EASL 2010: HBV DNA and HBsAg Levels Predict Likelihood of Sustained Response to Pegylated Interferon for Hepatitis B

Decreases in levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) while receiving treatment with pegylated interferon can help predict which hepatitis B "e" antigen (HBeAg) negative patients will ultimately achieve a sustained response, according to presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) this month in Vienna. Investigators recommended that people who do not experience adequate decreases in these levels by week 12 should discontinue therapy.

V. Rijckborst from Erasmus University Medical Center in Rotterdam and colleagues investigated the association between early serum HBsAg levels after starting therapy and sustained response in HBeAg negative chronic hepatitis B patients treated with pegylated interferon alfa-2a (Pegasys).

Pegylated interferon leads to sustained response in only a minority of HBeAg negative patients and adverse side effects are common, so it is useful to identify individuals who are likely to benefit early during the course of treatment, the researchers noted as background.

The present analysis included 107 HBeAg negative hepatitis B patients who participated in an international clinical trial and were randomly assigned to receive either 180 mcg/week pegylated interferon alfa-2a monotherapy or pegylated interferon plus 1000-1200 mg/day ribavirin for 48 weeks.

HBsAg levels were measured at baseline, during treatment (weeks 4, 8, 12, 24, 36, and 48), and during follow-up (weeks 60 and 72). Sustained response was defined as HBV DNA < 10,000 copies/mL and normal alanine aminotransferase (ALT) 24 weeks after completion of therapy. After sustained response rates were determined, data from the pegylated interferon monotherapy and combination therapy arms were merged for further analysis.

Results

• Sustained response rates were statistically similar in the pegylated interferon monotherapy and combination therapy arms (26% vs 19%, respectively).
• Sustained responders experienced larger and faster decreases in serum HBsAg levels, compared with only modest declines among non-responders (1.5 vs < 0.5 log IU/mL, respectively, at week 72).
• HBsAg declines were apparent by week 8 in sustained responders, but not until week 12-24 in non-responders.
• Serum HBV DNA levels also declined more in sustained responders compared with non-responders.
• After completing therapy, HBV viral load levels returned to baseline in non-responders, but remained suppressed in sustained responders.
• Decreases in HBsAg alone were of only limited value in predicting likelihood of sustained response.
• Sustained response was best predicted by a combination of decreases in HBsAg and HBV DNA.
• None of the 20 patients who had no decrease in serum HBsAg at week 12 and less than a 2 log decline in HBV DNA achieved sustained response (negative predictive value 100%).
• Participants who experienced either no HBsAg decline at week 12 but HBV DNA loss 2 logs, or evidence of HBsAg decline but viral load decrease < 2 logs, had intermediate sustained response rates of approximately 25%.
• In contrast, among participants with decreased HBsAg at week 12 and at least a 2 log decline in HBV viral load, the sustained response rate reached 39%.

"At week 12 of peginterferon alfa-2a treatment for HBeAg negative chronic hepatitis B a solid stopping rule was established using a combination of declines in serum HBV DNA and HBsAg level from baseline," the investigators concluded.

"Quantitative serum HBsAg in combination with HBV DNA enables on-treatment adjustment of peginterferon therapy" in HBeAg negative chronic hepatitis B patients, they added.

Gastroenterology and Hepatology & Epidemiology and Biostatistics, Erasmus MC University Medical Center, Rotterdam, Netherlands; Gastroenterohepatology, Istanbul University Medical School, Istanbul, Turkey; Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Infectious Diseases, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey; Gastroenterology, Turkiye Yuksek lhtisas Hospital, Ankara, Turkey; Infectious Diseases, Hepatology and Acquired Immune Deficiences, Medical University Wroclaw, Wroclaw, Poland; Gastroenterology, Ege University Faculty of Medicine, Izmir, Turkey; Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland; Virology, Erasmus MC University Medical Center, Rotterdam, Netherlands.

4/27/10

Reference

V Rijckborst, BE Hansen, Y Cakaloglu, and others. Early prediction of sustained response to peginterferon alfa-2a in HBeAg-negative patients: the role of on-treatment HBsAg and HBV DNA levels. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract 8).