Research ArticleImpact of peginterferon and ribavirin therapy on hepatocellular carcinoma: Incidence and survival in hepatitis C patients with advanced fibrosis
Introduction
According to the World Health Organization, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, accounting for 662,000 deaths every year throughout the world [1]. The overwhelming majority of HCC occurs in patients with chronic liver disease, 80–90% having cirrhosis, with most of the remainder having advanced fibrosis. Chronic viral hepatitis accounts for more than 80% of HCC cases worldwide [2]. Among patients with hepatitis C virus (HCV)-related cirrhosis, HCC is the most common complication. In a 17-year cohort study of 214 patients with chronic hepatitis C (CHC), HCC was the main cause of death (44%) and the first complication to develop in 27% of patients [3]. The incidence of HCV-related HCC is increasing in both the United States and Europe [4], [5], [6].
Previous studies have shown that interferon therapy may reduce the incidence of HCV-related HCC [7], [8], [9]. The majority of these studies were retrospective, raising the concern of selection bias (patients who did not receive therapy either had more advanced disease or were more likely to develop cancer) [10]. Indeed, a meta-analysis concluded that, although interferon treatment appeared to reduce the risk of HCC, the effect was slight and most evident among few patients with cirrhosis who achieved a sustained virological response (SVR) [11]. In the last few years, the efficacy of HCV therapy has evolved substantially, with improvement in the SVR rates from 10% with the initially recommended 24-week course of interferon monotherapy [12] to 50–60% with the combination of peginterferon and ribavirin for 48 weeks [13]. Importantly, data on the long-term follow-up and rates of HCC among Caucasian patients who received combination peginterferon and ribavirin therapy, are very limited [14]. Recently, the results from the HALT-C trial suggested that maintenance therapy with peginterferon monotherapy does not reduce the risk of HCC, thus highlighting the importance of achieving SVR in these patients [15]. Finally, SVR has been shown to be associated with eradication of the HCV virus [16], [17].
The aim of this study was to assess the influence of peginterferon and ribavirin combination therapy on the risk of HCC, liver-related complications, and liver-related death in a large cohort of patients with HCV-related bridging fibrosis or cirrhosis.
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Study population
All patients in this study had been included in clinical trials and followed up in a single center (Hôpital Beaujon). Subjects were identified through our clinical trial database. Individuals with CHC and biopsy-proven bridging fibrosis or cirrhosis who had been treated with interferon-based therapy in clinical trials between 1987 and 2007, were included in this study [7], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33]. CHC was documented by the
Study population
We identified a total of 307 CHC patients with bridging fibrosis (F3) or cirrhosis (F4). The last course of therapy consisted of peginterferon and ribavirin in 252 patients (82%), peginterferon monotherapy in 22 patients (7%), and conventional interferon with or without ribavirin in 33 patients (11%). Patients received a median of two treatment courses (range 1–6), with a median cumulative duration of 14 months (range 3–185 months). Patients were followed for a median period of 3.5 years (range
Discussion
This study provides information on the incidence of HCC, liver-related complications, and live-related death in a large cohort of Caucasian patients with HCV-related bridging fibrosis or cirrhosis who were treated with a combination of peginterferon and ribavirin. Importantly, SVR was assessed using a highly sensitive HCV RNA assay, thus avoiding possible bias due to misclassification of the response category in previous studies.
The overall SVR rate (33%) was lower than that observed in
Financial support
This study was supported by a grant from Schering Plough, but the sponsor had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript.
Disclosures
Patrick Marcellin received fees as a consultant or lecturer for Roche, Schering Plough, Novartis, Gilead Sciences, BMS, MSD, Vertex, Tibotec, Biolex, Zymmogenetics and grants from Gilead Sciences, Roche and Schering Plough. All other co-authors have no conflicts of interest to declare.
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These authors contributed equally to this work.