Long-term outcome in Caucasian patients with chronic hepatitis B virus infection after HBsAg seroclearance.

Background & Aims: The natural course after hepatitis B surface antigen (HBsAg) seroclearance in Caucasian patients with chronic hepatitis B virus (HBV) infection is not well-defined. To investigate the clinical characteristics and outcome in a series of European Caucasian patients with chronic HBV infection according to HBsAg response over time.

Methods: A total of 612 patients with compensated chronic HBV infection and without other cause of liver disease were prospectively followed up. Seventy-eight subjects cleared HBsAg and 534 remained HBsAg-positive. Clinical and virological examinations were periodically performed and development of cirrhosis and liver-related complications was monitored during a mean follow-up time of 9.9 years.

Results: After HBsAg seroclearance, serum HBV DNA was undetectable in 38 patients in whom it was tested and HBsAg reappearance was observed in two subjects (2.6%). At 15 years of follow-up, the cumulative probability of developing a liver-related complication was 11.6% in HBsAg-positive patients and 1.8% in those with HBsAg loss (P = 0.03), although this benefit was limited to patients with cirrhosis (P < 0.001) and to those who received therapy (P < 0.01). Among patients without cirrhosis and among those who did not receive therapy, the probability was not different between those who cleared the HBsAg and those who did not (P = 0.3 and P = 0.5 respectively).

Conclusion: Hepatitis B surface antigen loss confers a significant clinical benefit in Caucasian subjects with HBV-related cirrhosis and in those with chronic HBV infection who receive antiviral therapy. However, HBsAg reappearance can be observed in selected cases.