45-Year Follow-up of Hepatitis C Virus Infection in Healthy Young Adults

  1. Leonard B. Seeff, MD;
  2. Richard N. Miller, MD;
  3. Charles S. Rabkin, MD;
  4. Zelma Buskell-Bales, BS;
  5. Kelle D. Straley-Eason, MPH;
  6. Bonnie L. Smoak, MD;
  7. Leslye D. Johnson, PhD;
  8. Stephen R. Lee, PhD; and
  9. Edward L. Kaplan, MD
  1. From the Veterans Affairs Medical Center and Georgetown University School of Medicine, Institute of Medicine, and Walter Reed Army Institute of Research, Washington, D.C.; National Cancer Institute and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Ortho Clinical Diagnostics, Raritan, New Jersey; and University of Minnesota Medical School, Minneapolis, Minnesota.

    Abstract

    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.

    Article and Author Information

    • Disclaimer: The opinions and assertions contained herein are those of the authors and do not necessarily reflect the views or position of the National Academy of Sciences, the Institute of Medicine, the National Research Council, or the Department of Defense.

    • Acknowledgments: The authors thank the following: Valeria Tedeschi, PhD (Veterans Affairs Medical Center, Washington, D.C.), for performing polymerase chain reaction and genotyping studies; Dwight Johnson (University of Minnesota Medical School, Minneapolis, Minnesota); Harriet M. Crawford and Mary J. Junan (Medical Follow-Up Agency, Institute of Medicine, Washington, D.C.); and Francine Saccente and Jennifer Jones (Ortho Diagnostics, Raritan, New Jersey). They also thank Dr. Gilbert Beebe (National Cancer Institute, National Institutes of Health, Bethesda, Maryland) for his outstanding support, invaluable advice, and ever-constant wise counseling.

    • Grant Support: By the National Cancer Institute and National Institute of Allergy and Infectious Disease (through an InterAgency agreement with the Department of Veterans Affairs), the Department of Defense, and Ortho Diagnostics.

    • Requests for Reprints: Leonard B. Seeff, MD, Room 9A-18, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892-2560. For reprint orders in quantities exceeding 100, please contact the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

    • Current Author Addresses: Dr. Seeff: Room 9A-18, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892-2560.

    • Dr. Miller and Ms. Straley-Eason: Institute of Medicine, 2101 Constitution Avenue NW, Washington, DC 20418.

    • Dr. Rabkin: National Cancer Institute, 6120 Executive Boulevard, EPS 7248, Rockville, MD 20852.

    • Ms. Buskell-Bales: Veterans Affairs Medical Center, South Irving Street NW, Washington, DC 20422.

    • Dr. Smoak: Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799.

    • Dr. Johnson: National Institute of Allergy and Infectious Diseases, 6700-B Rockledge, Room 3109, Bethesda, MD 20892-7630.

    • Dr. Lee: Ortho Clinical Diagnostics, 1001 Highway 202, Raritan, NJ 08869.

    • Dr. Kaplan: Box 296, University of Minnesota Health Center Pediatrics Department, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455.

    • Author Contributions: Conception and design: L.B. Seeff, R.N. Miller, C.S. Rabkin, Z. Buskell-Bales, B.L. Smoak, E.L. Kaplan.

    • Analysis and interpretation of the data: L.B. Seeff, R.N. Miller, C.S. Rabkin, Z. Buskell-Bales, K.D. Straley-Eason, B.L. Smoak, L.D. Johnson, S.R. Lee, E.L. Kaplan.

    • Drafting of the article: L.B. Seeff, R.N. Miller, C.S. Rabkin, Z. Buskell-Bales, K.D. Straley-Eason, B.L. Smoak, L.D. Johnson, S.R. Lee.

    • Critical revision of the article for important intellectual content: L.B. Seeff, R.N. Miller, C.S. Rabkin, Z. Buskell-Bales, B.L. Smoak, S.R. Lee, E.L. Kaplan.

    • Final approval of the article: L.B. Seeff, R.N. Miller, C.S. Rabkin, Z. Buskell-Bales, B.L. Smoak, S.R. Lee, E.L. Kaplan.

    • Provision of study material or patients: L.B. Seeff, B.L. Smoak, S.R. Lee, E.L. Kaplan.

    • Statistical expertise: R.N. Miller, C.S. Rabkin, K.D. Straley-Eason, S.R. Lee.

    • Obtaining of funding: L.B. Seeff, R.N. Miller, C.S. Rabkin, B.L. Smoak, L.D. Johnson, S.R. Lee.

    • Administrative, technical, or logistic support: L.B. Seeff, Z. Buskell-Bales, B.L. Smoak, L.D. Johnson.

    • Collection and assembly of data: L.B. Seeff, R.N. Miller, Z. Buskell-Bales, B.L. Smoak, S.R. Lee, E.L. Kaplan.

    Summary for Patients

    • Summaries for Patients:45-Year Follow-up of Patients Infected with Hepatitis C as Young Adults Ann Intern Med January 18, 2000 132:105
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    1. Ann Intern Med January 18, 2000 vol. 132 no. 2 105-111
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