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 >10x upper reference limit could rule out a probability of ASL-HB.