title: 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.
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887, USA.
authors: Doan Y
authors: DY
authors: Dao
authors: Linda S
authors: LS
authors: Hynan
authors: He-Jun
authors: HJ
authors: Yuan
authors: Corron
authors: C
authors: Sanders
authors: Jody
authors: J
authors: Balko
authors: Nahid
authors: N
authors: Attar
authors: Anna S F
authors: AS
authors: Lok
authors: R Ann
authors: RA
authors: Word
authors: William M
authors: WM
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008099:Liver / Q000473:pathology / Q000821:virology; D017114:Liver Failure, Acute / Q000145:classification / Q000175:diagnosis* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D007075:Immunoglobulin M