Effects of indomethacin on viral replication markers in asymptomatic carriers of hepatitis B: a randomized, placebo-controlled trial.
OBJECTIVE
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).


METHODS
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.
Bahrami
Hossein
H
Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
Daryani
Nasser E
NE
Haghpanah
Babak
B
Moayyeri
Alireza
A
Moghadam
Katayoon Fayaz
KF
Mirmomen
Shahram
S
Kamangar
Farin
F
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002353:Carrier State / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007213:Indomethacin