The etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers

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Abstract
To study the etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers, paired sera were collected in acute and convalescence phases for measurement of HBeAg, anti-HBe, hepatitis B virus DNA and anti-delta from 76 adult patients with acute hepatitis who were HBsAg positive but IgM anti-HBc negative or positive only at low titer. None of them were IgM anti-hepatitis A virus positive on admission. Of the 34 patients who were HBeAg positive initially, two (5.9%) were diagnosed as having delta superinfection, and another two (5.9%) were suspected to have non-A, non-B virus superinfection because of a transient decrease of serum hepatitis B virus DNA. The remaining 30 (88.2%) cases were hepatitis B virus DNA negative with or without anti-HBe seroconversion on follow-up. The episodes of acute hepatitis in these cases may represent “immune clearance of HBeAg” or “immune clearance of hepatitis B virus with delayed anti-HBe seroconversion,” respectively, in the natural course of chronic hepatitis B virus infection. Of the patients who were anti-HBe positive initially, 23 (54.8%) were diagnosed as having delta superinfection, including eight with de novo seroconversion of anti-delta and 15 with a rising titer of anti-delta; 10 (23.8%) were positive for hepatitis B virus DNA and were considered as reactivation of hepatitis B virus, and the other nine (21.4%) were suspected as having non-A, non-B virus superinfection. We conclude that the vast majority of episodes of acute hepatitis in HBeAg carriers may represent immune clearance of hepatitis B virus in the natural history of chronic hepatitis B virus infection, and, by contrast, in anti-HBe carriers they are usually the result of superinfection with other non-B viruses, the majority of which are due to delta superinfection.