ANALYSES OF HEPATITIS A VIRUS GENOME FROM PATIENTS WITH FULMINANT TYPE A HEPATITIS

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Hepatitis A still possess a considerable problem not only in underdeveloped but also in developed countries. It is not revealed why some patients progress to fulminant hepatitis A and others do not. To examine whether genomic differences of hepatitis A virus (HAV) are responsible for the clinical severity, we are analyzing whole nucleotide sequences of HAV RNA in sera from fulminant and acute hepatitis A patients. We clarified that the severity of hepatitis A appears to be associated with the substitutions near the central part of the 5' nontranslated region of HAV,because in the cases with fulminant hepatitis only a small number of substitutions were observed while in the cases with self limited acute hepatitis considerable numbers of substitutions were observed. We further determined the sequences of structural protein region of HAV.Sera from 3 fulminant and 3 acute hepatitis A patients were examined. Structural region and non-strauctural regions of HAV RNA were amplified by long reverse transcription-polymerase chain reaction (RT-PCR) devided into 3188 bp including structural protein region and 4688 bp including non-structural protein region. Each PCR product was cloned and the nucleotide sequence of structural protein region was sequenced by automated sequencer. The genotypes of examined cases were all genotype1A.There were no such obvious differeces in structural protein region as found in 5' nontranslated region between fulminant and acute hepatitis A.We are now examining the sequences of non-structural protein region of HAV.