Hepatitis B virus is a common cause of cirrhosis, end-stage liver disease, and hepatocellular carcinoma, especially in areas with high rates of HBV infection. Although short-term studies have shown that tenofovir and other antiviral drugs can improve hepatic histopathological changes, however, the prolonged therapeutic effect of the above drugs against severe liver fibrosis or cirrhosis has not been established. Currently, researchers have evaluated the long-term effects of tenofovir on hepatic histopathological changes by studying a large number of HBV-infected patients. The study was based on another double-blind, phase III clinical trial with 641 patients that compared tenofovir with adefovir for 48 weeks. The investigators enrolled 585 of these patients in an open-label study funded by the manufacturer. In this study, participants will receive tenofovir treatment for an additional 7 years. Of these patients, 348 have had liver biopsies at baseline levels and after 240 weeks of treatment. At year 5 of treatment, 87% of patients had improved liver histopathological changes; those with the most severe pre-treatment liver injury showed the most significant improvement. Of particular note, 74% of the 96 patients with pre-treatment cirrhosis no longer had cirrhosis after 5 years of treatment. Patients with lower body mass index were more likely to have recurrent liver fibrosis. Only 12 patients developed hepatocellular carcinoma, and only 2 developed decompensated liver disease. Virologic breakthrough rarely occurred and no resistance to tenofovir was detected. This large trial demonstrated that long-term suppression of HBV viral replication improved hepatic histopathological changes, even in patients who developed cirrhosis prior to treatment. The lower incidence of hepatocellular carcinoma and end-stage liver disease in patients treated with tenofovir suggests that effective antiviral therapy improves the quality of survival, which is consistent with the findings of recent studies of successful treatment of hepatitis C virus infection.