Baseline MELD Score Predicts Hepatic Decompensation during Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis

Research Article

Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis 

Citation: Dultz G, Seelhof M, Herrmann E, Welker M-W, Friedrich-Rust M, et al. (2013)
Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis.
PLoS ONE 8(8): e71262. doi:10.1371/journal.pone.0071262

Editor: James Fung, The University of Hong Kong, Hong Kong

Received: February 28, 2013; Accepted: June 27, 2013; Published: August 1, 2013

Copyright: © 2013 Dultz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors have no support or funding to report.

Competing interests: The authors have declared that no competing interests exist.

Introduction Only

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Chronic hepatitis C virus (HCV) infection is a major health burden with more than 170 million infected individuals worldwide. Progression to liver cirrhosis is observed in 2–35% of the patients after 20–25 years of chronic infection and once liver cirrhosis is established, the cumulative 5-year risk to develop hepatocellular carcinoma (HCC) is estimated to be 17% [1], [2].

For more than one decade, available antiviral treatment consisted of a dual therapy with pegylated interferon alfa-2a or -2b (peginterferon) in combination with the guanosine analog ribavirin leading to sustained virologic response (SVR) rates in approximately half of the patients [3], [4]. Licensing of the new HCV protease inhibitors boceprevir and telaprevir, as part of a triple therapy for untreated HCV genotype 1 patients and those who failed previous treatment, represents a milestone in HCV treatment. Untreated patients undergoing triple therapy achieve significantly higher SVR rates (66–75%) as compared to those receiving the dual therapy alone (37–44%) [5], [6], [7]. Patients with a previous virologic relapse, partial response, or non-response to peginterferon and ribavirin also benefit when retreated with boceprevir or telaprevir-containing triple therapies [8], [9].

It is well established, that the presence of advanced fibrosis or compensated liver cirrhosis negatively influence a patient’s individual chance for achieving an SVR [10]. In turn, patients with advanced disease may benefit most from antiviral therapy since it was demonstrated in several long-term follow up cohort studies that SVR can prevent hepatic decompensation, development of hepatocellular carcinoma, and is associated with reduced overall mortality [11], [12], [13], [14]. Albeit still unsatisfactory, subanalyses of the pivotal boceprevir and telaprevir trials have shown that SVR rates for patients with advanced fibrosis and liver cirrhosis receiving triple therapy are higher as compared to those receiving peginterferon and ribavirin alone (52–62% vs. 33–38%) [5], [6].

In patients with more severe disease, e.g. patients with advanced cirrhosis and those on the waiting list for liver transplantation, successful antiviral therapy in selected cases may halt the progression of liver disease, can prevent HCV re-infection of the transplanted liver and subsequently leads to a decrease of post-transplant morbidity and mortality [15], [16], [17], [18], [19], [20]. However, SVR rates in those patients have been shown to be poorer (approximately 25%) and peginterferon and ribavirin in those patients is associated with potentially life-threatening side effects and discontinuation rates ranged from 20–100%.

Recently, preliminary data from the French early access program for telaprevir and boceprevir (CUPIC study) reporting antiviral efficacies and the occurrence of adverse events in more than 400 cirrhotic patients receiving antiviral triple therapy were presented [21]. About 38–48% of the cirrhotic patients experienced serious adverse events during the first 16 weeks of antiviral triple therapy and 8 patients died.

Thus, decision making for antiviral therapy in patients with (advanced) liver cirrhosis remains a clinical challenge facing the dilemma of increased SVR rates on the one hand and therapeutic schedules that are associated with increased complications and fatal outcomes on the other hand [22]. Moreover, predictive factors in cirrhotic patients that are associated with serious adverse events and/or hepatic decompensation during antiviral therapy are poorly defined.

The aim of this retrospective cohort study was to define baseline characteristics that can help to predict the risk for hepatic decompensation in HCV patients with advanced liver cirrhosis during antiviral therapy with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks.

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