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

Background Hepatitis B virus-related acute liver failure (HBV-ALF) may occur following 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 prior history of hepatitis B is not available. Quantitative measurements of anti-hepatitis B core immunoglobulin M (IgM anti-HBc) titers and of HBV viral loads (VLs) might allow separation of acute from chronic HBV-ALF. Methods Of 1602 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) to determine HBV VLs. Results 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, vs. 1.3, 0–750, p<0.001); a cut point for S/N ratio of 5.0 correctly identified 44/46 (96%) AHBV-ALFs and 16/23 (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, vs. 5.2 (2.0–8.7) log10 IU/mL for CHBV-ALF, p<0.025. Twenty percent (12/60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, while no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20/60) for AHBV-ALF vs. 11% (3/27) 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.

Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

“…Adding AFP to the combinations of IgM anti-HBc and HBV DNA or HBeAg could further heighten the positive predictive value. Dao et al 83 also found that a low or undetectable IgM anti-HBc, with elevated HBVDNA viral load > log10 IU/ mL, in a patient with what appears to be an acute illness, suggests that the patient probably has CHB-AE. They showed that the ratio of IgM anti-HBc to HBV viral load was higher in liver failure related to AVH-B than CHB-AE.…”

“…Dao et al 83 found that in HBV related acute liver failure (ALF), the viral loads at admission were lower in patients with AVH-B than in CHB-AE [3.9 (0-0.81) log10 IU/mL vs. 5.2 (2.0-8.7) IU/mL (P < 0.025)]. There was a significant overlap in admission viral loads between AVH-B and CHB-AE related ALF.…”

“…Dao et al 83 found that, the IgM anti-HBc levels by quantitative immunoassay were much higher in liver failure related to CHB-AE than in liver failure related to AVH-B with a signal-to-noise (S/N) ratio of 5.0 identifying 96% of AVH-B.…”

“…71 An early HBsAg clearance has been observed in 20% patients of AVH-B liver failure who had undetectable HBsAg on admission. 83 HBsAg becomes negative in the majority of AVH-B. Hence if the HBsAg continues to be positive six months after initial presentation of HBsAg-positive acute hepatitis patient, it suggests CHB-AE.…”

“…71,83 Kumar et al 8 found a combination of anti-HBeAg positivity, IgM anti-HBc titers < 1000, and HBVDNA >0.5 pg/mL were found to be useful in diagnosing CHB-AE (P < 0.01). Han et al 71 also found that a combination of IgM antiHBc, HBVDNA and HBeAg had a predictive value of 98.9% and a negative predictive value of 100.0%, similar to that of a combination of IgM anti-HBc and HBVDNA.…”