Published: 06/17/2009
Abstract
Background: Interferon (IFN-α)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results.
Aim: To investigate the natural course of IFNα-based -treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study.
Methods: We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFNα-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively.
Results: During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit.
Conclusions: IFNα-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR.
Background
Hepatitis C (HCV) infection is an important public health issue. An estimated 170 million persons are chronically infected with HCV worldwide,[1] while in the general population of Greece, HCV prevalence approximates 1-1.9%.[2,3] Chronic hepatitis C (CHC) has a variable course.[4,5] Although 20-25% of CHC infected patients maintain persistently normal serum aminotransferases and experience relatively slow histological progression,other patients present a more active biochemical course. Overall, 30% of the CHC patients may progress to cirrhosis in their lifetime, whereas 3-8% of cirrhotic patients may develop hepatocellular carcinoma (HCC) every year.
During the last two decades, standard and pegylated interferon alpha (IFNα), alone or in combination with ribavirin, has been used in the treatment of CHC with varying success. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results While treatment-induced sustained virological response in histologically mild CHC has been associated with a significantly better clinical outcome, it remains unclear whether the beneficial effects of treatment persist among nonsustained responders as well or even among those with advanced fibrosis or cirrhosis
For the last 5 years, we have conducted a nationwide Greek study collecting data on hepatitis C from 25 Hepatology Centres throughout the country. As a large percentage of cases had remained untreated for a considerable period of time, we compared their natural course with that of patients having received interferon-based therapy. As our study included a broad patient population (patients with various sources of infection; wide range of ages; varying disease stages) and a large number of patients, it provided us with the opportunity to study the natural history and the effect of treatment on both cirrhotic and noncirrhotic patients adjusting for other potential confounders.
2009 Annual Meeting of the European Association for the Study of the Liver*
April 22-26, 2009 | Copenhagen, Denmark
E.K. Manesis; G.V. Papatheodoridis; G. Touloumi; A. Karafoulidou; J. Ketikoglou; G.E. Kitis; A. Antoniou; S. Kanatakis; S.J. Koutsounas; I. Vafiadis; for the HEPNET.Greece Cohort Study
