Abstract OBJECTIVE: We aimed to investigate the association of viral genotype and the development of icteric flare-up (IF) in chronic hepatitis B virus (HBV) infection. METHODS: Twenty-one consecutive patients suffering from IF of chronic HBV infection, defined as elevation of ALT over five times the upper limit of normal, together with either bilirubin >50 IU/L or elevated bilirubin plus PT >3 s prolonged, were studied. Patients from three stages of HBV-related chronic liver disease were studied as controls: 1) asymptomatic carriers (31 patients), defined as persistent normal ALT for at least 2 yr; 2) active early cirrhosis (49 patients), defined as Child’s A liver cirrhosis plus HBV DNA >10 6 Eq/ml; and 3) decompensated cirrhosis (31 patients), defined as Child’s B or C liver cirrhosis with complications. Restriction fragment length polymorphism was used for genotyping. RESULTS: Only genotype B and C HBV were identified in our studied cohort. Ninety-one percent of patients suffering from IF were infected by genotype B HBV ( p <0.001 vs asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients). On the contrary, genotype C HBV was the predominant strain at different stages of chronic liver disease; no statistical difference was found on the relative prevalence of genotype B/C HBV among asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients. CONCLUSIONS: Genotype B HBV is associated with IF among chronic HBV-infected patients in Hong Kong, whereas genotype C HBV is more prevalent at all stages of chronic liver disease. Our findings suggested that the two different HBV genotypes might have different pathogenic mechanisms of liver damage.