Effects of indomethacin on viral replication markers in asymptomatic carriers of hepatitis B: A randomized, placebo-controlled trial

Objectives: Previous studies have suggested some benefits of nonsteroidal antiinflammatory drugs (NSAIDs) use in patients with chronic viral hepatitis. We evaluated potential effects of indomethacin in asymptomatic carriers of hepatitis B surface antigen (HBsAg). Design: Randomized, placebo-controlled, double-masked clinical trial. Methods: One hundred and twelve patients who were confirmed to be HBsAg carriers for at least 6 months and had normal liver function tests, normal abdominal sonography, and no sign of cirrhosis were randomly assigned into two groups. One group (56 participants, mean age (+/- SD) 31.7 (+/- 9.6) yr, 29 male, mean serum alanine aminotransferase (ALT) (+/- SD) 24.9 (+/- 9.2)) received indomethacin capsules (25 mg) three times daily and the other group (56 participants, mean age (+/- SD) 33.8 (+/- 10.2) yr, 33 male, mean serum ALT (+/- SD) 24.5 (+/- 8.7)) took placebo capsules with identical package and appearance. All participants were under treatment for 6 months and were followed 3 months thereafter. Statistical analyses were performed both by intention-to-treat and on-treatment methods. Results: Nine participants in the indomethacin group (16%) and 8 in the placebo group (14%) did not complete the trial. HBsAg seroconversion did not differ by treatment group (2 subjects in each group became seronegative). Hepatitis B virus DNA (HBV-DNA) became negative in sera of 7 participants in the indomethacin group but only in 1 in the placebo group (intention-to-treat p=0.06; on-treatment p=0.03). Seroconversion of HBeAg to anti-HBe occurred only in 5 participants in the indomethacin group (intention-to-treat p=0.06; on-treatment p=0.03). Adverse events included one case of hepatotoxicity and two cases of gastritis in the indomethacin group and one suspected gastritis in the placebo group. Conclusions: We suggest use of indomethacin only in the subgroup of asymptomatic HBsAg carriers who have detectable HBV-DNA or HBeAg in their sera.