Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease

N Engl J Med. 1999 Jul 1;341(1):22-6. doi: 10.1056/NEJM199907013410104.


Background: Hepatitis B virus (HBV) infections in patients who lack detectable hepatitis B surface antigen (HBsAg) are called occult infections. Although such infections have been identified in patients with chronic hepatitis C liver disease, their prevalence and clinical significance are not known.

Methods: With the polymerase chain reaction, we searched for HBV DNA in liver and serum samples from 200 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (147 with chronic hepatitis, 48 with cirrhosis, and 5 with minimal histologic changes). One hundred of the patients had detectable antibodies to the HBV core antigen (anti-HBc); 100 were negative for all HBV markers. Eighty-three were treated with interferon alfa. We also studied 50 patients with liver disease who were negative both for HBsAg and for HCV markers. In six patients found to have occult HBV infection, we evaluated possible genomic rearrangements through cloning or direct sequencing procedures.

Results: Sixty-six of the 200 patients with chronic hepatitis C liver disease (33 percent) had HBV sequences, as did 7 of the 50 patients with liver disease unrelated to hepatitis C (14 percent, P=0.01). Among the 66 patients, 46 were anti-HBc-positive and 20 were negative for all HBV markers (P<0.001). Twenty-two of these 66 patients (33 percent) had cirrhosis, as compared with 26 of the 134 patients with hepatitis C infection but no HBV sequences (19 percent, P=0.04). HBV sequences were detected in 26 of the 55 patients in whom interferon therapy was ineffective and 7 of the 28 patients in whom interferon therapy was effective (P=0.06). None of the sequenced HBV genomes had changes known to interfere with viral activity and gene expression.

Conclusions: Occult hepatitis B infection occurs frequently in patients with chronic hepatitis C liver disease and may have clinical significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • DNA, Viral / analysis*
  • DNA, Viral / blood
  • Female
  • Genome, Viral*
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis B / complications*
  • Hepatitis B / diagnosis
  • Hepatitis B / epidemiology
  • Hepatitis B / virology
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use
  • Liver / chemistry
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Interferon-alpha