Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection

Background & Aims: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance is a rare event in patients with chronic hepatitis B virus infection. The aim of this study was to clarify the controversy on long-term prognosis following spontaneous HBsAg seroclearance using a large series of patients. Methods: A total of 218 patients (172 men and 46 women) who had undergone spontaneous HBsAg seroclearance were followed up for 12-179 months (median, 61.7 months; mean, 63.4 +/- 38.5 months) with liver biochemistry, serology, measurement of alpha-fetoprotein level, and abdominal ultrasonography every 6 months or every 3 months for the 29 patients who had developed cirrhosis at the time of HBsAg seroclearance. Results: Of the 189 patients who were noncirrhotic at the time of HBsAg clearance, 3 (16%) developed cirrhosis, 2 (1.1%) developed hepatocellular carcinoma (HCC), and 1 died of HCC. These complications all developed in patients with concurrent hepatitis C virus or hepatitis delta virus infection (P < 0.001). The prognosis of the noncirrhotic patients without concurrent infection was significantly better than that of the matched control group (elevation of alanine aminotransferase level, 11.6% vs. 0%, P < 0.001; development of cirrhosis/HCC, 4% vs. 0%, P = 0.004). In contrast, of the 29 patients who had developed liver cirrhosis, 4 (13.8%) had hepatic decompensation and one died of HCC. Conclusions: The prognosis following spontaneous HBsAg seroclearance is excellent, except in patients with cirrhosis or those with concurrent hepatitis C virus or hepatitis delta virus infection.