326 The Korean Journal of Hepatology Vol. 17. No. 4, December 2011 incremental dose therapy, the patient became gradually transfusion-independent with increase of Hb level to 12.1 g/dL. Liver function tests showed AST of 22 IU/L, ALT 136 IU/L, alkaline phosphatase 285 IU/L, gamma-glutamyl transferase (GGT) 897 IU/L, and total bilirubin of 5.4 mg/dL. To exclude the possibility of fibrosing cholestatic hepatitis associated with immunosuppressive therapy, percutaneous liver biopsy was undertaken on February 12, which revealed hepatocellular and canalicular cholestasis, hepatocyte ballooning, and lobular spotty necrosis compatible with cholestatic hepatitis and extramedullary hematopoiesis (Fig. 2). Immunohistochemical staining was performed for detection of HAV antigens and HEV antigens using HAV antibody (Purified HAV, Abcam, Cambridge, UK; mouse monoclonal, 1:50) and HEV antibody (Abbiotec, CA, USA; 1:200), respectively. Strong cytoplasmic staining for HAV was noted, whereas staining was absent in specimens used for negative control (Fig. 3). In this case, there was no staining for HEV antigen (data not shown). After a 2 month-period of gradual tapering of prednisolone, complete recovery of liver function was achieved at 5 months after the patient’s initial admission. However, his IgM anti-HAV was positive until May 29, while both IgM anti- HEV and IgG anti-HEV (Genelabs Diganostics, Singapore) were negative. During the course of his illness, serial serum samples were available for detection of HAV RNA and HEV RNA, according to the method described in previous studies.4 All HAV RNA-positive samples were sequenced using the BigDye Terminator (ABI Prism 377 automatic sequencer, Toroed, Norway). Interestingly, initial HAV detected on January 14, 2009 was genotype IA, which was subsequently replaced by HAV genotype IIIA during the later phase of the illness (April 22, 2009), while HEV RNA was not detected by Okamoto’s method, as previously reported.5,6 DISCUSSION This report described a case of acute viral hepatitis coinfected by HAV genotype IA and genotype IIIA complicated with severe autoimmune hemolytic anemia, prolonged cholestasis, and coexistence of IgM anti-HEV, which was successfully treated by high dose (1.5 mg/kg/day) prednisolone therapy. There have been a few reports of severe Coombs-positive AIHA with or without pure red cell aplasia, complicating acute viral hepatitis.7 However, coinfection of HAV genotype IA and IIIA complicated with severe AIHA has not been reported. Genotype 1A HAV was a major genotype in Korea, however, during recent nationwide outbreak of hepatitis A, a rapid genotypic shift from genotype IA to IIIA has occurred.4,8 Therefore, at least two genotypes of HAV co-circulate in Korea. Coinfection of the HAV genotype IA and IIIA was a peculiar finding in this case. From onset of symptoms to development of AIHA, HAV genotype IA was consistently detected in the patient’s plasma and stool. Subsequently, during prolonged follow-up, his HAV genotype was replaced from genotype IA to IIIA. This replacement can be explained by initially mixed infection of HAV genotype IA and IIIA with a dominant population of HAV genotype IA and reciprocal inhibition of genotype IIIA. During his initial hepatitis course, vigorous immune responses may have controlled HAV genotype IA up to an undetectable level, and subsequent strong immunosuppression for the treatment of hemolytic anemia may support replication of HAV genotype IIIA, a minor population. To our knowledge, this is the first case of coinfection of hepatitis A genotype IA and IIIA documented. Coppola et al9 reported a case of acute hepatitis A complicated with prolonged cholestasis and coinfection of genotype IA and IB, and suggested that coinfection of two HAV subgenotypes may be a reason for prolonged cholestasis and viremia due to impairment of antibody production or neutralizing activity on the basis of the simultaneous antigenic stimulatory effect of the two HAV isolates. However, HAV has only one common serotype, and this finding was not supported by experimental data. The interesting finding of this case was that IgM anti- HEV at the first manifestation was negative, which turned out to be positive at the initiation of hemolytic anemia. Afterwards, the transiently positive result for IgM anti-HEV turned out to be negative, along with a negative result for IgG anti-HEV during the follow-up period. Both hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can be transmitted by the fecal-oral route with similar incubation periods and clinical presentations. Among patients with sporadic acute viral hepatitis, cases showing simultaneously positive results for immunoglobulin M (IgM) anti-HAV and IgM anti-HEV have been reported, and were regarded as coinfection of HAV and HEV.10,11 However, HEV RNA was not detected in serum and stool samples, while HAV RNA