title: Virological course of hepatitis A virus as determined by real time RT-PCR: Correlation with biochemical, immunological and genotypic profiles.
abstract: OBJECTIVE
  To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4(+)/ CD8(+) lymphocyte populations that control cell-mediated immunity.
  
  
  METHODS
  Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped.
  
  
  RESULTS
  Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The ALT level was significantly higher both in AHA (1070.9 +/- 894.3; P = 0.0014) and s-AH (1713.9 +/- 886.3; P = 0.001) compared to normal controls (23.6 +/- 7.2). The prothrombin time in s-AH patients (21.0 +/- 2.0; P = 0.02) was significantly higher than in AHA (14.3 +/- 1.1; P = 0.44). The CD4(+)/CD8(+) ratio in AHA patients (1.17 +/- 0.11; P = 0.22) and s-AH (0.83 +/- 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15th or 30th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT values collected during the entire course of the self-limited infection were directly correlated but this was not the case for s-AH patients.
  
  
  CONCLUSIONS
  Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.
authors.affiliation: Room No. 111, Department of Medicine, Maulana Azad Medical College, New Delhi 110002, India. hussainzahep@gmail.com
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
authors.forename: Bhudev C
authors.initials: BC
authors.lastname: Das
authors.forename: Syed A
authors.initials: SA
authors.lastname: Husain
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Polipalli
authors.forename: Tanzeel
authors.initials: T
authors.lastname: Ahmed
authors.forename: Nargis
authors.initials: N
authors.lastname: Begum
authors.forename: Subhash
authors.initials: S
authors.lastname: Medhi
authors.forename: Alice
authors.initials: A
authors.lastname: Verghese
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.forename: Apiradee
authors.initials: A
authors.lastname: Theamboonlers
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.forename: Premashis
authors.initials: P
authors.lastname: Kar
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006506:Hepatitis A / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D030041:Hepatitis A virus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D012367:RNA, Viral; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000503:physiopathology
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D000410:Alanine Transaminase