In a paper published in the August 2006 edition of the American Journal of Gastroenterology, Dr. Gang Chen and colleagues reported on the long-term significance of HBV viral load for chronic HBV carriers. In a prospective study with 11 years of follow-up conducted in Haimen City, China, the investigators tested for quantitative HBV viral load in blood samples collected in the early 1990s.

Blood samples were taken during mass screening efforts in this high-risk area of China. Adults between the ages of 25 and 65 were screened for the virus by hepatitis B surface antigen (HBsAg) tests, and the population was then followed for 11 years. Deaths from primary liver cancer or hepatocellular carcinoma (HCC), chronic liver disease (CLD), and other causes were recorded.

Approximately 15,000 HBsAg-positive samples were chosen for viral load testing by real-time PCR, a technique that was not available at the time the subjects entered the study. In the years following study entry, there were 447 deaths from all causes in this group, 231 from HCC, 85 from CLD, and 131 from non-liverrelated causes.

Based upon viral load at study entry, there was a significant increase in risk of HCC as viral load increased. Compared to subjects with no detected serum viral load, subjects with positive but low viral load (between 1.6x103 and 9.9x104 viral particles/mL) had a 70% increase in risk for HCC. Subjects with a high viral load (>105 viral particles/mL) had a risk of HCC that was 11 times higher than subjects with undetected viral load.

For CLD deaths, the increase in risk was similar: 50% in the lower viral load category, and 15-fold in the higher viral load group. In contrast, there was no significant increase in the risk of death from non-liver-related causes. In 2003, 1,683 surviving HBsAg-positive members of the original group were invited to return for additional blood testing. In this group, the severity of their liver disease in 2003 was strongly associated with the viral load level detectable in the serum samples collected when they originally entered the study 11 years earlier.

This study has important implications for our understanding of the natural history of chronic HBV infections. Because the subjects in the study were identified via mass screening in a high-risk population, most of them were unaware of their HBV infection status or their risk of liver disease, and this represents a very different type of population than that usually presented in clinical studies, where subjects have often sought medical care because of known liver disease.

Most of the Haimen City subjects were free of symptoms of liver disease at the time they entered the study, and antiviral medications were not generally available in this region during the time of follow-up. But in this population, HBV viral load was still a strong indicator of their future risk of HCC and CLD. Interestingly, the usefulness of the viral load measurement as a predictor of future HCC or CLD death did not seem to wane over time, i.e. the risk at 2-3 years after study entry was similar to risk after 9-10 years once other factors such as age and sex were accounted for statistically.

Viral load in HBV carriers has been used for some time as a clinical marker of disease progression and response to antiviral therapy. This study demonstrates its utility as an indicator of long-term prognosis and as an important potential target for reduction of risk, even in apparently otherwise healthy persons chronically infected with HBV.

Note: For a reprint of the full journal article “Past HBV Viral Load as Predictor of Mortality and Morbidity from HCC and Chronic Liver Disease in a Prospective Study”(Gang and Evans), please contact editor@hepb.org.