Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation

Picciotto, Francesco; Tritto, Giovanni; Lanza, A; Addario, Luigi; Luca, Massimo De; Costanzo, Giovan Giuseppe Di; Lampasi, F.; Tartaglione, M.T.; Marsilia, Giuseppina Marino; Calise, Fulvio; Cuomo, O.; Ascione, Antonio

doi:10.1016/j.jhep.2006.10.017

Cited by 183 publications

(154 citation statements)

References 34 publications

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“…On the other hand, they stress that patients with high liver stiffness 12 months after LT are at high risk of losing their graft, thus HCV eradication should be prompted in this population. Our results support previous studies that demonstrated that SVR to antiviral therapy after transplantation results in improved clinical outcomes (8)(9)(10)(11), and reveal that the improvement in survival is mainly driven by those patients with a more severe recurrence (those with high LSM 1 year after LT). This population should be the main target to undergo treatment with new direct acting antivirals.…”

Section: Discussionsupporting

confidence: 91%

“…Indeed, recurrent hepatitis C accounts for most graft losses after LT. Patients undergoing antiviral therapy with pegylated interferon and ribavirin after transplantation achieve sustained virological response (SVR) in only 30-35% of cases (6,7) but, importantly, SVR is associated with a significant improvement in clinical outcomes (8)(9)(10)(11). For these reasons, identification of hepatitis C virus (HCV)-infected LT recipients who are at risk of losing their graft (''rapid fibrosers'') is crucial in order to indicate antiviral therapy.…”

Section: Introductionmentioning

confidence: 99%

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Liver Stiffness 1 Year After Transplantation Predicts Clinical Outcomes in Patients With Recurrent Hepatitis C

Crespo

Lens

Gambato

et al. 2014

American Journal of Transplantation

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The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C-infected and 48 non-hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ! 8.7 kPa (p < 0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM < 8.7 kPa (p < 0.001) and 63% and 64% in patients with LSM ! 8.7 kPa, respectively (p < 0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ! 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Liver Stiffness 1 Year After Transplantation Predicts Clinical Outcomes in Patients With Recurrent Hepatitis C

Crespo

Lens

Gambato

et al. 2014

American Journal of Transplantation

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“…In the univariate analysis, IFN treatment reduced the risk of decompensation in patients who achieved an SVR. Although the significance of IFN treatment was lost in the multivariate analysis because the total number of patients who achieved an SVR was small, these results are in line with recent reports of a clinical benefit of SVR after LT. 19,20 For example, recent data from Carrion et al 21 demonstrated that in LT recipients, IFN treatment slows disease progression by its effects on the histology and hepatic venous pressure gradient, particularly in those with an SVR. The effect on the hepatic venous pressure gradient is a possible explanation for the reduced risk of decompensation with IFN treatment.…”

Section: Discussionmentioning

confidence: 99%

The natural history of hepatitis C cirrhosis after liver transplantation

et al. 2009

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Hepatitis C after liver transplantation leads to graft cirrhosis in up to 30% of patients within 5 years, but limited data exist regarding the clinical course of cirrhosis after transplantation. The aims of this study were to report the natural history of hepatitis C cirrhosis after liver transplantation and to identify risk factors for decompensation and survival. Hepatitis C patients underwent protocol liver biopsies yearly after liver transplantation. After cirrhosis was identified by biopsy, the outcomes of interest were the development of decompensation, death, or retransplantation for hepatitis C. Kaplan-Meier and Cox regression analysis was used to determine survival and risk factors for decompensation and mortality. Out of 502 liver transplants performed for hepatitis C, 88 patients (18%) had cirrhosis within 3.7 years. Seventy-one patients were compensated at diagnosis. The cumulative probability of decompensation 1 year after cirrhosis was 30%. A Model for End-Stage Liver disease score Ն 16 was predictive of decompensation and poor survival, whereas successful interferon treatment was found to reduce this risk (relative risk ϭ 0.05). Once decompensation occurred, 1-year survival was 46%. In conclusion, the results confirm an accelerated natural history of hepatitis C cirrhosis after liver transplantation and demonstrate poor survival after decompensation. The Model for End-Stage Liver Disease can stratify risk for decompensation and survival, whereas successful antiviral therapy may be protective. Hepatitis C virus (HCV) infection is a significant public health problem in the United States. The natural history after the development of HCV recurrence and graft cirrhosis is not well defined in the liver transplantation (LT) population. Unfortunately, fibrosis progression leading to cirrhosis and liver decompensation can occur after transplantation. As a result, both patients and clinicians need a thorough understanding of the natural history of the disease post-transplant as they face decisions in medical management and possibly retransplantation for HCV cirrhosis. Therefore, the aim of this study was to report the natural history of cirrhosis from HCV after LT and to identify prognostic factors for both decompensation and survival once cirrhosis occurs.The development of fibrosis in the LT population occurs at an accelerated rate (0.3-0.8 stage/year) in comparison with the immunocompetent patient population.1,2 As a result, cirrhosis occurs in about 25% of those transplanted for HCV within a median of 5 years.3-8 After the diagnosis of graft cirrhosis, liver decompensation occurs rapidly, with a 42% cumulative probability of decompensation at 1 year. 9 The limited available data that address the natural history of HCV cirrhosis in a transplant population come from 2 centers in Europe. The results are somewhat disparate and

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“…[3][4][5][6][7][8][9][10][11][12] Historically, recurrent HCV has been treated with peginterferon (PEG) and ribavirin (RBV) with rates of sustained virologic response (SVR) (undetectable HCV RNA at 6 months after end of treatment) of 28% to 45%. [13][14][15][16][17][18][19] Contributing to this relatively low SVR is a high prevalence of patients with HCV genotype 1 and the presence of cytopenias limiting the use of maximal dosing of PEG and RBV. 17,20,21 Interferon alfacon-1 or consensus interferon (CIFN) (Infergen, Boehringer Ingelheim, Austria, GmbH) is a synthetic interferon that has been shown to be effective in the retreatment of PEG/RBV nonresponders and partial responders pre-LT to achieve a SVR in 7% to 30% of patients depending on fibrosis stage and prior response to PEG/RBV.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: Hepatitis C virus infection universally recurs in liver transplant recipients. Peginterferon/-ribavirin achieves a sustained virologic response rate of 30% in recipients infected with hepatitis C virus genotype 1. Consensus-interferon plus ribavirin yields sustained virologic response rates to 30% in patients failing to achieve sustained virologic response with peginterferon/ribavirin pretransplant, but it has not been studied posttransplant. We sought to evaluate the efficacy and tolerability of consensus-interferon and ribavirin in treating posttransplant hepatitis C virus. Materials and Methods: Clinical, laboratory, and virologic data were collected retrospectively from all patients who received at least 1 dose of consensus-interferon after transplant between January 2008 and December 2011. A standardized treatment protocol was used. The primary aim was sustained virologic response defined by undetectable hepatitis C virus RNA at 24 weeks after completing therapy. Results: Twenty-three patients were treated with consensus-interferon/ribavirin; 15 with prior nonresponse (87%) or breakthrough (6.7%) during peginterferon/ribavirin, and 8 as initial therapy. The intention-to-treat sustained virologic response with consensus-interferon was 30%. Anemia, leukopenia, and growth factor requirement were similar between peginterferon and consensus-interferon cohorts. Conclusions: Consensus-interferon may rescue liver recipients who are nonresponders to peginterferonbased therapy. The efficacy of interferon-based treatment regimens may benefit from substitution of consensus-interferon for peginterferon.

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Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation

Cited by 183 publications

References 34 publications

Liver Stiffness 1 Year After Transplantation Predicts Clinical Outcomes in Patients With Recurrent Hepatitis C

Liver Stiffness 1 Year After Transplantation Predicts Clinical Outcomes in Patients With Recurrent Hepatitis C

The natural history of hepatitis C cirrhosis after liver transplantation

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