Analysis of the genotype-determining region of hepatitis A viral RNA in relation to disease severities

Although hepatitis A is still a considerable problem in Japan, correlation of genomic differences of hepatitis A virus (HAV) and the clinical status of hepatitis A has not been studied. To examine whether the HAV genotype is associated with the disease severity, we analyzed the HAV genotype-determining region in sera from patients with hepatitis A of various clinical degrees. Serum samples from 47 Japanese patients with sporadic hepatitis A from 4 different areas in Japan, including 8 with fulminant hepatitis, 11 with severe acute hepatitis (AHs), and 28 with AHs, were examined for HAV RNA. The 168 base pair sequence of the genotype-determining region, which is located at the VP1/2A junction, was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing. By comparing sequences for VP1/2A, we determined that 44 of 47 cases examined were of subgenotype IA, two were of subgenotype IB, and one was of subgenotype IIIA. With respect to subgenotype IA strains, individuals who were infected between 1990 and 1996 tended to show similar sequences, whereas those infected between 1997 and 1999 showed sequences slightly different from those of the 1990-1996 cases. There were no apparent associations between disease severity and sequences of the genotype-determining region. Hepatitis A of our study was caused by a variety of subgenotype IA strains, consistent with the sporadic spread of infection. Disease severity was not associated with the nucleotide sequence of the HAV genotype-determining region. (C) 2002 Published by Elsevier Science B.V.