Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels

Hepatology. 2012 Mar;55(3):676-84. doi: 10.1002/hep.24732. Epub 2012 Jan 31.

Abstract

Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV-ALFs and 16 of 23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86 (P < 0.001). AHBV-ALF median admission VL was 3.9 (0-8.1) log10 IU/mL versus 5.2 (2.0-8.7) log10 IU/mL for CHBV-ALF (P < 0.025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P = 0.030).

Conclusions: AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Anti-Idiotypic / blood
  • DNA, Viral / blood*
  • Diagnosis, Differential
  • Female
  • Genotype
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Core Antigens / blood
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / immunology
  • Hepatitis B virus* / isolation & purification
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / complications*
  • Humans
  • Immunoglobulin M / blood*
  • Liver / pathology
  • Liver / virology
  • Liver Failure, Acute / classification
  • Liver Failure, Acute / diagnosis*
  • Liver Failure, Acute / virology*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Young Adult

Substances

  • Antibodies, Anti-Idiotypic
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Immunoglobulin M