HBsAg Seroclearance in Chronic Hepatitis B in Asian Patients: Replicative Level and Risk of Hepatocellular Carcinoma

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 135; no. 4; pp. 1192 - 1199
• Main Authors: Yuen, Man–Fung, Wong, Danny Ka–Ho, Fung, James, Ip, Philip, But, David, Hung, Ivan, Lau, Kevin, Yuen, John Chi–Hang, Lai, Ching–Lung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2008
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group - statistics & numerical data; Carcinoma, Hepatocellular - ethnology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Child; Child, Preschool; DNA, Viral - blood; Female; Follow-Up Studies; Gastroenterology and Hepatology; Hepatitis B Antibodies - blood; Hepatitis B Surface Antigens - immunology; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - ethnology; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - pathology; Hong Kong - epidemiology; Humans; Infant; Liver - pathology; Liver - virology; Liver Cirrhosis - ethnology; Liver Cirrhosis - pathology; Liver Cirrhosis - virology; Liver Neoplasms - ethnology; Liver Neoplasms - pathology; Liver Neoplasms - virology; Longitudinal Studies; Male; Middle Aged; Risk Factors; Seroepidemiologic Studies; Hong Kong; chronic hepatitis B; cccDNA; CHB; covalently closed circular DNA
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2008.07.008

Background & Aims: Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance. Methods: We determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n = 229), liver histology, serum HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression. Results: The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages ≥50 years compared with those with HBsAg seroclearance at ages <50 ( P = .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement ( P = .001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5–10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels. Conclusions: HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.