HBV DNA Decline at 24 Weeks Predicts Sustained Response to Pegylated Interferon for Chronic Hepatitis B

SUMMARY: Patients who experience a significant decrease in hepatitis B virus (HBV) DNA, or viral load, during the first 24 weeks of treatment with pegylated interferon were more likely to achieve a long-term response, according to a study described in the July 2010 Journal of Medical Virology. If HBV DNA does not decline by at least 100-fold during this period, however, treatment is unlikely to be successful and should be discontinued, the researchers recommended.
By Liz Highleyman

Bettina Hansen from Erasmus University Medical Center in Rotterdam and colleagues aimed to develop a model that could better predict at baseline which chronic hepatitis B patients would respond to pegylated interferon, and to establish an early indicator for when treatment should be halted.

Pegylated interferon leads to virological response (undetectable HBV DNA) and hepatitis B "e" antigen (HBeAg) loss in only a minority of patients with HBeAg positive chronic hepatitis B. The treatment is expensive and can cause difficult side effects, so clinicians want to know when to stop therapy that is unlikely to produce a favorable outcome.

Known baseline predictors of response to pegylated interferon include HBV genotype (B responds better than D), pre-treatment HBV viral load, and alanine aminotransferase (ALT) level. The investigators looked at whether viral load reduction early in treatment also has predictive value.

This analysis included 136 chronic hepatitis B patients treated with pegylated interferon. Response was defined as HBV DNA < 10,000 copies/mL and HBeAg loss 26 weeks after completion of treatment. The researchers used logistic regression analysis to develop a dynamic prediction model using HBV DNA during the first 32 weeks of therapy.

Results

• The researchers identified an early clinically useful rule for continuation or discontinuation of treatment, with a grid of cut-off values for HBV DNA decline during treatment.
• Adding HBV DNA decline at weeks 4, 12, and 24 to baseline factors improved predictions of sustained response.
• HBV DNA decline of at least 2?log(10), or 100-fold, within 24 weeks of starting therapy was strongly associated with response when added to baseline predictors. 

These findings led the study authors to conclude, "A dynamic model including HBV DNA decline during treatment provides more accurate predictions of response to pegylated interferon."

"The model strongly supports individual decision making on treatment (dis)continuation in patients with HBeAg positive chronic hepatitis B," they continued. "It is recommended that pegylated interferon treatment is stopped by 24 weeks if HBV DNA declined < 2?log(10)."

Investigator affiliations: Departments of Gastroenterology & Hepatology, Biostatistics, and Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands; Department of L-Biostat, Catholic University of Leuven, Leuven, Belgium.

8/20/10

Reference
BE Hansen, EHCJ Buster, EW Steyerberg, and others. Prediction of the response to peg-interferon-alfa in patients with HBeAg positive chronic hepatitis B using decline of HBV DNA during treatment. Journal of Medical Virology 82(7): 1135-1142 (Abstract). July 2010.

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