Using a nested-PCR genotyping system, we analyzed the viral genotypes in HBV-infected patients from HBV clustering infection families (CIFs), as compared with HBV infected patients without familial infection history. The patients in the CIF group showed significantly increased prevalence of genotype C infection, while genotype B was absent. Additionally, in the genotype C carriers younger than 50 years old, the prevalence of HCC and LC were significantly increased in CIF compared to the control. We found that HBeAg-positive HBV genotype C carriers are prone to develop end-stage liver diseases earlier than those infected by genotype B.