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Liver Enzyme Flares and Occult HBV Infection in Patients with Untreated Chronic Hepatitis C

Occult hepatitis B virus (HBV) infection has been reported in numerous clinical settings, but it remains unclear whether occult HBV contributes to liver damage. Given that typical chronic HBV infection is often characterized by periodic flares in viral replication and liver inflammation, investigators from Johns Hopkins School of Medicine hypothesized that occult HBV might also be associated with flares in viral replication that are associated with increased liver enzyme levels.

The researchers screened hepatitis B surface antigen (HBsAg) negative injection drug users with untreated chronic hepatitis C for unexplained alanine aminotransferase (ALT) and aspartate aminotransferase (AST) flares.

To further enrich for individuals with possible occult HBV flares, they studied patients whose flares were associated with IgM antibodies to hepatitis B core antigen (HBcAg). Serum samples were tested for HBV DNA and serological testing was performed on serum collected 6 months before, during, and 6 months after the occurrence of flares. HCV RNA levels were also determined. Individuals who experienced ALT/AST flares but were negative for IgM antibodies to HBcAg served as control subjects.


  • 7 case patients with IgM antibodies and 8 control subjects were identified.
  • HBV DNA was detectable during liver enzyme flares in all 7 IgM positive patients compared with 3 of the 8 control subjects (P = 0.026).
  • Overall, HBV DNA levels during flares were low, averaging 1943 (+/-2341) copies/mL.
  • However, HBV viral loads were higher in case patients compared with control subjects (P = 0.002).
  • Liver enzyme flares were not associated with changes in HCV levels.

"In this population at high risk for occult HBV, AST/ALT flares can be associated with detection of HBV DNA," the authors concluded. "These findings may link occult hepatitis B to liver injury."



R Kannangai, P Vivekanandan, D Netski, and others. Liver enzyme flares and occult hepatitis B in persons with chronic hepatitis C infection. Journal of Clinical Virology 39(2): 101-105. June 2007.