The natural history of asymptomatic hepatitis B surface antigen carriers

Ann Intern Med. 1993 Feb 1;118(3):191-4. doi: 10.7326/0003-4819-118-3-199302010-00006.


Objective: To assess the long-term outcome in hepatitis B surface antigen (HBsAg) carriers who have normal liver function tests, focusing on survival and the development of severe liver disease and hepatocellular carcinoma.

Design: Cohort study with a mean follow-up of 130 months.

Setting: Liver clinic of a referral center.

Patients: Ninety-two HBsAg-positive blood donors with normal liver function tests.

Measurements: Histologic evaluation of liver specimens at baseline; clinical, biochemical, and serologic follow-up; and repeat liver biopsy if clinically indicated or after 10 years of follow-up.

Results: At baseline, 69 subjects had normal histologic findings or only minor abnormalities, 18 had chronic persistent hepatitis, and 5 had mild chronic active hepatitis. Serum enzyme levels remained normal in 58 of 68 patients who had regular follow-up. Three patients had biochemical changes consistent with hepatitis B virus (HBV) infection; in one of these patients, a later histologic evaluation showed progression to chronic active hepatitis. One patient developed alcoholic cirrhosis. Six other patients had mild or transient transaminase elevations, with no evidence of HBV replication, hepatitis D virus infection, hepatitis C virus (HCV) infection, or histologic deterioration. Liver histologic findings also remained unchanged in 21 patients who showed no biochemical changes during 10 years of follow-up and consented to have repeated liver biopsy. Ten patients showed loss of HBsAg; 2 of these patients acquired antibody to hepatitis B surface antigen (anti-HBs). All patients who did not have regular follow-up, except 1, were interviewed by telephone during 1990: All denied having liver disease. No patients developed hepatocellular carcinoma.

Conclusions: Italian HBsAg carriers with initially normal liver function tests have an excellent prognosis: Delta superinfection is infrequent and the risk for developing hepatocellular carcinoma is low.

MeSH terms

  • Adult
  • Carrier State / blood
  • Carrier State / pathology
  • Carrier State / physiopathology*
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Hepatitis Antibodies / blood
  • Hepatitis B / blood
  • Hepatitis B / pathology
  • Hepatitis B / physiopathology*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / genetics
  • Humans
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Middle Aged
  • Transaminases / blood
  • Virus Replication


  • DNA, Viral
  • Hepatitis Antibodies
  • Hepatitis B Surface Antigens
  • Transaminases