What Factors Predict Recovery From Chronic HBV Infection?

A low and rapidly decreasing level of Hepatitis B surface antigen (HBsAg) is a good sign for patients with chronic HBV infection, according to the March issue of Clinical Gastroenterology and Hepatology.

Tracking progression of chronic HBV infection can be complicated—patients can have high viral loads with no symptoms, and then develop active liver disease, and then revert back to inactive liver disease. Liver biopsies show active inflammation and fibrosis during periods of disease activity that can improve when the disease is inactive, only to reappear again if the infection is reactivated.

Several laboratory tests are used to define the phase of disease at a given timepoint and to attempt to predict patients’ outcomes, including measurements of alanine aminotransferase (ALT), hepatitis B e antigen (HBeAg, and an antibody against it) and HBV DNA levels.

Immune-based assays to measure the level of hepatitis B surface antigen (HBsAg) have also been developed and are commercially available in Europe. In patients with inactive, chronic HBV infection, HBsAg seroclearance is considered to be the closest thing to a cure (unless the patient has cirrhosis or other viral infections). However, clearance is a rare event that occurs at 1% to 2% per year, and there have been conflicting reports on what factors predict clearance.

Yi-Cheng Chen et al. retrospectively examined levels of HBsAg in 46 patients who had undergone spontaneous seroclearance of HBsAg. They analyzed serum samples collected 1 year, 3 years, and 5 years before the patients became HBsAg-negative. They found that HBsAg levels were significantly reduced during the 3 years before clearance, compared with matched patients who did not clear HBsAg.

Chen et al. determined positive predictive values of different levels of HBsAg, and found that “the combination of an HBsAg level below 200 IU/mL and a 1 log (or more) drop in the preceding 2 years had a positive predictive value of 100% for HBsAg seroclearance in 3 years”, as explained in a video abstract that accompanies the article.

Video abstract from Yi-Cheng Chen

The authors recommend quantifying HBsAg every 2 years in HBeAg-negative HBsAg carriers with persistently normal levels of ALT, to identify those that might clear HBsAg and therefore should be monitored more frequently. Chen et al. state that additional studies are needed to test whether these cut-off levels could be used to predict HBsAg seroclearance in response to antiviral therapy.

The rate of HBsAg reduction in this study was more rapid than reported in other studies, which might be related to HBV genotype; patients in this cohort were mainly infected with HBV genotype B, whereas those in European studies were mainly infected with HBV genotype D.

In an editorial that accompanies the article, Brian McMahon and Brenna Simons point out that although an accelerating drop in HBsAg level appears to predict which patients will remain in the inactive phase and clear HBsAg, they do not predict if or when patients will go from the more active phases of HBV infection, immune tolerant or immune active, to the inactive phase (see figure), or which patients in the inactive phase will reactivate disease.

Phases of Chronic HBV Infection.

The authors state that because HBsAg levels decreased, albeit at different rates, in patients that cleared the antigen but also in controls over the course of the study, it would be interesting to continue following both groups, to develop a model of HBsAg loss rate that could be applied to more patients.

Prospective studies are also needed to examine large numbers of treated and untreated patients with chronic HBV infection, with all HBV genotypes, and to determine how this data might be combined with levels of HBV to predict outcomes.

More Information on HBV Infection:

Read the article online.
Chen Y-C, Jeng W-J, Chu C-M, et al. Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive chronic hepatitis B virus infection. Clin Gastroenterol and Hepatol 2012;10:297–302.

Read the accompanying editorial.
McMahon B, Simons B. Interpreting hepatitis B surface antigen levels: useful clinical test or just another confusing assay? Clin Gastroenterol and Hepatol 2012;10:218–219.

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About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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