Past HBV Viral Load as Predictor of Mortality and Morbidity from HCC and Chronic Liver Disease in a Prospective Study

Abstract

In a prospective cohort study with 11 yr of follow-up, we assessed the relationship between past hepatitis B virus (HBV) viral load and mortality. Surviving cohort members were evaluated for current liver disease. We measured HBV viral load by real-time polymerase chain reaction on stored samples from cohort entry (1992-1993) in 2,763 hepatitis B surface antigen (HBsAg)-positive adults. Major end points were death from hepatocellular carcinoma (HCC) or chronic liver disease (CLD). There were 447 deaths. In the 1,683 survivors, we assessed severity of liver disease on a return visit in 2003. Viral load was divided into three categories: undetected (<1.6 x 10(3) copies/mL); low titer (<10(5) copies/mL); and high titer (> or =10(5) copies/mL). For HCC, there was a significant increase in mortality across viral load categories (p(trend) < 0.001). Compared to the HBV undetected category, the relative risk (RR) for HCC mortality in the low viral load group was 1.7 (95% confidence interval [CI] 0.5-5.7) and 11.2 (3.6-35.0) in the high viral load group. For CLD mortality, the RRs were 1.5 (0.2-12.1) and 15.2 (2.1-109.8), respectively (p(trend) < 0.001). The RR associated with high viral load did not change with increased follow-up time. In surviving cohort members evaluated for liver disease in 2003, there was also a significant association of viral load with disease severity. In this prospective study, viral load is associated with increased mortality from HCC and CLD in HBV-infected subjects. Viral load may be a useful prognostic tool in HBV infection, and interventions aimed at its reduction should be explored.