title: Association between severity of type A hepatitis and nucleotide variations in the 5' non-translated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions.
abstract: BACKGROUND
  Type A hepatitis is still a considerable problem in both underdeveloped and developed countries. Why some patients progress to fulminant type A hepatitis and others do not is unclear.
  
  
  OBJECTIVE
  To determine if nucleotide differences in the genome of hepatitis A virus (HAV) are responsible for the range of clinical severities, we analysed the 5' non-translated region (5'NTR) of the HAV genome, which has an internal ribosomal entry site and is important for cap independent translation of the viral message.
  
  
  METHODS
  Serum samples from 84 Japanese patients with sporadic type A hepatitis from five distant regions of Japan, comprising 12 patients with fulminant hepatitis (FH), 13 with severe acute hepatitis (AHs), and 59 with acute hepatitis (AH), were examined for HAV RNA. The fragment between nucleotides 75 and 638 of the 5'NTR was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing.
  
  
  RESULTS
  Comparison of sequences of the 5'NTR revealed relatively fewer nucleotide substitutions in FH and AHs patients compared with the considerable sequence variations found in strains of AH. This tendency was most prominent between nucleotides 200 and 500. Strains from FH and AHs cases had fewer nucleotide substitutions (p<0.001) in this region.
  
  
  CONCLUSIONS
  Nucleotide variations in the central portion of the 5'NTR of HAV may influence the severity of type A hepatitis.
authors.affiliation: First Department of Internal Medicine, Chiba University School of Medicine, Chiba, Chiba 260-8670, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: O
authors.initials: O
authors.lastname: Yokosuka
authors.forename: T
authors.initials: T
authors.lastname: Ehata
authors.forename: H
authors.initials: H
authors.lastname: Saisho
authors.forename: N
authors.initials: N
authors.lastname: Saotome
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Okita
authors.forename: K
authors.initials: K
authors.lastname: Kiyosawa
authors.forename: M
authors.initials: M
authors.lastname: Omata
mesh_terms: D020121:5' Untranslated Regions; D000208:Acute Disease; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D006506:Hepatitis A / Q000821:virology*; D017957:Hepatitis A Virus, Human / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D020121:5' Untranslated Regions; D018076:DNA, Complementary; D004279:DNA, Viral; D012367:RNA, Viral