Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels

Gastroenterology. 2000 Apr;118(4):760-4. doi: 10.1016/s0016-5085(00)70145-4.


Background & aims: Some patients with serum hepatitis C virus (HCV) have persistently normal aminotransferase (ALT) levels and are affected by cirrhosis. This study prospectively evaluated progression of the disease in a group of anti-HCV-positive patients with persistently normal ALT levels.

Methods: Thirty-seven subjects were studied. Each subject underwent liver biopsy at baseline and after 5 years of follow-up. At baseline, serum samples were tested for genotypes and HCV RNA load. ALT levels and serum HCV RNA were tested every other month and every 6 months, respectively. Patients with increased ALT were discharged from the study and treated with IFN. Five years after the end of IFN therapy, a liver biopsy was performed.

Results: Liver biopsy at baseline showed chronic hepatitis in 34 patients and normal histology in 3 patients, 2 of whom were negative for HCV RNA and 1 positive. HCV genotypes were distributed as follows: 2a, 56%; 1b, 41%; and 1a, 3%. At the end of 7-year follow-up, 73% of the patients still had normal ALT values. Liver histology after 5 years was comparable to that observed at entry to study.

Conclusions: Most patients with persistently normal ALT serum levels have very mild chronic hepatitis. However, healthy anti-HCV-positive subjects exist. In patients with HCV-related chronic hepatitis associated with persistently normal ALT levels, the grade of disease activity does not increase over years and progression to cirrhosis is slow or absent.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Biopsy
  • Carrier State / blood
  • Carrier State / pathology
  • Carrier State / physiopathology*
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C*
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Reference Values


  • RNA, Viral
  • Alanine Transaminase