Clinical, biochemical, immunological and virological profiles of, and differential diagnosis between, patients with acute hepatitis B and chronic hepatitis B with acute flare

Background and Aim: In areas with high or intermediate endemicity for chronic hepatitis B virus (HBV) infection, it is difficult to distinguish acute hepatitis B (AHB) from chronic hepatitis B with an acute flare (CHB‐AF) in patients whose prior history of HBV infection has been unknown. The present study aimed to screen laboratory parameters other than immunoglobulin M antibody to hepatitis B core antigen (IgM anti‐HBc) to discriminate between the two conditions. Methods: A retrospective and prospective study was conducted in patients first presenting clinically as HBV‐related acute hepatitis to sort out acute self‐limited hepatitis B (ASL‐HB). Then, clinical and laboratory profiles were compared between patients with ASL‐HB and CHB‐AF. Parameters closely associated with ASL‐HB were chosen to evaluate sensitivity, specificity, accuracy, positive predictive values and negative predictive values for diagnosing AHB. Results: There were significant differences between patients with ASL‐HB and CHB‐AF in relation to clinical and laboratory aspects, with many outstanding differences in levels of serum HBV‐DNA, hepatitis B e antigen (HBeAg) and alpha‐fetoprotein (AFP) as well as IgM anti‐HBc. In particular, there was a greater difference between the two groups in low levels of HBeAg (ratio of the optical density of the sample to the cut‐off value [S/CO] <20) than in negativity for HBeAg (42.7% and 13.5% vs 49.3% and 45.9%). 1:10 000 IgM anti‐HBc had a sensitivity and specificity of 96.2% and 93.1%, respectively, for predicting ASL‐HB. Combining it with AFP, HBeAg or HBV‐DNA could improve diagnostic power. A combination of IgM anti‐HBc, HBV‐DNA 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 HBV‐DNA. Adding AFP to the combinations of IgM anti‐HBc and HBV‐DNA or HBeAg could further heighten the positive predictive value. The positive predictive value and negative predictive value of the combination of IgM anti‐HBc, HBV‐DNA and AFP were both 100.0%. Conclusions: (i) There are significant differences with respect to clinical, biochemical, immunological and virological aspects between ASL‐HB and CHB‐AF. (ii) Of several diagnostic combinations, IgM anti‐HBc jointing HBV‐DNA is most effective and most practicable in distinguishing ASL‐HB from CHB‐AF. (iii) A low HBeAg level is more useful than negative HBeAg in differential diagnosis between ASL‐HB and CHB‐AF. (iv) In those patients with a high level of IgM anti‐HBc, serum AFP level >10× upper reference limit could rule out a probability of ASL‐HB.