scholarly journals The Impact of Sirolimus on hepatitis C Recurrence after Liver Transplantation

2011 ◽  
Vol 25 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Sonal Asthana ◽  
Christian Toso ◽  
Glenda Meeberg ◽  
David L Bigam ◽  
Andrew Mason ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Hepatitis C ◽  
Patient Survival ◽  
De Novo ◽  
Survival Rates ◽  
Area Under The Curve ◽  
Immunosuppressive Drugs ◽  
Initial Recurrence ◽  
The Impact

BACKGROUND: While some immunosuppression strategies may accelerate hepatitis C virus (HCV) recurrence after liver transplantation (LT), the impact of sirolimus (SRL) is not known.OBJECTIVE: To assess the risk of biopsy-proven HCV recurrence and patient survival using known and suspected risk factors for HCV recurrence as covariates.METHODS: A retrospective analysis of 141 consecutive patients, including 88 who received de novo SRL therapy, who had undergone a first LT for HCV cirrhosis was conducted. Known and suspected risk factor covariates including transplant era, donor and recipient age, Model for End-stage Liver Disease score, cold ischemia time, immunosuppressive drugs and steroid treatment rejection rates were used in the assessment.RESULTS: Overall, 72.3% of the cohort developed biopsy-proven HCV recurrence. The incidence of HCV recurrence was not significantly different for patients treated with SRL (75% versus 69.8%; P=0.5). There was no difference found for time to recurrence, nor did mean activity or fibrosis scores differ at the time of initial recurrence. However, on follow-up using serial biopsies in patients with recurrence, the mean activity and fibrosis scores were significantly lower in the SRL group. Donor age and acute rejection episodes were the only factors affecting the HCV recurrence rate (expB 1.02 [95% CI 1.01 to 1.03]); P=0.03; and expB 2.8 [95% CI 1.8 to 4.3]; P<0.01], respectively). SRL treatment did not alter patient survival rates. Among patients treated with SRL-based immunosuppression, higher drug area under the curve levels were associated with a trend to lower disease activity and fibrosis at diagnosis; however, higher SRL levels were associated with shorter recurrence-free survival (P=0.038).CONCLUSION: Results of the present analysis suggest that de novo SRL-based immunosuppression can be safely used in patients undergoing LT for HCV-associated liver disease; however, SRL-based immunosuppression did not significantly affect the timing or severity of post-transplant HCV recurrence. HCV recurrence in SRL-treated patients had lower progressive activity and fibrosis levels on serial biopsy.

scholarly journals Hepatitis C virus recurrence after liver transplantation in Hungary. Trends over the past 10 years

2013 ◽  
Vol 154 (27) ◽  
pp. 1058-1066 ◽  
Author(s):  
Fanni Gelley ◽  
György Gámán ◽  
Zsuzsanna Gerlei ◽  
Gergely Zádori ◽  
Dénes Görög ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Graft Survival ◽  
Patient Survival ◽  
De Novo ◽  
Antiviral Treatment ◽  
Survival Rates ◽  
Early Recurrence ◽  
The Past

Introduction: Management of hepatitis C virus recurrence is a challenge after liver transplantation. Aim: The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors. Method: The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012. Results: 156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p<0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p<0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p<0.001). Conclusions: Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation. Orv. Hetil., 2013, 154, 1058–1066.

DE NOVO HEPATITIS C DECREASES PATIENT SURVIVAL AFTER LIVER TRANSPLANTATION.

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S314
Author(s):  
Elisa Prados ◽  
Sonia Garcia-Vizuete ◽  
Angel Garcia-Villalon ◽  
Jose M. Moreno ◽  
Clara Salas ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C ◽  
Patient Survival ◽  
De Novo

scholarly journals A207 DE NOVO DONOR-SPECIFIC ANTIBODY FORMATION IN LIVER TRANSPLANTS: RISK FACTORS FOR DEVELOPMENT AND IMPACT ON GRAFT SURVIVAL.

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 236-237
Author(s):  
C Wang ◽  
A J Montano-Loza ◽  
P M Campbell ◽  
V Bain
Keyword(s):  
Risk Factors ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Organ Transplantation ◽  
Graft Survival ◽  
Patient Survival ◽  
De Novo ◽  
Single Center ◽  
Liver Transplants ◽  
Post Transplant

Abstract Background Antibody mediated rejection (AMR) is an area of great importance in solid organ transplantation. Donor-specific antibodies (DSA) have emerged as relevant biomarkers in predicting graft function and survival. DSA detected post-transplant may either be preformed or de novo and emerging evidence suggests de novo DSA, in particular, is associated with inferior graft outcomes. In contrast to the clear role that AMR plays in renal and thoracic organ transplantation, its importance in liver transplants remains controversial. Aims The aim of this study was to determine the risk factors associated with de novo DSA formation and to evaluate its role in determining clinical outcomes after liver transplantation. Methods This single-center retrospective study compiled data on liver transplants performed between 2005 and 2019 in Edmonton, Canada. Data collected from medical charts included gender, age at transplant, reason for transplant, and immunosuppressive regimens, among several others. The presence of DSA was determined by single antigen flow beads until 2009 and by Luminex thereafter. Potential predictors of DSA formation were evaluated using Cox proportional hazard models. Graft survival estimates were obtained using the Kaplan-Meier method and comparisons between patient groups were conducted using the log-rank test. Results Between 2005–2019, 131 patients had measurements of DSA both before and after liver transplantation. In this cohort, 17 patients (13%) tested negative on DSA screening before transplant but developed new antibodies against either Class I or Class II molecules post-transplant. Risk factor analysis revealed transplants performed in the setting of autoimmune liver disease (PSC, PBC, and autoimmune hepatitis) had higher risks of developing de novo DSA post-transplant (p=0.002. See Table 1). Graft survival probability at 5- and 10-years was 72% and 61% in those with de novo DSA formation, compared to 93% and 89% in patients without de novo DSA formation (p=0.04. See Figure 1). Overall patient survival was similar between the two groups. Conclusions In this single-center study, a transplant done in the setting of autoimmune liver disease had a higher risk of de novo DSA formation. Furthermore, de novo DSA formation lead to a decreased graft survival time in liver transplant patients but overall patient survival was not significantly decreased. A standard approach to DSA monitoring, especially in high risk populations, is required to better understand its prevalence and impact in liver transplantation. Funding Agencies None

Mechanisms of liver damage in COVID-19

2020 ◽  
Vol 1 (19) ◽  
pp. 39-46
Author(s):  
T. V. Pinchuk ◽  
N. V. Orlova ◽  
T. G. Suranova ◽  
T. I. Bonkalo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Risk Factor ◽  
Liver Disease ◽  
Liver Function ◽  
Liver Damage ◽  
The World ◽  
Coronavirus Infection ◽  
The Impact ◽  
Analyze Data

At the end of 2019, a new coronavirus (SARS-CoV-2) was discovered in China, causing the coronavirus infection COVID-19. The ongoing COVID-19 pandemic poses a major challenge to health systems around the world. There is still little information on how infection affects liver function and the significance of pre-existing liver disease as a risk factor for infection and severe COVID-19. In addition, some drugs used to treat the new coronavirus infection are hepatotoxic. In this article, we analyze data on the impact of COVID-19 on liver function, as well as on the course and outcome of COVID-19 in patients with liver disease, including hepatocellular carcinoma, or those on immunosuppressive therapy after liver transplantation.

scholarly journals THU0433 TREATMENT WITH PEGLOTICASE IMPROVES HEPATIC FIBROSIS ESTIMATED BY FIBROSIS-4 INDEX IN SUBJECTS WITH CHRONIC REFRACTORY GOUT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 454.1-454
Author(s):  
N. Schlesinger ◽  
A. Yeo ◽  
P. Lipsky
Keyword(s):  
Liver Disease ◽  
Linear Regression ◽  
Rank Order ◽  
Linear Regression Analysis ◽  
Area Under The Curve ◽  
Serum Urate ◽  
Complete Analysis ◽  
Alcoholic Fatty Liver ◽  
Significant Difference ◽  
The Impact

Background:Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD)1,2, but the relationship to fibrosis remains uncertain3. Moreover, it is not known whether lowering serum urate will affect the course of NAFLD. The availability of data from two randomized trials of pegloticase, a pegylated recombinant mammalian uricase, that profoundly decreases serum urate afforded the opportunity to test the hypothesis that lowering urate might improve NAFLD.Objectives:To determine whether treatment of chronic refractory gout patients with pegloticase was associated with improvement in NAFLD determined by Fibrosis 4 index (Fib4).Methods:Databases from patients with chronic refractory gout who participated in two randomized 6 month clinical trials (RCTs) of pegloticase were analyzed4. Sub-sets who had persistent urate lowering to levels <1 mg/dL in response to biweekly pegloticase (Responders, n=36) were compared to those who received placebo (n=43). Since liver biopsy information was not available on these subjects, we relied on Fib4, a validated non-invasive estimate of liver fibrosis in a variety of liver diseases5,6calculated from measurements of AST, ALT, platelet count and age (Age x AST/platelets x √ALT). A Fib4 value of 1.3 is an indication that further evaluation of liver disease is warranted.Results:At baseline, the mean Fib4 values were 1.40 ± 0.86 in pegloticase responders and 1.04 ± 0.53 in subjects receiving placebo. As shown in figure 1, subjects receiving placebo exhibited a change of 0.26 ± 0.41 in the Fib4 score over the six months of the RCTs compared with 0.13 ± 0.62 in the pegloticase responders (p=0.048; by linear regression). When only the subjects with a Fib4 value > 1.3 were considered, a significant difference in the change in the Fib4 values over the 6 months of the trial between pegloticase responders and those receiving placebo was also observed (-0.15 ± 0.67 vs 0.37 ± 0.42, p=0.004, by linear regression). The correlations between serum urate area under the curve (AUC) over the 6 months of the trial and the change in Fib4 value was rs=0.33, p=0.0.0004 (Spearman rank-order correlation coefficient). Finally, multiple linear regression analysis indicated serum urate AUC (as a surrogate measure for group) is the main contributor to the change in Fib4 (p=0.018 by linear regression).Conclusion:The data are consistent with the conclusion that persistent lowering of serum urate had a significant impact on Fib4 levels, implying a possible effect on the course of NAFLD. The results support a more complete analysis involving biopsy examination of the impact of urate on liver inflammation and fibrosis.References:[1]Yang C et al. PlosOne2017; 12:e0177249[2]Jaruvongvanich V et al. Eur J Gastroenterol Hepatol 2017; 29:1031[3]Jaruvongvanich V et al. Eur J Gastroenterol Hepatol 2017; 29:694[4]Sundy JS, et al. JAMA. 2011; 306 (7):711-20[5]Sterling RK et al. Hepatol 2006; 43:1317[6]Shah AG et al. Clin Gastroenterol Hepatol 2009;7:1104Disclosure of Interests: :Naomi Schlesinger Grant/research support from: Pfizer, Amgen, Consultant of: Novartis, Horizon Therapeutics, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Anthony Yeo Employee of: Horizon Therapeutics, Peter Lipsky Consultant of: Horizon Therapeutics

scholarly journals Virological Factors Associated with Failure to the Latest Generation of Direct Acting Agents (DAA) and Re-Treatment Strategy: A Narrative Review

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 432
Author(s):  
Lorenzo Onorato ◽  
Mariantonietta Pisaturo ◽  
Mario Starace ◽  
Carmine Minichini ◽  
Alessandra Di Fraia ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Clinical Problem ◽  
Narrative Review ◽  
Factors Associated ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

The availability of all oral direct acting antiviral agents (DAAs) has revolutionized the management of HCV infections in recent years, allowing to achieve a sustained virological response (SVR) in more than 95% of cases, irrespective of hepatitis C Virus (HCV) genotype or staging of liver disease. Although rare, the failure to the latest-generation regimens (grazoprevir/elbasvir, sofosbuvir/velpatasvir, pibrentasvir/glecaprevir) represents a serious clinical problem, since the data available in the literature on the virological characteristics and management of these patients are few. The aim of the present narrative review was to provide an overview of the impact of baseline RASs in patients treated with the latest-generation DAAs and to analyze the efficacy of the available retreatment strategies in those who have failed these regimens.

scholarly journals HIV and Liver transplantation: The British Columbia Experience, 2004 to 2013

2014 ◽  
Vol 25 (3) ◽  
pp. 159-162 ◽  
Author(s):  
Clara Tan-Tam ◽  
Pamela Liao ◽  
Julio S Montaner ◽  
Mark W Hull ◽  
Charles H Scudamore ◽  
...  
Keyword(s):  
British Columbia ◽  
Liver Transplantation ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Liver Transplant ◽  
Clinical Outcomes ◽  
Disease Status ◽  
Transplant Program ◽  
End Stage

BACKGROUND: The demand for definitive management of end-stage organ disease in HIV-infected Canadians is growing. Until recently, despite international evidence of good clinical outcomes, HIV-infected Canadians with end-stage liver disease were ineligible for transplantation, except in British Columbia (BC), where the liver transplant program of BC Transplant has accepted these patients for referral, assessment, listing and provision of liver allograft. There is a need to evaluate the experience in BC to determine the issues surrounding liver transplantation in HIV-infected patients.METHODS: The present study was a chart review of 28 HIV-infected patients who were referred to BC Transplant for liver transplantation between 2004 and 2013. Data regarding HIV and liver disease status, initial transplant assessment and clinical outcomes were collected.RESULTS: Most patients were BC residents and were assessed by the multidisciplinary team at the BC clinic. The majority had undetectable HIV viral loads, were receiving antiretroviral treatments and were infected with hepatitis C virus (n=16). The most common comorbidities were anxiety and mood disorders (n=4), and hemophilia (n=4). Of the patients eligible for transplantation, four were transplanted for autoimmune hepatitis (5.67 years post-transplant), nonalcoholic steatohepatitis (2.33 years), hepatitis C virus (2.25 years) and hepatitis B-delta virus coinfection (recent transplant). One patient died from acute renal failure while waiting for transplantation. Ten patients died during preassessment and 10 were unsuitable transplant candidates. The most common reason for unsuitability was stable disease not requiring transplantation (n=4).CONCLUSIONS: To date, interdisciplinary care and careful selection of patients have resulted in successful outcomes including the longest living HIV-infected post-liver transplant recipient in Canada.

scholarly journals De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation

2021 ◽  
Vol 13 (12) ◽  
pp. 1991-2004
Author(s):  
Ma Ai Thanda Han ◽  
Raquel Olivo ◽  
Catherine J Choi ◽  
Nikolaos Pyrsopoulos
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Metabolic Dysfunction

scholarly journals THERAPY OF RECURRENT HEPATITIS C AFTER TRANSPLANTATION OF THE LIVER WITH DIRECT ACTING ANTI-HEPATITIS C VIRUS DRUGS: EXPERIENCE OF THREE RUSSIAN CENTERS

2018 ◽  
Vol 23 (1) ◽  
pp. 4-14
Author(s):  
Vladimir E. Syutkin ◽  
E. N Bessonova ◽  
M. N Davydenko
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C ◽  
De Novo ◽  
Virologic Response ◽  
Resistance Mutations ◽  
Virus Genotype ◽  
Serious Adverse Events ◽  
Recurrent Hepatitis ◽  
Recurrent Hepatitis C ◽  
Direct Acting

The results of a retrospective analysis of the experience of three Russian regional liver transplantation centers in relation to antiviral therapy of recurrent hepatitis C in liver recipients are presented. There were studied six different therapeutic schedules with direct antiviral drugs (DAVD) administered in 91 patients. The frequency of the persistent virologic response in 12 weeks after the completion of therapy (PVR12) amounted to 92.3%. In recipients, the use of a combination of sofosbuvir and daclatasvir seems to be the most promising as following its administration relapses observed in only 3 out of the 57 recipients were associated with drug resistance mutations to NS5A inhibitors. There were no serious adverse events related to the use of DAVD. The frequency of the reactivation of HBV infection against the background of DAVD therapy in liver recipients did not exceed the previously reported frequency of de novo hepatitis B in non-endemic regions. In recurrent hepatitis C patients after the liver transplantation effects of both the virus genotype, the pronouncement of graft fibrosis and the addition of ribavirin, on the frequency of SVO12 have not been revealed.

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