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

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. (H EPATOLOGY 2011)