Molecular and genomic biomarkers for risk prediction of long-term end-stage liver diseases in patients with chronic viral hepatitis

Abstract

Chronic hepatitis B and C virus (HBV; HBC) infections are worldwide public health challenges. Molecular and genomic biomarkers for the prediction of long-term risk of end-stage liver diseases in patients affected with chronic viral hepatitis are important for the clinical management of the diseases. The REVEAL-HBV/HCV study is a community-based prospective cohort study aimed to evaluate the risk predictors of progression of chronic HBV and HCV in Taiwan. A total of 23,820 participants were enrolled between 1991 and 1992 from seven townships in Taiwan. Their serum samples were collected at study entry and follow-up examinations and tested for antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg) and e antigen (HBeAg), serum levels of alanine aminotransferase (ALT), HCV RNA, HBV DNA, HBsAg, and α-fetoprotein. Genotypes and mutant types of HBV and HCV in serum samples were also examined. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC) were ascertained through follow-up examination and data linkage with profiles from the National Cancer Registry, National Health Insurance Database, and Death Certification System. Age, sex, elevated serum levels of ALT, HBV DNA and HBsAg, HBeAg serostatus, HBV genotype, family HCC history, and alcohol drinking habits are important biomarkers for the prediction of HBV-related HCC and cirrhosis. Age, elevated serum levels of ALT and HCV RNA, and HCV genotype are important biomarkers for the prediction of HCV-related HCC. Risk calculators have been developed for the long-term risk prediction of HCC for patients with chronic HBV and HCV. These risk calculators have been documented to have good validity for the prediction of risk of HCC and cirrhosis.