from hepatic insufficiency. Fifteen patients (11%) died within 90 days after surgery, 10 of them of liver failure. On multivariate analysis, predictors of postoperative hepatic insufficiency (all ppreoperative cholangitis (odds ratio [OR]=3.2), future liver remnant (FLR) volume preoperative total bilirubin level >3 mg/dl (OR=4), and albumin level preoperative cholangitis (OR=7.5, p=.016) and FLR volume Preoperative cholangitis and insufficient FLR volume are major determinants of hepatic insufficiency and postoperative liver failure–related death. Given the association between biliary drainage and cholangitis, the preoperative approach to patients with HCCA should be optimized to minimize the risk of cholangitis. PMID:27049784

  4. HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure.

    Science.gov (United States)

    Yang, Runkuan; Zou, Xiaoping; Tenhunen, Jyrki; Tønnessen, Tor Inge

    2017-01-01

    Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  5. HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Acute liver failure (ALF is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT. BT triggers/induces systemic inflammatory responses syndrome (SIRS, which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  6. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests

    DEFF Research Database (Denmark)

    Korman, J.D.; Volenberg, I.; Balko, J.

    2008-01-01

    Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF...... patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp

  7. Changes in the Prevalence of Hepatitis C Virus Infection, Nonalcoholic Steatohepatitis, and Alcoholic Liver Disease Among Patients With Cirrhosis or Liver Failure on the Waitlist for Liver Transplantation.

    Science.gov (United States)

    Goldberg, David; Ditah, Ivo C; Saeian, Kia; Lalehzari, Mona; Aronsohn, Andrew; Gorospe, Emmanuel C; Charlton, Michael

    2017-04-01

    Concurrent to development of more effective drugs for treatment of hepatitis C virus (HCV) infection, there has been an increase in the incidence of nonalcoholic fatty liver disease. Data indicate that liver transplantation prolongs survival times of patient with acute hepatitis associated with alcoholic liver disease (ALD). We compared data on disease prevalence in the population with data from liver transplantation waitlists to evaluate changes in the burden of liver disease in the United States. We collected data on the prevalence of HCV from the 2010 and 2013-2014 cycles of the National Health and Nutrition Examination Survey. We also collected data from the HealthCore Integrated Research Database on patients with cirrhosis and chronic liver failure (CLF) from 2006 through 2014, and data on patients who received transplants from the United Network for Organ Sharing from 2003 through 2015. We determined percentages of new waitlist members and transplant recipients with HCV infection, stratified by indication for transplantation, modeling each calendar year as a continuous variable using the Spearman rank correlation, nonparametric test of trends, and linear regression models. In an analysis of data from the National Health and Nutrition Examination Survey (2013-2014), we found that the proportion of patients with a positive HCV antibody who had a positive HCV RNA was 0.5 (95% confidence interval, 0.42-0.55); this value was significantly lower than in 2010 (0.64; 95% confidence interval, 0.59-0.73) (P = .03). Data from the HealthCore database revealed significant changes (P liver transplant waitlist, or undergoing liver transplantation, for CLF, there was a significant decrease in the percentage with HCV infection and increases in percentages of patients with nonalcoholic fatty liver disease or ALD. Among patients new to the liver transplant waitlist or undergoing liver transplantation for HCC, proportions of those with HCV infection, nonalcoholic fatty liver

  8. Fatal Acute Liver Failure as a Consequence of Regorafenib Treatment in a Metastatic Colon Cancer

    Directory of Open Access Journals (Sweden)

    Dominique Béchade

    2017-08-01

    Full Text Available Regorafenib is a multikinase inhibitor which showed benefits in pretreated metastatic colorectal cancer patients. Hepatotoxicity has been described as a frequent side effect. We report the case of a 65-year-old patient presenting with jaundice, fever, and hepatocellular insufficiency which led to death of the patient. She had previously been treated with several lines of chemotherapy for sub- and diaphragmatic ganglionic metastases of a colon adenocarcinoma. There were no liver metastases. The fatal liver failure occurred at the beginning of treatment with regorafenib at a dosage of 3 tablets per day. No concomitant treatment was given, and other causes of liver damage were eliminated. The liver biopsy showed hepatocyte necrosis with lymphocyte infiltration. This observation illustrates the risk of severe hepatic involvement typically occurring within the first 2 months of treatment. Monitoring liver biology every 2 weeks is essential during the first 2 months to detect any hepatotoxicity.

  9. Acetaminophen - Dose-dependent Drug Hepatotoxicity and Acute Liver Failure in Patients

    Science.gov (United States)

    Jaeschke, Hartmut

    2015-01-01

    Background Drug-induced liver injury (DILI) is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure (ALF) at therapeutic doses in a very limited number of patients (paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and ALF after intentional and unintentional overdoses. Key Messages APAP overdose is responsible for more ALF cases in the US or UK than all other etiologies combined. Because APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late presenting patients. Conclusions The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent ALF and to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome. PMID:26159260

  10. Hepatic failure in a rapidly involuting congenital hemangioma of the liver: failure of embolotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zenzen, Wendy; Alomari, Ahmad I. [Children' s Hospital Boston, Division of Vascular and Interventional Radiology, Department of Radiology, Boston, MA (United States); Perez-Atayde, Antonio R. [Children' s Hospital Boston and Harvard Medical School, Department of Pathology, Boston, MA (United States); Elisofon, Scott A. [Children' s Hospital Boston and Harvard Medical School, Division of Gastroenterology, Boston, MA (United States); Bae Kim, Heung [Children' s Hospital Boston and Harvard Medical School, Department of Surgery, Boston, MA (United States)

    2009-10-15

    We report the clinical course, imaging findings, and management of a rare case of rapidly involuting congenital hemangioma of the liver in a newborn girl. The baby presented with severe progressive hepatic dysfunction and cardiomegaly. Multimodality imaging demonstrated a large hypervascular solitary hepatic mass with marked transhepatic shunting, consistent with rapidly involuting congenital hemangioma. Because medical therapy failed, transarterial and transvenous embolization was performed with the main intention to improve the hepatic perfusion and function. Unfortunately, despite improvement in the cardiac overload, liver function continued to deteriorate. The baby eventually underwent successful liver transplantation. (orig.)

  11. Tacrolimus Aggravated Tube Feeding Syndrome with Acute Renal Failure in a Pediatric Liver Transplant Recipient

    OpenAIRE

    Kula, R.; Melter, M.; Kunkel, J.; D?rfler, C.; Alikadic, S.; Knoppke, B.; Zant, R.

    2017-01-01

    Acute renal failure can be caused by calcineurin inhibitors (CNIs), due to arteriolopathy and altered tubular function. Within this context, we present the case of a 14-month-old liver transplant recipient who suffered an acute polyuric renal failure during a short episode of hypercaloric feeding. In our case, CNI-induced distal RTA led to nephrocalcinosis and therefore to secondary nephrogenic diabetes insipidus. The diet with high renal solute load consequently resulted in an acute polyuric...

  12. [Correction of cronic liver failure by transplantation of liver cells suspension and cell-engineering designs (experimental investigation)].

    Science.gov (United States)

    Got'e, S V; Shagidulin, M Iu; Onishchenko, N A; Krasheninnikov, M E; Il'inskiĭ, I M; Mozheĭko, N P; Liundup, A V; Volkova, E A; Petrakov, K I; Avramov, P V; Perova, N V; Sevast'ianov, V I

    2013-01-01

    On an experimental model of chronic fibrotic liver damage (male rats Wistar (n-60), damage of CCl4, the duration of the experiment 90 days) it was studied the effectiveness of cell therapy for the correction of chronic liver failure. These rats were divided into 3 experimental groups: in the Ist-group (control, n=10) isotonic saline (650 mkl.) was injected; in the IInd-group (n=20) suspension of liver cells was applicated in a dose 8 - l0 x 10(6) cells; in the IIIrd-group (n=30) suspension of liver cells and bone marrow cells (mesenchymal stromal cells) in ratio 5:1 were used as cell associates on microparticles intjectable heterogeneous biopolymer hydrogel "SpheroGEL" (cell-engineering design) in common dose 8 - l0 x 10(6) It was ascertained that in the 2nd and in the 3rd groups the accelerated normalization of disturbed liver functional indices (ALT, AST, ALP) took place - to 30 days, but in the control group only to 90 days. The reliable differences in rats ofnormalization offunctional indices were absent between the IInd and the IIIrd groups. But in 90 days by using special histological dyeing it was found out that defibrotic processes in liver tissue were more expressed in the IIIrd group in comparison with the IIIrd group. Received results were consequence of prolonged vital activity of cells (liver cells and mesenchymal stromal bone marrow cells) into cell-engineering designs, which were transplanted in the IIIrd group. The obtained effect can be explained by that the developed cell-engineering designs provide adequate conditions for prolonged vital activity of the transplanted cells.

  13. Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List.

    Science.gov (United States)

    Urrunaga, Nathalie H; Magder, Laurence S; Weir, Matthew R; Rockey, Don C; Mindikoglu, Ayse L

    2016-01-01

    Although renal dysfunction is a known complication of acute liver failure (ALF), its frequency, severity, and impact among patients with ALF on the US liver transplant list are not well defined. Organ Procurement and Transplantation data for ALF patients listed as status 1/1A from 2002 to 2012 were analyzed. The frequency and severity of renal dysfunction at the time of listing [the latter was categorized in 5 stages using estimated GFR (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation] were determined and the association between renal dysfunction and waiting list mortality was assessed using Cox proportional hazard regression analysis. There were a total of 2280 adult patients with ALF, including 56 % with renal dysfunction (defined as eGFR renal dysfunction was among those with ALF caused by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, fatty liver disease of pregnancy, heat stroke/hyperthermia, hepatitis A virus, and drug-induced liver injury due to acetaminophen APAP, phenytoin, trimethoprim-sulfamethoxazole, and macrolides. Despite the fact that 69 % (468/674) of patients with APAP-induced ALF listed as status 1/1A had renal dysfunction, only 0.9 % underwent simultaneous liver-kidney transplantation. Six-week survival probabilities in patients with ALF on the liver transplant waiting list were 71, 59, 56, 59, and 42 % with renal dysfunction stages of 1, 2, 3, 4, and 5, respectively. Multivariate analysis showed that after controlling for age, etiology of ALF, INR, total bilirubin, and region, the relative risk of death increased progressively as eGFR declined (P renal dysfunction was common (overall prevalence of 56 %). Most importantly, severe renal dysfunction was associated with significantly increased mortality.

  14. Hepatitis A related acute liver failure by consumption of contaminated food

    NARCIS (Netherlands)

    Chi, Heng; Haagsma, Elizabeth B.; Riezebos-Brilman, Annelies; van den Berg, Arie P.; Metselaar, Herold J.; de Knegt, Robert J.

    2014-01-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the

  15. Liver failure caused by prolonged state of malnutrition following bariatric surgery

    NARCIS (Netherlands)

    W.J. Lammers (Wim); van Tilburg, A.J.P. (Antonie J.P.); Apers, J.A. (Jan A.); J. Wiebolt (Janneke)

    2018-01-01

    textabstractBariatric surgery is an effective tool in the treatment of patients with morbid obesity. In these case reports we describe 2 patients who developed liver failure after currently-practiced types of bariatric surgery, caused by a prolonged state of malnutrition provoked by psychiatric

  16. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure

    NARCIS (Netherlands)

    Korpela, K.; Mutanen, A.; Salonen, A.; Savilahti, E.; Vos, de W.M.; Pakarinen, M.P.

    2017-01-01

    BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent

  17. Pediatric acute liver failure : variations in referral timing are associated with disease subtypes

    NARCIS (Netherlands)

    Sturm, Ekkehard; Lexmond, Willem S.; Verkade, Henkjan J.

    2015-01-01

    In pediatric acute liver failure (PALF), rapid referral to a transplant center (TC) is advocated. Clinical variability of PALF may influence referral timing. We aimed to analyze early or late timing of referral in relation to clinical characteristics and outcome in PALF. We conducted a

  18. Quantitative multivoxel H-1 MR spectroscopy of the brain in children with acute liver failure

    NARCIS (Netherlands)

    Sijens, Paul E.; Alkefaji, Heyder; Lunsing, Roelineke J.; van Spronsen, Francjan J.; Meiners, Linda C.; Oudkerk, Matthijs; Verkade, Henkjan J.

    2008-01-01

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx)

  19. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P.N.; Hauerberg, J.; Frederiksen, Hans-Jørgen

    2008-01-01

    AIM: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated...

  20. A Systematic Review on Prognostic Indicators of Acute Liver Failure and Their Predictive Value for Poor Outcome

    NARCIS (Netherlands)

    Wlodzimirow, Kama A.; Eslami, Saeid; Abu-Hanna, Ameen; Nieuwoudt, Martin; Chamuleau, Robert A. F. M.

    2014-01-01

    This review provides a large amount of information, including the extensive list of worldwide used indicators to predict outcome in patients with acute liver failure. There is large heterogeneity in prognostic indicators of acute liver failure, methods of measurement, complexity of calculation and

  1. Haemophagocytic lymphohistiocytosis presenting as liver failure following Epstein-Barr and prior hepatitis A infections.

    Science.gov (United States)

    Pinto-Patarroyo, Gineth Paola; Rytting, Michael E; Vierling, John Moore; Suarez-Almazor, Maria E

    2013-08-13

    Haemophagocytic lymphohistiocytosis (HLH) is associated with high mortality even after prompt diagnosis. We present a young man with HLH triggered by two common viral diseases, infectious mononucleosis and hepatitis A. This patient presented with fever, rapidly progressive liver failure, anasarca and cholestasis, followed by anaemia and neutropenia. His carbohydrate antigen 19-9 reached over 9000 U/mL. Initial bone marrow and liver biopsies did not show histological features of malignancy or HLH. The patient was finally diagnosed and treated almost 1 year after the initial symptoms started, and had an excellent response with etoposide and dexamethasone. This case is unusual because it was triggered following mononucleosis in a patient with positive total antibodies against hepatitis A, with rapidly developing liver failure, and also because the patient's response was excellent despite the delay in treatment. It underscores the importance of suspecting HLH when severe systemic illness develops after a viral infection, even in the absence of clear histological features.

  2. Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome

    Energy Technology Data Exchange (ETDEWEB)

    Cavet, Madeleine; Balu, Marie; Garel, Catherine; Ducou le Pointe, Hubert [Universite Pierre et Marie Curie Paris VI, Service de Radiologie, Hopital d' enfants Armand-Trousseau, Paris (France); Mitanchez, Delphine; Alexandre, Marie [Universite Pierre et Marie Curie Paris VI, Service de Neonatologie, Hopital d' enfants Armand-Trousseau, Paris (France); Renolleau, Sylvain [Universite Pierre et Marie Curie Paris VI, Service de Reanimation, Hopital d' enfants Armand-Trousseau, Paris (France); Pariente, Daniele [Hopital de Bicetre, Service de Radiologie Pediatrique, Paris (France)

    2008-10-15

    Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia. (orig.)

  3. Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome

    International Nuclear Information System (INIS)

    Cavet, Madeleine; Balu, Marie; Garel, Catherine; Ducou le Pointe, Hubert; Mitanchez, Delphine; Alexandre, Marie; Renolleau, Sylvain; Pariente, Daniele

    2008-01-01

    Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia. (orig.)

  4. Clinical features and risk factors for patients with liver failure complicated by invasive pulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    XIAO Erhui

    2016-07-01

    Full Text Available ObjectiveTo investigate the clinical features and risk factors for patients with liver failure complicated by invasive pulmonary aspergillosis (IPA, and to provide a reference for clinical diagnosis and treatment. MethodsThe clinical data of 477 patients with liver failure who were diagnosed and treated in Henan Provincial People′s Hospital from January 2010 to December 2014 were collected, and the clinical features, laboratory markers, and results of imaging examinations of patients with IPA were retrospectively analyzed. Another 49 patients with liver failure who were hospitalized within the same period, had similar ages, and were not complicated by pulmonary infection were randomly selected as controls. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test or Fisher′s exact test were used for comparison of categorical data between groups, and multivariate logistic regression analysis was performed to analyze the risk factors for liver failure complicated by IPA. ResultsAmong the 447 patients with liver failure, 43(96% were complicated by IPA. Age (P=0.023, hepatic encephalopathy (P=0.021, long-term use of broad-spectrum antibiotics (P=0.007, use of hormone (P=0.016, and deep venous catheterization (P<0.001 were independent risk factors for the development of IPA. Clinical manifestations of liver failure patients with IPA lacked specificity. Lung CT scan showed multiple nodules, masses, and wedge-shaped consolidation near the pleura in both lungs, but typical halo sign and air crescent sign were rarely seen. Among the 35 patients who received antifungal therapy, 30 were improved or cured, 3 died of digestive tract bleeding, 2 clied of plumonary infection, and all the other patients who did not receive therapy also died. ConclusionPatients with liver failure have various risk factors for the development of IPA, and the clinical manifestations are not typical, with high incidence

  5. Etiologies, outcomes, and prognostic factors of pediatric acute liver failure: A single center's experience in Turkey.

    Science.gov (United States)

    Özçay, Figen; Karadağ Öncel, Eda; Barış, Zeren; Canan, Oğuz; Moray, Gökhan; Haberal, Mehmet

    2016-09-01

    Our aim was to determine the etiologies, outcomes, and prognostic indicators in children with acute liver failure. Ninety-one patients who were followed for pediatric acute liver failure (PALF) over a 15-year period were included. Patients who survived with supportive therapy were designated as Group 1, while those who died or underwent liver transplantation were designated as Group 2. There were 37 (40.6%) patients in Group 1 (spontaneous recovery) and 54 (59.4%) patients in Group 2. Thirty-two patients (35.2%) underwent liver transplantation. Infectious and indeterminate causes were the most common etiologies (33% each). Among the infectious causes, hepatitis A (76%) was the most frequent. Hepatic encephalopathy grade 3-4 on admission and during follow-up and high Pediatric Risk of Mortality (PRISM) and Pediatric End-Stage Liver Disease (PELD) scores within the first 24 h were related with a poor prognosis. Group 2 had a more prolonged prothrombin time, higher international normalized ratio, more prolonged activated partial thromboplastin time (aPTT), and higher levels of total and direct bilirubin, ammonia, and lactate (for all, pLiver transplantation was the only curative treatment for patients with poor prognoses and resulted in high survival rates (1-, 5-, and 10-year survival rates of 81.3%, 81.3%, and 75%, respectively) in our study.

  6. Transient fulminant liver failure as an initial presentation in citrullinemia type I.

    Science.gov (United States)

    Faghfoury, Hannaneh; Baruteau, Julian; de Baulny, Helene Ogier; Häberle, Johannes; Schulze, Andreas

    2011-04-01

    Citrullinemia type I (CTLN1) is a urea cycle disorder which typically presents in the neonatal period or infancy with hyperammonemia and concurrent neurologic deterioration. We report a 15-month-old female with CTLN1 who presented with encephalopathy and seizures with hyperammonemia requiring emergency treatment. Although there was a rapid resolution of her hyperammonemia, she developed fulminant liver failure. The severe increase of transaminases (aspartate aminotransferase and alanine aminotransferase levels peaking at 19,794 UI/L and 19,938 UI/L, respectively) and concurrent disturbances in her hepatic synthetic functions led to the consideration of a liver transplantation. However, there was a normalization of her liver function tests over the course of weeks with supportive therapy alone. Molecular analysis of the ASS1 gene confirmed the diagnosis of CTLN1 by revealing the known mutation c.1087C>T (p.R363W) on the paternal allele and an intronic nucleotide exchange leading to an insertion of 69 bp on the transcript resulting in a frameshift and premature stop of translation on the maternal allele. We also briefly report another case of CTLN1 where liver failure was a prominent feature of the presentation. Fulminant liver failure has been described with a variety of other urea cycle disorders, but has been described in infantile onset presentation of CTLN1 in only two other cases recently. Our observation suggests that in some cases of CTLN1 with acute liver failure, emergency intervention such as transplantation is not warranted despite evidence of severe hepatotoxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

    Science.gov (United States)

    Mangus, Richard S; Bush, Weston J; Miller, Christina; Kubal, Chandrashekhar A

    2017-11-01

    Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores. Children younger than 19 years with end-stage liver, kidney, or intestine failure and with pretransplant computed tomography (CT) imaging were selected from the transplant database. Age- and sex-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences. There were 81 subjects included in the final analysis (liver [n = 35], kidney [n = 20], and intestine [n = 26]). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat, and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat, and a 46% increase in subcutaneous fat. These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients, which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney), or malabsorption (intestine).

  8. Acetaminophen Adducts Detected in Serum of Pediatric Patients With Acute Liver Failure.

    Science.gov (United States)

    Alonso, Estella M; James, Laura P; Zhang, Song; Squires, Robert H

    2015-07-01

    Previous studies in patients with acute liver failure identified acetaminophen (APAP) protein adducts in the serum of 12% and 19% of children and adults, respectively, with acute liver failure of indeterminate etiology. This article details the testing of APAP adducts in a subset (n = 393) of patients with varied diagnoses in the Pediatric Acute Liver Failure Study Group (PALFSG). Serum samples were available from 393 participants included in the PALFSG registry. Adduct measurement was performed using validated methods. Participants were grouped by diagnostic category as known APAP overdose, known other diagnosis, and indeterminate etiology. Demographic and clinical characteristics and participant outcomes were compared by adduct status (positive or negative) within each group. APAP adduct testing was positive in 86% of participants with known APAP overdose, 6% with other known diagnoses, and 11% with an indeterminate cause of liver failure. Adduct-positive participants were noted to have marked elevation of serum alanine aminotransferase and aspartate aminotransferase coupled with total serum bilirubin that was significantly lower than adduct-negative patients. In the indeterminate group, adduct-positive patients had different outcomes than adduct-negative patients (P = 0.03); spontaneous survival was 16 of 21 (76%) in adduct-positive patients versus 75 of 169 (44%) in adduct-negative patients. Prognosis did not vary by adduct status in patients with known diagnoses. Furthermore, study is needed to understand the relation of APAP exposure, as determined by the presence of APAP adducts, to the clinical phenotype and outcomes of children with acute liver failure.

  9. Treatment of acute liver failure with hemodetoxification techniques.

    Science.gov (United States)

    Splendiani, G; Tancredi, M; Daniele, M; Giammaria, U

    1990-06-01

    The exact pathogenesis of hepatic coma is unknown and this fact has stimulated research in the field of hemodetoxification treatment. We studied 31 patients (19 M and 12 F) with acute hepatic failure and used different detoxification techniques such as hemodialysis, hemoperfusion, hemofiltration and plasmaferesis. We evaluated blood tests, degree of coma and serum levels of middle-molecular weight substances (by gel-chromatography) for each patient. Our results show that there was an improvement of consciousness and general clinical state in 40% of patients who underwent HD, in 50% of patients treated with HP, in 37.5% of those treated with PF and 78% of patients treated with HF. Unfortunately, the improvement did not last long. In conclusion we can say that artificial support improves hepatic coma and state of consciousness. This improvement could be due to the better regeneration possibilities of hepatic cells. For this reason hemodetoxification treatment should be started as soon as possible.

  10. Acute Liver Failure: Pathophysiologic Basis, and The Current and Emerging Therapies

    Directory of Open Access Journals (Sweden)

    Graziella Privitera

    2014-05-01

    Full Text Available Acute liver failure (ALF is a devastating condition that occurs in patients who previously had a normal liver. Although the outcome of patients with ALF has improved, without liver transplantation (LT mortality rates remain in the range of 35-50% in different geographical areas and therefore, its treatment remains an unmet need. In the Western world toxic liver injury from acetaminophen remains one of the common causes but, in the East, hepatitis of unknown aetiology remains the most common cause. Treatment options are limited to meticulous attention to multi-organ support, use of N-acetyl cysteine, judicious use of antibiotics, and timely LT. This review describes the state-of-the-art techniques in the issues related to prognosis, outcome, and treatment of this devastating syndrome.

  11. [Psychosocial indication of liver transplantation for alcohol-related liver failure: current controversies and imminent issues in Japanese society].

    Science.gov (United States)

    Kiuchi, Tetsuya

    2012-10-01

    Organ transplant therapy is becoming a usual practice also in Japan, which dramatically improves the length and quality of life in patients with end-stage organ disease. Liver transplantation was resumed in Japan much later than that in the West and is continued now under unique circumstances where more than 90% of grafts come from living donors. Nevertheless the number of liver transplantation for alcohol-related liver failure shows a sharp rise to the level comparable to the West, and not a few physical and/or psychosocial problems caused by recidivism after transplantation are coming up. To find appropriate solutions to how to predict recidivism and define psychosocial indication of liver transplantation in our society, and to how to monitor and support sobriety after transplantation, there is an urgent need for multidisciplinary management by hepatologist, transplant surgeon, psychiatrist, and dependence specialist. Life-saving therapy and dependence management are expected to work closely together from the viewpoints of transparency, equity, utility, and autonomy requested in transplant therapy, protection of living donors, and consideration for donor family and public emotion.

  12. Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group.

    Science.gov (United States)

    Ng, Vicky L; Li, Ruosha; Loomes, Kathleen M; Leonis, Mike A; Rudnick, David A; Belle, Steven H; Squires, Robert H

    2016-09-01

    Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P pediatric acute liver failure prognostication schema are needed.

  13. Acute liver failure due to Human Herpesvirus 6 in an infant

    Directory of Open Access Journals (Sweden)

    G.M. Tronconi

    2012-10-01

    Full Text Available We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus, drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6 genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases’ review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus’s genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  14. Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure.

    Science.gov (United States)

    Narkewicz, Michael R; Horslen, Simon; Belle, Steven H; Rudnick, David A; Ng, Vicky L; Rosenthal, Philip; Romero, Rene; Loomes, Kathleen M; Zhang, Song; Hardison, Regina M; Squires, Robert H

    2017-02-01

    The purpose of the present study is to estimate autoantibody (auto-AB) frequency, clinical characteristics, and 21-day outcome of participants in the Pediatric Acute Liver Failure Study Group (PALFSG) by antinuclear antibody, smooth muscle antibody, and liver-kidney microsomal (LKM) antibody status. Auto-ABs were determined at local and/or central laboratories. Subjects were assigned to autoimmune hepatitis (AIH), indeterminate, and other diagnoses groups. Between 1999 and 2010, 986 subjects were enrolled in the PALFSG. At least 1 auto-AB result was available for 722 (73.2%). At least 1 auto-AB was positive for 202 (28.0%). Diagnoses for auto-AB+ subjects were AIH (63), indeterminate (75), and other (64). Auto-ABs were more common in Wilson disease (12/32, 37.5%) compared with other known diagnoses (52/253, 20.6%, P = 0.03). LKM+ subjects were younger (median 2.4 vs 9.1 years, P liver transplantation (53.3% vs 31.4% P = 0.02) than other auto-AB+/LKM- subjects. Steroid treatment of subjects who were auto-AB+ was not significantly associated with survival and the subgroup with known diagnoses other than AIH had a higher risk of death. Auto-ABs are common in children with acute liver failure, occurring in 28%. Auto-AB+ subjects have similar outcomes to auto-AB negative subjects. LKM+ children are younger and more likely to undergo liver transplantation compared with other auto-AB+ subjects. Although auto-AB may indicate a treatable condition, positivity does not eliminate the need for a complete diagnostic evaluation because auto-ABs are present in other conditions. The significance of auto-AB in pediatric acute liver failure remains uncertain, but LKM+ appears to identify a unique population of children who merit further study.

  15. Prognosis for children with acute liver failure due to Amanita phalloides poisoning

    Science.gov (United States)

    Wachulski, Marcin F.; Kamińska-Gocał, Diana; Dądalski, Maciej; Socha, Piotr; Mulawka, Jan J.

    2011-10-01

    The primary objective of this article is to find new effective methods of diagnosis of urgent liver transplantation after Amanita phalloides intoxication amongst pediatric patients. The research was carried out using a medical database of pediatric patients who suffered from acute liver failure after amatoxin consumption. After data preprocessing and attribute selection steps, a two-phase experiment was conducted, which incorporated a wide variety of data mining algorithms. The results deliver two equivalent classification models with simple decision structure and reasonable quality of surgery prediction.

  16. Liver Inflammation Relates to Decreased Canalicular Bile Transporter Expression in Pediatric Onset Intestinal Failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2017-02-23

    Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.

  17. Hepatitis A acute liver failure: follow-up of paediatric patients in southern Brazil.

    Science.gov (United States)

    Ferreira, C T; Vieira, S M G; Kieling, C O; Silveira, T R

    2008-10-01

    We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 +/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area.

  18. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

    Science.gov (United States)

    Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

    2017-02-01

    Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

  19. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.

    Science.gov (United States)

    Xiao, Yong-Tao; Cao, Yi; Zhou, Ke-Jun; Lu, Li-Na; Cai, Wei

    2016-12-15

    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.

  20. Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure.

    Science.gov (United States)

    Lear, Christopher A; Davidson, Joanne O; Booth, Lindsea C; Wassink, Guido; Galinsky, Robert; Drury, Paul P; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair J

    2014-08-15

    Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg(-1)·24 h(-1) for a further 96 h) or the same volume of saline (n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV. Copyright © 2014 the American Physiological Society.

  1. Liver Progenitor Cell Line HepaRG Differentiated in a Bioartificial Liver Effectively Supplies Liver Support to Rats with Acute Liver Failure

    NARCIS (Netherlands)

    Nibourg, Geert A. A.; Chamuleau, Robert A. F. M.; van der Hoeven, Tessa V.; Maas, Martinus A. W.; Ruiter, An F. C.; Lamers, Wouter H.; Oude Elferink, Ronald P. J.; van Gulik, Thomas M.; Hoekstra, Ruurdtje

    2012-01-01

    A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into

  2. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure.

    Science.gov (United States)

    Lu, Brandy R; Zhang, Song; Narkewicz, Michael R; Belle, Steven H; Squires, Robert H; Sokol, Ronald J

    2013-05-01

    To examine the predictive value of the Liver Injury Units (LIU) and admission values (aLIU) of bilirubin and prothrombin time and international normalized ratio scores in a large cohort from the Pediatric Acute Liver Failure (PALF) Study Group, a multinational prospective study. LIU and aLIU scores were calculated for 461 and 579 individuals, respectively, enrolled in the PALF study from 1999 to 2008. Receiver operator characteristic curves were used to evaluate the scores with respect to survival without liver transplantation (LT), death, or LT by 21 days after enrollment. At 21 days, 50.3% of participants were alive without LT, 36.2% underwent LT, and 13.4% died. The c-indices for transplant-free survival were 0.81 based on the LIU score with the international normalized ratio (95% CI, 0.78-0.85) and 0.76 based on the aLIU score (95% CI, 0.72-0.79). The LIU score predicted LT better than it predicted death (c-index for LT 0.84, c-index for death 0.76). Based on data from a large, multicenter cohort of patients with PALF, the LIU score was a better predictor of transplant-free survival than was the aLIU score. The LIU score might be a helpful, dynamic tool to predict clinical outcomes in patients with PALF. Copyright © 2013 Mosby, Inc. All rights reserved.

  3. [Four patients with hepatitis A presenting with fulminant hepatitis and acute renal failure and who underwent liver transplantation].

    Science.gov (United States)

    Oh, Se Hoon; Lee, Joon Hyoek; Hwang, Ji Won; Kim, Hye Young; Lee, Chang Hoon; Gwak, Geum Youn; Choi, Moon Seok; Koh, Kwang Chul; Paik, Seung Woon; Yoo, Byung Chul

    2009-09-01

    Hepatitis A is generally known as a mild, self-limiting disease of the liver, but in rare instances it can progress to fulminant hepatitis, which may require liver transplantation for recovery. Such cases are known to be related to old age and underlying liver disease. We report four cases of hepatitis A in which patients presented with fulminant hepatitis and acute renal failure and underwent liver transplantation. The following common features were observed in our cases: (1) occurrence in relatively old age (>/=39 years old), (2) association with acute renal failure, (3) presence of hepatomegaly, and (4) microscopic features of submassive hepatic necrosis.

  4. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  5. A Patient with Nafcillin-Associated Drug-Induced Liver Failure.

    Science.gov (United States)

    Rao, Qin; Schuster, Isaiah; Seoud, Talal; Zarrabi, Kevin; Goolsarran, Nirvani

    2017-01-01

    Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient's lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient's liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

  6. A Patient with Nafcillin-Associated Drug-Induced Liver Failure

    Directory of Open Access Journals (Sweden)

    Qin Rao

    2017-09-01

    Full Text Available Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient’s lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient’s liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

  7. Acute lymphocytic cholangitis and liver failure in an Amur tiger (Panthera tigris altaica).

    Science.gov (United States)

    Crook, Erika K; Carpenter, Nancy A

    2014-03-01

    An adult male Amur tiger (Panthera tigris altaica) with confirmed inflammatory bowel disease developed acute severe icterus, bilirubinuria, bilirubinemia, and elevated bile acids after a diet change. Liver biopsies showed moderate lymphoplasmacytic cholangiohepatitis (lymphocytic cholangitis). The tiger developed neurologic signs including ataxia, tremors, and seizures, as well as epistaxis. Therapy consisted of antibiotics, a steroid anti-inflammatory, vitamins, pro-coagulants, and liver-supportive medicines. The tiger improved from acute liver failure within 3 wk, while the epistaxis began at 3.5 wk and did not resolve until 10.5 wk. The long-term maintenance plan consists of oral prednisolone, metronidazole, ursodiol, and an all muscle-meat beef diet.

  8. [Use of fractional plasma separation and adsorption (Prometheus technology) in the treatment of acute liver failure].

    Science.gov (United States)

    Denisova, E N; Sharipova, V R; Purlo, N V; Sukhanova, G A; Biriukova, L S

    2009-01-01

    This paper presents the results of treating 8 patients with acute liver failure, by using the separation and adsorption of fractional plasma (Prometheus technology). Twenty-five procedures lasting 5-6 hours were performed. Anticoagulation with heparin was made under guidance of coagulogram parameters. The results of testing blood parameters before and after a procedure and hemodynamic parameters are given. The investigations have demonstrated the effectiveness and safety of the procedure.

  9. Acute liver failure in a pediatric patient with congenital dyserythropoietic anemia type I treated with deferasirox

    Directory of Open Access Journals (Sweden)

    Galina Ling

    2015-09-01

    Full Text Available Congenital dyserythropoietic anemias (CDA represent a heterogeneous group of disorders characterized by morphological abnormalities of erythroid precursor cells and various degrees of hemolysis. Iron overload is a result of continuous hemolysis and recurrent transfusions. It is treated with iron chelators, including deferasirox. We present here a case of acute liver failure in a 12 years old girl with CDA type I treated with deferasirox and discuss the approach to treatment.

  10. Usefulness of virtual touch quantification for staging liver fibrosis in patients with hepatitis C, and factors affecting liver stiffness measurement failure compared with liver biopsy.

    Science.gov (United States)

    Tsukano, Natsumi; Miyase, Shiho; Saeki, Tatsuhiko; Mizobe, Keiko; Iwashita, Hirofumi; Arima, Nobuyuki; Fujiyama, Shigetoshi

    2017-12-11

    The assessment of liver fibrosis in patients with hepatitis C is important to predict carcinogenesis. In this study, we evaluated the usefulness of virtual touch quantification (VTQ) for staging liver fibrosis, and investigated factors causing discrepancies between the estimated fibrosis stage using VTQ and the pathological fibrosis stage. Patients with hepatitis C (n = 302) were assessed using VTQ and underwent pathological liver investigation within 1 week before and after VTQ. A receiver operator characteristic (ROC) curve was obtained for VTQ, fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index (APRI), and each area under the ROC curve (AUROC) was compared to predict fibrosis stage. We used univariate and multivariate analyses to investigate the factors related to the discrepancy between the estimated fibrosis stage using VTQ and the pathological fibrosis stage. At any stage, VTQ was the most accurate for staging liver fibrosis. The VTQ cut-off values were 1.33 m/s (AUROC = 0.822) for ≥F2, 1.51 m/s (AUROC = 0.836) for ≥F3, and 1.92 m/s (AUROC = 0.890) for F4. Skin liver capsule distance (SCD) was the most relevant factor for the discrepancy between the estimated fibrosis stage using VTQ and the pathological fibrosis stage. The SCD cut-off value was 17.5 mm. Virtual touch quantification is a non-invasive, simple method that is more accurate for staging liver fibrosis than the FIB-4 index and APRI. However, when the SCD is longer than 17.5 mm, there may be measurement failures. © 2017 The Japan Society of Hepatology.

  11. Impact of preoperative chronic renal failure on liver transplantation: a population-based cohort study

    Directory of Open Access Journals (Sweden)

    Chung PC

    2016-12-01

    Full Text Available Peter Chi-Ho Chung,1,2 Hsiu-Pin Chen,1,2 Jr-Rung Lin,3,4 Fu-Chao Liu,1,2 Huang-Ping Yu1,2 1Department of Anesthesiology, Chang Gung Memorial Hospital, 2College of Medicine, 3Clinical Informatics and Medical Statistics Research Center, 4Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan Purpose: The purpose of this study was to assess whether preoperative chronic renal failure (CRF affects the rates of postoperative complications and survival after liver transplantation. Methods: This population-based retrospective cohort study included 2,931 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. Patients were divided into two groups, based on the presence or absence of preoperative CRF. Results: The overall estimated survival rate of liver transplantation recipients (LTRs with preoperative CRF was significantly lower than that of patients without preoperative CRF (P=0.0085. There was no significant difference between the groups in terms of duration of intensive care unit stay, total hospital stay, bacteremia, postoperative bleeding, and pneumonia during hospitalization. Long-term adverse effects, including cerebrovascular disease and coronary heart disease, were not different between patients with versus without CRF. Conclusion: These findings suggest that LTRs with preoperative CRF have a higher rate of mortality. Keywords: chronic renal failure, cohort study, survival rate, liver transplantation, population-based study

  12. TIMP-1 attenuates blood–brain barrier permeability in mice with acute liver failure

    Science.gov (United States)

    Chen, Feng; Radisky, Evette S; Das, Pritam; Batra, Jyotica; Hata, Toshiyuki; Hori, Tomohide; Baine, Ann-Marie T; Gardner, Lindsay; Yue, Mei Y; Bu, Guojun; del Zoppo, Gregory; Patel, Tushar C; Nguyen, Justin H

    2013-01-01

    Blood–brain barrier (BBB) dysfunction in acute liver failure (ALF) results in increased BBB permeability that often precludes the patients from obtaining a life-saving liver transplantation. It remains controversial whether matrix metalloproteinase-9 (MMP-9) from the injured liver contributes to the deregulation of BBB function in ALF. We selectively upregulated a physiologic inhibitor of MMP-9 (TIMP-1) with a single intracerebroventricular injection of TIMP-1 cDNA plasmids at 48 and 72 hours, or with pegylated-TIMP-1 protein. Acute liver failure was induced with tumor necrosis factor-α and 𝒟-(+)-galactosamine in mice. Permeability of BBB was assessed with sodium fluorescein (NaF) extravasation. We found a significant increase in TIMP-1 within the central nervous system (CNS) after the administration of TIMP-1 cDNA plasmids and that increased TIMP-1 within the CNS resulted in an attenuation of BBB permeability, a reduction in activation of epidermal growth factor receptor and p38 mitogen-activated protein kinase signals, and a restoration of the tight junction protein occludin in mice with experimental ALF. Pegylated TIMP-1 provided similar protection against BBB permeability in mice with ALF. Our results provided a proof of principle that MMP-9 contributes to the BBB dysfunction in ALF and suggests a potential therapeutic role of TIMP-1 in ALF. PMID:23532086

  13. Chronic liver disease and hepatic encephalopathy: Clinical profile ...

    African Journals Online (AJOL)

    Two patients had acute encephalopathy, while others had acute-on chronic encephalopathy. The risk factors for liver disease included significant alcohol ingestion, hepatitis B virus infection, and previous jaundice, while other complications of liver disease noted were deepening jaundice, ascites, bleeding tendencies, and ...

  14. Circulating mannan-binding lectin, M-, L-, H-ficolin and collectin-liver-1 levels in patients with acute liver failure

    DEFF Research Database (Denmark)

    Laursen, Tea Lund; Sandahl, Thomas D; Støy, Sidsel

    2015-01-01

    BACKGROUND & AIMS: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M......-, L-, and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome. METHODS: Serum samples from 75 patients enrolled by the US ALF Study Group were collected on days 1 and 3. We...

  15. Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.

    Science.gov (United States)

    Miwa, S; Hashikura, Y; Mita, A; Kubota, T; Chisuwa, H; Nakazawa, Y; Ikegami, T; Terada, M; Miyagawa, S; Kawasaki, S

    1999-12-01

    The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.

  16. Tacrolimus Aggravated Tube Feeding Syndrome with Acute Renal Failure in a Pediatric Liver Transplant Recipient

    Directory of Open Access Journals (Sweden)

    R. Kula

    2017-01-01

    Full Text Available Acute renal failure can be caused by calcineurin inhibitors (CNIs, due to arteriolopathy and altered tubular function. Within this context, we present the case of a 14-month-old liver transplant recipient who suffered an acute polyuric renal failure during a short episode of hypercaloric feeding. In our case, CNI-induced distal RTA led to nephrocalcinosis and therefore to secondary nephrogenic diabetes insipidus. The diet with high renal solute load consequently resulted in an acute polyuric renal failure with severe hypernatremic dehydration. In conclusion, a hypercaloric diet in children with potentially impaired renal function due to therapy with CNIs requires precise calculation of the potential renal solute load and the associated fluid requirements.

  17. Use of serial assessment of disease severity and liver biopsy for indication for liver transplantation in pediatric Epstein-Barr virus-induced fulminant hepatic failure.

    Science.gov (United States)

    Nakazawa, Atsuko; Nakano, Natsuko; Fukuda, Akinari; Sakamoto, Seisuke; Imadome, Ken-Ichi; Kudo, Toyoichiro; Matsuoka, Kentaro; Kasahara, Mureo

    2015-03-01

    The decision to perform liver transplantation (LT) in patients with Epstein-Barr virus (EBV)-induced fulminant hepatic failure (FHF) relies on a precise assessment of laboratory and pathological findings. In this study, we analyzed clinical and laboratory data as well as the pathological features of the liver in order to evaluate the pathogenesis and the need for LT in 5 patients with EBV-induced FHF. According to the King's College criteria, the Acute Liver Failure Early Dynamic (ALFED) model, and the Japanese criteria (from the Acute Liver Failure Study Group of Japan), only 1 patient was considered to be a candidate for LT. However, explanted liver tissues in 3 cases exhibited massive hepatocellular necrosis together with diffuse CD8-positive T cell infiltration in both the portal area and the sinusoid. EBV was detected in the liver, plasma, and peripheral blood mononuclear cells (PBMNCs). In 2 cases indicated to be at moderate risk by the ALFED model, liver biopsy showed CD8-positive and EBV-encoded RNA signal-positive lymphocytic infiltration predominantly in the portal area, but massive hepatocellular necrosis was not observed. These patients were treated with immunosuppressants and etoposide under the diagnosis of EBV-induced hemophagocytic lymphohistiocytosis or systemic EBV-positive T cell lymphoproliferative disease of childhood. EBV DNA was detected at a high level in PBMNCs, although it was negative in plasma. On the basis of the pathological analysis of the explanted liver tissues, LT was proposed for the restoration of liver function and the removal of the EBV-infected lymphocytes concentrated in the liver. Detecting EBV DNA by a quantitative polymerase chain reaction in plasma and PBMNCs was informative. An accurate evaluation of the underlying pathogenesis is essential for developing a treatment strategy in patients with EBV-induced FHF. © 2015 American Association for the Study of Liver Diseases.

  18. Peritransplant pancreatitis: A marker of high mortality and graft failure in liver transplant patients.

    Science.gov (United States)

    Russell, Tara A; Park, Sarah; Agopian, Vatche G; Zarrinpar, Ali; Farmer, Douglas G; O'Neill, Sean; Korayem, Islam; Ebaid, Samer; Gornbein, Jeffrey; Busuttil, Ronald W; Kaldas, Fady M

    2017-07-01

    Perioperative pancreatitis is a significant comorbid condition in surgical patients. However, the degree to which pancreatitis affects graft and overall survival in liver transplant recipients has not been evaluated. This study assesses the impact of pancreatitis on graft and patient survival in adult orthotopic liver transplantation (OLT). All patients undergoing OLT at a single academic institution from 2007 to 2015 were reviewed. Pancreatitis was classified by method of diagnosis (intraoperative/radiographic [IO/R] versus isolated serologic diagnosis) and timing (preoperative versus postoperative diagnosis). Twenty-three patients were identified with peritransplant pancreatitis (within 30 days preoperatively or postoperatively). A control group of patients without pancreatitis undergoing OLT was composed of 775 patients. Graft failure/death rates for patients with versus without pancreatitis were 7.4% versus 7.4% at 30 days, 33.3% versus 12.6% at 90 days, and 44.4% versus 26.9% at 12 months. Four patients with pancreatitis (17.4%) required emergent retransplantation and subsequently died within 90 days of their second transplant. Overall, 6 patients with pancreatitis (26.1%) died within 90 days of transplantation. Patients with pancreatitis had a hazard ratio (HR) for death or graft failure of 2.28 as compared with controls (P pancreatitis is most pronounced among those diagnosed by IO/R findings, with an adjusted HR of 2.53 (P pancreatitis is associated with early graft failure and patient mortality, regardless of the method or timing of the diagnosis. Given these results, IO/R findings of pancreatitis should induce caution and potentially preclude OLT until resolved. Liver Transplantation 23 925-932 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  19. Acetaminophen (Paracetamol induced acute liver failure – A social problem in an era of increasing tendency to self-treatment

    Directory of Open Access Journals (Sweden)

    Tadeusz Wróblewski

    2015-12-01

    Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

  20. The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Frederiksen, Hans-Jørgen

    2012-01-01

    Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA......), an extracorporeal liver support system, on cerebral amino acids and lactate to pyruvate ratio....

  1. Early treatment with N-acetylcysteine in children with acute liver failure secondary to hepatitis A.

    Science.gov (United States)

    Sotelo, Norberto; de los Angeles Durazo, María; Gonzalez, Alejandro; Dhanakotti, Nagasharmila

    2009-01-01

    Hepatitis A virus can evolve to acute liver failure with a fatal outcome if it is not reversed. We describe the clinical course of 12 children who presented with hepatitis A acute liver failure and received treatment with oral N-acetylcysteine (NAC). Of the seventy-two patients with viral hepatitis A, 12 patients who had acute hepatic failure were included. The variables evaluated were age, sex, duration of clinical features prior to hospitalization, signs and symptoms, laboratory parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), partial thromboplastin time (PTT), internal normalization ratio and ammonia], treatment (oral NAC 100 mg/kg/day, lactulose, neomycin and general measures) and clinical course during hospitalization. Six males and six females were included. School-aged and adolescent children predominated. All presented with jaundice, nausea, vomiting and hepatomegaly. Two had stage 2 neurological signs as per the West-Haven scale. All had altered laboratory parameters. All received NAC, six patients for a week and the remaining six for 9-36 days. Treatment was not ceased until patients showed clinical and laboratory improvement. All data were analyzed using both student's t test and Wilcoxon signed rank with alpha = 0.05, the ALT with P = 0.0003 and 0.005, AST with P = 0.0001 and 0.0005, PT with P = 0.0237 and 0.0005, PTT with P = 0.0515 and 0.0039, ammonia with P = 0.0197 and 0.0015 and direct bilirubin with P = 0.0190 and 0.068. There was good tolerance to medications and a satisfactory clinical course. The use of oral NAC appears to be an effective therapeutic alternative for hepatitis A-induced liver failure if it is offered appropriately. It can modify the clinical course to a favorable one and prevent the fatal outcome of hepatic encephalopathy.

  2. Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

    Directory of Open Access Journals (Sweden)

    S. V. Gautier

    2017-01-01

    Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

  3. Targeting Albumin Binding Function as a Therapy Goal in Liver Failure: Development of a Novel Adsorbent for Albumin Dialysis.

    Science.gov (United States)

    Dominik, Adrian; Stange, Jan; Baumann, Anja K; Pfensig, Claudia; Suraj, Matthias; Ibrahim, Badr; Eggert, Martin

    2017-12-20

    Liver failure results in impaired hepatic detoxification combined with diminished albumin synthesis and is associated with secondary organ failure. The accumulation of liver toxins has shown to saturate albumin binding sites. This was previously demonstrated by an in vitro test for albumin binding capacity (ABiC) that has shown to inversely correlate with the established MELD (Model for End-Stage Liver Disease) score. In this study, we introduced a new adsorbent material for albumin dialysis treatments that improves albumin binding capacity. The new charcoal adsorbent was developed by an evolutionary test schedule. Batch testing of charcoals was performed as steady-state experiments. The charcoal reflecting the highest increase in albumin binding capacity was then introduced to kinetic models: Perfusion tests were designed to evaluate adsorption capacity and kinetics for liver failure marker toxins. A dynamic recirculation model for liver failure was used for upscaling and comparison against conventional MARS adsorbents as the gold standard in an albumin dialysis setting. Batch tests revealed that powdered activated Hepalbin charcoal displayed the highest ABiC score. Hepalbin charcoal also demonstrated higher adsorptive capacity and kinetics for liver failure marker toxins as determined by perfusion tests. These findings translated to tests of upscaled adsorbents in a dynamic model for liver failure: upscaled Hepalbin adsorbent removes bile acids, direct bilirubin and indirect bilirubin significantly better than MARS adsorbents and significantly increases ABiC. The novel adsorbent Hepalbin offers a significant improvement over both MARS adsorbents concerning liver failure marker toxin removal and ABiC improvement. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  4. Recreational Exposure during Algal Bloom in Carrasco Beach, Uruguay: A Liver Failure Case Report.

    Science.gov (United States)

    Vidal, Flavia; Sedan, Daniela; D'Agostino, Daniel; Cavalieri, María Lorena; Mullen, Eduardo; Parot Varela, María Macarena; Flores, Cintia; Caixach, Josep; Andrinolo, Dario

    2017-08-31

    In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child's case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II-III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr -1 tissue) and [D-Leu¹]MC-LR (75.4 ng·gr -1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis.

  5. Mars and Prometheus: our clinical experience in acute chronic liver failure.

    Science.gov (United States)

    Faenza, S; Baraldi, O; Bernardi, M; Bolondi, L; Coli, L; Cucchetti, A; Donati, G; Gozzetti, F; Lauro, A; Mancini, E; Pinna, A D; Piscaglia, F; Rasciti, L; Ravaioli, M; Ruggeri, G; Santoro, A; Stefoni, S

    2008-05-01

    In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

  6. The Role of Bone Marrow Mesenchymal Stem Cells in the Treatment of Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Shufang Yuan

    2013-01-01

    Full Text Available Objective. This study is to investigate the effects of bone marrow mesenchymal stem cell (BMSC transplantation on acute liver failure (ALF. Methods. BMSCs were separated from rat bone marrow, cultured, and identified by flow cytometry. Rat model with ALF was established by injecting D-galactosamine and lipopolysaccharide. Rats were randomly divided into the control group and BMSC transplantation group. The serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST were measured at 24 h, 120 h, and 168 h after BMSC transplantation. Apoptosis was detected by TUNEL assay. The expression of VEGF and AFP proteins was detected by immunofluorescence. Caspase-1 and IL-18 proteins and mRNA were detected by immunohistochemistry and RT-PCR. Results. Compared with the control group, levels of ALT, AST, caspase-1 and IL-18 proteins, and mRNA in the transplantation group were significantly lower at 120 h and 168 h after BMSCs transplantation. Apoptosis was inhibited by BMSCs transplantation. The VEGF protein levels were increased with the improvement of liver function, and the AFP protein levels were increased with the deterioration of the liver function after BMSCs transplantation. Conclusions. BMSCs transplantation can improve liver function and inhibit hepatocyte apoptosis as well as promote hepatocyte proliferation in rat model with ALF.

  7. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  8. Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation

    Directory of Open Access Journals (Sweden)

    Lu Li

    2014-01-01

    Full Text Available This study aimed to investigate the role of 5-lipoxygenase (5-LO in acute liver failure (ALF and changes in macrophage activation by blocking it. ALF was induced in rats by administration of D-galactosamine (D-GalN/lipopolysaccharide (LPS. Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor, 24 hr before D-GalN/LPS administration. After D-GalN/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT, aspartate transaminase (AST, total bilirubin (Tbil, and tumor necrosis factor- (TNF-α. Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8 hr after D-GalN/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF-α was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.

  9. Liver function tests in patients with acute heart failure and associated outcomes : insights from ASCEND-HF

    NARCIS (Netherlands)

    Samsky, Marc D.; Dunning, Allison; DeVore, Adam D.; Schulte, Phillip J.; Starling, Randall C.; Tang, W. H. Wilson; Armstrong, Paul W.; Ezekowitz, Justin A.; Butler, Javed; McMurray, John J.; Teerlink, John R.; Voors, Adriaan A.; Metra, Marco; Mentz, Robert J.; O'Connor, Christopher M.; Patel, Chetan B.; Hernandez, Adrian F.

    AimsWe aimed to characterize abnormal liver function tests in patients with heart failure (HF), as they are commonly encountered yet poorly defined. Methods and resultsWe used data from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) to characterize

  10. Liver failure caused by prolonged state of malnutrition following bariatric surgery.

    Science.gov (United States)

    Lammers, Willem J; van Tilburg, Antonie Jp; Apers, Jan A; Wiebolt, Janneke

    2018-03-27

    Bariatric surgery is an effective tool in the treatment of patients with morbid obesity. In these case reports we describe 2 patients who developed liver failure after currently-practiced types of bariatric surgery, caused by a prolonged state of malnutrition provoked by psychiatric problems. Despite intensive guidance of a psychologist and dieticians after surgery, our patients deteriorated psychologically, resulting in a prolonged state of severe malnutrition and anorexia. Finally, a state of starvation was reached, passing a critical level of the liver capacity. Patients who present with signs of severe protein malnutrition after bariatric surgery should be closely monitored and checked for nutritional status. Specific attention should be given to patients who develop psychiatric problems post-bariatric surgery. If refeeding does not result in clinical improvement, reversal surgery should be considered in a timely manner.

  11. Acute liver failure in adults: an evidence-based management protocol for clinicians.

    Science.gov (United States)

    Patton, Heather; Misel, Michael; Gish, Robert G

    2012-03-01

    With the goal of providing guidance on the provision of optimal intensive care to adult patients with acute liver failure (ALF), this paper defines ALF and describes a protocol for appropriately diagnosing this relatively rare clinical entity and ascertaining its etiology, where possible. This paper also identifies the few known therapies that may be effective for specific causes of ALF and provides a comprehensive approach for anticipating, identifying, and managing complications. Finally, one of the more important aspects of care for patients with ALF is the determination of prognosis and, specifically, the need for liver transplantation. Prognostic tools are provided to help guide the clinician in this critical decision process. Management of patients with ALF is complex and challenging, even in centers where staff members have high levels of expertise and substantial experience. This evidence-based protocol may, therefore, assist in the delivery of optimal care to this critically ill patient population and may substantially increase the likelihood of positive outcomes.

  12. Renal Failure in Patients with End Stage Liver Disease and its Impact on Clinical Outcome

    International Nuclear Information System (INIS)

    Qureshi, M. O.; Shafqat, F.; Dar, F. S.; Salih, M.; Khokhar, N.

    2014-01-01

    Objective: To evaluate the prevalence of renal failure (RF) in the patients of end stage liver disease (ESLD), to determine the causes of RF in these patients and its impact on patient's outcome. Study Design: Descriptive, analytical study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from May 2011 to March 2013. Methodology: A total of 523 patients with end stage liver disease (ESLD) were evaluated, renal failure (RF) and its causes were recognized in these patients according to established criteria. Outcome of these patients was assigned as reversal of RF or mortality. Data was analyzed using SPSS version 16. Chi-square test was used for comparing proportions and t-test was used for comparing mean values. P < 0.05 was considered significant. Results: Out of 523 patients, 261 (49.9%) had RF. Acute kidney injury (AKI) was the most common presentation seen in 160 (61%) patients. Hypovolemia and infections were the most frequent causes of RF. Mortality was significantly higher in the patients with RF, when compared to the patients without RF (31% vs. 4.5%, p < 0.001). Reversal of RF was seen in 98 (37%) of the affected patients. Reversal was more common in the patients with hypovolemia. The mortality was higher in the patients with hepatorenal syndrome (HRS) and infections. Conclusion: Renal failure in the end stage liver disease is an important prognostic factor. Etiology of RF is the key factor in patients' outcome. Patients of ESLD with RF had higher mortality. Majority of the cases of RF were reversible in patients of ESLD coming in the setup. (author)

  13. Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Koivusalo, Antti I; Rintala, Risto J; Pakarinen, Mikko P

    2013-08-01

    The aim of this study was to evaluate the long-term effects of pediatric intestinal failure (IF) on liver histology. Altogether, 38 IF patients (median age: 7.2 years; range, 0.2-27) underwent liver biopsy, gastroscopy, abdominal ultrasound, and laboratory tests. Sixteen patients were on parenteral nutrition (PN) after 74 PN months (range, 2.5-204). Twenty-two had weaned off PN 8.8 years (range, 0.3-27) earlier, after 35 PN months (range, 0.7-250). Fifteen transplant donor livers served as controls. Abnormal liver histology was found in 94% of patients on PN and 77% of patients weaned off PN (P = 0.370). During PN, liver histology weighted with cholestasis (38% of patients on PN versus 0% of patients weaned off PN; P = 0.003) and portal inflammation (38% versus 9%; P = 0.050) were found. Fibrosis (88% versus 64%; P = 0.143; Metavir stage: 1.6 [range, 0-4] versus 1.1 [range, 0-2]; P = 0.089) and steatosis (50% versus 45%; P = 1.000) were equally common during and after weaning off PN. Plasma alanine aminotransferase (78 U/L [range, 19-204] versus 34 [range, 9-129]; P = 0.009) and conjugated bilirubin (43 μmol/L [range, 1-215] versus 4 [range, 1-23]; P = 0.037) were significantly higher during than after weaning off PN. Esophageal varices were encountered in 1 patient after weaning off PN. Metavir stage was associated with small bowel length (r = -0.486; P = 0.002) and number of septic episodes (r = 0.480; P = 0.002). In a multivariate analysis, age-adjusted small bowel length (ß = -0.533; P = 0.001), portal inflammation (ß = 0.291; P = 0.030), and absence of an ileocecal valve (ß = 0.267; P = 0.048) were predictive for fibrosis stage. Despite resolution of cholestasis and portal inflammation, significant liver fibrosis and steatosis persist after weaning off PN. Extensive small intestinal resection was the major predictor for liver fibrosis stage. Copyright © 2013 American Association for the Study of Liver Diseases.

  14. Technical Failure of MR Elastography Examinations of the Liver: Experience from a Large Single-Center Study.

    Science.gov (United States)

    Wagner, Mathilde; Corcuera-Solano, Idoia; Lo, Grace; Esses, Steven; Liao, Joseph; Besa, Cecilia; Chen, Nelson; Abraham, Ginu; Fung, Maggie; Babb, James S; Ehman, Richard L; Taouli, Bachir

    2017-08-01

    Purpose To assess the determinants of technical failure of magnetic resonance (MR) elastography of the liver in a large single-center study. Materials and Methods This retrospective study was approved by the institutional review board. Seven hundred eighty-one MR elastography examinations performed in 691 consecutive patients (mean age, 58 years; male patients, 434 [62.8%]) in a single center between June 2013 and August 2014 were retrospectively evaluated. MR elastography was performed at 3.0 T (n = 443) or 1.5 T (n = 338) by using a gradient-recalled-echo pulse sequence. MR elastography and anatomic image analysis were performed by two observers. Additional observers measured liver T2* and fat fraction. Technical failure was defined as no pixel value with a confidence index higher than 95% and/or no apparent shear waves imaged. Logistic regression analysis was performed to assess potential predictive factors of technical failure of MR elastography. Results The technical failure rate of MR elastography at 1.5 T was 3.5% (12 of 338), while it was higher, 15.3% (68 of 443), at 3.0 T. On the basis of univariate analysis, body mass index, liver iron deposition, massive ascites, use of 3.0 T, presence of cirrhosis, and alcoholic liver disease were all significantly associated with failure of MR elastography (P analysis, only body mass index, liver iron deposition, massive ascites, and use of 3.0 T were significantly associated with failure of MR elastography (P technical failure rate of MR elastography with a gradient-recalled-echo pulse sequence was low at 1.5 T but substantially higher at 3.0 T. Massive ascites, iron deposition, and high body mass index were additional independent factors associated with failure of MR elastography of the liver with a two-dimensional gradient-recalled-echo pulse sequence. © RSNA, 2017.

  15. [Early detection, prevention and management of renal failure in liver transplantation].

    Science.gov (United States)

    Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

    2014-10-01

    Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  16. Renal failure after treatment with interferon alpha 2b

    NARCIS (Netherlands)

    Roeloffzen, WWH; Hospers, GAP; De Vries, EGE; Navis, GJ

    2002-01-01

    Although there has been considerable experience with interferons in the treatment of malignancy and viral illnesses, acute renal failure as a side-effect of interferon treatment has rarely been reported. We present the case of a patient who developed acute on chronic renal failure 16 months after

  17. Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.

    Science.gov (United States)

    Sasbón, Jorge S; Buamscha, Daniel; Gianivelli, Silvina; Imventarza, Oscar; Devictor, Denis; Moreiro, Rita; Cambaceres, Carlos; Salip, Gonzalo; Ciocca, Mirta; Cuarterolo, Miriam; Vladimirsky, Sara; Otegui, Lucio; Castro, Raúl; Brajterman, Leonardo; Soto, Sonia; González, Jorge; Munné, María S

    2010-05-01

    To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. None. Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid

  18. Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach.

    Directory of Open Access Journals (Sweden)

    Luciana Haddad

    Full Text Available Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied.A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py (95% CI: 15.1-17.3, and the graft failure rate was 1.8 per 100 py (95% CI: 1.5-2.2. Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9-19.2. The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56-2.08], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27-1.72], Na+ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47-1.97], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41-1.90], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68-0.97] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11-1.48], male gender [RR = 1.19(95% CI: 1.03-1.37], dobutamine use [RR = 0.54 (95% CI: 0.36-0.82] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10-1.34] affected the negative outcome rate.The current study confirms that both donor and

  19. Evaluation of a scoring system for assessing prognosis in pediatric acute liver failure.

    Science.gov (United States)

    Lu, Brandy R; Gralla, Jane; Liu, Edwin; Dobyns, Emily L; Narkewicz, Michael R; Sokol, Ronald J

    2008-10-01

    Pediatric acute liver failure (PALF) results in death or need for liver transplantation (LT) in up to 50% of patients. A scoring system for predicting death or LT (Liver Injury Units [LIU] score) in PALF was previously derived by our group, and used peak values during hospital admission of total bilirubin, prothrombin time/international normalized ratio, and ammonia as significant predictors of outcome. The aims of this study were to test the predictive value of the LIU score in a subsequent validation set of patients and to derive a hospital admission LIU (aLIU) score predictive of outcome. Data were obtained from 53 children admitted with PALF from 2002 to 2006. Outcome was defined at 16 weeks as alive without LT, death, or LT. Survival without LT at 16 weeks for each LIU score quartile was 92%, 44%, 60%, and 12%, respectively (P < .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 86.3. An admission LIU score was derived using admission total bilirubin and prothrombin time/international normalized ratio. Survival without LT at 16 weeks for each quartile using the aLIU score was 85%, 77%, 69%, and 31% (P = .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 83.7. The original LIU score is a valid predictor of outcome in PALF. The aLIU score is promising and needs to be validated in subsequent patients.

  20. Data-Driven Modeling for Precision Medicine in Pediatric Acute Liver Failure.

    Science.gov (United States)

    Zamora, Ruben; Vodovotz, Yoram; Mi, Qi; Barclay, Derek; Yin, Jinling; Horslen, Simon; Rudnick, David; Loomes, Kathleen M; Squires, Robert H

    2016-11-23

    Absence of early outcome biomarkers for Pediatric Acute Liver Failure (PALF) hinders medical and liver transplant decisions. We sought to define dynamic interactions among circulating inflammatory mediators to gain insights into PALF outcome sub-groups. Serum samples from 101 participants in the PALF study, collected over the first 7 days following enrollment, were assayed for 27 inflammatory mediators. Outcomes (Spontaneous survivors [S, n=61], Non-survivors [NS, n=12], and liver transplant patients [LTx, n=28]) were assessed at 21 days post-enrollment. Dynamic interrelations among mediators were defined using data-driven algorithms. Dynamic Bayesian Network inference identified a common network motif with HMGB1 as a central node in all patient sub-groups. The networks in S and LTx were similar, and differed from NS. Dynamic Network Analysis suggested similar dynamic connectivity in S and LTx, but a more highly-interconnected network in NS that increased with time. A Dynamic Robustness Index calculated to quantify how inflammatory network connectivity changes as a function of correlation stringency differentiated all three patient sub-groups. Our results suggest that increasing inflammatory network connectivity is associated with non-survival in PALF, and may ultimately lead to better patient outcome stratification.

  1. The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations.

    Directory of Open Access Journals (Sweden)

    Dong Ji

    Full Text Available To investigate the frequency and determinants of liver stiffness measurement (LSM failure by means of FibroScan in "real-life" Chinese patients.A total of 38,464 "real-life" Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC, alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m and M probe (for adults were used. LSM failure defined as zero valid shots (unsuccessful LSM, or the ratio of the interquartile range to the median of 10 measurements (IQR/M greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM.LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464, among them, there were 958 cases (2.49% with unsuccessful LSM, and 328 patients (0.85% with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI greater than 30 kg/m(2, female sex, age greater than 50 years, intercostal spaces (IS less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001.The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.

  2. Renal Dysfunction Is an Independent Risk Factor for Mortality after Liver Resection and the Main Determinant of Outcome in Posthepatectomy Liver Failure

    Directory of Open Access Journals (Sweden)

    M. G. Wiggans

    2013-01-01

    Full Text Available Introduction. The aim of this study was to assess the interaction of liver and renal dysfunction as risk factors for mortality after liver resection. Materials and Methods. A retrospective analysis of 501 patients undergoing liver resection in a single unit was undertaken. Posthepatectomy liver failure (PHLF was defined according to the International Study Group of Liver Surgery (ISGLS definition (assessed on day 5 and renal dysfunction according to RIFLE criteria. 90-day mortality was recorded. Results. Twenty-three patients died within 90 days of surgery (4.6%. The lowest mortality occurred in patients without evidence of PHLF or renal dysfunction (2.7%. The mortality rate in patients with isolated PHLF or renal dysfunction was 20% compared to 45% in patients with both. Diabetes (, renal dysfunction (, and PHLF on day 5 ( were independent predictors of 90-day mortality. Discussion. PHLF and postoperative renal dysfunction are independent predictors of 90-day mortality following liver resection but the predictive value for mortality is significantly higher when failure of both organ systems occurs simultaneously.

  3. Liver failure after hepatectomy: A risk assessment using the pre-hepatectomy shear wave elastography technique

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hong, E-mail: han.hong@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032 (China); Hu, Hao; Xu, Ya Dan [Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 200032 (China); Wang, Wen Ping, E-mail: puguang61@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032 (China); Ding, Hong; Lu, Qing [Department of Ultrasound, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032 (China)

    2017-01-15

    Objective: To determine the efficacy of liver stiffness (LS) measurements utilizing the Shear Wave Elastography (SWE) technique for predicting post-hepatectomy liver failure (PHLF) among patients with hepatocellular carcinoma (HCC). Methods: Data from eighty consecutive patients who were undergoing hepatectomy for HCC were prospectively identified and evaluated with preoperative SWE. The SWE was measured with advanced ultrasound equipment (Philips EPIQ7; Philips Healthcare, Seattle, WA, USA). PHLF classification was defined according to the International Study Group of Liver Surgery Recommendations (ISGLS). Results: SWE was successfully performed in 77 patients. According to the ISGLS criteria, PHLF occurred in 35.1% of patients (27 patients), including 2/25 patients with Grade A/B, respectively. Elevated SWE values (P = 0.002) and histological cirrhosis (P = 0.003) were independent predictors of PHLF according to the multivariate analysis. Patients with SWE values higher than or equal to 6.9 kPa were identified at higher risk of PHLF (area under the curve: 0.843, sensitivity: 77.8% and specificity: 78.0%). Postoperative dynamic course of the median the Model For End-stage Liver Disease (MELD) score showed irregular changes among patients with an SWE >6.9 kPa. Patients with an SWE <6.9 kPa, postoperative dynamic course of the median MELD score gradually decreased. Conclusion: LS measured with SWE is a valid and reliable method for the prediction of PHLF grade A/B among patients with HCC. SWE could become a routine examination for the preoperative evaluation of PHLF.

  4. New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure.

    Directory of Open Access Journals (Sweden)

    Nélson R Carvalho

    Full Text Available The acute liver failure (ALF induced by acetaminophen (APAP is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe2], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe2 to the N-acetylcysteine (NAC during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg, (PhSe2 (15.6 mg/kg, NAC (1200 mg/kg, APAP+(PhSe2 or APAP+NAC, where the (PhSe2 or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe2. The effectiveness of (PhSe2 was similar at a lower dose than NAC. In summary, (PhSe2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.

  5. Emerging role of liver X receptors in cardiac pathophysiology and heart failure.

    Science.gov (United States)

    Cannon, Megan V; van Gilst, Wiek H; de Boer, Rudolf A

    2016-01-01

    Liver X receptors (LXRs) are master regulators of metabolism and have been studied for their pharmacological potential in vascular and metabolic disease. Besides their established role in metabolic homeostasis and disease, there is mounting evidence to suggest that LXRs may exert direct beneficial effects in the heart. Here, we aim to provide a conceptual framework to explain the broad mode of action of LXRs and how LXR signaling may be an important local and systemic target for the treatment of heart failure. We discuss the potential role of LXRs in systemic conditions associated with heart failure, such as hypertension, diabetes, and renal and vascular disease. Further, we expound on recent data that implicate a direct role for LXR activation in the heart, for its impact on cardiomyocyte damage and loss due to ischemia, and effects on cardiac hypertrophy, fibrosis, and myocardial metabolism. Taken together, the accumulating evidence supports the notion that LXRs may represent a novel therapeutic target for the treatment of heart failure.

  6. [Pediatric acute liver failure. Working group of the Latinamerican Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN).

    Science.gov (United States)

    Ciocca, Mirta; Costagdta, Alejandro; Cuarterolo, Miriam; Delgado, Laura; Garcete, Lidia; Godoy, Marcela; López, Carmen Esther; López, Carola; Ramonet, Margarita

    2016-03-01

    Pediatric acute liver failure is a syndrome ofsevere and sudden dysfunction of the hepatocytes which produces a failure in synthetic and detoxifyingfunction. It is an infrequent and severe disease butpotentiallyfatal, occurring in children with no prior history of liver disease. Etiology is related to the age and geographic region of the patient, recognizing the origin: metabolic, infectious, drug exposure, autoinmune, vascular and oncologic. Indeterminate cause where all the etiological search is negative, can range between 18 and 47%, depending on the center and access to the realization of etiological studies. The process which determines the liver injury is still not well known and is considered multifactorial. Essentially, it depends on host susceptibility, the cause and severity of the damage and the ability of liver regeneration. The clinical presentation depends on the etiology, which usually begins with an episode ofacute hepatitis, that in the following days or weeks presents unfavorable outcome, deepening jaundice, affecting the general state and presenting severe coagulopathy that characterizes the syndrome. The treatment consists of general measures which take into account the metabolic disorders, nutritional aspect, and the prevention and treatment of all complications that occur in the evolutionary course (infectious, neurological, etc). Besides it is also vital to implement the specific treatment of those diseases which can benefit from it (alloimmune hepatitis, galactosemia, tyrosinemia, herpes simplex infection, Wilson's disease, etc.). However, despite therapeutic advances, acute liver failure results in death or liver transplantation in over 45% ofcases.

  7. Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Jørgensen, Linda

    2010-01-01

    The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations...... of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively)....

  8. Several issues regarding evaluation of renal injury and renal insufficiency in patients with liver disease

    Directory of Open Access Journals (Sweden)

    HAO Kunyan

    2016-07-01

    Full Text Available In patients with liver disease such as viral hepatitis and liver cirrhosis, renal injury and renal insufficiency can be generally classified as acute kidney injury (AKI, chronic kidney disease, and acute-on-chronic nephropathy. AKI can be classified as stage 1 (risk stage, stage 2 (injury stage, and stage 3 (failure stage. Traditionally hepatorenal syndrome is classified as types Ⅰ and Ⅱ, and in recent years, type Ⅲ hepatorenal syndrome with organic renal injury has been proposed. Hepatorenal disorder(HRD is used to describe any renal disease which occurs in patients with liver cirrhosis. At present, sensitive and accurate biochemical parameters used to evaluate renal function in patients with liver disease in clinical practice include estimated glomerular filtration rate, increase in serum creatinine within unit time, and serum cystatin C level, and urinary microalbumin level also plays an important role in the early diagnosis of nephropathy. Causes of liver disease, severity, complications including infection, nutritional status, therapeutic drugs, and underlying nephropathy may be associated with renal injury and renal insufficiency in patients with liver disease and should be differentiated.

  9. Serum plant sterols, cholestanol, and cholesterol precursors associate with histological liver injury in pediatric onset intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Nissinen, Markku J; Lohi, Jouko; Heikkilä, Päivi; Gylling, Helena; Pakarinen, Mikko P

    2014-10-01

    Increased serum concentrations of plant sterols, including stigmasterol, during parenteral nutrition (PN) have been linked with serum biochemical signs of intestinal failure-associated liver disease (IFALD), whereas clinical data on their correlation to histologic liver injury have been limited. We studied interrelations between serum noncholesterol sterols and histologic liver injury in pediatric-onset intestinal failure (IF). Serum plant sterols (stigmasterol, avenasterol, sitosterol, and campesterol), cholestanol, and cholesterol precursors (cholestenol, lathosterol, and desmosterol) were measured in 50 IF patients at a median age 7.3 y and in 86 matched controls. Forty patients underwent liver biopsies. Sixteen patients had been receiving PN for 45 mo, and 34 patients had received PN for 9.1 mo but had not received PN for 5.4 y. Serum plant sterols were higher in patients who were currently receiving PN than in controls and were related to conjugated bilirubin (r = 0.799-0.541, P 2-fold higher in patients with persistent liver steatosis than in those without steatosis or controls (P liver steatosis after weaning off PN. Serum cholestanol reflects liver injury in IF patients. © 2014 American Society for Nutrition.

  10. Results of treatment of acute liver failure patients with use of the prometheus FPSA system.

    Science.gov (United States)

    Grodzicki, M; Kotulski, M; Leonowicz, D; Zieniewicz, K; Krawczyk, M

    2009-10-01

    Herein we have presented the results of treatment of acute liver failure (ALF) patients with the use of the Prometheus FPSA dialysis system. To January 2009, we performed 278 FPSA procedures in 114 patients, including 52 experience and ALF. The patients who underwent the FPSA procedure consisted of 32 women and 20 men of overall mean age of 33 +/- 12 years. The causes of ALF were: Wilson's disease (n = 15), unknown origin ALF (n = 11), amanita phalloides intoxication (n = 7), paracetamol intoxication (n = 8), acute hepatitis B virus (HBV)/hepatitis C virus (HCV) infection (n = 7), liver insufficiency after parenchymal resection (n = 2) drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome (n = 1), rabdomyolysis (n = 1), or primary nonfunction (PNF) after orthotopic liver transplantation (OLT) (n = 1). All procedures were performed using the Prometheus 4008H Fresenius Medical Care liver support system. The average number of treatments per patient was 2.41 and the average time for each FPSA treatment was 6.3 hours. The average heparin dose used during the procedure was 750 IU/h. After the whole treatment regimen, we observed significant improvements in the biochemical results. The average concentrations improved: serum ammonia (before 249.2 mug/dL versus after 109.7 mug/dL); serum bilirubin (before 21.53 mg/dL versus after 8.81 mg/dL), serum aspartate aminotransferase (AST; before 2456.4 U/L versus after 1068.8 U/L); serum alanine aminotransferase (ALT; before 2958.2 U/L versus after 1595.8 U/L); serum urea (before 58.5 mg/dL versus after 21.1 mg/dL); serum creatinine (before 2.9 mg/dL versus after 1.7 mg/dL); and pH value (before 7.11 versus after 7.32). After Prometheus treatment OLT was performed in 33 patients. Among the 28 who survived (53.8%), 22 underwent OLT and 6 did not have OLT. Among the 24 patients who died (46.2%), 13 were before OLT and 11 after OLT. The Prometheus 4008H Fresenius Medical Care Liver support system was useful method of

  11. Soluble CD163 from activated macrophages predicts mortality in acute liver failure

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Grønbaek, Henning; Schiødt, Frank V

    2007-01-01

    BACKGROUND/AIMS: Soluble CD163 (sCD163) is a scavenger receptor shed in serum during inflammatory activation of macrophages. We investigated if sCD163 was increased and predicted outcome in acute liver failure (ALF). METHODS: Samples from 100 consecutive patients enrolled in the U.S. ALF Study.......65-5.6), pliver cirrhosis (9.8mg/l (3.6-16.9), p=0.0002). sCD163 on day 1 correlated significantly with ALT, AST, bilirubin, and creatinine. sCD163 concentrations on day 3 were elevated in patients with fatal outcome of disease compared to spontaneous survivors, 29.0mg/l (7...

  12. SIRS score reflects clinical features of non-acetaminophen-related acute liver failure with hepatic coma.

    Science.gov (United States)

    Miyake, Yasuhiro; Yasunaka, Tetsuya; Ikeda, Fusao; Takaki, Akinobu; Nouso, Kazuhiro; Yamamoto, Kazuhide

    2012-01-01

    In acetaminophen-induced acute liver failure (ALF), the hepatic coma grade worsens and mortality rates increase, as the number of systemic inflammatory response syndrome components fulfilled (SIRS score) increases. This study aimed to investigate the impact of SIRS score on clinical features of non-acetaminophen-related ALF. Ninety-nine patients with non-acetaminophen-related ALF with hepatic coma who did not undergo liver transplantation were investigated. Each patient was given a SIRS score of 0, 1, 2, 3 or 4 at the time of diagnosis. At the diagnosis of ALF with hepatic coma, with the increase of SIRS score, hepatic coma grade and prothrombin activity were deteriorated. After the diagnosis of ALF with hepatic coma, 25 patients (25%) developed acute respiratory distress syndrome (ARDS), 31 patients (31%) developed disseminated intravascular coagulation (DIC), and 21 patients (22%) developed acute renal failure (ARF). Thirty-eight patients (38%) developed MOF. With the increase of SIRS score, frequencies of the development of ARDS, DIC and MOF increased. ARF was more frequently developed in patients with a SIRS score of 2 or higher. Overall, 36 patients (36%) survived. Overall survival rate was 66% in 29 patients with a score of 0, 43% in 21 patients with a score of 1, 17% in 29 patients with a score of 2 and 15% in 20 patients with a score of 3 or 4. SIRS score will be useful for predicting not only the overall survival but also the development of complications such as ARDS, DIC and MOF in non-acetaminophen-related ALF with hepatic coma.

  13. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

    Science.gov (United States)

    Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

    2011-01-01

    BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

  14. Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure.

    Science.gov (United States)

    Ramanathan, Rajesh; Pettinato, Giuseppe; Beeston, John T; Lee, David D; Wen, Xuejun; Mangino, Martin J; Fisher, Robert A

    2015-08-01

    Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF. Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF. A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen. Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Sequential analysis of variable markers for predicting outcomes in pediatric patients with acute liver failure.

    Science.gov (United States)

    Uchida, Hajime; Sakamoto, Seisuke; Fukuda, Akinari; Sasaki, Kengo; Shigeta, Takanobu; Nosaka, Shunsuke; Kubota, Masaya; Nakazawa, Atsuko; Nakagawa, Satoshi; Kasahara, Mureo

    2017-11-01

    Our aim was to analyze serial changes in the predictive variables and a scoring system retrospectively adapted to evaluate outcomes in pediatric patients with acute liver failure (ALF). We retrospectively collected data on 65 patients with ALF. The 65 patients were divided into two groups according to the need for liver transplantation (LT) as follows: LT group (n = 54) and non-LT group (n = 11). The early determination scoring system of the indications for LT proposed by the Intractable Hepato-Biliary Diseases Study Group of Japan (JIHBDSG) was used in our study. The area under the receiver operating characteristic curve (AUROC) was calculated for the JIHBDSG score between the LT group and non-LT group at the time of diagnosis (day 0) and day 3, and day 5 after the diagnosis. A JIHBDSG score of >3 at day 5 was found to identify the patients requiring LT with 83.7% sensitivity, 81.8% specificity, and 83.3% diagnostic accuracy. Based on a comparison of AUROC values, the JIHBDSG score on day 5 (AUROC 0.91) was higher than that on day 0 (AUROC 0.75) and day 3 (AUROC 0.84). We showed that a serial analysis of the JIHBDSG score might be useful for predicting outcomes of ALF in pediatric patients who fulfilled the criteria of LT indication in our center. However, further studies are needed to validate our results. © 2016 The Japan Society of Hepatology.

  16. Prodromal fever indicates a high risk of liver failure in acute hepatitis B.

    Science.gov (United States)

    Du, Wen-Jun; Liu, Li; Sun, Chao; Yu, Jin-Hong; Xiao, Di; Li, Qiang

    2017-04-01

    The role of prodromal fever in the clinical course of acute hepatitis B virus (HBV) infection is still largely unclear. This study was conducted to investigate the factors associated with prodromal fever and its role in the development of acute liver failure (ALF) in patients with acute hepatitis B (AHB). Inpatients with AHB diagnosed between January 2006 and December 2010 were evaluated and followed. Clinical manifestations, results of laboratory tests, and outcomes were compared between patients with and without prodromal fever. The diagnosis of AHB was based on the discrete onset of symptoms, jaundice, abnormal liver function tests, the detection of high-titer IgM antibody to hepatitis B core antigen (anti-HBc), and a compatible clinical history. A total of 618 AHB inpatients were identified during the study period, of whom 102 (16.5%) had prodromal fever and 41 (6.6%) developed ALF. Prodromal fever indicated more severe liver injury and was independently associated with hepatitis B e antigen (HBeAg) negativity. The occurrence of ALF was more common in febrile patients than in non-febrile patients (18.6% vs. 4.3%, pfever and temperature >38.0°C to be independently associated with the risk of ALF, with an odds ratio (95% confidence interval) of 3.5 (1.4-8.6) and 7.1 (2.6-19.7), respectively. AHB patients with prodromal fever, which is associated with a lack of HBeAg due to HBV mutation, are at high risk of ALF. Febrile patients with AHB should be managed with particular care. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

    Science.gov (United States)

    Stutchfield, Benjamin M.; Antoine, Daniel J.; Mackinnon, Alison C.; Gow, Deborah J.; Bain, Calum C.; Hawley, Catherine A.; Hughes, Michael J.; Francis, Benjamin; Wojtacha, Davina; Man, Tak Y.; Dear, James W.; Devey, Luke R.; Mowat, Alan M.; Pollard, Jeffrey W.; Park, B. Kevin; Jenkins, Stephen J.; Simpson, Kenneth J.; Hume, David A.; Wigmore, Stephen J.; Forbes, Stuart J.

    2015-01-01

    Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients

  18. Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test. A prospective study.

    Directory of Open Access Journals (Sweden)

    Magnus F Kaffarnik

    Full Text Available To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test and endothelin-1, TNF-α and IL-6 in septic surgical patients.28 septic patients (8 female, 20 male, age range 35-80y were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test.Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10. For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005. IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001, TNF-α (-0.515; P <0.001 and IL-6 (-0.590; P <0.001.Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

  19. Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

    Directory of Open Access Journals (Sweden)

    Alireza Hosseinnezhad

    2011-05-01

    Full Text Available Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL, thrombocytopenia (platelet count 74,000/UL, elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L and elevated creatine phosphokinase (CPK 5885 U/L. Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.

  20. Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement.

    Science.gov (United States)

    Narkewicz, Michael R; Dell Olio, Dominic; Karpen, Saul J; Murray, Karen F; Schwarz, Kathy; Yazigi, Nada; Zhang, Song; Belle, Steven H; Squires, Robert H

    2009-12-01

    To describe the frequency of diagnostic testing for the 4 most common causes of pediatric acute liver failure (PALF) (drugs, metabolic disease, autoimmune process, and infections) in indeterminate PALF within the PALF Study Group Database. PALF was defined by severe hepatic dysfunction within 8 weeks of onset of illness, with no known underlying chronic liver disease in patients from birth through 17 years of age. Of the 703 patients in the database, 329 (47%) had indeterminate PALF. In this group, a drug history was obtained in 325 (99%) urine toxicology screenings performed in 118 (36%) and acetaminophen level measured in 124 (38%) patients. No testing for common metabolic diseases was done in 179 (54%) patients. Anti-nuclear antibody, anti-smooth muscle antibody, and anti-liver kidney microsomal autoantibodies associated with autoimmunity were determined in 239 (73%), 233 (71%), and 208 (63%) patients, and no tests were obtained in 70 (21%). Testing was performed for hepatitis A virus, hepatitis B virus, and Epstein Barr virus in 80%, 86%, and 68%, respectively. Current practice indicates that investigation for metabolic and autoimmune causes of PALF are infrequent in patients ultimately given a diagnosis of indeterminate acute liver failure. This offers an opportunity to improve diagnosis and potential treatment options in children with acute liver failure.

  1. Whole Blood Polymerase Chain Reaction in a Neonate with Disseminated Herpes Simplex Virus Infection and Liver Failure

    Directory of Open Access Journals (Sweden)

    Jennifer A. Scoble

    2013-10-01

    Full Text Available A late preterm neonate born by cesarean section with intact membranes presented at 9 days of life with shock and liver failure. Surface cultures were negative but whole blood polymerase chain reaction was positive for herpes simplex virus type 2, underscoring the value of this test in early diagnosis of perinatally acquired disseminated herpes simplex virus infection without skin lesions.

  2. Abnormal liver function tests in acute heart failure: relationship with clinical characteristics and outcome in the PROTECT study

    NARCIS (Netherlands)

    Biegus, Jan; Hillege, Hans L.; Postmus, Douwe; Valente, Mattia. A. E.; Bloomfield, Daniel M.; Cleland, John G. F.; Cotter, Gad; Davison, Beth A.; Dittrich, Howard C.; Fiuzat, Mona; Givertz, Michael M.; Massie, Barry M.; Metra, Marco; Teerlink, John R.; Voors, Adriaan A.; O'Connor, Christopher M.; Ponikowski, Piotr

    Aims Episodes of acute heart failure (AHF) unfavourably affect multiple organs, which may have an adverse impact on the outcomes. We investigated the prevalence and clinical consequences of abnormal liver function tests (LFTs) in AHF patients enrolled in the PROTECT study. Methods and results The

  3. Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Jørgensen, Linda

    2010-01-01

    of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively)....

  4. Use of Renal Replacement Therapy May Influence Graft Outcomes following Liver Transplantation for Acute Liver Failure: A Propensity-Score Matched Population-Based Retrospective Cohort Study.

    Science.gov (United States)

    Knight, Stephen R; Oniscu, Gabriel C; Devey, Luke; Simpson, Kenneth J; Wigmore, Stephen J; Harrison, Ewen M

    2016-01-01

    Acute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal replacement therapy. A retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use. Three-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (Prenal replacement therapy was a predictor of both patient death (hazard ratio (HR) 1.59, 95% CI 1.01-2.50, P = 0.044) but not graft loss (HR 1.39, 95% CI 0.92-2.10, P = 0.114). In groups fully matched on baseline covariates, those not receiving renal replacement therapy with a serum creatinine greater than 175 μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy. In patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.

  5. A new prognostic formula for adult acute liver failure using computer tomography-derived hepatic volumetric analysis

    International Nuclear Information System (INIS)

    Yamagishi, Yoshiyuki; Saito, Hidetsugu; Ebinuma, Hirotoshi

    2009-01-01

    King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score are useful and widely-employed prognostic markers for acute liver failure (ALF). We previously reported that liver atrophy is an important prognostic factor for ALF. The aim of the present study was to assess the value of liver volumetry and to generate a new prognostic formula. Computed tomography-derived liver volume (CTLV) and standardized liver volume (SLV) of 30 adult ALF patients were calculated at the time of diagnosis. Patients were assigned to one of two groups: group A consisted of 13 patients who recovered without surgical intervention, and group B consisted of 17 patients who died due to liver failure or who underwent living donor liver transplantation (LDLT). The median CTLV/SLV ratios of groups A and B were 1.019 and 0.757, respectively (P=0.0009). The difference was most significant (P=0.0002) at the probability cutoff point of 0.80 for CTLV/SLV ratio; the sensitivity and specificity were 76.5% and 92.3%, respectively. Serum total bilirubin (TB) levels and CTLV/SLV ratio were selected as independent prognostic factors by multivariate analysis. A prognostic formula including volumetric analysis was established: Z=-2.3813-[0.15234 x TB (mg/dl)]+[4.5734 x CTLV/SLV] (area under the ROC curve (AUC)=0.87783, P=0.0002). The CTLV/SLV ratio is a very useful marker for predicting the prognosis of adult ALF. Our prognostic formula including only the CTLV/SLV ratio and TB is simple and useful and awaits validation in a future larger-scale prospective study. (author)

  6. Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing.

    Science.gov (United States)

    Suzuki, Takako; Kawada, Jun-Ichi; Okuno, Yusuke; Hayano, Satoshi; Horiba, Kazuhiro; Torii, Yuka; Takahashi, Yoshiyuki; Umetsu, Syuichiro; Sogo, Tsuyoshi; Inui, Ayano; Ito, Yoshinori

    2017-11-01

    Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. This finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Neuropsychological functioning and health-related quality of life: pediatric acute liver failure study group results.

    Science.gov (United States)

    Sorensen, Lisa G; Neighbors, Katie; Zhang, Song; Limbers, Christine A; Varni, James W; Ng, Vicky L; Squires, Robert H; Alonso, Estella M

    2015-01-01

    Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF. This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale. A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P = 0.009), but motor coordination was worse (P = 0.04). Teachers (P = 0.04 to P < 0.0001) and parents (P = 0.005) reported more executive deficits versus norms, and participants had worse attention (P = 0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P = 0.001 to P < 0.0001) and parent proxy report was lower on the fatigue scales (P = 0.001 to P < 0.0001). Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.

  8. Acute liver failure in a term neonate after repeated paracetamol administration

    Directory of Open Access Journals (Sweden)

    Fabio Bucaretchi

    2014-03-01

    Full Text Available Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L, hypoglycemia (18mg/dL, increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL after receiving oral paracetamol (10mg/kg/dose every 4 hours for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL. Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

  9. Expert beliefs regarding novel lipid-based approaches to pediatric intestinal failure-associated liver disease.

    Science.gov (United States)

    Diamond, Ivan R; Grant, Robert C; Feldman, Brian M; Tomlinson, George A; Pencharz, Paul B; Ling, Simon C; Moore, Aideen M; Wales, Paul W

    2014-08-01

    To determine expert beliefs regarding the probability of intestinal failure-associated liver disease (IFALD) with novel lipid-based approaches (lipid minimization/ω-3 lipids) in managing IFALD to facilitate Bayesian analyses of clinical trials of these therapies. Structured interviews were conducted using a validated approach to belief elicitation with 60 intestinal failure (IF) experts from across North America. Participants were asked to estimate, in an average population of infants referred for management of IF with early IFALD, the probability of advanced IFALD at 3 months following referral in each of 3 scenarios: (1) conventional lipid, (2) ω-3 lipids, and (3) lipid minimization. Probability distributions of the risk of advanced IFALD with each strategy were developed. Distributions of the elicited treatment effect for the novel approaches, relative to conventional lipid, were calculated. Median duration of experience of participants managing patients with IF was 8.5 (range, 2-35) years. The median probability of advanced IFALD using conventional lipid was 32.5%; ω-3 lipids, 17.5%; and lipid minimization, 13%. The median of the elicited treatment effects relative to conventional lipid was a relative risk of 0.53 for the ω-3 lipid and 0.45 for lipid minimization. There was consistent expert opinion that the novel lipid-based approaches are superior to conventional therapy, with similar estimates of treatment efficacy for the 2 approaches. The distributions of the elicited treatment effects can be used as prior distributions in Bayesian analyses of clinical trials of these novel strategies. © 2013 American Society for Parenteral and Enteral Nutrition.

  10. [Comparison of curative effect of low flow rate plasma exchange combined with hemofiltration for treatment of liver failure].

    Science.gov (United States)

    Yang, Yong-feng; Huang, Ping; Zhang, Ning; Gai, Xiao-dong; Feng, Xiao-ning; Zhong, Yan-dan; Wang, Li-rong; Yang, Yi-jun; Zhao, Wei

    2009-02-01

    To investigate the effect of plasma exchange (PE) combined with hemofiltration (HF) on liver failure. Seventy-seven inpatients with liver failure admitted during January 2006 to August 2007 were randomly assigned to receive PE combined with HF (PE+HF group, 38 cases), or PE alone (PE group, 39 cases). Forty-one inpatients with liver failure who had not received artificial liver support treatment were assigned to serve as control group. The survival rates and biochemical parameters of three groups were compared. There was no significant difference in biochemical parameters before treatment among three groups. Compared with pre-treatment values, albumin (Alb), cholinesterase (ChE) and prothrombin activity (PTA) of both PE group and PE+HF group were significantly increased after treatment, and total bilirubin (TBIL), alanine transaminase (ALT), aspartate transaminase (AST) of both PE group and PE+HF group were significantly decreased after treatment (Prate of PE group, PE+HF group and control group was 48.7% (19/39), 68.4% (26/38), and 29.3% (12/41) respectively. The survival rate of PE+HF group was significantly higher than that of control group (chi(2)=12.11, Prate of recovery of consciousness of patients with hepatic encephalopathy in PE+HF group was higher than that of PE group (42.8% vs. 0, P<0.05). Compared with PE alone, the result was better when it was combined with HF in correction of electrolyte disturbance and acid-base imbalance (19/23 vs. 0/21, P<0.05). Treatment of liver failure by PE combined with HF is safe and effective, and its efficacy is higher than PE alone.

  11. Isoniazid-Induced Severe Hepatotoxicity: An Infrequent but Preventable Cause of Liver Failure in Children Treated for Latent Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Dan Desrochers

    2011-01-01

    Full Text Available Isoniazid (INH monotherapy has gained widespread acceptance as an efficacious therapy for latent tuberculosis infection (LTBI especially in low-prevalence settings. Although INH related hepatotoxicity is well recognized, progression to severe liver dysfunction requiring care at a transplant center remains unpredictable. We report the management of a five year-old girl who developed progressive liver failure due to INH prophylaxis. This highlights the potential severity of INH related hepatic injury and underscores the significance of vigilant clinical monitoring throughout the duration of the therapy in children.

  12. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P.N.; Hauerberg, J.; Frederiksen, Hans-Jørgen

    2008-01-01

    AIM: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated...... with a rise in the glutamine concentration and ICP. PATIENTS AND METHODS: In 13 patients with ALF (8F/5M; median age 46 (range 18-66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion...... pressure (CPP). RESULTS: The cerebral glutamine concentration was 4,396 (1,011-9,712) microM, lactate 2.15 (1.1-4.45) mM, and pyruvate 101 (43-255) microM. The lactate-pyruvate ratio was 21 (16-40), ICP 20 (2-28) mmHg, and CPP 72 (56-115) mmHg. Cerebral glutamine concentration correlated with the lactate...

  13. Hepatitis E Virus Induced Acute Liver Failure with Scrub Typhus Coinfection in a Pregnant Woman.

    Science.gov (United States)

    Verma, Nipun; Sharma, Megha; Biswal, Manisha; Taneja, Sunil; Batra, Nitya; Kumar, Abhay; Dhiman, Radha K

    2017-06-01

    Coinfections contribute significantly to diagnostic challenges of acute febrile illnesses, especially in endemic areas. The confusion caused by overlapping clinical features impedes timely management. Herein, we report an unusual, previously unreported case of a pregnant woman suffering from a coinfection of scrub typhus and hepatitis E virus. A 25-year-old, 31-week pregnant woman presented with jaundice for 5 days and altered sensorium for 2 days. She had features of both viral acute liver failure (ALF) and tropical infections mimicking ALF, including hyperbilirubinemia, coagulopathy, anemia, thrombocytopenia, intravascular hemolysis, and hepatosplenomegaly. Etiological workup revealed rare coinfection of hepatitis E and scrub typhus. Despite all supportive measures, the patient succumbed to her illness (i.e., absent brainstem reflexes and intracranial bleed secondary to coagulopathy) and had poor fetal outcome, which resulted in stillbirth. ALF in a pregnant woman is a medical and obstetric emergency. It can result from varied etiologies that though differ in their incidence, mode of occurrence, and pregnancy outcome, can clinically masquerade as each other, causing diagnostic dilemma. This unusual case report highlights the significance of keeping all such possibilities in mind while managing a pregnant woman with ALF, especially in a country like India where maternal and perinatal mortality rates, the core indicators of national health, are still among the highest in the world.

  14. Lactate and Lactate: Pyruvate Ratio in the Diagnosis and Outcomes of Pediatric Acute Liver Failure.

    Science.gov (United States)

    Feldman, Amy G; Sokol, Ronald J; Hardison, Regina M; Alonso, Estella M; Squires, Robert H; Narkewicz, Michael R

    2017-03-01

    To assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P  ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days. Retrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day. Of 986 participants, 110 had lactate and pyruvate levels collected on the same day. Of the 110, the etiology of PALF was a mitochondrial disorder in 8 (7%), indeterminate in 65 (59%), and an alternative diagnosis in 37 (34%). Lactate, pyruvate, and L:P were similar among the 3 etiologic groups. There was no significant association between the initial lactate or L:P and biochemical variables of clinical severity or clinical outcome at 21 days. A serum lactate ≥ 2.5 mmol/L and/or elevated L:P was common in all causes of PALF, not limited to those with a mitochondrial etiology, and did not predict 21-day clinical outcome. ClinicalTrials.gov: NCT00986648. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Liver transplantation for acute liver failure: a 5 years experience Transplante hepático na hepatite fulminante: uma experiência de 5 anos

    Directory of Open Access Journals (Sweden)

    Cyntia Ferreira Gomes Viana

    2008-09-01

    Full Text Available BACKGROUND: Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. AIM: To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. METHODS: A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. RESULTS: Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2% at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. CONCLUSION: Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients.RACIONAL: OBJETIVO: Avaliar a evolução de 20 pacientes com insuficiência hepática aguda e indicação de

  16. [Predictive value of pediatrics end-stage liver disease or model for end-stage liver disease score in the prognosis of pediatric acute liver failure treated with artificial liver support system].

    Science.gov (United States)

    Jinhao, Tao; Weiming, Chen; Jing, Hu; Jun, He; Jian, Ma; Peng, Shi; Zhujin, Lu; Guoping, Lu; Yimin, Zhu

    2015-04-01

    To investigate the predictive value of pediatrics end-stage liver disease (PELD) or the model for end-stage liver disease (MELD) in the prognosis of pediatric acute liver failure (PALF) treated with artificial liver support system (ALSS). The clinical data of 47 children with acute liver failure seen from August 2008 to July 2013 treated in Children's Hospital, Fudan University were analyzed. Thirty children were treated with ALSS in addition to conventional comprehensive medical treatment (ALSS group). Seventeen children were treated with only conventional comprehensive medical treatment (control group). The main biochemical parameters and coagulation function parameters before and after treatment were compared in the ALSS group and the mortality rates were compared between the two groups. The patients were graded by PELD or MELD when they were hospitalized and the relationship of PELD or MELD scores and mortalities of child patients with the receiver operating characteristic curve (ROC) were analyzed. There were significant differences in total bilirubin (TB) ((302 ± 208) vs. (161 ± 129) µmol/L); alanine aminotransferase (ALT) ((161 ± 225) vs. (761 ± 834) U/L); aspartate aminotransferase ( AST) (66 (35, 123 ) vs. 447 (184, 1,129 ) U/L) ; international normalized ratio (INR) ((2.6 ± 1.6) vs. (5.1 ± 4.0)); prothrombin time activity percentage (PTA) ((42 ± 25)% vs. (22 ± 13)%); albumin( ALB) ((35 ± 5) vs. (33 ± 6) g/L) in the ALSS group after treatment. Through the ROC curve analysis, the best PELD/MELD threshold was 25 to predict the patients survival after ALSS therapy, with a sensitivity of 92. 3% , and a specificity of 94.1% at the cutoff point. The area under the ROC curve was 0. 912. The mortality of patients with PELD or MELD score below 25 in the ALSS group (1/13) was lower than the control group (3/4) (P = 0.022), and the mortality of patients with PELD or MELD score over 25 (16/17) was higher than that of the control group (10/13) (P = 0

  17. Plasma exchange combining with plasma bilirubin adsorption effectively removes toxic substances and improves liver functions of hepatic failure patients.

    Science.gov (United States)

    Che, X-Q; Li, Z-Q; Chen, Z; Guo, D; Jia, Q-Y; Jiang, S-C; Cai, J

    2018-02-01

    Hepatic failure (HF) is a kind of complex disease characterizing with liver dysfunction and a few clinical complications. Artificial liver support system (ALSS) has been applied to HF patients to improve dysfunctional liver in recent years. This study aims to evaluate therapeutic effects of ALSS approaches, including plasma exchange (PE), plasma diafiltration (PDF) and plasma bilirubin adsorption (PBA), on liver function of HF patients. This study is a retrospective analysis involving 516 patients diagnosed as HF between February 2014 and February 2015. Patients were randomly divided into PE, PDF, PE plus PBA, and PDF plus PBA group. Meanwhile, single-drug group and combined-drug group were also divided. The liver functions, capability of removing toxic substances and coagulation functions were evaluated both pre-treatment and post-treatment. The side effects and hospital improvement rate were also observed post-treatment. Hospital improvement rate achieves to 69.6%. TBIL levels and MELD scores were significantly decreased post-treatment compared to pre-treatment (phigher compared to PE and PDF group (p=0.002, 0.002, respectively). MELD scores were significantly decreased post-treatment compared to pre-treatment in each group (pbetter role in removing toxic substances, improving liver functions of HF patients.

  18. Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure-Associated Liver Disease in Pediatric Patients.

    Science.gov (United States)

    Rumbo, Carolina; Martinez, María Inés; Cabanne, Ana; Trentadue, Julio; Fernández, Adriana; Gondolesi, Gabriel

    2017-07-01

    Intestinal failure-associated liver disease (IFALD) is a frequent indication for intestinal transplantation. Liver biopsy (LBX) is the gold standard test for its diagnosis. Identifying noninvasive markers of fibrosis progression would be of considerable clinical use. Aspartate aminotransferase/platelet ratio index (APRI) has a good correlation in adult patients with chronic liver disease; few studies have been performed in children with IFALD. To evaluate APRI in a cohort of children with IFALD. Retrospective analysis of a prospective database of patients failure and at least 1 LBX, registered in our unit from March 2006 to December 2014. Forty-nine LBX were done on 36 patients: 20 were male, and 31 had short gut. Fibrosis was found in 71% of LBX. Biopsies were grouped according to the fibrosis stage (METAVIR [M]): (1) group 1 (G1) LBX with M 0, 1, 2 (n = 33) and (2) group 2 (G2) LBX with M 3, 4 (n = 16). The median APRI score was 0.92 (interquartile range [IQR] 0.63-1.50) for G1 and 2.50 (IQR 1.81-5.82) for G2 ( P = .001) The c statistic of the receiving operating characteristic curve was 0.79 (95% CI 0.64-0.94; P 1.6 correlates with advanced fibrosis.

  19. Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

    Directory of Open Access Journals (Sweden)

    Cao Hongcui

    2012-06-01

    Full Text Available Abstract Background Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF. Methods hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis. Results hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig

  20. Effects of haemoperfusion through charcoal or XAD-2 resin on an animal model of fulminant liver failure

    Science.gov (United States)

    Weston, M. J.; Gazzard, B. G.; Buxton, B. H.; Winch, J.; Machado, A. L.; Flax, H.; Williams, Roger

    1974-01-01

    In a group of dogs in whom fulminant liver failure had been induced, perfusion of blood through activated charcoal resulted in a significantly longer survival than that of a similar group of dogs whose blood was not so treated. An otherwise progressive rise in blood ammonia concentration was halted in the treatment group. In another group of dogs with fulminant liver failure perfusion of blood through the resin Amberlite XAD-2 was associated with a fall in the serum bilirubin concentration and complete clearance from the blood of 14C-labelled sodium glycocholate. Survival in this group of animals was not significantly prolonged. This was due at least in part to the occurrence of haemorrhage due to thrombocytopenia. Platelets adhere to the resin but do not adhere to the same degree to charcoal coated with a thin layer of polymer. PMID:4851751

  1. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial.

    Science.gov (United States)

    Squires, Robert H; Dhawan, Anil; Alonso, Estella; Narkewicz, Michael R; Shneider, Benjamin L; Rodriguez-Baez, Norberto; Olio, Dominic Dell; Karpen, Saul; Bucuvalas, John; Lobritto, Steven; Rand, Elizabeth; Rosenthal, Philip; Horslen, Simon; Ng, Vicky; Subbarao, Girish; Kerkar, Nanda; Rudnick, David; Lopez, M James; Schwarz, Kathleen; Romero, Rene; Elisofon, Scott; Doo, Edward; Robuck, Patricia R; Lawlor, Sharon; Belle, Steven H

    2013-04-01

    N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those pediatric drug trials, regardless of results in adults. Copyright © 2012 American Association for the Study of Liver Diseases.

  2. Prognostic value of (13)C-phenylalanine breath test on predicting survival in patients with chronic liver failure.

    Science.gov (United States)

    Gallardo-Wong, I; Morán, S; Rodríguez-Leal, G; Castañeda-Romero, B; Mera, R; Poo, J; Uribe, M; Dehesa, M

    2007-09-14

    To evaluate the prognostic value of percentage of (13)C-phenylalanine oxidation ((13)C-PheOx) obtained by (13)C-phenylalanine breath test ((13)C-PheBT) on the survival of patients with chronic liver failure. The hepatic function was determined by standard liver blood tests and the percentage of (13)C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of (13)C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of (13)C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival. Percentage of (13)C-PheOx obtained by (13)C-PheBT is a strong predictor of survival in patients with chronic liver disease.

  3. Prognostic value of 13C-phenylalanine breath test on predicting survival in patients with chronic liver failure

    Science.gov (United States)

    Gallardo-Wong, I; Morán, S; Rodríguez-Leal, G; Castañeda-Romero, B; Mera, R; Poo, J; Uribe, M; Dehesa, M

    2007-01-01

    AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival. CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease. PMID:17729409

  4. Porcine Adipose-Derived Mesenchymal Stem Cells Retain Their Stem Cell Characteristics and Cell Activities While Enhancing the Expression of Liver-Specific Genes after Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Chenxia Hu

    2016-01-01

    Full Text Available Acute liver failure (ALF is a kind of complicated syndrome. Furthermore, adipose-derived mesenchymal stem cells (ADMSCs can serve as a useful cell resource for autotransplantation due to their abundance and micro-invasive accessability. However, it is unknown how ALF will influence the characteristics of ADMSCs and whether ADMSCs from patients suffering from end-stage liver diseases are potential candidates for autotransplantation. This study was designed to compare various properties of ALF-derived ADMSCs with normal ADMSCs in pig models, with regard to their cellular morphology, cell proliferative ability, cell apoptosis, expression of surface antigens, mitochondrial and lysosomal activities, multilineage potency, and expression of liver-specific genes. Our results showed that ALF does not influence the stem cell characteristics and cell activities of ADMSCs. Intriguingly, the expression levels of several liver-specific genes in ALF-derived ADMSCs are higher than in normal ADMSCs. In conclusion, our findings indicate that the stem cell characteristics and cell activities of ADMSCs were not altered by ALF and these cells can serve as a new source for regenerative medicine.

  5. Retrospective evaluation of acute liver failure in dogs (1995-2012): 49 cases.

    Science.gov (United States)

    Lester, Carrie; Cooper, Johanna; Peters, Rachel M; Webster, Cynthia R L

    2016-07-01

    To characterize the clinical presentation and outcome of dogs with acute liver failure (ALF). Retrospective case series from January 1995 to December 2012. University teaching hospital. Forty-nine dogs were diagnosed with ALF defined as the acute onset of clinical signs accompanied by serum hyperbilirubinemia and coagulopathy (prothrombin time >1.5 times the upper limit of the reference interval) with or without signs of hepatic encephalopathy. Medical records were retrospectively analyzed for clinical presentation, history, physical examination findings, clinicopathologic data, diagnostic imaging findings, hepatic histopathology, treatment, and outcome. Presenting signs included anorexia (28/49, 57%), vomiting (25/49, 51%), neurologic abnormalities (17/49, 35%), and polydipsia/polyuria (10/49, 20%). Neurologic impairment compatible with hepatic encephalopathy occurred at some point during hospitalization in 28/49 (57%) of dogs. Common clinicopathologic abnormalities on presentation other than hyperbilirubinemia and increased serum liver enzyme activity included thrombocytopenia (25/49, 51%), hypoalbuminemia (23/49, 46%), leukocytosis (17/49, 34%), anemia (14/49, 29%), hypokalemia (13/49, 27%), and hypoglycemia (10/49, 20%). The causes of ALF included neoplasia (13/49, 27%), presumptive leptosporosis (4/49, 8%), and ischemia (1/49, 2%). The remaining cases were idiopathic although 15 of these dogs had exposure to possible hepatotoxins. Common lesions in the 35/49 (71%) dogs that had hepatic histopathology were necrosis (19/39, 48%), lipidosis (16/39, 41%), vacuolar change (7/49, 14%), and inflammation (4/49, 8%). Complications included ascites (20/49, 41%), bleeding tendencies (14/49, 29%), pancreatitis (12/49, 24%), and acute tubular necrosis (11/49, 22%). Seven (14%) dogs survived to discharge. Survivors had higher alanine aminotransferase activity, and were more likely to maintain normal albumin concentrations and not develop clinical bleeding or ascites during

  6. Modifications of intracranial pressure after molecular adsorbent recirculating system treatment in patients with acute liver failure: case reports.

    Science.gov (United States)

    Pugliese, F; Ruberto, F; Perrella, S M; Cappannoli, A; Bruno, K; Martelli, S; Celli, P; Summonti, D; D'Alio, A; Tosi, A; Novelli, G; Morabito, V; Poli, L; Rossi, M; Berloco, P B; Pietropaoli, P

    2007-01-01

    Cerebral dysfunction may be fatal in patients with acute liver failure (ALF); intracranial pressure (ICP) monitoring may be mandatory to direct measures to prevent further cerebral edema. Recently the introduction of dialysis with the molecular adsorbent recirculating system (MARS) has improved the outcomes among patients with ALF. The aim of this study was to evaluate ICP changes after MARS treatment among patients with ALF. Three patients -- 14, 18 and 16 years old -- were admitted to the ICU for acute liver failure induced by HBV in two cases and by acetaminophen in the other one. Because of Glasgow Coma Score (GCS) MARS treatments were performed in all patients. The patients received MARS treatments every day after their admission to liver transplantation. After MARS therapy the ICP decreased on average from 21 to 7 mm Hg. Significant hemodynamic modifications were not observed and their neurological conditions improved. MARS treatment improved the clinical pictures of these patients increasing the available time to obtain an urgent liver graft.

  7. Liver dysfunction assessed by model for end-stage liver disease excluding INR (MELD-XI scoring system predicts adverse prognosis in heart failure.

    Directory of Open Access Journals (Sweden)

    Satoshi Abe

    Full Text Available AIMS: Liver dysfunction due to heart failure (HF is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. METHODS AND RESULTS: We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289 and Group H (MELD-XI ≥10, n = 273. We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days, 104 deaths (62 cardiac deaths and 42 non-cardiac deaths were observed. The event (cardiac death, non-cardiac death, all-cause death-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively. In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively. CONCLUSIONS: The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF.

  8. Inhibition of sphingosine kinase 1 ameliorates acute liver failure by reducing high-mobility group box 1 cytoplasmic translocation in liver cells.

    Science.gov (United States)

    Lei, Yan-Chang; Yang, Ling-Ling; Li, Wen; Luo, Pan; Zheng, Pei-Fen

    2015-12-14

    To determine the therapeutic potential of sphingosine kinase 1 (Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure (ALF). Balb/c mice were randomly assigned to different groups, with ALF induced by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot. The expression of Sphk1 in liver tissue and PBMCs was upregulated in GalN/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells, the resident macrophages of the liver. The survival rates of mice in the N,N-dimethylsphingosine (DMS, a specific inhibitor of SphK1) treatment group were significantly higher than that of the control group (P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6, 12, and 24 h compared with that of the control group (P < 0.01 for all). Serum HMGB1 levels at 6, 12, and 24 h, as well as serum TNF-α, IL-6, and IL-1β levels at 12 h, were significantly lower in the DMS treatment group than in the control group (P < 0.01 for all). Furthermore, hepatic inflammation, necrosis, and HMGB1 cytoplasm translocation in liver cells were significantly decreased in

  9. Surveillance for infectious complications in pediatric acute liver failure - a prospective study.

    Science.gov (United States)

    Mekala, Suresh; Jagadisan, Barath; Parija, Subhash Chandra; Lakshminarayanan, Subitha

    2015-03-01

    To prospectively evaluate infectious complications (IC) in pediatric acute liver failure (PALF) by employing surveillance cultures. From 2011 to 2013, children with PALF in a tertiary care centre received a standard protocolised management. Prophylactic parenteral antibiotics were used without antifungals. Surveillance cultures of blood, urine, ascites and tracheal aspirates were sent. Biochemical and clinical parameters and outcomes were compared between children with and without IC. Of the 29 children with PALF admitted during the study period (median age 36 mo, range 12-90 mo), 13.8 % had blood stream infections (BSI) at admission. Organisms were isolated in 8.8 % (12/136) of the blood cultures, 13.7 % (11/80) of the urine cultures, 30.8 % (8/26) of the tracheal aspirates and 7.1 % (1/14) of the ascitic fluid cultures. Gram negative bacteriae (n = 17) were the commonest, followed by fungi (n = 13) and gram positive bacteriae (n = 2). Klebsiella pneumoniae and Candida nonalbicans group were the commonest bacteria and fungi respectively. After admission, fungal BSI and urinary tract infections were diagnosed at a median time of 4 d (range 3-8 d) and 3.5 d (range 3-6 d) respectively. ICs were not associated with other complications and increased mortality but with longer hospital and pediatric intensive care unit (PICU) stay. In this study BSI was a common finding at admission in PALF. Inspite of prophylactic antibiotics, break through gram negative bacterial and fungal ICs were common. Empirical treatment of IC should include broad spectrum antibiotics. Fungal IC occurred beyond 48 h. Prophylactic antifungals at admission may be considered to decrease their frequency. IC prolongs PICU and hospital stay.

  10. Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts.

    Science.gov (United States)

    Tanemura, Kouichi; Ohtaki, Tadatoshi; Kuwahara, Yasushi; Tsumagari, Shigehisa

    2017-01-20

    Uridine 5'-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17β as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (Pcows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high-level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17β glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows.

  11. Basiliximab treatment for steroid-resistant rejection in pediatric patients following liver transplantation for acute liver failure.

    Science.gov (United States)

    Shigeta, Takanobu; Sakamoto, Seisuke; Uchida, Hajime; Sasaki, Kengo; Hamano, Ikumi; Kanazawa, Hiroyuki; Fukuda, Akinari; Kawai, Toshinao; Onodera, Masafumi; Nakazawa, Atsuko; Kasahara, Mureo

    2014-12-01

    An IL-2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6-12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno-occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. [Changes in the composition of intestinal microbiota in mice with acute liver failure induced by D-galactosamine].

    Science.gov (United States)

    Hu, Y X; Yu, L; Liu, H J; Cheng, M L

    2017-04-20

    Objective: To investigate the changes in the composition of intestinal microbiota in mice with acute liver failure and identify characteristic bacteria, and to provide a basis for the diagnosis and treatment of acute liver failure with intestinal microbiota disorders. Methods: A total of 30 specific pathogen-free male BALB/c mice were used in this study, including 25 mice in the model group and 5 mice in the control group. An acute liver failure model was induced by D-galactosamine. Microbial DNA was extracted from intestinal contents in different segments of the lower digestive tract (ileum and colon) and feces and then were amplified using PCR. The regions of 16S V3-V4 were subjected to high-throughput sequencing, followed by bioinformatics analyses, including OTU hierarchical clustering, species annotation, alpha-diversity analysis, and LEfSe (LDA Effect Size) analysis. Comparison of continuous data was made using t-test, while comparison of categorical data was made using χ2 test. Results: A total of 10 mice survived in the two groups, with 80% mortality rate in the model group. The alpha-diversity analysis revealed increased bacterial diversity and abundance in the ileum, increased bacterial diversity and reduced bacterial abundance in the colon, and reduced bacterial diversity and insignificantly changed bacterial abundance in feces in the model group compared with the control group. Based on the optimized classification level, significantly reduced abundance of Clostridiaceae (44.95% ± 19.28% vs 7.51% ± 16.57%, P = 0.011) in the ileum, whereas significantly increased abundance of Rikenellaceae (1.08% ± 1.01% vs 4.18% ± 2.39%, P = 0.028), S24-7 (4.75% ± 4.87% vs 22.77% ± 13.05%, P = 0.020), and F16 (0.24% ± 0.28% vs 2.18% ± 1.61%, P = 0.029) in the colon were found in model group compared with the control group. The LEfSe analysis demonstrated that there were significant differences in Staphylococcaceae and S24-7 between the two groups, and S24

  13. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure.

    Science.gov (United States)

    Kamat, Pradip; Kunde, Sachin; Vos, Miriam; Vats, Atul; Gupta, Nitika; Heffron, Thomas; Romero, Rene; Fortenberry, James D

    2012-01-01

    Pediatric acute liver failure is often accompanied by hepatic encephalopathy, cerebral edema, and raised intracranial pressure. Elevated intracranial pressure can be managed more effectively with intracranial monitoring, but acute-liver-failure-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early intracranial pressure monitoring in acute liver failure in children listed for liver transplantation. Retrospective review of all intubated pediatric acute liver failure patients with grade III and grade IV encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant who were identified from an institutional liver transplant patient database from 1999 to 2009. None. A total of 14 patients were identified who met the inclusion criteria. Their ages ranged from 7 months to 20 yrs. Diagnoses of acute liver failure were infectious (three), drug-induced (seven), autoimmune hepatitis (two), and indeterminate (two). Grade III and IV encephalopathy was seen in ten (71%) and four (29%) patients, respectively. Computed tomography scans before intracranial pressure monitor placement showed cerebral edema in five (35.7%) patients. Before intracranial pressure monitor placement, fresh frozen plasma, vitamin K, and activated recombinant factor VIIa were given to all 14 patients, with significant improvement in coagulopathy (p liver transplant, with 100% surviving neurologically intact. Four of 14 (28%) patients had spontaneous recovery without liver transplant. Two of 14 (14%) patients died due to multiple organ failure before transplant. One patient had a small 9-mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection. In our series of patients, intracranial pressure monitoring had a low complication rate and was associated with a high survival rate despite severe

  14. Management of acute liver failure in infants and children: consensus statement of the pediatric gastroenterology chapter, Indian academy of pediatrics.

    Science.gov (United States)

    Bhatia, Vidyut; Bavdekar, Ashish; Yachha, Surender Kumar

    2013-05-08

    Selected members were requested to prepare guidelines on specific issues, which were reviewed by two other members. These guidelines were then incorporated into a draft statement, which was circulated to all members. On 17th December 2011, Kunwar Viren Oswal round table conference was organized by the Apollo Center for Advanced Pediatrics, Indraprastha Apollo Hospital, New Delhi and the Sub-specialty Chapter of Pediatric Gastroenterology, Indian Academy of Pediatrics. Presentations, ensuing discussions, and opinions expressed by the participants were incorporated into the final draft. To formulate comprehensive evidence based guidelines for management of acute liver failure in India. Viral hepatitis is the leading cause of acute liver failure (ALF) in India. Search for metabolic etiology, particularly in infants and neonates, and in apparently idiopathic cases needs to be done. Planning for early transfer is important as the risks involved with patient transport may increase or even preclude transfer at later stages. Management should be in an intensive care setting in select situations. There is currently insufficient evidence to routinely prescribe branched-chain amino acids, non-absorbable antibiotics or lactulose. Group recommends use of N-acetyl cysteine routinely in patients with ALF. Administration of antibiotics is recommended where infection is present or the likelihood of impending sepsis is high. Enteral nutrition is preferred to parenteral nutrition. Protein restriction is not recommended. An international normalized ratio >4 or Factor V concentration of liver transplantation. Overall 40-50% of ALF patients survive without transplantation. Survival in patients fulfilling criteria for liver transplantation and not transplanted is 10-20%. Liver transplantation is a definite treatment for ALF with high one-and five-year survival rates.

  15. The failure rate of nonoperative management in children with splenic or liver injury with contrast blush on computed tomography: a systematic review

    NARCIS (Netherlands)

    van der Vlies, Cornelis H.; Saltzherr, Teun P.; Wilde, Jim C. H.; van Delden, Otto M.; de Haan, Rob J.; Goslings, J. Carel

    2010-01-01

    Purpose: Nonoperative management (NOM) is the treatment of choice for hemodymically stable pediatric patients with spleen or liver trauma. The aim of this study was to assess the failure rate of NOM in children with blunt liver and/or splenic injury when a contrast blush is present on a computed

  16. Full-length genome characterization and genetic relatedness analysis of hepatitis A virus outbreak strains associated with acute liver failure among children.

    Science.gov (United States)

    Vaughan, Gilberto; Forbi, Joseph C; Xia, Guo-Liang; Fonseca-Ford, Maureen; Vazquez, Roberto; Khudyakov, Yury E; Montiel, Sonia; Waterman, Steve; Alpuche, Celia; Gonçalves Rossi, Livia Maria; Luna, Norma

    2014-02-01

    Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes. © 2013 Wiley Periodicals, Inc.

  17. [Clinical features of patients with fulminant hepatitis A requiring emergency liver transplantation: comparison with acute liver failure due to other causes].

    Science.gov (United States)

    Kim, Jin Dong; Choi, Jong Young; Park, Chung Hwa; Song, Myeong Jun; Jang, Jeong Won; Bae, Si Hyun; Yoon, Seung Kew; Lee, Young Sok; You, Young Kyoung; Kim, Dong Goo

    2010-03-01

    According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure (ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgM-positive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; PLiver Failure Study Group prognostic index, King's College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A.

  18. Removal selectivity of Prometheus: a new extracorporeal liver support device.

    Science.gov (United States)

    Rifai, Kinan; Ernst, Thomas; Kretschmer, Ulrich; Haller, Hermann; Manns, Michael Peter; Fliser, Danilo

    2006-02-14

    To evaluate whether treatment with the Prometheus reg system significantly affects cytokines, coagulation factors and other plasma proteins. We studied nine patients with acute-on-chronic liver failure and accompanying renal failure. Prometheus reg therapy was performed on 2 consecutive days for up to 6 h in all patients. Several biochemical parameters and blood counts were assessed at regular time points during Prometheus reg treatment. We observed a significant decrease of both protein-bound (e.g. bile acids) and water-soluble (e.g. ammonia) substances after Prometheus reg therapy. Even though leukocytes increased during treatment (P0.5). Further, antithrombin 3, factor II and factor V plasma levels did not decrease during Prometheus reg therapy (all P>0.5), and the INR remained unchanged (P=0.4). Plasma levels of total protein, albumin, and fibrinogen were also not altered during Prometheus reg treatment (all P>0.5). Finally, platelet count did not change significantly during therapy (P=0.6). Despite significant removal of protein-bound and water-soluble substances, Prometheus reg therapy did not affect the level of cytokines, coagulation factors or other plasma proteins. Thus, the filters and adsorbers used in the system are highly effective and specific for water-soluble substances and toxins bound to the albumin fraction.

  19. Efficacy of fractionated plasma separation and adsorption system (Prometheus) for treatment of liver failure due to mushroom poisoning.

    Science.gov (United States)

    Vardar, Rukiye; Gunsar, Fulya; Ersoz, Galip; Akarca, Ulus Salih; Karasu, Zeki

    2010-01-01

    Consuming wild mushrooms is an ordinary habit in late summer and autumn in our region. Every year, several cases of hepatic toxicity secondary to mushroom poisoning are observed because of poor identification of the mushrooms. Unfortunately some of them are fatal. Prometheus system is a newly developed extracorporeal liver support device for fractionated plasma separation and adsorption (FPSA) that enables removal of albumin-bound and water-soluble toxins. Therefore, it may be a promising treatment option for patients with liver failure due to mushroom poisoning. We studied 8 patients with mushroom poisoning. All patients underwent 1 to 4 consecutive FPSA (Prometheus)-system in addition to medical and supportive treatment such as fluid replacement, Penicillin G, N-acetylcysteine (NAC) and silymarin. A variety of clinical and biochemical parameters were assessed. We had improvement of the biochemical parameters after first treatment with FPSA-system. Seven of 8 patients survived and were discharged to resume an independent life. One patient who had grade III encephalopathy when admitted to hospital died. No major adverse events were observed during the application of this therapy modality. FPSA-system may be a safe and effective treatment option for patient with mushroom poisoning. Early hospitalization is essential in order to be successful. Controlled studies are needed to evaluate the efficacy of this new treatment choice on survival of patients with acute liver failure (ALF) due to mushroom poisoning.

  20. Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure.

    Science.gov (United States)

    Wen, Zongmei; Lei, Zhen; Yao, Lu; Jiang, Ping; Gu, Tao; Ren, Feng; Liu, Yan; Gou, Chunyan; Li, Xiuhui; Wen, Tao

    2016-09-29

    Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production. d-galactosamine plus lipopolysaccharide (GalN/LPS), concanavalin A (ConA), and acetaminophen (APAP) were given to C57BL/6N mice to induce liver injury, respectively, and the pathogenic role of circulating histones was studied. Besides, the protective effect of nonanticoagulant heparin, which can bind histones, was evaluated with in vivo and ex vivo investigations. We observed that circulating histones were significantly increased in patients with ALF, and correlated with disease severity and mortality. Significant systemic inflammation was also pronounced in ALF patients, which were associated with histone levels. ALF patients' sera induced significant L02 cell death and stimulated U937 cells to produce cytokines, which were abrogated by nonanticoagulant heparin. Furthermore, circulating histones were all released remarkably in GalN/LPS, ConA, and APAP-treated mice, and associated with high levels of inflammatory cytokines. Heparin reduced systemic inflammation and liver damage in mice, suggesting that it could interfere with histone-associated liver injury. Collectively, these findings demonstrate that circulating histones are critical mediators of systemic inflammation and cellular damage in ALF, which may be potentially translatable for clinical use.

  1. Risk of Acute Liver Failure in Patients With Drug-Induced Liver Injury: Evaluation of Hy's Law and a New Prognostic Model.

    Science.gov (United States)

    Lo Re, Vincent; Haynes, Kevin; Forde, Kimberly A; Goldberg, David S; Lewis, James D; Carbonari, Dena M; Leidl, Kimberly B F; Reddy, K Rajender; Nezamzadeh, Melissa S; Roy, Jason; Sha, Daohang; Marks, Amy R; De Boer, Jolanda; Schneider, Jennifer L; Strom, Brian L; Corley, Douglas A

    2015-12-01

    Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Hy's Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76-0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71-0.99) and a specificity value of 0.76 (95% CI, 0.75-0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52-1.00) in the validation analysis. Hy's Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and

  2. Prognostic indicators for acute liver failure development and mortality in patients with hepatitis A: consecutive case analysis.

    Science.gov (United States)

    Shin, Hye Sun; Kim, Sae Pyul; Han, Sang Hoon; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Park, Jun Yong

    2014-07-01

    Due to the seroepidemiological shift in hepatitis A (HA), its severity, mortality, and complications have increased in recent years. Thus, the aim of this study was to identify predictive factors associated with poor prognosis among patients with HA. A total of 304 patients with HA admitted to our institution between July 2009 and June 2011 were enrolled consecutively. Patients with complications defined as acute liver failure (ALF) were evaluated, and mortality was defined as death or liver transplantation. The mean age of patients (204 males, 100 females) was 32 years. Eighteen (5.9%) patients had progressed to ALF. Of the patients with ALF, 10 patients (3.3%) showed spontaneous survival while 8 (2.6%) died or underwent liver transplantation. Multivariate regression analysis showed that Model for End-Stage Liver Disease (MELD) and systemic inflammatory response syndrome (SIRS) scores were significant predictive factors of ALF. Based on receiver operating characteristics (ROC) analysis, a MELD≥23.5 was significantly more predictive than a SIRS score≥3 (area under the ROC: 0.940 vs. 0.742, respectively). In addition, of patients with a MELD score≥23.5, King's College Hospital criteria (KCC) and SIRS scores were predictive factors associated with death/transplantation in multivariate analysis. MELD and SIRS scores≥23.5 and ≥3, respectively, appeared to be related to ALF development. In addition, KCC and SIRS scores≥3 were valuable in predicting mortality of patients with a MELD≥23.5.

  3. Can contrast-enhanced MRI with gadoxetic acid predict liver failure and other complications after major hepatic resection?

    Science.gov (United States)

    Costa, A F; Tremblay St-Germain, A; Abdolell, M; Smoot, R L; Cleary, S; Jhaveri, K S

    2017-07-01

    To determine whether a combination of clinical factors, the future liver remnant (FLR) ratio, and hepatic uptake of gadoxetic acid can be used to predict post-hepatectomy liver failure (PHLF) and other major complications (OMC). Sixty-five consecutive patients who underwent pre-hepatectomy gadoxetic acid-enhanced magnetic resonance imaging (MRI) between October 2010 and December 2013 were included. The relative liver enhancement (RLE) of gadoxetic acid was calculated from regions of interest on MRI, and FLR ratios were obtained from computed tomography (CT). PHLF and OMC were defined by the International Study Group of Liver Surgery criteria and Clavien-Dindo grade of ≥3, respectively. Multivariate logistic regression modelling was performed to identify predictors of PHLF and OMC, including RLE, FLR ratio, age, sex, chemotherapy history, intra-operative blood loss, and intra-operative transfusion. Nine patients experienced PHLF and another nine patients experienced OMC. RLE was comparable to the FLR ratio in predicting PHLF (areas under the receiver operating characteristic [AUROC] curves, 0.665 and 0.705), but performed poorly in predicting OMCs (AUROCs, 0.556 and 0.702). Combining all clinical and imaging parameters as predictors yielded the best performing predictive models (AUROCs, 0.875 and 0.742 for PHLF and OMC, respectively). A model based on clinical parameters, the FLR ratio, and RLE of gadoxetic acid may improve pre-hepatectomy risk assessment. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  4. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism.

    Science.gov (United States)

    Valencia, C Alexander; Wang, Xinjian; Wang, Jin; Peters, Anna; Simmons, Julia R; Moran, Molly C; Mathur, Abhinav; Husami, Ammar; Qian, Yaping; Sheridan, Rachel; Bove, Kevin E; Witte, David; Huang, Taosheng; Miethke, Alexander G

    2016-01-01

    The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis. A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF.

  5. Necrostatin-1 protects against reactive oxygen species (ROS-induced hepatotoxicity in acetaminophen-induced acute liver failure

    Directory of Open Access Journals (Sweden)

    Kenji Takemoto

    2014-01-01

    Full Text Available Excessive acetaminophen (APAP use is one of the most common causes of acute liver failure. Various types of cell death in the damaged liver are linked to APAP-induced hepatotoxicity, and, of these, necrotic cell death of hepatocytes has been shown to be involved in disease pathogenesis. Until recently, necrosis was commonly considered to be a random and unregulated form of cell death; however, recent studies have identified a previously unknown form of programmed necrosis called receptor-interacting protein kinase (RIPK-dependent necrosis (or necroptosis, which is controlled by the kinases RIPK1 and RIPK3. Although RIPK-dependent necrosis has been implicated in a variety of disease states, including atherosclerosis, myocardial organ damage, stroke, ischemia–reperfusion injury, pancreatitis, and inflammatory bowel disease. However its involvement in APAP-induced hepatocyte necrosis remains elusive. Here, we showed that RIPK1 phosphorylation, which is a hallmark of RIPK-dependent necrosis, was induced by APAP, and the expression pattern of RIPK1 and RIPK3 in the liver overlapped with that of CYP2E1, whose activity around the central vein area has been demonstrated to be critical for the development of APAP-induced hepatic injury. Moreover, a RIPK1 inhibitor ameliorated APAP-induced hepatotoxicity in an animal model, which was underscored by significant suppression of the release of hepatic enzymes and cytokine expression levels. RIPK1 inhibition decreased reactive oxygen species levels produced in APAP-injured hepatocytes, whereas CYP2E1 expression and the depletion rate of total glutathione were unaffected. Of note, RIPK1 inhibition also conferred resistance to oxidative stress in hepatocytes. These data collectively demonstrated a RIPK-dependent necrotic mechanism operates in the APAP-injured liver and inhibition of this pathway may be beneficial for APAP-induced fulminant hepatic failure.

  6. Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts

    OpenAIRE

    TANEMURA, Kouichi; OHTAKI, Tadatoshi; KUWAHARA, Yasushi; TSUMAGARI, Shigehisa

    2016-01-01

    Uridine 5?-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17? as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P

  7. Postoperative bleeding after tooth extraction in the pretransplant liver failure patient.

    OpenAIRE

    JoÃo Paulo Veloso PerdigÃo

    2011-01-01

    Liver transplantation is the gold standard treatment for patients with cirrhosis and hepatocellular carcinoma. The Brazilian Registry of Transplantation revealed that liver transplantation was the second solid organ most transplanted in 2010. With the purpose to eliminate foci of infection and reduce the risk of infection on the postransplant stage, these patients should undergo dental treatment to the removal of dental foci, with special care regarding the hemostasis impairment, mainly relat...

  8. [Biological and non-biological elimination therapy of acute liver failure. Experimental study on large laboratory animal].

    Science.gov (United States)

    Ryska, M; Lásziková, E; Pantoflícek, T; Kieslichová, E; Ryska, O; Prazák, J; Koblihová, E; Skibová, J

    2008-01-01

    Development of biological and non-biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL - bioartificial liver) and non-biological (FPSA - Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. Surgical model of ALF with liver devascularization in pigs (weight 25-40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non-parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 +/- 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 +/- 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 +/- 6.54 vs. 29.84 +/- 9.99 at 9 hour 11.94 +/- 4.14 vs. 29.95 +/- 12.36 and at 12 hour 13.88 +/- 6.31 vs. 26.10 +/- 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 +/- 4.09 vs. 24.1 +/- 2.85, 10 hour 21.9 +/- 3.63 vs. 25.1 +/- 2.19, 11 hour 22.5 +/- 3.98 vs. 26.3 +/- 3.50 and 12 hour 24.0 +/- 4.66 vs. 29.8 +/- 5.88 mm Hg. Significant improvement of bilirubin

  9. Estimation of liver parameters and oxidative stress in chronic renal failure patients on hemodialysis in Erbil governorate

    Science.gov (United States)

    Kakey, Musher Ismail Salih; Abdoulrahman, Kamaran Kaiani

    2017-09-01

    The present study aims to evaluate iron related parameters in chronic renal failure (CRF) patients on hemodialysis (HD). The study was carried out in Kidney Dialysis Center of Hawler Teaching Hospital in Erbil governorate. This study comprised (76) patients with chronic renal failure on hemodialysis and 41 healthy subjects as a control group of same ages. All hemodialysis patients were taking erythropoietin. The blood samples were taken from the patients before and after the process of hemodialysis for liver parameters and oxidative stress estimations. The results of this study showed lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, total protein and total antioxidant capacity (TAC), while higher levels of alkaline phosphatase (ALP), direct bilirubin and malondialdeyhde (MDA) before analysis was seen. Hemodialysis causes increasing in AST, ALT, albumin, total bilirubin, total protein and decreasing in ALP, direct bilirubin MDA and TAC.

  10. High-volume plasma exchange in patients with acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Schmidt, Lars Ebbe; Bernsmeier, Christine

    2016-01-01

    % of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. METHODS: In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus...... HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof...

  11. Analysis of serum inflammatory mediators identifies unique dynamic networks associated with death and spontaneous survival in pediatric acute liver failure.

    Science.gov (United States)

    Azhar, Nabil; Ziraldo, Cordelia; Barclay, Derek; Rudnick, David A; Squires, Robert H; Vodovotz, Yoram

    2013-01-01

    Tools to predict death or spontaneous survival are necessary to inform liver transplantation (LTx) decisions in pediatric acute liver failure (PALF), but such tools are not available. Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure. We hypothesized that specific, dynamic, and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF. We assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group (PALFSG) collected within 7 days after enrollment. Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors, non-survivors, and LTx recipients. Data were subjected to statistical analysis, patient-specific Principal Component Analysis (PCA), and Dynamic Bayesian Network (DBN) inference. Raw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes. However, DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died. The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died, a finding supported by PCA. The application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF. Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died. DBN-based analyses might lead to a better prediction of outcome in PALF, and could also have more general utility in other complex diseases with an inflammatory etiology.

  12. Analysis of serum inflammatory mediators identifies unique dynamic networks associated with death and spontaneous survival in pediatric acute liver failure.

    Directory of Open Access Journals (Sweden)

    Nabil Azhar

    Full Text Available Tools to predict death or spontaneous survival are necessary to inform liver transplantation (LTx decisions in pediatric acute liver failure (PALF, but such tools are not available. Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure. We hypothesized that specific, dynamic, and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF.We assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group (PALFSG collected within 7 days after enrollment. Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors, non-survivors, and LTx recipients. Data were subjected to statistical analysis, patient-specific Principal Component Analysis (PCA, and Dynamic Bayesian Network (DBN inference.Raw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes. However, DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died. The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died, a finding supported by PCA.The application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF. Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died. DBN-based analyses might lead to a better prediction of outcome in PALF, and could also have more general utility in other complex diseases with an inflammatory etiology.

  13. Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist

    Directory of Open Access Journals (Sweden)

    Hui-Hui Tan

    2011-01-01

    Full Text Available Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.

  14. Effects of long-term parenteral nutrition on serum lipids, plant sterols, cholesterol metabolism, and liver histology in pediatric intestinal failure.

    Science.gov (United States)

    Kurvinen, Annika; Nissinen, Markku J; Gylling, Helena; Miettinen, Tatu A; Lampela, Hanna; Koivusalo, Antti I; Rintala, Risto J; Pakarinen, Mikko P

    2011-10-01

    Plant sterols (PS) in parenteral nutrition (PN) may contribute to intestinal failure-associated liver disease. We investigated interrelations between serum PS, liver function and histology, cholesterol metabolism, and characteristics of PN. Eleven patients with intestinal failure (mean age 6.3 years) receiving long-term PN were studied prospectively (mean 254 days) and underwent repeated measurements of serum lipids, noncholesterol sterols, including PS, and liver enzymes. PS contents of PN were analyzed. Liver biopsy was obtained in 8 patients. Twenty healthy children (mean age 5.7 years) served as controls. Median percentage of parenteral energy of total daily energy (PN%) was 48%, including 0.9 g · kg(-1) · day(-1) of lipids. Respective amounts of PN sitosterol, campesterol, avenasterol, and stigmasterol were 683, 71, 57, and 45 μg · kg(-1) · day(-1). Median serum concentrations of sitosterol (48 vs 7.5 μmol/L, P liver enzymes remained close to normal range. Glutamyl transferase correlated with serum PS (r = 0.61-0.62, P Liver fibrosis in 5 patients reflected increased serum PS (r = 0.55-0.60, P = 0.16-0.12). Serum PS moderately increase during olive oil-based PN, and correlate positively with PN% and glutamyl transferase. Despite well-preserved liver function, histology often revealed significant liver damage.

  15. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism.

    Directory of Open Access Journals (Sweden)

    C Alexander Valencia

    Full Text Available The etiology of acute liver failure (ALF remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism.Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis.A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA content <30% of controls, and reduced respiratory chain complex activity; both patients had good post-transplant outcome. One infant with severe lactic acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy.Targeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF.

  16. Clinical effect of artificial liver support system on serum hs-CRP level in patients with hepatic failure

    Directory of Open Access Journals (Sweden)

    DONG Dandan

    2014-10-01

    Full Text Available ObjectiveTo evaluate the clinical effect of artificial liver support system (ALSS on serum high-sensitivity C-reactive protein (hs-CRP level and investigate the influence of the change in hs-CRP level on clinical prognosis among patients with hepatic failure. MethodsPatients were recruited into three groups: group one included 60 patients who received ALSS due to hepatic failure; group two included 37 patients with hepatic failure without ALSS treatment; and group three included 37 patients with chronic hepatitis B. The serum levels of hs-CRP were measured in groups two and three, and in group one before and after ALSS treatment. Comparison of continuous data between groups was made by t test, and comparison of categorical data was made by chi-square test. ResultsThe levels of hs-CRP in group one before treatment and in groups two and three were 12.89±9.39, 12.22±9.73, and 2.83±6.79, respectively. No significant difference in hs-CRP level between group one and group two was observed (P>0.05. However, the hs-CRP level in group three was significantly different from those in group one and group two (P<0.001. The improvement rate in group one after ALSS treatment (783% was significantly higher compared with that in group two (54.05% (χ2=6.315, P<0.05. ALSS treatment (t=5.179, P<0.05. ALSS treatment was selectively effective in a subgroup of patients and greatly decreased the hs-CRP level in these patients (t=5344,P=0.000), resulting in a significant difference from the patients who were unresponsive to ALSS treatment (t=2.368, P=0038. ConclusionArtificial liver support system can decrease the hs-CRP level in patients with hepatic failure. Serum level of hs-CRP can be used as a clinical indicator of disease progression and predict the clinical outcomes of ALSS in patients with hepatic failure.

  17. Effect of nitric oxide pathway regulation on water/sodium balance and renal function in a rodent model of acute liver and renal failure.

    Science.gov (United States)

    Saracyn, Marek; Ząbkowski, Tomasz; Zdanowski, Robert; Brytan, Marek; Patera, Janusz; Nowak, Zbigniew; Kade, Grzegorz; Wańkowicz, Zofia

    2014-09-27

    The pathomechanism of acute hepatorenal syndrome (HRS), a particular form of acute renal failure that occurs in the course of acute liver injury, is still poorly understood. The aim of our study was to estimate the influence of the activation and inhibition of the nitric oxide pathway on the water/sodium balance and development of acute renal failure in the course of HRS. We used male Sprague-Dawley rats in the acute galactosamine (Ga1N) model of HRS. The nitric oxide synthase (NOS) inhibitors L-NAME and L-arginine were administered intraperitoneally before and after liver damage. HRS developed in all tested groups. L-NAME increased osmotic clearance and urine volume more effectively before liver injury. Furthermore, administration of L-NAME increased creatinine clearance both before and after Ga1N injection. A double dose of L-NAME did not yield further improvement before Ga1N injection, but improved creatinine clearance after Ga1N intoxication. Injection of L-arginine increased sodium excretion and urine volume, but only after liver injury. Moreover, L-arginine injected after Ga1N caused significant improvement of the creatinine clearance in a dose-dependent manner. Our study shows that inhibition of the nitric oxide pathway improves parameters of water and sodium balance and prevents development of acute renal failure in the course of acute liver injury and liver failure. Activation of the nitric oxide system also has a favorable influence on water/sodium balance and renal failure, but only after liver injury.

  18. The Prometheus device for extracorporeal support of combined liver and renal failure.

    Science.gov (United States)

    Rifai, Kinan; Ernst, Thomas; Kretschmer, Ulrich; Hafer, Carsten; Haller, Hermann; Manns, Michael Peter; Fliser, Danilo

    2005-01-01

    Prometheus is a newly developed extracorporeal liver support system that combines removal of albumin-bound substances (adsorption on resin adsorbers) and water-soluble substances (diffusion during high-flux hemodialysis). Therefore, it is a promising treatment option for patients with hepatorenal syndrome (HRS). We studied 10 patients with HRS in a prospective clinical study. All patients underwent 2 consecutive Prometheus treatments. A variety of clinical and biochemical parameters were assessed. Prometheus treatment was uncomplicated and safe. A statistically significant improvement of serum creatinine and urea concentrations as well as blood pH was observed after Prometheus treatment. Furthermore, liver detoxification was supported by a significant decrease of serum levels of conjugated bilirubin, bile acids and ammonia. Prometheus is a safe treatment for patients with HRS. Both, albumin-bound and water-soluble substances were effectively removed. Controlled studies will evaluate the effect of this new treatment option on survival in patients with HRS. (c) 2005 S. Karger AG, Basel.

  19. CIRCULATING LEVELS OF SOLUBLE RAGE AND RAGE-LIGANDS IN PATIENTS WITH ACUTE LIVER FAILURE

    OpenAIRE

    Basta, Giuseppina; Turco, Serena Del; Navarra, Teresa; Lee, William M

    2015-01-01

    Animal studies suggest that receptor for advanced glycation end-product (RAGE)-dependent mechanisms contribute to acetaminophen-induced liver damage. We examined whether circulating levels of soluble RAGE (sRAGE) or RAGE ligands including extracellular newly identified RAGE binding protein (EN-RAGE), High-Mobility Group Box 1 (HMGB1) and Nɛ-(Carboxymethyl) lysine-adducts (CML), could aid prognostication following acetaminophen overdose.

  20. Liver transplantation in the context of organ shortage: toward extension and restriction of indications considering recent clinical data and ethical framework.

    Science.gov (United States)

    Lucidi, Valerio; Gustot, Thierry; Moreno, Christophe; Donckier, Vincent

    2015-04-01

    The scarcity of liver grafts requires to optimize the results of transplantation. Extensions and alternatives of liver transplantation have to be regularly evaluated. Acute-on-chronic liver failure and severe alcoholic hepatitis may represent potential extensions of transplant indications. In these diseases, selected patients could obtain a significant benefit from liver transplantation, whereas long-term outcomes and global impact on waiting lists remain to be evaluated prospectively. Alternatives to transplantation may be represented by recent progress in the management of hepatitis C and the treatment of hepatocellular carcinoma. In hepatitis C, new drug combinations may improve the disease control, reducing the progression to cirrhosis and also the risk of post-transplant reinfection allowing to anticipate a future decrease in the indications for transplantation and retransplantation in these patients. In hepatocellular carcinoma, thanks to improvements in operative techniques and better identification of prognostic factors of cancer recurrency, surgical resection or radiofrequency destruction could appear now as true alternatives to transplant in highly selected patients. Before implementation of these potential changes into decisional algorithms for listing and organ allocation, their consequences, either for patient's individual benefit or for global transplant outcomes, should be closely evaluated using objective long-term end points and taking into account the ethical recommendations for organ transplantation.

  1. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

    Directory of Open Access Journals (Sweden)

    Marco A De León-Nava

    Full Text Available We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group. Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT levels, CYP2E1 protein, interleukin (IL- 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group, whereas only one-third of uninfected animals exposed to acetaminophen (APAP group died. Uninfected (Control group and infected (Tc group mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

  2. Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells

    NARCIS (Netherlands)

    Cano, N.; Sturm, J. M.; Meijer, A. J.; El-Mir, M. Y.; Novaretti, R.; Reynier, J. P.; Leverve, X. M.

    2004-01-01

    Background Et aims: Decreased ureagenesis and gluconeogenesis from atanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. Methods: In hepatocytes

  3. Parvovirus B19 in an Immunocompetent Adult Patient with Acute Liver Failure: An Underdiagnosed Cause of Acute Non-A-E Viral Hepatitis

    Directory of Open Access Journals (Sweden)

    J Kee Ho

    2005-01-01

    Full Text Available There are occasional pediatric reports of parvovirus B19-associated transient acute hepatitis and hepatic failure. A case of a 34-year-old immunocompetent woman who developed severe and prolonged but self-limited acute hepatitis and myelosuppression following acute parvovirus B19 infection is reported. Parvovirus B19 may be the causative agent in some adult cases of acute non-A-E viral hepatitis and acute liver failure.

  4. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

    Directory of Open Access Journals (Sweden)

    Olympia Anastasiou

    Full Text Available Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS, have been described in many diseases. However, the relationship between acute liver failure (ALF and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR. TSH, free thyroxine (fT4, free triiodothyronine (fT3, T4, and T3 were determined.More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

  5. CPAP by helmet for treatment of acute respiratory failure after pediatric liver transplantation.

    Science.gov (United States)

    Chiusolo, F; Fanelli, V; Ciofi Degli Atti, M L; Conti, G; Tortora, F; Pariante, R; Ravà, L; Grimaldi, C; de Ville de Goyet, J; Picardo, S

    2018-02-01

    ARF after pediatric liver transplantation accounts for high rate of morbidity and mortality associated with this procedure. The role of CPAP in postoperative period is still unknown. The aim of the study was to describe current practice and risk factors associated with the application of helmet CPAP. In this retrospective observational cohort study, 119 recipients were divided into two groups based on indication to CPAP after extubation. Perioperative variables were studied, and determinants of CPAP application were analyzed in a multivariate logistic model. Sixty patients (60/114) developed ARF and were included in the CPAP group. No differences were found between the two groups for primary disease, graft type, and blood product transfused. At multivariate analysis, weight 148 mL/kg (OR = 4.0; 95% CI = 1.6-10.1; P = .004) were the main determinants of CPAP application. In the CPAP group, five patients (8.4%) needed reintubation. Pediatric liver recipients with lower weight, higher need of inotropes/vasopressors, higher positive fluid balance after surgery, and lower PaO 2 /FiO 2 before extubation were at higher odds of developing ARF needing CPAP application. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Acute liver failure in a patient with sickle cell/β+ thalassaemia

    International Nuclear Information System (INIS)

    Wigg, A.J.; Mounkley, A.D.; Cochlan, D.; Somers, S.

    2001-01-01

    We describe a rare, severe, vaso-occlusive presentation of sickle cell disease, named sickle cell intrahepatic cholestasis (SCIC). Patients with sickle cell/β + thalassaemia frequently have mild vaso-occlusive symptoms and only one case of SCIC developing in a patient with sickle cell/β + thalassaemia has been previously described in the world literature. The present report represents only the second described case of SCIC in a patient with sickle cell/β + thalassaemia. An abdominal computed tomography scan and Doppler ultrasound studies demonstrated massive hepatomegaly (25 cm span). Liver biopsy was performed and demonstrated dilatation and congestion of erythrocytes, severe cholestasis and fibrosis. The case demonstrates the importance of early recognition and institution of adequate therapy. Initial and correct diagnosis does not require biopsy or surgery which carry substantial risks of bleeding and mortality

  7. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Abidullah Khan

    2016-01-01

    Full Text Available Background. Hyperammonemia resulting from chronic liver disease (CLD can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33±7.60. The mean duration (years of CLD was 10.15±3.53 while the mean Child-Pugh (CP score was 8.84±3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE. The frequency of hyperammonemia was 67.3%, more frequent in males (N=81, z-score = 2.4, and P<0.05 than in females (N=34, z-score = 2.4, and P<0.05, and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2 = 27.46, P<0.001, Phi = 0.40, and P<0.001. Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P<0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy.

  8. Variability of resting energy expenditure in infants and young children with intestinal failure-associated liver disease.

    Science.gov (United States)

    Duro, Debora; Mitchell, Paul D; Mehta, Nilesh M; Bechard, Lori J; Yu, Yong-Ming; Jaksic, Tom; Duggan, Christopher

    2014-05-01

    The aim of the study was to determine, in a cohort of young children with intestinal failure (IF), whether the estimates of basal metabolic rate (BMR) by standard equations can approximate measured resting energy expenditure (REE) by indirect calorimetry (IC). IC was performed using the dilutional canopy technique. REE measurements were compared with standard, age-based estimation equations (World Health Organization) for BMR. Subjects were classified as hypermetabolic (REE > 110% BMR), hypometabolic (REE BMR), or normal (REE = 90%-110% BMR). Twenty-eight IF patients (11 girls, 17 boys) had an underlying diagnosis of necrotizing enterocolitis (n = 10) or a congenital gastrointestinal defect (n = 18). Median age was 5.3 months. Median interquartile range (IQR) REE was 46 (42-58) kcal · kg · day. Median (IQR) total energy intake provided 209% (172%-257%) of REE, with parenteral nutrition providing 76% (23%) of total energy intake. REE was variable, with 39% (n = 11) of measurements hypermetabolic, 39% (n = 11) hypometabolic, and the remaining 21% (n = 6) normal. Although REE was well correlated with estimated BMR (r = 0.82, P BMR was not consistently an adequate predictor of REE. BMR over- or underestimated REE by >10 kcal · kg · day in 15 of 28 (54%) patients. REE was not significantly correlated with severity of liver disease, nutritional status, total energy intake, or gestational age. Energy expenditure is variable among children with IF and IF-associated liver disease, with approximately 80% of our cohort exhibiting either hypo- or hypermetabolism. Standard estimation equations frequently do not correctly predict individual REE. Longitudinal studies of energy expenditure and body composition may be needed to guide provision of nutrition regimens.

  9. The clinical features and outcomes of acute liver failure associated with dengue infection in adults: a case series

    Directory of Open Access Journals (Sweden)

    Soek-Siam Tan

    Full Text Available OBJECTIVE: To describe the clinical manifestations and outcome of acute liver failure (ALF associated with dengue viral infection, a rare but severe complication. METHODS: One hundred and fifty five consecutive patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described. RESULTS: All patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum age was 33.5 (17, 47 years with 50% female. The median (minimum, maximum duration from the onset of fever to development of ALF was 7.5 (5, 13 days and the maximum hepatic encephalopathy (HE grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase [median admission 1140.5 u/L (639, 4161; median peak 2487 u/L (998, 5181], serum bilirubin [median admission 29 µmol/L (23, 291; median peak 127 µmol/L (72, 592], and prothrombin time [median admission 16.8 s (15.3, 26.2; median peak 22 s (15.3, 40.7]. The survival rate with standard medical therapy alone was 100%. CONCLUSIONS: Dengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.

  10. Failure of nonoperative management of pediatric blunt liver and spleen injuries: A prospective Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium study.

    Science.gov (United States)

    Linnaus, Maria E; Langlais, Crystal S; Garcia, Nilda M; Alder, Adam C; Eubanks, James W; Maxson, R Todd; Letton, Robert W; Ponsky, Todd A; St Peter, Shawn D; Leys, Charles; Bhatia, Amina; Ostlie, Daniel J; Tuggle, David W; Lawson, Karla A; Raines, Alexander R; Notrica, David M

    2017-04-01

    Nonoperative management (NOM) is standard of care for most pediatric blunt liver and spleen injuries (BLSI); only 5% of patients fail NOM in retrospective reports. No prospective studies examine failure of NOM of BLSI in children. The aim of this study was to determine the frequency and clinical characteristics of failure of NOM in pediatric BLSI patients. A prospective observational study was conducted on patients 18 years or younger presenting to any of 10 Level I pediatric trauma centers April 2013 and January 2016 with BLSI on computed tomography. Management of BLSI was based on the Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium pediatric guideline. Failure of NOM was defined as needing laparoscopy or laparotomy. A total of 1008 patients met inclusion; 499 (50%) had liver injury, 410 (41%) spleen injury, and 99 (10%) had both. Most patients were male (n = 624; 62%) with a median age of 10.3 years (interquartile range, 5.9, 14.2). A total of 69 (7%) underwent laparotomy or laparoscopy, but only 34 (3%) underwent surgery for spleen or liver bleeding. Other (nonexclusive) operations were for 21 intestinal injuries; 15 hematoma evacuations, washouts, or drain placements; 9 pancreatic injuries; 5 mesenteric injuries; 3 diaphragm injuries; and 2 bladder injuries. Patients who failed were more likely to receive blood (52 of 69 vs. 162 of 939; p liver or spleen injury. For children failing NOM due to bleeding, the mortality was 24%. Therapeutic study, level II.

  11. A switch in the source of ATP production and a loss in capacity to perform glycolysis are hallmarks of hepatocyte failure in advance liver disease.

    Science.gov (United States)

    Nishikawa, Taichiro; Bellance, Nadège; Damm, Aaron; Bing, Han; Zhu, Zhen; Handa, Kan; Yovchev, Mladen I; Sehgal, Vasudha; Moss, Tyler J; Oertel, Michael; Ram, Prahlad T; Pipinos, Iraklis I; Soto-Gutierrez, Alejandro; Fox, Ira J; Nagrath, Deepak

    2014-06-01

    The cause of hepatic failure in the terminal stages of chronic injury is unknown. Cellular metabolic adaptations in response to the microenvironment have been implicated in cellular breakdown. To address the role of energy metabolism in this process we studied mitochondrial number, respiration, and functional reserve, as well as cellular adenosine-5'-triphosphate (ATP) production, glycolytic flux, and expression of glycolysis related genes in isolated hepatocytes from early and terminal stages of cirrhosis using a model that produces hepatic failure from irreversible cirrhosis in rats. To study the clinical relevance of energy metabolism in terminal stages of chronic liver failure, we analyzed glycolysis and energy metabolism related gene expression in liver tissue from patients at different stages of chronic liver failure according to Child-Pugh classification. Additionally, to determine whether the expression of these genes in early-stage cirrhosis (Child-Pugh Class A) is related to patient outcome, we performed network analysis of publicly available microarray data obtained from biopsies of 216 patients with hepatitis C-related Child-Pugh A cirrhosis who were prospectively followed up for a median of 10years. In the early phase of cirrhosis, mitochondrial function and ATP generation are maintained by increasing energy production from glycolytic flux as production from oxidative phosphorylation falls. At the terminal stage of hepatic injury, mitochondria respiration and ATP production are significantly compromised, as the hepatocytes are unable to sustain the increased demand for high levels of ATP generation from glycolysis. This impairment corresponds to a decrease in glucose-6-phosphatase catalytic subunit and phosphoglucomutase 1. Similar decreased gene expression was observed in liver tissue from patients at different stages of chronic liver injury. Further, unbiased network analysis of microarray data revealed that expression of these genes was down

  12. Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications.

    Directory of Open Access Journals (Sweden)

    Anne Chastre

    Full Text Available Acute liver failure (ALF due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE, a serious neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM hepatotoxicity.Mice were administered saline or etanercept (10 mg/kg; i.p. 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001 and CD40L levels (3.7-fold; p<0.001 compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05, attenuated microglial activation (assessed by OX-42 immunoreactivity, and increased brain glutathione concentrations.These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting liver transplantation.

  13. Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats.

    Science.gov (United States)

    Cauli, Omar; López-Larrubia, Pilar; Rodrigo, Regina; Agusti, Ana; Boix, Jordi; Nieto-Charques, Laura; Cerdán, Sebastián; Felipo, Vicente

    2011-02-01

    Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans blue-albumin extravasation. Increased IP arises from an early increase of blood-brain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Cirrhotic Multiorgan Syndrome

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming

    2015-01-01

    complications such as hepatorenal syndrome. In patients with chronic organ dysfunction, various precipitating events may induce an acute-on-chronic renal failure and acute-on-chronic liver failure that negatively affect the prognosis. Future research on the pathophysiologic mechanisms of the complications...

  15. Predictors of failure of fish-oil therapy for intestinal failure–associated liver disease in children12

    OpenAIRE

    Nandivada, Prathima; Baker, Meredith A; Mitchell, Paul D; O’Loughlin, Alison A; Potemkin, Alexis K; Anez-Bustillos, Lorenzo; Carlson, Sarah J; Dao, Duy T; Fell, Gillian L; Gura, Kathleen M; Puder, Mark

    2016-01-01

    Background: Parenteral fish-oil (FO) therapy is a safe and effective treatment for intestinal failure–associated liver disease (IFALD). Patients whose cholestasis does not resolve with FO may progress to end-stage liver disease.

  16. Galactose protects hepatocytes against TNF-α-induced apoptosis by promoting activation of the NF-κB signaling pathway in acute liver failure.

    Science.gov (United States)

    Liu, Yanmin; Zhu, Liuluan; Liang, Shuntao; Yao, Shanshan; Li, Rui; Liu, Sanhai; Ma, Yaluan; Zhou, Xiaobing; Zhang, Jinliang; Zeng, Hui; Wang, Xianbo

    2015-05-01

    Saccharides are reported to protect hepatocytes from acute liver injury through distinct mechanisms. To date, the protective role of galactose against acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) has been attributed to competition with D-GalN. Here, we showed that in addition to its effects on LPS/D-GalN and tumor necrosis factor alpha (TNF-α)/D-GalN models, galactose improves hepatic injury in mice challenged with LPS alone or TNF-α/actinomycin D. Consistent with this result, galactose enhanced the viability of TNF-α-stimulated Chang Liver and Hu7.5 hepatic cell lines. Specifically, galactose prevented TNF-α-induced apoptosis of hepatocytes through promoting phosphorylation of nuclear factor kappa B (NF-κB) p65. Additionally, galactose enhanced expression of the anti-apoptotic genes, c-IAP1 and A20, and inhibited cleavage of caspase-8 and caspase-3. These findings collectively suggest that galactose prevents TNF-α-induced liver injury through activation of the NF-κB signaling pathway. Considering that monosaccharides protect against liver injury via distinct mechanisms, these compounds may represent a promising clinical approach to treat acute liver failure.

  17. A pilot study of autologous CD34-depleted bone marrow mononuclear cell transplantation via the hepatic artery in five patients with liver failure.

    Science.gov (United States)

    Park, Chung-Hwa; Bae, Si Hyun; Kim, Hee Yeon; Kim, Ja Kyung; Jung, Eun Sun; Chun, Ho Jong; Song, Myeong Jun; Lee, Sung-Eun; Cho, Seok Goo; Lee, Jong Wook; Choi, Jong Young; Yoon, Seung Kew; Han, Nam Ik; Lee, Young Sok

    2013-12-01

    Many rodent experiments and human studies on stem cell therapy have shown promising therapeutic approaches to liver diseases. We investigated the clinical outcomes of five patients with liver failure of various causes who received autologous CD34-depleted bone marrow-derived mononuclear cell (BM-MNC) transplantation, including mesenchymal stromal cells, through the hepatic artery. CD34-depleted BM-MNCs were obtained from five patients waiting for liver transplantation by bone marrow aspiration and using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Bergisch Gladbach, Germany), and autologous hepatic artery infusion was performed. The causes of hepatic decompensation were hepatitis B virus (HBV), hepatitis C virus (HCV), propylthiouracil-induced toxic hepatitis and Wilson disease. Serum albumin levels improved 1 week after transplantation from 2.8 g/dL, 2.4 g/dL, 2.7 g/dL and 1.9 g/dL to 3.3 g/dL, 3.1 g/dL, 2.8 g/dL and 2.6 g/dL. Transient liver elastography data showed some change from 65 kPa, 33 kPa, 34.8 kPa and undetectable to 46.4 kPa, 19.8 kPa, 29.1 kPa and 67.8 kPa at 4 weeks after transplantation in a patient with Wilson disease, a patient with HCV, and two patients with HBV. Ascites decreased in two patients. One of the patients with HBV underwent liver transplantation 4 months after the infusion, and the hepatic progenitor markers (cytokeratin [CD]-7, CD-8, CD-9, CD-18, CD-19, c-Kit and epithelial cell adhesion molecule [EpCAM]) were highly expressed in the explanted liver. Serum albumin levels, liver stiffness, liver volume, subjective healthiness and quality of life improved in the study patients. Although these findings were observed in a small population, the results may suggest a promising future for autologous CD34-depleted BM-MNC transplantation as a bridge to liver transplantation in patients with liver failure. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  18. Immune- and Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants of Herpes Simplex Virus-Induced Generalized Infections and Acute Liver Failure.

    Science.gov (United States)

    Parker, Zachary M; Pasieka, Tracy Jo; Parker, George A; Leib, David A

    2016-12-01

    The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR -/- mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR -/- (AG129) and wild-type (WT; 129SvEv) mice to probe the underlying IFN-dependent mechanisms that control HSV-1 pathogenesis. After infection, WT mice with either IFN-αβγR -/- or WT marrow exhibited comparable survival, while IFN-αβγR -/- mice with WT marrow had a significant survival advantage over their counterparts with IFN-αβγR -/- marrow. Furthermore, using bioluminescent imaging to maximize data acquisition, we showed that the transfer of IFN-competent hematopoietic cells controlled HSV-1 replication and damage in the livers of IFN-αβγR -/- mice. Consistent with this, the inability of IFN-αβγR -/- immune cells to control liver infection in IFN-αβγR -/- mice manifested as profoundly elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels, indicative of severe liver damage. In contrast, IFN-αβγR -/- mice receiving WT marrow exhibited only modest elevations of AST and ALT levels. These studies indicate that IFN responsiveness of the immune system is a major determinant of viral tropism and damage during visceral HSV infections. Herpes simplex virus 1 (HSV-1) infection is an incurable viral infection with the most significant morbidity and mortality occurring in neonates and patients with compromised immune systems. Severe pathologies from HSV include the blindness

  19. Peroxisome proliferator-activated receptor alpha acts as a mediator of endoplasmic reticulum stress-induced hepatocyte apoptosis in acute liver failure

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2016-07-01

    Full Text Available Peroxisome proliferator-activated receptor α (PPARα is a key regulator to ameliorate liver injury in cases of acute liver failure (ALF. However, its regulatory mechanisms remain largely undetermined. Endoplasmic reticulum stress (ER stress plays an important role in a number of liver diseases. This study aimed to investigate whether PPARα activation inhibits ER stress-induced hepatocyte apoptosis, thereby protecting against ALF. In a murine model of D-galactosamine (D-GalN- and lipopolysaccharide (LPS-induced ALF, Wy-14643 was administered to activate PPARα, and 4-phenylbutyric acid (4-PBA was administered to attenuate ER stress. PPARα activation ameliorated liver injury, because pre-administration of its specific inducer, Wy-14643, reduced the serum aminotransferase levels and preserved liver architecture compared with that of controls. The protective effect of PPARα activation resulted from the suppression of ER stress-induced hepatocyte apoptosis. Indeed, (1 PPARα activation decreased the expression of glucose-regulated protein 78 (Grp78, Grp94 and C/EBP-homologous protein (CHOP in vivo; (2 the liver protection by 4-PBA resulted from the induction of PPARα expression, as 4-PBA pre-treatment promoted upregulation of PPARα, and inhibition of PPARα by small interfering RNA (siRNA treatment reversed liver protection and increased hepatocyte apoptosis; (3 in vitro PPARα activation by Wy-14643 decreased hepatocyte apoptosis induced by severe ER stress, and PPARα inhibition by siRNA treatment decreased the hepatocyte survival induced by mild ER stress. Here, we demonstrate that PPARα activation contributes to liver protection and decreases hepatocyte apoptosis in ALF, particularly through regulating ER stress. Therefore, targeting PPARα could be a potential therapeutic strategy to ameliorate ALF.

  20. Failure to Rescue as a Quality Improvement Approach in Transplantation: A First Effort to Evaluate This Tool in Pediatric Liver Transplantation.

    Science.gov (United States)

    Cramm, Shannon L; Waits, Seth A; Englesbe, Michael J; Bucuvalas, John C; Horslen, Simon P; Mazariegos, George V; Soltys, Kyle A; Anand, Ravinder; Magee, John C

    2016-04-01

    Significant intercenter variation exists in mortality and death-censored graft loss (DCGL) after transplantation. Failure to rescue (FTR, death after a major complication) is an emerging tool in quality improvement and may underlie this variation. This study is the first effort to investigate the relationship between FTR and outcomes in transplantation to assess its utility in care improvement. Using the Studies of Pediatric Liver Transplantation database, we identified 2330 children undergoing primary liver transplants at 21 centers. Centers were ranked by risk-adjusted mortality and sorted into tertiles. We then compared mortality, complications, and FTR across tertiles. Overall mortality was 4.9%, ranging from 1.4% to 8.1% in the low and high mortality tertiles (P pediatric liver transplantation recipients. This preliminary study indicates that FTR may provide a useful quality improvement tool for the field of transplantation and warrants further investigation.

  1. Novel syndrome of four-limb proximal fragility fractures associated with HIV infection, cholestatic liver failure, and histiocytic infiltration of bone marrow.

    Science.gov (United States)

    Yu, Run; Nissen, Nicholas N; Balzer, Bonnie; Fan, Xuemo

    2012-01-01

    We report a syndrome of four-limb proximal fragility fractures associated with HIV infection, cholestatic liver failure, and histiocytic infiltration of bone marrow in a 40-year-old African American man. The patient presented with multiple fractures in the proximal humeri and femurs without osteopenia in the vertebrae. His right humerus appeared normal on chest X-ray film 3 years before presentation when he was first diagnosed with HIV infection and abnormal liver functions. At presentation, the patient had vitamin D deficiency, hypogonadism, and low IGF- 1 levels, but did not have hyperparathyroidism. Bone biopsy showed diffuse foamy histiocytic infiltration of bone marrow at all fracture sites without evidence of infectious or neoplastic processes. Exhaustive search did not identify any similar cases in the English literature. Our case likely represents a novel syndrome, the etiology of which is probably multifactorial and includes HIV infection, cholestatic liver failure, immobility, and endocrine abnormalities. The case further calls for the need for monitoring of bone health in patients with HIV infection or liver disease.

  2. Hemoadsorption of high-mobility-group box 1 using a porous polymethylmethacrylate fiber in a swine acute liver failure model.

    Science.gov (United States)

    Amemiya, Ryusuke; Shinoda, Masahiro; Yamada, Masayuki; Ueno, Yoshiyuki; Shimada, Kaoru; Fujieda, Hiroaki; Yagi, Hiroshi; Mizota, Takamasa; Nishiyama, Ryo; Oshima, Go; Yamada, Shingo; Matsubara, Kentaro; Abe, Yuta; Hibi, Taizo; Kitago, Minoru; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

    2018-04-01

    High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber. First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model. Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column. The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.

  3. NLRP3 inflammasome activation in D-galactosamine and lipopolysaccharide-induced acute liver failure: role of heme oxygenase-1.

    Science.gov (United States)

    Kim, Seok-Joo; Lee, Sun-Mee

    2013-12-01

    D-Galactosamine (GalN) and lipopolysaccharide (LPS) are commonly used to study mechanisms of hepatic malfunction that result in hepatic inflammation and subsequent fulminant hepatic failure. Inflammasomes are intracellular multiprotein complexes that in response to cellular danger signals trigger the biological maturation of proinflammatory cytokines. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that induces anti-inflammatory and antioxidant activity against oxidative cellular stress. This study examined activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in GalN/LPS-induced hepatic injury and the role of HO-1 in the signaling pathways of inflammasome. Mice (C57BL/6) were pretreated twice with hemin (HO-1 inducer, 30 mg/kg) and zinc protoporphyrin (ZnPP; HO-1 inhibitor, 10mg/kg) at 12 and 2h before GalN (800 mg/kg)/LPS (40 μg/kg) administration. HO-1 induction with hemin reversed the lethality induced by GalN/LPS administration, and ZnPP pretreatment blocked this change. Lipid peroxidation markedly increased after GalN/LPS treatment, whereas glutathione content decreased in the GalN/LPS group. These changes were attenuated by hemin, but ZnPP reversed the effects of hemin. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β increased after GalN/LPS treatment; these increases were attenuated by hemin. Hepatic mRNA levels of TNF-α, IL-1β, and NLRP3 increased after GalN/LPS treatment, and hemin attenuated increases in TNF-α and IL-1β. After GalN/LPS treatment, the hepatic expression of NLRP3, ASC, and caspase-1 (p10) was increased. In immunoprecipitation studies, hemin attenuated the interaction of NLRP3 with ASC and caspase-1. GalN/LPS induced expression of the thioredoxin-interacting protein (TXNIP) gene and the interaction between NLRP3 and TXNIP; again, hemin attenuated these effects. The effects of hemin were reversed by ZnPP. Our findings suggest that activation of the NLRP3 inflammasome leads

  4. A.S.P.E.N. clinical guidelines: support of pediatric patients with intestinal failure at risk of parenteral nutrition-associated liver disease.

    Science.gov (United States)

    Wales, Paul W; Allen, Nancy; Worthington, Patricia; George, Donald; Compher, Charlene; Teitelbaum, Daniel

    2014-07-01

    Children with severe intestinal failure and prolonged dependence on parenteral nutrition are susceptible to the development of parenteral nutrition-associated liver disease (PNALD). The purpose of this clinical guideline is to develop recommendations for the care of children with PN-dependent intestinal failure that have the potential to prevent PNALD or improve its treatment. A systematic review of the best available evidence to answer a series of questions regarding clinical management of children with intestinal failure receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. (1) Is ethanol lock effective in preventing bloodstream infection and catheter removal in children at risk of PNALD? (2) What fat emulsion strategies can be used in pediatric patients with intestinal failure to reduce the risk of or treat PNALD? (3) Can enteral ursodeoxycholic acid improve the treatment of PNALD in pediatric patients with intestinal failure? (4) Are PNALD outcomes improved when patients are managed by a multidisciplinary intestinal rehabilitation team? © 2014 American Society for Parenteral and Enteral Nutrition.

  5. THE SUCCESSFUL TREATMENT OF A PERIPHERAL VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION FOR SEVERE ACUTE RESPIRATORY FAILURE IN THE EARLY PERIOD AFTER ADULT LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2014-01-01

    Full Text Available Aim: of our clinical study was to present own experience of veno-venous extracorporeal membrane oxygenation (VV ECMO for the treatment of an adult patient (female, 28 yrs, 150 cm, 35 kg with acute respiratory distress syndrome (ARDS in the early period after liver transplantation against satisfactory liver graft function. Materials and methods. Double-lumen cannula 22 F was placed percutaneously in the right internal jugular vein. The ext- racorporeal contour reduced in length and the polymethylpeptene oxygenator (priming volume 175 ml were also. Results. In 1 hour after the beginning of VV ECMO, we registered the noted improvement of arterial blood gas and acid-base balance (regress of respiratory acidosis, improvement of arterial oxygenation which allowed us to use the «protective» mode of mechanical ventilation. Improvement of gas exchange and regress of clinical and radiological manifestations of ARDS allowed for VV ECMO weaning and decannulation on day 7. The patient was discharged from ICU and then from our Centre to a homestay respectively on the 9th and 16th day after VV ECMO weaning with the satisfactory liver graft and lungs function. Conclusion. VV ECMO can be successfully applied to correct the life-threatening acute respiratory failure in the early period after liver transplantation. 

  6. Domino Liver Transplantation from a Child with Propionic Acidemia to a Child with Idiopathic Fulminant Hepatic Failure

    Directory of Open Access Journals (Sweden)

    Marina Moguilevitch

    2018-01-01

    Full Text Available Domino liver transplant has emerged as a viable strategy to increase the number of grafts available for transplantation. In the domino transplant organs explanted from one patient are transplanted into another patient. The first successful domino liver transplant was performed in Portugal in 1995. Since then this innovative concept has been applied to several genetic or biochemical disorders that are treated by liver transplantation. An important consideration during this operation is that such livers can pose a risk of the de novo development of the disease in the recipient. That is why this surgical procedure requires careful planning, proper selection of the patients, and informed consent of both donor and recipient.

  7. Transplantation of Porcine Hepatocytes Cultured with Polylactic Acid-O-Carboxymethylated Chitosan Nanoparticles Promotes Liver Regeneration in Acute Liver Failure Rats

    Directory of Open Access Journals (Sweden)

    Zhong Chen

    2011-01-01

    Full Text Available In this study, free porcine hepatocytes suspension (Group A, porcine hepatocytes embedded in collagen gel (Group B, porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel (Group C, and PLA-O-CMC nanoparticles alone (Group D were transplanted into peritoneal cavity of ALF rats, respectively. The result showed that plasma HGF levels were elevated post-transplantation with a peak at 12 hr. The rats in Group C showed highest plasma HGF levels at 2, 6, 12, 24 and 36 hr post-transplantation and lowest HGF level at 48 hr. Plasma VEGF levels were elevated at 48 hr post-transplantation with a peak at 72 hr. The rats in Group C showed highest plasma HGF levels at 48, 72, and 96 hr post-transplantation. The liver functions in Group C were recovered most rapidly. Compared with Group B, Group C had significant high liver Kiel 67 antigen labeling index (Ki-67 LI at day 1 post-HTx (P<.05. Ki-67 LI in groups B and C was higher than that in groups A and D at days 5 and 7 post-HTx. In conclusion, intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can promote significantly liver regeneration in ALF rats.

  8. A Single Case of Rosai-Dorfman Disease Marked by Pathologic Fractures, Kidney Failure, and Liver Cirrhosis Treated with Single-Agent Cladribine

    Directory of Open Access Journals (Sweden)

    Koji eSasaki

    2014-10-01

    Full Text Available Rosai-Dorfman disease (RDD is a proliferative histiocytic disorder of unknown etiology which is characterized by sinus histiocytosis with massive lymphadenopathy. In most cases, RDD has a benign course and treatment is not necessary. However, severe cases of RDD require treatment, and the treatment strategy is determined on the basis of the severity of the disease or the extranodal involvement of vital organs. We report a single case of RDD with atypical presentation of persistent constitutional symptoms, progressing pathologic fractures, and end-organ dysfunction, including acute kidney failure and liver cirrhosis with esophageal varices.

  9. Loss of ileum decreases serum fibroblast growth factor 19 in relation to liver inflammation and fibrosis in pediatric onset intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2015-06-01

    The pathogenesis of intestinal failure (IF) associated liver disease (IFALD) is uncertain, we therefore investigated the role of FGF19 and pro-inflammatory cytokines has on this disease state. Serum FGF19, IL-6 and, TNF-α were measured in 52 IF patients at median age 6.0 years (IQR 2.2-13) after 10 months (4.1-39) on parenteral nutrition (PN). Thirty-nine patients underwent liver biopsies. In IF patients, FGF19 concentrations were lower and those of IL-6 and TNF-α higher compared to healthy matched controls (p ⩽ 0.001 for all). FGF19 concentrations were further decreased in patients without a remaining ileum [37 pg/ml (IQR 30-68) vs. 74 (35-135) p=0.028], and correlated with remaining ileum length (r = 0.333, p = 0.018) and markers of cholesterol synthesis (r = -0.552 to -0.643, p pediatric onset of IF, total or partial loss of ileum decreases serum FGF19 concentration corresponding to hepatic inflammation and fibrosis, along with increased cholesterol synthesis. In contrast, serum IL-6 increases during PN and may associate with concurrent cholestasis. These data suggests that FGF19 may contribute to the pathogenesis of IFALD. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  10. The dimethylarginine (ADMA)/nitric oxide pathway in the brain and periphery of rats with thioacetamide-induced acute liver failure: Modulation by histidine.

    Science.gov (United States)

    Milewski, Krzysztof; Hilgier, Wojciech; Albrecht, Jan; Zielińska, Magdalena

    2015-09-01

    Hepatic encephalopathy (HE) is related to variations in the nitric oxide (NO) synthesis and oxidative/nitrosative stress (ONS), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases (NOSs). In the present study we compared the effects of acute liver failure (ALF) in the rat TAA model on ADMA concentration in plasma and cerebral cortex, and on the activity and expression of the ADMA degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), in brain and liver. ALF increased blood and brain ADMA, and the increase was correlated with decreased DDAH activity in both brain and liver. An i.p. administration of histidine (His), an amino acid reported to alleviate oxidative stress associated with HE (100 mg/kg b.w.), reversed the increase of brain ADMA, which was accompanied by the recovery of brain DDAH activity (determined ex vivo), and with an increase of the total NOS activity. His also activated DDAH ex vivo in brain homogenates derived from control and TAA rats. ALF in this model was also accompanied by increases of blood cyclooxygenase activity and blood and brain TNF-α content, markers of the inflammatory response in the periphery, but these changes were not affected by His, except for the reduction of TNF-α mRNA transcript in the brain. His increased the total antioxidant capacity of the brain cortex, but not of the blood, further documenting its direct neuroprotective power. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    International Nuclear Information System (INIS)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

    2016-01-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

  12. The extent of intestinal failure-associated liver disease in patients referred for intestinal rehabilitation is associated with increased mortality: an analysis of the pediatric intestinal failure consortium database.

    Science.gov (United States)

    Javid, Patrick J; Oron, Assaf P; Duggan, Christopher; Squires, Robert H; Horslen, Simon P

    2017-09-05

    The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome. The multicenter, retrospective Pediatric Intestinal Failure Consortium (PIFCon) database was used to identify all subjects with baseline bilirubin data. Conjugated bilirubin (CBili) was used as a marker for IFALD, and we stratified baseline bilirubin values as CBili4 mg/dL. The association between baseline CBili and mortality was examined using Cox proportional hazards regression. Of 272 subjects in the database, 191 (70%) children had baseline bilirubin data collected. 38% and 28% of patients had CBili >4 mg/dL and CBili 4 mg/dL, prematurity, race, and small bowel atresia. On regression analysis controlling for age, prematurity, and diagnosis, the risk of mortality was increased by 3-fold for baseline CBili 2-4 mg/dL (HR 3.25 [1.07-9.92], p=0.04) and 4-fold for baseline CBili >4 mg/dL (HR 4.24 [1.51-11.92], p=0.006). On secondary analysis, CBili >4 mg/dL at baseline was associated with a lower chance of attaining enteral autonomy. In children with intestinal failure treated at intestinal rehabilitation programs, more advanced IFALD at referral is associated with increased mortality and decreased prospect of attaining enteral autonomy. Early referral of children with intestinal failure to intestinal rehabilitation programs should be strongly encouraged. Treatment Study, Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Transcriptome Analysis of Porcine PBMCs Reveals the Immune Cascade Response and Gene Ontology Terms Related to Cell Death and Fibrosis in the Progression of Liver Failure

    Directory of Open Access Journals (Sweden)

    YiMin Zhang

    2018-01-01

    Full Text Available Background. The key gene sets involved in the progression of acute liver failure (ALF, which has a high mortality rate, remain unclear. This study aims to gain a deeper understanding of the transcriptional response of peripheral blood mononuclear cells (PBMCs following ALF. Methods. ALF was induced by D-galactosamine (D-gal in a porcine model. PBMCs were separated at time zero (baseline group, 36 h (failure group, and 60 h (dying group after D-gal injection. Transcriptional profiling was performed using RNA sequencing and analysed using DAVID bioinformatics resources. Results. Compared with the baseline group, 816 and 1,845 differentially expressed genes (DEGs were identified in the failure and dying groups, respectively. A total of five and two gene ontology (GO term clusters were enriched in 107 GO terms in the failure group and 154 GO terms in the dying group. These GO clusters were primarily immune-related, including genes regulating the inflammasome complex and toll-like receptor signalling pathways. Specifically, GO terms related to cell death, including apoptosis, pyroptosis, and autophagy, and those related to fibrosis, coagulation dysfunction, and hepatic encephalopathy were enriched. Seven Kyoto Encyclopedia of Genes and Genomes (KEGG pathways, cytokine-cytokine receptor interaction, hematopoietic cell lineage, lysosome, rheumatoid arthritis, malaria, and phagosome and pertussis pathways were mapped for DEGs in the failure group. All of these seven KEGG pathways were involved in the 19 KEGG pathways mapped in the dying group. Conclusion. We found that the dramatic PBMC transcriptome changes triggered by ALF progression was predominantly related to immune responses. The enriched GO terms related to cell death, fibrosis, and so on, as indicated by PBMC transcriptome analysis, seem to be useful in elucidating potential key gene sets in the progression of ALF. A better understanding of these gene sets might be of preventive or

  14. Predicting outcome on admission and post-admission for acetaminophen-induced acute liver failure using classification and regression tree models.

    Directory of Open Access Journals (Sweden)

    Jaime Lynn Speiser

    Full Text Available Assessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF patients often presents significant challenges. King's College (KCC has been validated on hospital admission, but little has been published on later phases of illness. We aimed to improve determinations of prognosis both at the time of and following admission for APAP-ALF using Classification and Regression Tree (CART models.CART models were applied to US ALFSG registry data to predict 21-day death or liver transplant early (on admission and post-admission (days 3-7 for 803 APAP-ALF patients enrolled 01/1998-09/2013. Accuracy in prediction of outcome (AC, sensitivity (SN, specificity (SP, and area under receiver-operating curve (AUROC were compared between 3 models: KCC (INR, creatinine, coma grade, pH, CART analysis using only KCC variables (KCC-CART and a CART model using new variables (NEW-CART.Traditional KCC yielded 69% AC, 90% SP, 27% SN, and 0.58 AUROC on admission, with similar performance post-admission. KCC-CART at admission offered predictive 66% AC, 65% SP, 67% SN, and 0.74 AUROC. Post-admission, KCC-CART had predictive 82% AC, 86% SP, 46% SN and 0.81 AUROC. NEW-CART models using MELD (Model for end stage liver disease, lactate and mechanical ventilation on admission yielded predictive 72% AC, 71% SP, 77% SN and AUROC 0.79. For later stages, NEW-CART (MELD, lactate, coma grade offered predictive AC 86%, SP 91%, SN 46%, AUROC 0.73.CARTs offer simple prognostic models for APAP-ALF patients, which have higher AUROC and SN than KCC, with similar AC and negligibly worse SP. Admission and post-admission predictions were developed.• Prognostication in acetaminophen-induced acute liver failure (APAP-ALF is challenging beyond admission • Little has been published regarding the use of King's College Criteria (KCC beyond admission and KCC has shown limited sensitivity in subsequent studies • Classification and Regression Tree (CART methodology allows the

  15. Doppler ultrasound velocities and resistive indexes immediately after pediatric liver transplantation: normal ranges and predictors of failure.

    Science.gov (United States)

    Jamieson, Lucy H; Arys, Bo; Low, Gavin; Bhargava, Ravi; Kumbla, Surekha; Jaremko, Jacob L

    2014-07-01

    We sought to determine the ranges of Doppler ultrasound findings immediately after pediatric liver transplantation that are associated with successful outcomes or postoperative complications. This study included consecutive children who underwent Doppler ultrasound less than 48 hours after liver transplantation from 2001 to 2011. Operative reports and clinical outcome data were recorded. We had 110 patients (54% girls) with mean age at transplantation of 2.9 years (median, 1.3 years; range, 0-14 years) and a median follow-up interval of 3.5 years. Two pediatric radiologists reviewed ultrasound images in consensus. We computed descriptive statistics, interindex correlations, and analysis of variance. Twenty-four of 110 patients had a vascular complication, most commonly hepatic arterial thrombosis (seven patients). Compared with published adult normal values, normal pediatric Doppler parameters at postoperative day 1 trended toward higher normal velocities and resistive indexes (up to 0.95). Absent or low-velocity common hepatic artery flow less than 50 cm/s or a common hepatic artery resistive index less than 0.50 were significantly associated with hepatic artery thrombosis, whereas absent or low-velocity portal venous flow less than 30 cm/s or low-velocity hepatic venous flow less than 25 cm/s were significantly associated with vascular complications and a monotonic hepatic venous waveform was significantly associated with venous complications. Flow in a pediatric liver on the first day after transplantation is normally hyperdynamic, especially in the youngest transplant recipients, and, as a result, low velocities or resistive indexes are particularly concerning for complications. The pediatric-specific ranges of expected posttransplantation Doppler ultrasound findings presented in this article should assist in identifying normal variation and potentially life-threatening complications.

  16. [Neonatal hemochromatosis: Another entity that is no longer orphan. Advances in the diagnosis and management of the main cause of neonatal acute liver failure].

    Science.gov (United States)

    Molera Busoms, C; Quintero Bernabeu, J; Martín de Carpi, J

    2015-09-01

    Neonatal hemochromatosis is the most common cause of acute liver failure in the neonatal period. It is associated with high morbidity and mortality due to iron overload in hepatic and extra-hepatic tissues. New evidence has emerged during the last few years as regards its alloimmune etiology, which have had an important repercussion on the diagnosis, treatment and prognosis of these patients. Treatment with immunoglobulins and exchange transfusions has radically changed the prognosis without liver transplant. Another great success has been the preventive use of immunoglobulin in pregnant women with a past history of neonatal hemochromatosis, thus decreasing the rate of disease recurrence up to 70%. This new paradigm has led to an entity with a poor prognosis becoming a curable disease if diagnosed and treated early. Nevertheless, a large widespread ignorance of the disease persists, with medical implications that result in significant health problems, due to the delayed referral of these patients to specialized centers. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  17. Utility of the Mayo End-Stage Liver Disease (MELD score in assessing prognosis of patients with alcoholic hepatitis

    Directory of Open Access Journals (Sweden)

    Patel Tushar

    2002-01-01

    Full Text Available Abstract Background Alcoholic hepatitis is characterized by acute, or acute-on-chronic hepatic failure and associated with a high mortality. Specific therapies should be considered for those at high risk of mortality. The Mayo End-Stage Liver Disease (MELD score is a marker of disease severity and mortality in persons with chronic alcoholic liver disease. Our aims were to assess the utility of the MELD score as a predictor of short-term mortality in persons with alcoholic hepatitis. Methods We assessed the utility of the MELD score and compared it with the Discriminant Function (DF as a predictor of mortality in 34 patients hospitalized with alcoholic hepatitis. Results The area under the curve of a receiver operating characteristic curve for the MELD score was 0.82 (confidence intervals 0.65–0.98, and for the DF was 0.86 (confidence intervals 0.70–1.00. However, the sensitivity and specificity in predicting 30-day mortality for a MELD score of greater than 11 was 86% and 81%, but for a DF greater than 32 was 86% and 48% respectively. The presence of ascites and bilirubin greater than 8 mg/dL were also highly predictive of mortality with a sensitivity of 71% and a specificity of 96%. Conclusions Alcoholic hepatitis remains associated with a high mortality in hospitalized patients. The MELD score performs as well as the DF in predicting mortality at 30 days. A MELD score of greater than 11, or the presence of both ascites and an elevated bilirubin greater than 8 mg/dL should prompt consideration of specific therapeutic interventions to reduce mortality.

  18. Acute renal failure and renal replacement therapy in the postoperative period of orthotopic liver transplant patients versus nonelective abdominal surgery patients.

    Science.gov (United States)

    Biagioni, E; Cavazzuti, I; Busani, S; Trevisan, D; Zavatti, L; Ferrari, E; Girardis, M; Massimo, G

    2011-05-01

    Acute renal failure (ARF) often complicates the postoperative period of patients undergoing orthotopic liver transplantation (OLT); it is habitually associated with high mortality rates. Similarly, patients undergoing major nonelective abdominal surgery are prone to ARF because of their frequent preexistent morbidities, abdominal sepsis, and needed for extended surgical procedures. The aim of this study was to evaluate the incidence of ARF and use of renal replacement therapy (RRT) among OLT versus nonelective abdominal surgery patients and associations with clinical outcomes. We studied all the patients admitted to a surgical intensive care unit (ICU) from January 2008 to December 2009 after OLT or nonelective abdominal surgery. The inclusion criteria were an ICU stay of at least 48 hours and without prior end-stage renal failure. OLT patients (n=84) were younger and less severly ill than surgery patients (n=60). ARF occurrence was lower among the OLT (29%) than the surgery group (47%) requiring RRT in 71% and 53% of patients due to ARF, respectively. The ICU mortality of ARF patients in both groups (29% OLT and 51% surgery) were greater than among subjects without ARF (2% and 6%). The occurrence of ARF is common among these two patient groups, and associated with increased risk of death among in surgery (+45%) versus in OLT (+27%) patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Decline in HAV-associated fulminant hepatic failure and liver transplant in children in Argentina after the introduction of a universal hepatitis A vaccination program

    Directory of Open Access Journals (Sweden)

    Cervio G

    2011-09-01

    Full Text Available Guillermo Cervio1, Julio Trentadue2, Daniel D'Agostino3, Carlos Luque4, Mariano Giorgi5, Judith Armoni6, Roberto Debbag6 1Unidad de Transplante Hepatico, Hospital Prof Dr Juan P Garrahan, 2Unidad de Terapia Intensiva, Hospital Universitario Fundación Favaloro, 3Unidad de Gastroenterología, Hospital Italiano De Buenos Aires, 4Unidad de Transplante Hepatico, Hospital Universitario Austral, 5Departamento de Farmacologia, Escuela de Medicina de la Universidad Austral, 6Sanofi Pasteur, Buenos Aires, Argentina Introduction: Hepatitis A virus (HAV infection is a vaccine-preventable disease. The most severe complication in children is fulminant hepatic failure (FHF, estimated to occur in 0.4% of cases; patients with FHF often require a liver transplant (LT. Following another outbreak of HAV infection in Argentina during 2003–2004, a one-dose HAV universal immunization (UI program was started in 2005, resulting in a reduction in the incidence of HAV infection. We have investigated the impact of HAV UI on the trends in the occurrence of FHF and LT in children. Methods: All pediatric cases of FHF admitted to four pediatric centers in Buenos Aires during March 1993–July 2005 were retrospectively reviewed, and data of cases during August 2005–December 2008 were collected. Information about demography, HAV infections and vaccination status, diagnostic data for FHF using the Pediatric Acute Liver Failure criteria, clinical laboratory results, encephalopathy, the severity of liver disease using the Pediatric End Stage Liver Disease score, assessment of patients on the LT waiting list using King's College Criteria for LT, treatment given for FHF (pre- and post-transplant, and clinical outcome were collected using a case report form. The frequency and outcomes of HAV-associated FHF and LT cases before and after UI were analyzed. Results: During the pre-immunization period, March 1993–July 2005, 54.6% (N = 165 of FHF cases were caused by HAV; HAV

  20. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within

  1. Liver disease in menopause.

    Science.gov (United States)

    Brady, Carla W

    2015-07-07

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

  2. Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure.

    Science.gov (United States)

    Valbusa, Filippo; Bonapace, Stefano; Agnoletti, Davide; Scala, Luca; Grillo, Cristina; Arduini, Pietro; Turcato, Emanuela; Mantovani, Alessandro; Zoppini, Giacomo; Arcaro, Guido; Byrne, Christopher; Targher, Giovanni

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, pacute HF.

  3. Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure.

    Science.gov (United States)

    Chiang, Chih-Hung; Wu, Wai-Wah; Li, Hsin-Yang; Chien, Yueh; Sun, Cho-Chin; Peng, Chi-Hsien; Lin, Alex Tong-Long; Huang, Chi-Shuan; Lai, Ying-Hsiu; Chiou, Shih-Hwa; Hung, Shuen-Iu; Chang, Yuh-Lih; Lan, Yuan-Tzu; Liu, Dean-Mo; Chien, Chian-Shiu; Huo, Teh-Ia; Lee, Shou-Dong; Wang, Chien-Ying

    2015-01-01

    Acute hepatic failure (AHF) is a severe liver injury leading to sustained damage and complications. Induced pluripotent stem cells (iPSCs) may be an alternative option for the treatment of AHF. In this study, we reprogrammed human dental pulp-derived fibroblasts into iPSCs, which exhibited pluripotency and the capacity to differentiate into tridermal lineages, including hepatocyte-like cells (iPSC-Heps). These iPSC-Heps resembled human embryonic stem cell-derived hepatocyte-like cells in gene signature and hepatic markers/functions. To improve iPSC-Heps engraftment, we next developed an injectable carboxymethyl-hexanoyl chitosan hydrogel (CHC) with sustained hepatocyte growth factor (HGF) release (HGF-CHC) and investigated the hepatoprotective activity of HGF-CHC-delivered iPSC-Heps in vitro and in an immunocompromised AHF mouse model induced by thioacetamide (TAA). Intrahepatic delivery of HGF-CHC-iPSC-Heps reduced the TAA-induced hepatic necrotic area and rescued liver function and recipient viability. Compared with PBS-delivered iPSC-Heps, the HGF-CHC-delivered iPSC-Heps exhibited higher antioxidant and antiapoptotic activities that reduced hepatic necrotic area. Importantly, these HGF-CHC-mediated responses could be abolished by administering anti-HGF neutralizing antibodies. In conclusion, our findings demonstrated that HGF mediated the enhancement of iPSC-Hep antioxidant/antiapoptotic capacities and hepatoprotection and that HGF-CHC is as an excellent vehicle for iPSC-Hep engraftment in iPSC-based therapy against AHF.

  4. Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum.

    Directory of Open Access Journals (Sweden)

    Santosh Singh

    Full Text Available BACKGROUND AND PURPOSE: Liver dysfunction led hyperammonemia (HA causes a nervous system disorder; hepatic encephalopathy (HE. In the brain, ammonia induced glutamate-excitotoxicity and oxidative stress are considered to play important roles in the pathogenesis of HE. The brain ammonia metabolism and antioxidant enzymes constitute the main components of this mechanism; however, need to be defined in a suitable animal model. This study was aimed to examine this aspect in the rats with acute liver failure (ALF. METHODS: ALF in the rats was induced by intraperitoneal administration of 300 mg thioacetamide/Kg. b.w up to 2 days. Glutamine synthetase (GS and glutaminase (GA, the two brain ammonia metabolizing enzymes vis a vis ammonia and glutamate levels and profiles of all the antioxidant enzymes vis a vis oxidative stress markers were measured in the cerebral cortex and cerebellum of the control and the ALF rats. RESULTS: The ALF rats showed significantly increased levels of ammonia in the blood (HA but little changes in the cortex and cerebellum. This was consistent with the activation of the GS-GA cycle and static levels of glutamate in these brain regions. However, significantly increased levels of lipid peroxidation and protein carbonyl contents were consistent with the reduced levels of all the antioxidant enzymes in both the brain regions of these ALF rats. CONCLUSION: ALF activates the GS-GA cycle to metabolize excess ammonia and thereby, maintains static levels of ammonia and glutamate in the cerebral cortex and cerebellum. Moreover, ALF induces oxidative stress by reducing the levels of all the antioxidant enzymes which is likely to play important role, independent of glutamate levels, in the pathogenesis of acute HE.

  5. Serum testosterone levels and androgen receptor CAG polymorphism correlate with hepatitis B virus (HBV-related acute liver failure in male HBV carriers.

    Directory of Open Access Journals (Sweden)

    Bao-Yan Xu

    Full Text Available BACKGROUND: Augmentation of androgen/androgen receptor (AR pathway may influence chronic hepatitis B (CHB more likely in males. AR activity is modulated by a polymorphic CAG repeat sequence in AR exon 1. This study aimed to investigate the relationship between serum testosterone levels, CAG repeat numbers and hepatitis B virus (HBV-related acute liver failure (ALF. METHODS: Three hundred and seventy eight male CHB patients with ALF and 441 asymptomatic HBV carriers (AsCs were recruited. AR CAG repeats numbers were analyzed. The serum testosterone levels of AsCs, ALFs and patients with hepatitis B flare groups, and sequential serum samples, were assessed quantitatively. RESULTS: The median CAG repeat (M-CAG frequency was significantly higher in ALF patients than AsCs (P<0.001. Patients with M-CAG alleles (P<0.001, OR 3.0, 95% CI 2.1-4.2 had the highest risk for ALF. Serum testosterone levels were significantly higher (P<0.001 at hepatitis flare point (8.2 ± 3.0 ng/mL than inactive phase (6.4 ± 2.0 ng/mL. CHB (8.30 ± 2.71 ng/mL, P = 7.6 × 10(-6 and ALF group (2.61 ± 1.83 ng/mL, P = 1.7 × 10(-17 had significantly different levels of testosterone in comparison with AsCs group (6.56 ± 2.36 ng/mL. The serum testosterone levels sharply decreased from hepatitis flare phase to liver failure phase, and tended to be normal at the recovery phase. Male AsCs with M-CAG alleles had significantly lower serum testosterone levels (P<0.05. CONCLUSIONS: There was a serum testosterone fluctuation during hepatitis B flare and HBV-related ALF, and the median CAG repeats in AR gene exon 1 were associated with lower serum testosterone levels in asymptomatic HBV carriers and an increased susceptibility to HBV-related ALF.

  6. Intraparenchymal intracranial pressure monitoring in patients with acute liver failure Monitoreo intraparenquimatoso de presión intracraneana en pacientes con falla hepática aguda

    Directory of Open Access Journals (Sweden)

    Alejandra T. Rabadán

    2008-06-01

    Full Text Available BACKGROUND: Elevated intracranial pressure (ICP is a common cause of death in acute liver failure (ALF and is determinant for decision-making regarding the timing of liver transplantation. The recommended type ICP monitoring device is controversial in ALF patients. Epidural devices had less risk of hemorrhagic complications, but they are less reliable than intraparenchymal ones. METHOD: Twenty-three patients with ALF were treated, and 19 of them received a liver transplant. Seventeen patients had ICP monitoring because of grade III-IV encephalopathy. All patients received fresh plasma (2-3 units before and during placing the intraparenchymal device. RESULTS: Eleven cases (64.7% had elevated ICP, and 6 patients (35.2% had normal values. One patient (5.9% had an asymptomatic small intraparenchymal haemorrhage ANTECEDENTES: La presión intracraneana elevada (PIC es una causa frecuente de muerte en la falla hepática aguda (FHA y es determinante para la toma de decisiones respecto del momento del transplante hepático. El tipo de dispositivo para el monitoreo de OIC es controversial em los pacientes em FHA. Los dispositivos epidurales tienen menos riesgo de complicaciones hemorrágicas, pero son menos confiables que los intraparenquimatosos. MÉTODO: Veintitrés pacientes con FHA fueron tratados, y 19 de ellos recibieron un transplante hepático. diecisiete pacientes tuvieron monitoreo de PIC debido a encefalopatía grado III-IV. Todos los pacientes recibieron plasma fresco (2-3 unidades antes y durante la colocación de la fibra intraparenquimatosa. RESULTADOS: Once casos (64.7% tuvieron PIC elevada, y 6 pacientes (35.2% tuvieron valores normales. Un paciente (5.9% tuvo una pequeña hemorragia intraparenquimatosa asintomática <1cm³ en TAC, la cual no impidió el transplante hepático. CONCLUSIÓN: En nuestra experiencia, el monitoreo intraparenquimatoso de presión intracraneana en pacientes con FHA parece ser un método preciso y con bajo riesgo

  7. Post-operative delayed elevation of ALT correlates with early death in patients with HBV-related hepatocellular carcinoma and Post-hepatectomy Liver Failure.

    Science.gov (United States)

    Yu, Liang-He; Yu, Wen-Long; Zhao, Teng; Wu, Meng-Chao; Fu, Xiao-Hui; Zhang, Yong-Jie

    2018-01-16

    Post-hepatectomy Liver Failure (PHLF) remains the primary cause of perioperative death. The kinetics of transaminase levels are usually measured as markers of hepatocellular injury following partial hepatectomy, but their correlation with PHLF and post-operative mortality is unclear. The aim of study was to compare the post-operative transaminase kinetics with short term survival in those patients that developed PHLF. A retrospective review of patients with HBV-related HCC and who developed PHLF was performed. Logistic regression analysis was conducted to analyze risk factors for postoperative delayed elevation of ALT (PDE-ALT) PHLF and lethal PHLF. Of the 69 patients who developed PHLF 36 (52%) died. In those patients who died the mean ± SD ALT and AST rose from day (POD) 1-3 and continued to fluctuate with highly abnormal levels beyond day 3 with a mean ± SD peak ALT level beyond POD 3 of 1851 ± 1644 U/L (p ALT indicates an increased risk of death in HBV-related HCC patients with PHLF. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  8. The heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Dümcke, Christine Winkler; Krag, Aleksander

    2009-01-01

    Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek...... against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease...

  9. Extracorporal hemodialysis with acute or decompensated chronical hepatic failure

    Directory of Open Access Journals (Sweden)

    Wasem, Jürgen

    2006-04-01

    Full Text Available Background: Conventional diagnostic procedures and therapy of acute liver failure (ALF and acute-on-chronic liver failure (ACLF focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can only marginally be substituted by conventional conservative therapy. To improve this component of the liver function is the main objective of extracorporal liver support systems. The following principles of liver support systems can be differentiated: Artificial systems, bioartifical systems and extracorporal liver perfusion systems. This HTA report focuses on artificial systems (e.g. BioLogic-DT/-DTPF, MARS, Prometheus, because only these approaches currently are relevant in the German health care system. In 2004 a category "Extracorporal liver assist device" was introduced in the list of "additional payments" in the German DRG-system, which makes reimbursement for hospitals using the technology in inpatient care possible, based on an hospital's individual contract with statutory sickness funds. Objectives: To report the present evidence and future research need on medical efficacy and economic effectiveness of extracorporal liver support devices for treatment of patients with ALF or ACLF based on published literature data. Are artificial liver support systems efficient and effective in the treatment of ALF or ACLF? Methods: An extensive, systematic literature search in medical, economic, and HTA literature data bases was performed. Relevant data were extracted and synthesised. Results: Relevant controlled trials were detected for BioLogic-DT and MARS. No randomised controlled trial on Prometheus was found. None of the included studies on BioLogic-DT showed

  10. Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure.

    Directory of Open Access Journals (Sweden)

    Filippo Valbusa

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is an emerging risk factor for heart failure (HF. Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR for the associations between NAFLD and the outcome(s of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes. Patients with NAFLD (n = 109; 51.4% had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, p<0.0001 after adjustment for established risk factors and potential confounders. Similar results were found for 1-year cardiac re-hospitalization (adjusted-hazard ratio 8.05, 95% confidence intervals 3.77-15.8, p<0.0001. In conclusion, NAFLD and its severity were strongly and independently associated with an increased risk of 1-year all-cause and cardiac re-hospitalization in

  11. Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice.

    Science.gov (United States)

    Gong, Xiaobao; Yang, You; Huang, Ligua; Zhang, Qingyan; Wan, Rong-Zhen; Zhang, Peng; Zhang, Baoshun

    2017-05-01

    To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/d-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/d-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E 2 (PGE 2 ). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/d-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/d-GalN-induced ALF in the future. Copyright © 2017. Published by Elsevier B.V.

  12. Intravenous Fish Oil and Pediatric Intestinal Failure-Associated Liver Disease: Changes in Plasma Phytosterols, Cytokines, and Bile Acids and Erythrocyte Fatty Acids.

    Science.gov (United States)

    Calkins, Kara L; DeBarber, Andrea; Steiner, Robert D; Flores, Martiniano J; Grogan, Tristan R; Henning, Susanne M; Reyen, Laurie; Venick, Robert S

    2017-05-01

    Soybean oil (SO) emulsions are associated with intestinal failure-associated liver disease (IFALD); fish oil (FO) emulsions are used to treat IFALD. SO and FO differ with respect to their fatty acid and phytosterol content. In children with IFALD whose SO was replaced with FO, we aimed to (1) quantify changes in erythrocyte fatty acids and plasma phytosterols, cytokines, and bile acids and (2) correlate these changes with direct bilirubin (DB). This study enrolled IFALD children who received 6 months of FO. Blood samples were collected prior to FO, and after 2 weeks and 3 and 6 months of FO. The primary outcome was 3-month vs baseline biomarker concentrations. At study initiation, the median patient age was 3 months (interquartile range, 3-17 months), and mean ± standard deviation DB was 5.6 ± 0.7 mg/dL (n = 14). Cholestasis reversed in 79% of subjects. Eicosapentaenoic and docosahexaenoic acid was greater than baseline ( P < .001, all time points). Linoleic and arachidonic acid and sitosterol and stigmasterol were less than baseline ( P < .05, all time points). Three- and 6-month interleukin-8 (IL-8) and total and conjugated bile acids were less than baseline ( P < .05). Baseline IL-8 was correlated with baseline DB ( r = 0.71, P < .01). Early changes in stigmasterol and IL-8 were correlated with later DB changes ( r = 0.68 and 0.75, P < .05). Specific fat emulsion components may play a role in IFALD. Stigmasterol and IL-8 may predict FO treatment response.

  13. The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure

    Directory of Open Access Journals (Sweden)

    Lv Sa

    2009-09-01

    Full Text Available Abstract Background Spontaneous bacterial peritonitis (SBP is a common clinical disease and one of the most severe complications of acute liver failure (ALF. Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1 protein in a mouse model of ALF. Methods We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed. Results Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1 antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. Conclusion TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.

  14. Liver Transplants for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    RJ Fingerote

    1991-01-01

    Full Text Available Alcohol related end-stage liver disease is a principal cause of liver failure. The scarcity of donor livers and the predominance of alcohol related end-stage liver disease has raised the issue of including alcoholics as candidates for liver transplantation. In rationalizing the arguments for and against the treatment of alcoholic end-stage liver disease with transplantation, factors such as recidivism, resource allocation and principles of medical practice must be considered. Public confidence in organ transplantation depends on the scientific validity and moral integrity of the policies adopted. Sound policies will prove defensible while policies based on perceptions or prejudices will, in the long run, harm the process.

  15. Insuficiência Hepática Aguda da Gravidez Experiência Clínica com Sete Casos Acute Liver Failure of Pregnancy ¾ Clinical Experience with Seven Cases

    Directory of Open Access Journals (Sweden)

    Marcelo Perosa

    2001-04-01

    Full Text Available Objetivos: avaliar a dificuldade diagnóstica, o tratamento e seu resultado em casos de insuficiência hepática aguda da gravidez. Métodos: sete pacientes com insuficiência hepática aguda da gravidez admitidas em nosso Serviço nos últimos quatro anos foram estudadas com ênfase nos sintomas presentes, achados laboratoriais, curso clínico, complicações maternas e sobrevida fetal. Resultados: a média de idade foi de 25,8 anos (sendo duas primigestas com idade gestacional média de 30,1. Destas, quatro receberam diagnóstico final de esteatose hepática aguda da gravidez e três de colestase intra-hepática da gravidez. Os principais sinais e sintomas encontrados foram: anorexia, náusea, dor abdominal, icterícia e encefalopatia. Ocorreu morte materna em dois casos: uma paciente por falência hepática enquanto aguardava órgão para transplante e outra por falência hepática, coagulopatia grave e choque hemorrágico após biópsia hepática. Uma paciente com esteatose hepática aguda evoluiu para cronicidade e encontra-se viva um ano após transplante hepático. Nos quatro casos restantes houve completa remissão do quadro com as medidas de suporte, associadas à interrupção da gravidez. As mortalidades materna e fetal foram, respectivamente, 28,6% e 57,1%. Conclusões: concluiu-se, nesta experiência inicial, que a insuficiência hepática aguda da gravidez constitui evento clínico grave, de elevada mortalidade materno-fetal, e que seu pronto reconhecimento e encaminhamento para centros terciários especializados em fígado, além da imediata interrupção da gestação, são fatores decisivos para o sucesso do tratamento.Purpose: to evaluate the diagnostic difficulties, treatment and outcome in cases of acute liver failure of pregnancy. Methods: seven patients with acute liver failure of pregnancy, managed during the past 4 years, were studied with emphasis on presenting symptoms, laboratory findings, clinical course, maternal

  16. Liver disease associated with intestinal failure in the small bowel syndrome Doença hepática associada à falência intestinal na síndrome do intestino curto

    Directory of Open Access Journals (Sweden)

    Rafael Kemp

    2006-01-01

    Full Text Available The introduction of the Total Parenteral Nutrition (TPN has given rise to a new hope in the treatment of intestinal failure (LF associated with the Short Bowel Syndrome (SBS. However, together with the TPN and the increase of survival of these patients, new problems and questions have emerged, as well as new therapeutical procedures. Taking into consideration this emerging reality, this paper has the purpose to undertake a review of current concepts and available treatments for patients with IF associated-liver disease. Although TPN provides an increase of survival of patients with intestinal failure, it is a potential source of complication such as: septicemia, hyperglycemia, venous thrombosis and liver disease. There are several hypothesis conceived to explain the liver disease associated to intestinal failure, however the only definite treatment as a potential to reverse the non-cirrhotic liver disease is the small intestine transplantation. Despite indications for intestine transplantation are not entirely defined in literature, the trend is its early indication in high-risk patients, preserving the liver integrity and preventing the eventual need of both liver and intestine transplantations altogether.A introdução da Nutrição Parenteral Total (NPT despertou uma nova esperança para o tratamento da falência intestina (FI associada a Síndrome do Intestino Curto (SIC. No entanto, junto com a NPT e o aumento da sobrevida destes pacientes, novos problemas e perguntas emergiram, assim como novas terapêuticas. Tendo em vista esta realidade emergente, o intuito deste artigo é realizar uma revisão dos conceitos atuais e dos tratamentos disponíveis para pacientes com doença hepática associada a FI. A NPT apesar de proporcionar aumento da sobrevida nos pacientes com falência intestinal é fonte potencial de complicações, como: septicemia, hiperglicemia, trombose venosa e doença hepática. Diversas são as hipóteses aventadas para

  17. Pediatric obesity and the liver

    NARCIS (Netherlands)

    Koot, B.G.P.

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

  18. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  19. The heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Dümcke, Christine Winkler; Krag, Aleksander

    2009-01-01

    to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities, termed cirrhotic cardiomyopathy. Pathophysiological mechanisms include reduced......Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek...

  20. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage...... that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  1. Liver metastases

    Science.gov (United States)

    ... Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases ... through the probe that causes ice crystals to form around the probe. The cancer cells are frozen ...

  2. Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

    DEFF Research Database (Denmark)

    Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars

    2013-01-01

    BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39...... MP subsets were analyzed by fluorescence-activated cell sorting. RESULTS: HSC and CD133 MP levels were significantly increased only in the plasma of wild-type mice with acetaminophen hepatotoxicity (P

  3. Liver Transplantation for Cirrhosis in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    T Lamireau

    2006-01-01

    Full Text Available BACKGROUND: Liver disease is the third most common cause of death in children with cystic fibrosis (CF. Liver transplantation is an effective treatment in children with hepatic failure.

  4. Use of Pediatric Health Information System database to study the trends in the incidence, management, etiology, and outcomes due to pediatric acute liver failure in the United States from 2008 to 2013.

    Science.gov (United States)

    Kulkarni, Sakil; Perez, Carla; Pichardo, Caren; Castillo, Lina; Gagnon, Michael; Beck-Sague, Consuelo; Gereige, Rani; Hernandez, Erick

    2015-12-01

    Data were collected of children admitted with ALF to 16 US pediatric liver transplant centers from 2008 to 2013 using the PHIS for a retrospective analysis of PALF trends. Patient data linked to the principal diagnosis code for acute necrosis of the liver (570.00) were analyzed for the following: demographics, regional differences, changes over time, pharmaceutical trends, procedural trends, associated diagnoses, and patient outcomes. In 52.5% of 583 patients who met the selection criteria for PALF, the etiology remained undetermined. Acetaminophen toxicity (18.7%) was the most common identifiable etiology, and hepatic encephalopathy (38.6%) was the most common complication. Mortality was lower than previously reported; 95.4% survived and 73.2% survived without a liver transplant. Acute respiratory failure (OR = 3.4, p = 0.035), acute kidney injury (OR = 3.6, p = 0.003), and cerebral edema (OR = 3.6, p = 0.02) were independently associated with increased risk of mortality. The use of N-acetylcysteine in non-acetaminophen-related ALF, the use of intracranial pressure monitoring, and the proportion of sepsis decreased significantly during the study period. The PHIS database can be a useful tool to study the future trends of PALF patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure.

    Science.gov (United States)

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

    2016-04-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

  6. Computational Modeling in Liver Surgery

    Directory of Open Access Journals (Sweden)

    Bruno Christ

    2017-11-01

    Full Text Available The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

  7. Adult liver stem cells in hepatic regeneration and cancer

    NARCIS (Netherlands)

    Nantasanti, Sathidpak

    2015-01-01

    An alternative source of livers for transplantation in patients with (genetic) liver diseases and liver failure is needed because liver donors are scarce. HPC-derived hepatocyte-like cells could be one of the options. Because dogs and humans share liver-pathologies and disease-pathways, the dog is

  8. Current development of liver transplantation in China

    Directory of Open Access Journals (Sweden)

    ZHENG Shusen

    2014-01-01

    Full Text Available As the only effective way for the treatment of end-stage liver disease, liver transplantation has been developed rapidly in China over recent years. The latest developments of liver transplantation in China are reviewed, including establishment of selection criteria for the liver cancer recipients of liver transplantation——Hangzhou Criteria; latest application of salvage liver transplantation and downstaging therapy in liver transplantation for liver cancer; progress in liver transplantation combined with artificial liver support system for treatment of severe acute liver failure; breakthrough in technology innovation of living donor liver transplantation and organ donation and transplantation after cardiac death in China. Facing the problem of organ shortage, a scientific and standardized organ donation system should be established in line with the national conditions of China, so as to benefit the people and further improve the reputation of China in the international organ transplant community.

  9. Liver Hemangioma

    Science.gov (United States)

    Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

  10. Hydroxycut-induced Liver Toxicity

    African Journals Online (AJOL)

    hanumantp

    reducing and anti-cancer properties, contains Camellia Sinensis. There have been several cases that show an association of Camellia Sinensis with liver toxicity ranging from acute hepatitis to liver failure.[14-17]. Although, it is difficult to prove a ...

  11. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  12. Dermatose perfurante adquirida associada à insuficiência hepática em paciente transplantado de fígado Acquired perforating dermatosis associated with hepatic failure in a liver-transplanted patient

    Directory of Open Access Journals (Sweden)

    Daniela Badziak

    2007-02-01

    Full Text Available A dermatose perfurante adquirida é entidade clinicopatológica caracterizada por eliminação transepitelial de material dérmico degenerado, ocorrendo em muitas condições, entre elas diabetes mellitus, insuficiência renal crônica e colangite esclerosante. Relata-se o caso de paciente de 17 anos, com dermatose perfurante adquirida associada à insuficiência hepática crônica, conseqüente à complicação hepática de transplante de fígado para tratamento de sua doença de base, a glicogenose tipo I.Acquired perforating dermatosis is characterized by transepithelial elimination of degenerated dermal substances. It occurs in many conditions, such as: diabetes mellitus, chronic renal failure and sclerosing cholangitis. This article describes a 17-year-old Caucasian female with type I glucogenosis and acquired perforating dermatosis due to chronic hepatic failure caused by hepatic complication of liver transplant.

  13. Metabolite profiles reveal energy failure and impaired beta-oxidation in liver of mice with complex III deficiency due to a BCS1L mutation.

    Directory of Open Access Journals (Sweden)

    Heike Kotarsky

    Full Text Available BACKGROUND & AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2O(2 production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.

  14. Liver transplantion in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure Transplante hepático em um paciente com complexo parkinsonismo-demência rapidamente progressivo induzido por manganismo devido a insuficiência hepática

    Directory of Open Access Journals (Sweden)

    Giorgio Fabiani

    2007-09-01

    Full Text Available Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.Hiperintesidades simétricas e bilaterais dos gânglios da base são observadas em imagens de ressonância magnética encefálica (RM ponderadas em T1 na maioria dos pacientes com insuficiência hepática crônica devidas ao acúmulo de manganês. Nós relatamos o caso de um homem, com 53 anos de idade, com um complexo parkinsonismo-demência rapidamente progressivo associado com o acúmulo de manganês no cérebro, secundariamente a insuficiência hepática. Uma RM encefálica foi realizada e foram observadas imagens hiperintensas/hipersinal nas imagens ponderadas em T1 no globo pálido e, também, na substância branca dos hemisférios cerebrais ponderadas em T2. Devido à falta de resposta ao tratamento clinico optamos pelo transplante hepático. O paciente faleceu no 7º dia de PO. Nossos achados corroboram o conceito dos efeitos tóxicos do manganês nos gânglios da base/globo pálido. O tratamento desta forma de parkinsonismo é controverso e o transplante hepático não deverá ser considerada uma opção terapêutica de primeira linha, porém como um tratamento alternativo considerando-se os riscos

  15. Artificial liver support in the third millennium

    NARCIS (Netherlands)

    Chamuleau, Robert A. F. M.

    2003-01-01

    Analogous to the artificial kidney there is a need for an effective and safe liver support system to bridge patients with hepatic failure to liver transplantation or own liver regeneration. An over-view is given of the biological and non-biological systems used in clinical practice in the past and

  16. Wegener s granulomatosis with granulomatous liver involvement.

    Science.gov (United States)

    Holl-Ulrich, Konstanze; Klass, Monika

    2010-01-01

    We report on a patient with biopsy proven systemic Wegener's granulomatosis (WG) with a granulomatous necrotising manifestation of WG in the liver, lung, parotid gland and skin with subsequent death of liver failure. Liver involvement in WG is an exceedingly rare, though potentially fatal, organ manifestation of WG.

  17. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...... months. At present 12 patients are alive, relieved of symptoms and with good graft function. CONCLUSIONS: We conclude that patients treated for PLD by LTX have a good long-term prognosis and excellent relief of symptoms and that LTX might be considered in severe cases of PLD, where conventional surgery...

  18. Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant

    Directory of Open Access Journals (Sweden)

    Pablo Obando-Pacheco

    Full Text Available Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants.

  19. Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant.

    Science.gov (United States)

    Obando Pacheco, Pablo; Martínez-Martínez, Patricia Luisa; Pérez de Eulate Bazán, Yolanda; de la Mota Ybancos, José Luis; Milano Manso, Guillermo; Sierra Salinas, Carlos

    2016-12-01

    Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum) have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum) infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants.

  20. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    Science.gov (United States)

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Platelet-Derived Serotonin Mediates Liver Regeneration

    Science.gov (United States)

    Lesurtel, Mickael; Graf, Rolf; Aleil, Boris; Walther, Diego J.; Tian, Yinghua; Jochum, Wolfram; Gachet, Christian; Bader, Michael; Clavien, Pierre-Alain

    2006-04-01

    The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.

  2. Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition

    Science.gov (United States)

    Kuroda, Noriyuki; Inoue, Kouji; Ikeda, Tadayuki; Hara, Yaiko; Wake, Kenjiro; Sato, Tetsuji

    2014-01-01

    HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality. In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury. At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated. Administration of LPS/GalN precipitated tissue injury associated with time-dependent alteration in HMGB1 serum levels. At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci. The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine. Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method. On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR. The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL. The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence. PMID:24690901

  3. The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology.

    Science.gov (United States)

    Yamada, Yohei; Hoshino, Ken; Irie, Rie; Tomita, Hirofumi; Kato, Mototoshi; Shimojima, Naoki; Fujino, Akihiro; Hibi, Taizo; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kawachi, Shigeyuki; Tanabe, Minoru; Sakamoto, Michiie; Kitagawa, Yuko; Kuroda, Tatsuo

    2016-08-01

    The outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid-resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995-2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re-LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels

    DEFF Research Database (Denmark)

    Dao, Doan Y; Hynan, Linda S; Yuan, He-Jun

    2012-01-01

    Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements...... of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative...... immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P

  5. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  6. Therapeutic effects of the traditional medicinal plant Ipomoea stolonifera for the treatment of liver diseases

    NARCIS (Netherlands)

    Bai, Xueting

    2016-01-01

    Liver diseases are categorized into acute liver failure (ALF) and chronic liver failure (CLF). Massive cell death is a hallmark of ALF and leads to a dramatic loss of liver function. Therefore, specific interventions targeted to prevent or attenuate this massive cell death may be very effective in

  7. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  8. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

  9. Fatty Liver

    Science.gov (United States)

    ... Drug Interactions Pill Identifier Commonly searched drugs Aspirin Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News ... Rarely, fat accumulates in the liver during late pregnancy. This disorder, called fatty liver of pregnancy or ...

  10. Liver Biopsy

    Science.gov (United States)

    ... instrument called a cannula to remove the liver tissue sample. What is the liver and what does it do? ... who specializes in diagnosing diseases—looks at the tissue with a microscope and sends a report to the person's health care provider. What are the risks of liver biopsy? The risks ...

  11. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    OpenAIRE

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent signifi...

  12. Fatty Liver

    International Nuclear Information System (INIS)

    Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

    1991-01-01

    The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

  13. Acute ventilatory failure complicating obesity hypoventilation: update on a 'critical care syndrome'.

    Science.gov (United States)

    BaHammam, Ahmed

    2010-11-01

    Obesity can result in serious complications, including obesity hypoventilation syndrome (OHS). OHS patients may present with acute-on-chronic ventilatory failure, necessitating acute care management. The purpose of this review is to discuss the recent literature on acute ventilatory failure in OHS patients. Obese persons can develop acute hypercapnic respiratory failure and sleep hypoventilation due to disorders in lung mechanics, ventilatory drive, and neurohormonal and neuromodulators of breathing. Although there are no clearly defined predictors for OHS patients who are likely to develop acute hypercapnic respiratory failure, most such patients are middle-aged (mid-50s), morbidly obese, and have daytime hypercapnia, hypoxemia, and low serum pH values. Immediate ventilatory support, without sleep study confirmation, is necessary in most such patients. Patients with respiratory acidemia (pH care unit monitoring. Noninvasive application of bilevel positive airway pressure therapy is the recommended initial ventilatory support under close monitoring. Prompt initiation of noninvasive positive pressure ventilation reduces the need for invasive mechanical ventilation and rapidly improves the levels of blood gases. Obese patients with sleep hypoventilation have an increased risk of acute hypercapnic respiratory failure. Early diagnosis and implementation of noninvasive positive pressure ventilation is recommended for these patients.

  14. Combined adenovirus-mediated artificial microRNAs targeting mfgl2, mFas, and mTNFR1 protect against fulminant hepatic failure in mice.

    Directory of Open Access Journals (Sweden)

    Dong Xi

    Full Text Available Hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF has a poor prognosis with high in-hospital mortality. Hepatic and circulating inflammatory cytokines, such as fibrinogen like protein 2 (fgl2, FasL/Fas, and TNFα/TNFR1, play a significant role in the pathophysiology of ACLF. This study aimed to investigate the therapeutic effect of recombinant adenoviral vectors carrying constructed DNA code for non-native microRNA (miRNA targeting mouse fgl2 (mfgl2 or both mFas and mTNFR1 on murine hepatitis virus (MHV-3-induced fulminant hepatitis in BALB/cJ mice. Artificial miRNA eukaryotic expression plasmids against mfgl2, mFas, and mTNFR1 were constructed, and their inhibitory effects on the target genes were confirmed in vitro. pcDNA6.2-mFas-mTNFR1- miRNA,which expresses miRNA against both mFas and mTNFR1 simultaneously,was constructed. To construct a miRNA adenovirus expression vector against mfgl2, pcDNA6.2-mfgl2-miRNA was cloned using Gateway technology. Ad-mFas-mTNFR1- miRNA was also constructed by the same procedure. Adenovirus vectors were delivered by tail-vein injection into MHV-3-infected BALB/cJ mice to evaluate the therapeutic effect. 8 of 18 (44.4% mice recovered from fulminant viral hepatitis in the combined interference group treated with Ad-mfgl2-miRNA and Ad-mFas-mTNFR1-miRNA. But only 4 of 18 (22.2% mice receiving Ad-mfgl2-miRNA and 3 of 18 (16.7% mice receiving Ad-mFas-mTNFR1- miRNA survived. These adenovirus vectors significantly ameliorated inflammatory infiltration, fibrin deposition, hepatocyte necrosis and apoptosis, and prolonged survival time. Our data illustrated that combined interference using adenovirus-mediated artificial miRNAs targeting mfgl2, mFas, and mTNFR1 might have significant therapeutic potential for the treatment of fulminant hepatitis.

  15. Improved outcomes in pediatric liver transplantation for acute liver failure.

    Science.gov (United States)

    Miloh, Tamir; Kerkar, Nanda; Parkar, Sanobar; Emre, Sukru; Annunziato, Rachel; Mendez, Carlos; Arnon, Ronen; Suchy, Frederick; Rodriguez-Laiz, Gonzalo; Del Rio Martin, Juan; Sturdevant, Mark; Iyer, Kishore

    2010-11-01

    OLT is a life-saving option for ALF. To evaluate our outcomes in pediatric OLT for ALF. Retrospective review of our data between 1992 and 2007. Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty-three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one- and five-yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups. We report the largest single-center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high-risk cohort and contribute to our excellent outcomes. © 2010 John Wiley & Sons A/S.

  16. Liver Transplant

    Science.gov (United States)

    ... Nutrition Clinical Trials Primary Biliary Cholangitis Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Liver Transplant View or Print All Sections Definition & ...

  17. Acute Liver Failure in a Deployed Soldier

    Science.gov (United States)

    2017-10-13

    Maleoyl-beta-alanine 1 Pulse (Legion) Caffeine n-Hexadecanoic acid tetramethyl- ethyl ester, L-Lysine Desoxy-isosteviol methyl ester Methyl...Steviol Hydroxydehydrostevic acid Vitamin E Acetate Pantolactone 3-methyl-4-propyl-2,5-Furandione 5-hydroxymethylfurfural 2 Spark Energy 4-methyl-5...No Xplode N-Maleoyl-beta-alanine Caffeine N-Formyl-L-tyrosine 2-hydroxy-1-(hydroxymethyl) ethyl ester hexadecanoic acid 2-hydroxy-1-(hydroxymethyl

  18. Liver Transplantation Update: 2014.

    Science.gov (United States)

    Dogan, Serkan; Gurakar, Ahmet

    2015-01-01

    The first liver transplantation (LT) was performed by Thomas E Starzl five decades ago, and yet it remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF) and certain early-stage liver tumors. Post-liver transplantation survival has also dramatically improved over the last few decades despite increasing donor and recipient age and more frequent use of marginal organs to overcome the organ shortage. Currently, the overall 1 year survival following LT in the United States is reported as 85 to 90%, while the 10 years survival rate is ~50% (http://www.unos.org). The improvements are mainly due to progress in surgical techniques, postoperative intensive care, and the advent of new immunosuppressive agents. There are a number of factors that influence the outcomes prior to transplantation. Since 2002, the model for end-stage liver disease (MELD) score has been considered a predicting variable. It has been used to prioritize patients on the transplant waiting list and is currently the standard method used to assess severity in all etiologies of cirrhosis. Hepatocellular carcinoma (HCC) is the most common standard MELD exception because the MELD does not necessarily reflect the medical urgency of patients with HCC. The criteria for candidates with HCC for receiving LT have evolved over the past decade. Now, patients with HCC who do not meet the traditional Milan (MC) or UCSF criteria for LT often undergo downstaging therapy I an effort to shrink the tumor size. The shortage of donor organs is a universal problem. In some countries, the development of a deceased organ donation program has been prevented due to socioeconomic, cultural, legal and other factors. Due to the shortage of cadaveric donors, several innovative techniques have been developed to expand the organ donor pool, such as split liver grafts, marginal- or extended-criteria donors, live donor liver transplantation (LDLT), and the use

  19. Normothermic machine perfusion for donor liver preservation

    NARCIS (Netherlands)

    Tolboom, H.

    2012-01-01

    Currently, liver transplantation is the only treatment for end-stage liver failure. Unfortunately, a sever shortage of donor organs causes significant mortality amongst patients awaiting transplantation. The donor organ shortage could be alleviated by using organs that are normally not accepted for

  20. TYPICAL FORMS OF LIVER PATHOLOGY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Peter F. Litvitskiy

    2018-01-01

    Full Text Available This lecture for the system of postgraduate medical education analyzes causes, types, key links of pathogenesis, and manifestations of the main typical forms of liver pathology — liver failure, hepatic coma, jaundice, cholemia, acholia, cholelithiasis, and their complications in children. To control the retention of the lecture material, case problems and multiple-choice tests are given.

  1. Kidney Failure

    Science.gov (United States)

    ... enough red blood cells. This is called kidney failure. If your kidneys fail, you need treatment to ... providers, family, and friends, most people with kidney failure can lead full and active lives. NIH: National ...

  2. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such as ... need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  3. Liver regeneration

    NARCIS (Netherlands)

    Chamuleau, R. A.; Bosman, D. K.

    1988-01-01

    Despite great advances in analysing hemodynamic, morphological and biochemical changes during the process of liver regeneration, the exact (patho)physiological mechanism is still unknown. A short survey of literature is given of the kinetics of liver regeneration and the significance of different

  4. Clinical implications of advances in liver regeneration

    Directory of Open Access Journals (Sweden)

    Yong Jin Kwon

    2015-03-01

    Full Text Available Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

  5. Heart Failure

    DEFF Research Database (Denmark)

    Jorsal, Anders; Wiggers, Henrik; McMurray, John J V

    2018-01-01

    This article briefly discusses the epidemiology of heart failure and diabetes and summarizes the key findings from the recent cardiovascular outcome trials in patients with type 2 diabetes, with a focus on heart failure as an endpoint.......This article briefly discusses the epidemiology of heart failure and diabetes and summarizes the key findings from the recent cardiovascular outcome trials in patients with type 2 diabetes, with a focus on heart failure as an endpoint....

  6. Heart Failure

    Science.gov (United States)

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  7. Bioartificial liver support anno 2001

    NARCIS (Netherlands)

    Chamuleau, Robert A. F. M.

    2002-01-01

    Despite maximal intensive care, mortality of acute fulminant hepatic failure is high: 60%-75% in several studies. In addition patients with chronic liver insufficiency suffer from a bad quality of life: all patients suffer from fatigue; symptoms of hepatic encephalopathy, jaundice, and itching are

  8. The gut-liver axis

    NARCIS (Netherlands)

    Visschers, Ruben G. J.; Luyer, Misha D.; Schaap, Frank G.; Olde Damink, Steven W. M.; Soeters, Peter B.

    2013-01-01

    The liver adaptively responds to extra-intestinal and intestinal inflammation. In recent years, the role of the autonomic nervous system, intestinal failure and gut microbiota has been investigated in the development of hepatic, intestinal and extra-intestinal disease. The autonomic nervous system

  9. Protective effect of Coptisine from Rhizoma Coptidis on LPS/D-GalN-induced acute liver failure in mice through up-regulating expression of miR-122.

    Science.gov (United States)

    Chai, Fang-Ni; Zhang, Jiang; Xiang, Hong-Mei; Xu, He-Shan; Li, Yuan-Feng; Ma, Wen-Yu; Li, Xue-Gang; Ye, Xiao-Li

    2018-02-01

    Coptisine (COP), one of the main active ingredients of Rhizoma Coptidis, reportedly has anti-inflammatory, anti-colon cancer properties, but it remains elusive whether COP owns hepatoprotective activity. Mice were pretreated with COP for 7d prior to lipopolysaccharide/d-galactosamine (LPS/D-GalN) administration to detect the hepatic protective effects of COP. The mechanism was explored in using HepG2 cells with low level of miR-122 and LO2 cells with high level of miR-122, combining with miR-122 agomir transfection by means of detecting the expression of miR-122 and proteins, clinical index and apoptosis. COP ameliorated the LPS/D-GalN-induced liver failure by lowering serum levels of ALT and AST, raising hepatic GSH and SOD levels, and maintaining the morphology of hepatocytes, along with an increase in miR-122 expression in mice. The results in vitro indicated that, after miR-122 mimic administration, the alone treatment of COP and the co-treatment of COP and LPS transfection obviously promoted the apoptosis of HepG2, which was increased by 152.67% and 113.97% compared with NC (P LPS significantly induced the apoptosis of L02 cells, but COP treatment attenuated that of L02 cells. Further analysis showed that COP increased the miR-122 level and the expression of Bax, cleaved-casp3 and decreased Bcl-2, Bcl-xL in LPS-treated HepG2 cells. COP increased the miR-122 level but decreased the expression of TLR4, Bcl-2, Bcl-xL in LPS-treated L02 cells. COP attenuated LPS/D-GalN-induced ALF by up-regulating the level of miR-122, synergistically promoting apoptosis, and suggesting COP which showed a potential protective effect on ALF. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Hepatoadrenal syndrome in Egyptian children with liver cirrhosis ...

    African Journals Online (AJOL)

    Amel A.M. Elfaramawy

    2012-08-03

    Aug 3, 2012 ... Abstract The similarities between septic shock and liver failure led to the proposal of the term hep- atoadrenal syndrome. Adrenal insufficiency has been demonstrated in patients with severe liver disease irrespective of the presence of sepsis. The objective of this study was to evaluate children with liver cir-.

  11. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  12. Liver transplant

    Science.gov (United States)

    ... a liver becomes available. Make sure that, no matter where you are going, you can be contacted ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  13. Liver Transplant

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Liver Transplant Back In ...

  14. Enlarged Liver

    Science.gov (United States)

    ... of liver damage. Medicinal herbs. Certain herbs, including comfrey, ma huang and mistletoe, can increase your risk ... herbs to avoid include germander, chaparral, senna, mistletoe, comfrey, ma huang, valerian root, kava, celandine and green ...

  15. Paracetamol overdose: the liver unit perspective.

    LENUS (Irish Health Repository)

    Iqbal, M

    2012-09-01

    Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.

  16. <