Predicting Progression to Cirrhosis in Chronic Hepatitis C Virus Infection

A. J. Freeman, M. G. Law, J. M. Kaldor, G. J. Dore


J Viral Hepat. 2003;10(4) 

In This Article

Summary and Introduction

A systematic evaluation of published studies was undertaken to identify factors associated with accelerated fibrosis progression in patients with chronic hepatitis C virus (HCV) infection. An ecologic analysis was used to estimate relative risk (RR) of cirrhosis across four study methodologies: liver clinic series, post-transfusion cohorts, community-based studies and blood donor series. In each study category, the following factors were independently associated with disease progression: male sex (RR = 1.08); heavy alcohol consumption (RR = 1.61); elevated serum ALT levels (RR = 1.23) and histology demonstrating high-grade necro-inflammatory activity. After adjusting for these cofactors, older age at HCV infection and acquisition of HCV through blood transfusion were not implicated in influencing disease outcome. Although not able to be examined in this study,co-infection with HIV, and to a lesser extent HBV, is also likely to result in worse outcomes for patients with chronic HCV infection. Virological factors such as HCV genotype, viral load and quasispecies diversity are less likely to be important. A Weibull distribution was used to model disease progression at a population level. The influence of cofactors on individual prognosis was examined and an algorithm to predict the risk of subsequently developing cirrhosis is presented.

The majority of cases of primary hepatitis C virus (HCV) infection result in persistent viraemia.[1] Progression to cirrhosis marks the onset of risk for complications such as liver failure and hepatocellular carcinoma.[2,3,4,5] However, while liver disease progression appears more indolent than previously reported, it is highly variable[6,7] Identifying factors that influence outcome is important in order to counsel individuals regarding prognosis and facilitate decisions related to clinical management. A number of factors have been proposed as promoting HCV-related liver fibrosis. These include: host ethnicity, gender, obesity, alcohol consumption, smoking, age at infection, mode of HCV acquisition, serum transaminase levels, histological grade of inflammation, co-infection with hepatitis B virus (HBV) or HIV, HCV genotype, viral load and quasispecies diversity.[6,8]

We recently completed a systematic review of HCV natural history studies in which study methodology was shown to greatly influence disease progression estimates. For example, cirrhosis prevalence after 20 years infection was estimated at 24% in cross-sectional liver clinic series, but only 7% in community-based studies.[7] We have therefore examined studies included in this review to identify factors that influence liver disease progression, and to assess consistency of cofactors across study settings.


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