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


Fifty-seven studies that examined stage of liver disease in people with chronic HCV infection were included in the analysis. Most studies provided demographic information, mode of HCV acquisition and data regarding the proportion of cases with an elevated alanine aminotransferase (ALT) ( Table 1 ). However, many did not provide information on other factors such as alcohol consumption, HCV genotype and viral load. People with HIV and HBV were either excluded or made up only a small proportion, therefore, this analysis was unable to examine the impact of coinfection with either HIV or HBV on HCV-related liver disease progression. Data was also not available to examine obesity, smoking and quasispecies diversity.

Univariate analysis demonstrated that the following factors influenced progression to cirrhosis: gender, alcohol consumption, serum ALT levels, HAI and age at infection ( Table 2 ). Despite different rates of progression to cirrhosis,[7] regression line slopes were not significantly different across the study categories for these cofactors. Mode of HCV acquisition was not implicated as influencing prognosis. Multivariate analysis demonstrated that male sex was associated with heavy alcohol consumption and elevated ALT was associated with higher HAI. However, after adjusting for these associations, gender, alcohol consumption, serum ALT levels and HAI were demonstrated to independently influence progression to cirrhosis (Fig. 1). After adjusting for these factors more clearly associated with fibrosis progression, age at HCV infection was no longer significantly associated with cirrhosis.

Factors identified as independently influencing progression to cirrhosis: (a) gender; (b) alcohol consumption; (c) serum ALT level; (d) histological activity index. Studies were grouped into four categories: liver clinic series diamond, post-transfusion cohorts square, community-based studies cross and blood donor series triangle. Mean linear regression line slope across the four categories was calculated as outlined in methods.

A Weibull distribution was generated to estimate cirrhosis prevalence and model the influence of cofactors on disease progression (Fig. 2). An algorithm ( Table 3 ) was used to predict progression to cirrhosis based on risk factor profile ( Table 4 ). For example, a woman with an elevated ALT and an HAI of five would have an estimated risk of cirrhosis of 7% (4-10%) after 20 years infection if she was not a heavy drinker. Her risk would increase to 11% (6-15%) in the setting of heavy alcohol consumption. Risk of cirrhosis at 30 years ranged from 10% for women with no cofactors associated with disease progression, to 25% for men with elevated ALT levels, a high HAI score and heavy alcohol intake.

Progression to cirrhosis in patients with chronic HCV infection. (a) Estimated cirrhosis prevalence, cirrhosis (T), after 20 years chronic HCV infection, cirrhosis (20) = 6.5% (95% confidence interval 3.5-9.5%), and after 40 years infection, cirrhosis (40) = 20% (10-40%). Progression to cirrhosis was estimated using a Weibull distribution as outlined in Methods: αλ = -7.89,1.73(-8.02,1.56; -9.36, 2.36). (b) The influence of cofactors on progression to cirrhosis. Relative risk (RR), was based on the cofactors described in Table 2 and normalized to the nine commu- nity-based studies.


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