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.

Copyright © 2011 American Association for the Study of Liver Diseases.

Figures

Figure 1. Study schema

Of the 1,602 acute liver failure (ALF) patients in the US ALF Study Group, there were 105 hepatitis B virus-related ALF (HBV-ALF) patients identified. Eighteen were excluded: 2 co-infected with hepatitis C virus, one determined to have hepatocellular carcinoma and 15 whom we were unable to define as either acute or chronic. Sixty were identified as AHBV-ALF of whom 47 had sera collected on admission and 14 had sera collected serially up to the 4th day. Twenty-seven patients were identified as CHBV-ALF; 9 appeared to show spontaneous exacerbation (non-immunosuppressed CHBV-ALF) and 18 were considered immunosuppressed; admission and serial sera over 4 days in these groups are also listed.

Figure 2. IgM anti-HBc levels for the various groups

Admission IgM anti-HBc levels were much higher in AHBV-ALFs than in the overall CHBV-ALF group. Median IgM anti-HBc index value (signal/noise), on admission to hospital in the 46 AHBV-ALFs was 88.5 (0–1,120), significantly higher than that of the 23 overall CHBV-ALFs [1.30 (0–750), p

Figure 3. Hepatitis B viral loads for the various groups

Median admission viral load (VL) in 51 patients with AHBV-ALF was 3.9 (0–8.1) log10 IU/mL, significantly lower than observed for the 24 patients in the overall CHBV-ALF group [5.2 (2.0–8.7) log10 IU/mL, p=0.025], but not for the 8 non-immunosuppressed CHBV-ALF patients [3.8 (2.5–8.7) log10 IU/mL, p=0.982]. The median (range) for the 16 in the immunosuppressed subgroup was 6.28 (1.97–8.28) log10 IU/mL. There were no significant differences in admission VLs between the two CHBV-ALF subgroups; horizontal line in each bar graph represents median VL.

Figure 4. ANCOVA for VLs measured over time for AHBV-ALF and the overall CHBV-ALF groups adjusting for baseline IgM anti-HBc levels

The decrease in VLs was significant for each of the two groups (p