45-year follow-up of hepatitis C virus infection in healthy young adults

Ann Intern Med. 2000 Jan 18;132(2):105-11. doi: 10.7326/0003-4819-132-2-200001180-00003.


Background: The sequelae during the first two decades after acute hepatitis C virus (HCV) infection have been well studied, but the outcome thereafter is unknown.

Objective: To conduct an extended study of the natural history of HCV infection by using archived serum specimens originally collected between 1948 and 1954.

Design: Retrospective cohort study.

Setting: A university, a Veterans Affairs medical center, and a medical follow-up agency that had access to the serum specimens and accompanying demographic and medical records.

Participants: 8568 military recruits who were evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954. Blood samples were taken from the recruits and, after testing, were stored frozen for almost 45 years.

Measurements: The presence of antibodies to HCV was determined by enzyme-linked immunoassay, supplementary recombinant immunoblot assay, and polymerase chain reaction for HCV RNA. Morbidity and mortality were also assessed.

Results: Of 8568 persons, 17 (0.2%) had positive results on enzyme-linked immunosorbent assay and recombinant immunoblot assay. The rate was 1.8% among the African-American persons and 0.1% among the white persons in the total sample (relative risk, 25.9 [95% CI, 8.4 to 80.0]). During the 45-year follow-up, liver disease occurred in 2 of the 17 HCV-positive persons (11.8%) and 205 of the 8551 HCV-negative persons (2.4%) (ethnicity-adjusted relative risk, 3.56 [CI, 0.94 to 13.52]). Seven of the 17 HCV-positive persons (41 %) and 2226 of the 8551 HCV-negative persons (26%) had died by December 1996 (ethnicity-adjusted relative risk, 1.48 [CI, 0.8 to 2.6]). Of persons who were HCV-positive, 1 (5.9%) died of liver disease 42 years after the original phlebotomy, 5 (29%) died of non-liver-related disease a median of 37 years after the original phlebotomy, and 1 (5.9%) died of unknown causes. One hundred nineteen HCV-negative persons (1.4%) died of liver disease.

Conclusions: The rate of HCV infection from 1948 to 1954 among a sample of military recruits parallels that among present-day military recruits and volunteer blood donors. During 45 years of follow-up, HCV-positive persons had low liver-related morbidity and mortality rates. This suggests that healthy HCV-positive persons may be at less risk for progressive liver disease than is currently thought.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Cause of Death
  • Data Interpretation, Statistical
  • Disease Progression
  • Follow-Up Studies
  • Hepacivirus / immunology
  • Hepatitis C / complications*
  • Hepatitis C / diagnosis
  • Hepatitis C / mortality
  • Hepatitis C Antibodies / blood
  • Humans
  • Liver Diseases / epidemiology
  • Liver Diseases / etiology*
  • Liver Diseases / mortality
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Retrospective Studies
  • Survival Rate


  • Hepatitis C Antibodies