Clinical, epidemiological and virological features of acute hepatitis B in Italy.

Purpose: To evaluate the association of hepatitis B virus (HBV) genotypes, basal core promoter (BCP)/precore (PC) and S gene mutations with the clinical-epidemiological characteristics of acute hepatitis B (AHB) in Italy.

Methods: During July 2005-January 2007, 103 symptomatic AHB patients were enrolled and prospectively followed up at 15 national hospitals. HBV genotypes, BCP/PC and S gene variants were determined by nested-PCR and direct sequence analysis.

Results: Genotype D, A and F were detected in 49, 45 and 6% of patients, respectively. BCP, PC, and BCP plus PC variants were found in 3.1, 11.3 and 7.2% of patients, respectively. At enrollment, 68.3% of patients were hepatitis B e antigen (HBeAg)-positive and 31.7% HBeAg-negative. BCP/PC mutations were more common in HBeAg-negative than in HBeAg-positive patients (p < 0.0001). Compared to genotype D patients, those harboring non-D genotypes were more frequently males (p = 0.023), HBeAg-positive (p < 0.001), had higher bilirubin (p = 0.014) and viremia (p = 0.034) levels and less frequently carried BCP/PC mutations (p < 0.001). Non-D genotype patients more often were from Central Italy (p = 0.001) and reported risky sexual exposure (p = 0.021). Two patients had received vaccination before AHB: one harbored genotype F; the other showed a S gene mutation. Four patients developed fulminant AHB; mutations were found in 2 of 3 patients who underwent BCP/PC sequencing. After a 6-month follow-up, only 2 (2.8%) patients developed persistent infection.

Conclusion: AHB by non-D genotypes is increasing in Italy and is associated with risky sexual exposure. The ability of some genotypes to cause persistent and/or severe infection in Italy warrants larger studies for clarification.