Predictors of cirrhosis and hepatocellular carcinoma

U.S. Department of Health and Human Services
National Institutes of Health

The most important predictors of cirrhosis and hepatocellular carcinoma in persons who have chronic HBV are persistently elevated HBV DNA and ALT levels in blood. Other risk factors include HBV genotype C infection, male sex, older age, family history of hepatocellular carcinoma, and co-infection with HCV or HIV. The major goals of anti-HBV therapy are to prevent the development of progressive disease, specifically cirrhosis, and liver failure, as well as hepatocellular carcinoma development and death. To date, no RCTs of anti-HBV therapies have demonstrated a beneficial impact on overall mortality, liver specific mortality, or development of hepatocellular carcinoma. Most published reports of hepatitis therapy use cahnges in short-term virologic, biochemical and histological parameters to infer likelihood of long-term benefit. Approved therapies are associated with improvements in intermediate biomarkers, including HBV DNA, HBeAG loss or seroconversion, decreases in ALT levels, and improvement in liver histology. Although various monitoring practices have been recommended, no clear evidence exists for an optimal approach. The most important research needs include representative prospective cohort studies to define the natural history of the disease and large RCTs of monotherapy and combined therapies, including placebo-controlled trials, that measure the effects on clinical health outcomes.