It is a challenge to monitor the course of chronic hepatitis B. Patients still carry the Hepatitis B surface antigen (HBsAg) but have varying levels of viral DNA, HBeAg, and liver inflammation—and remain at risk for developing hepatocellular carcinoma (HCC). Two papers in this month’s issue of Gastroenterology investigate Hepatitis B surface antigen (HBsAg) as a marker of disease progression.
Quantification of serum levels of HBsAg can be used to distinguish carriers of inactive virus from those with active infection. Maurizia Rossana Brunetto et al. tracked serum levels of HBsAg (along with HBV DNA, transaminases, and other markers of virus activity) in 209 carriers of HBV genotype D for an average of 29 months. They found that levels of HBsAg were significantly lower in carriers of inactive viral infections (below 1000 IU/mL in more than 90% of patients with inactive virus but only 5.7% of patients with active, chronic infections), compared with active ones. Quantification of both HBV DNA (<2000 IU/mL) and HBsAg (<1000 IU/mL) accurately identified almost 95% of inactive carriers. The authors concluded that this noninvasive test might improve management of patients with chronic HBV infection—loss of HBsAg has been associated with a sustained virologic response to antiviral therapies. However, the tests require validation in a larger cohort, patients with different HBV genotypes, and those at earlier stages of infection. See accompanying video abstract by Dr. Brunetto.
What factors contribute to loss of HBsAg? Jessica Liu et al. followed 3087 patients with chronic HBV infections for 8 years; 562 trial participants cleared HBsAg. Surprisingly, older age, lower baseline levels (or rapid loss) of HBV DNA, cigarette smoking, and the presence of obesity were all correlated with sero-clearance. The authors proposed that antiviral therapy to lower serum levels of HBV DNA (lower viral load) maximizes chances of HBsAg clearance—once HBV DNA reached undetectable levels, it took patients about 100 months to clear the viral antigen. Further studies are needed to determine how smoking and obesity might clear the virus. See accompanying video abstract by Ms. Liu.
In an accompanying editorial Brian McMahon points out that although patients with inactive virus (based on loss of HBsAg) do not develop liver decompensation or cirrhosis, some still develop HCC. This might be because low levels of HBV can still integrate into the DNA of hepatocytes and transform the cells. Patients that have cleared HBsAg should therefore still be monitored for signs of liver cancer.
More Information on Hepatitis B:
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Read the articles online:
Brunetto MR, Oliveri F, Colombatto P, et al. Hepatitis b surface antigen serum levels help to distinguish active from inactive hepatitis b virus genotype d carriers. Gastroenterology 2010;139:483–490.
Liu J, Yang H–I, Lee M–E, et al. Incidence and determinants of spontaneous hepatitis b surface antigen seroclearance: a community-based follow-up study. Gastroenterology 2010;139:474–482.
Read the accompanying editorial:
McMahon, B.J. Hepatitis b surface antigen (HBSAG): a 40-year-old hepatitis b virus seromarker gets new life. Gastroenterology 2010;139:380–382