Hepatitis B: liver fibrosis and hepatocellular carcinoma.

Chronic hepatitis B virus (HBV) infection is estimated to be the cause of 55-60% of hepatocellular carcinoma (HCC) in the world. It has been estimated that up to 40% of HBV-related HCC occur in persons who do not have cirrhosis while almost all cases of hepatitis C virus (HCV)-related HCC occur in the setting of cirrhosis. Data on the performance of non-invasive tests for liver fibrosis in patients with hepatitis B are limited. FibroTest may be superior to the Forns index, APRI, Goteborg University Cirrhosis Index (GUCI) and Hui model in detecting significant fibrosis (Metavir>F2) or cirrhosis (Metavir F4) but an algorithm that uses APRI for screening, FibroTest for confirmation, and biopsy for indeterminate cases has the greatest accuracy. Liver stiffness correlates with fibrosis stages but may be influenced by necroinflammatory activity with falsely high values in patients with alanine aminotransferase (ALT) flares and falsely low values in patients with viral suppression and ALT normalization during antiviral therapy. Therefore, additional studies are needed to determine the clinical settings in which liver stiffness measurement can accurately predict liver fibrosis and to establish cutoff values for differentiating different stages of fibrosis or cirrhosis. These studies should also compare the performance of liver stiffness measurement with serum markers of fibrosis in patients with varying degrees of necroinflammation and in untreated patients as well as patients receiving antiviral therapy. Until recently, older age, male gender and cirrhosis were the major risk factors associated with HCC development. Recent studies showed that HBV replication status, HBV genotype and mutations in the basal core promoter region play an important role in HCC development. These data indicate that algorithms incorporating demographics, viral factors, degree of necroinflammation and extent of fibrosis may be more accurate in predicting the risk of HBV-related HCC than fibrosis staging alone.