Specific Demographics Result in Greater Hepatitis B e Ag Loss

William M. Lee, MD

Various demographics are at an increased risk for hepatitis B e antigen (HBeAg) loss, according to a new study on hepatitis B virus (HBV) patients.

A team, led by William M. Lee, UT Southwestern Medical Center, determined the rate and predictors of HBeAg loss in a cohort of patients with chronic HBV infections.

HBeAg

Hepatitis B e antigen is a soluble viral protein in the plasma of patients with HBV infections that is associated with high viral replication. HBeAg loss can be the first stage of viral antigen clearance.

The viral protein produced from the preCore/Core gene of HBV that has been associated with higher levels of viremia and increased infectivity and risk of hepatocellular carcinoma (HCC).

HBeAg negative patients also have a much lower HBV DNA and aminotransferase levels compared to HBeAg positive patients and are perceived to have better clinical outcomes over time.

“HBeAg loss and hepatitis B e antibody (anti-HBe) development is a desired therapeutic goal and can lead to HBV (nucleoside analogue) medication discontinuation in certain circumstances,” the authors wrote. “However, detailed prospective studies of host and viral factors associated with HBeAg loss among North American chronic hepatitis B (CHB) patients are lacking.”

The Study

In the study, the investigators examined adults with chronic HBV without HIV, HCV, or HDV co-infections in North America. The study included 819 HBeAg positive patients that were enrolled in the Hepatitis B Research Network, 577 of which were followed every 25-48 weeks.

The investigators defined HBeAg loss as the first HBeAg negative value, while sustained HBeAg loss was defined as at least 2 consecutive HBeAg negative values at least 24 weeks apart.

The primary goal of the study was to determine the rate and clinical predictors of HBeAg loss, with secondary aims of determining the durability of HBeAg loss in the presence or absence of HBV medication and to describe the serological outcomes following HBeAg loss.

The primary outcomes was HBeAg loss and secondary outcomes were sustained HBeAg loss.

Results

A total of 164 patients experienced HBeAg loss during a median follow-up of 1.8 years, a rate of 11.4 (95% CI, 9.8-13.3) per 100 person-years.

The investigators then adjusted for confounders and found HBeAg loss rate was significantly higher in various demographics, including males (14.2, 95% CI, 11.5-17.7), older individuals (e.g., 18.3, 95% CI, 12.6-26.7, for those over 50 years), Caucasians (22.5, 95% CI, 13.8-36.7) or African-Americans (20.3, 95% CI, 11.5-35.7), individuals with genotype A2 or B, and in individuals with basal core promoter/precure mutations.

Other predictors of higher rates of HBeAg loss included an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or hepatitis B virus DNA levels. The investigators also found 88% of patients with HBeAg loss had sustained HBeAg loss.

“In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies,” the authors wrote.

The study, “Hepatitis B e Antigen Loss in Adults and Children with Chronic Hepatitis B Living in North America: A Prospective Cohort Study,” was published online in the Journal of Viral Hepatitis.