Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection. Whereas, the long-term effect of TAF to liver fibrosis is still unknown. Here, we enrolled treatment naive CHB patients with biopsy-proven significant fibrosis (METAVIR fibrosis stage ≥ F2). All enrolled subjects will be treated with TAF monotherapy for 96 weeks. After 96 weeks of therapy, the second liver biopsy will be performed to evaluate the rate of liver fibrosis regression. During this study, all subjects will be assessed for laboratory tests, imaging examination at baseline, first 12-week and every 24-week during follow-up.

Inclusion Criteria:

• 18-69 years old (inclusive);
• BMI (18-30 kg/m2);
• Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months; or chronic hepatitis B proven by live biopsy;
• Not received nucleoside (acid) analogue and/or interferon therapy (treatment-naive);
• Liver biopsy performed within 6 months before treatment and had readable biopsy slides or agrees to have a biopsy performed prior to baseline;
• METAVIR fibrosis stage ≥ F2;
• For patients without cirrhosis (F2/3), HBV DNA levels >2000 IU/mL before treatment; For patients with cirrhosis (F4), HBV DNA >20 IU/mL before treatment;
• ALT≤10 ULN before treatment;
• Creatinine clearance ≥ 50 mL/min;
• Agreement not to undertake other HBV systemic antiviral or interferon (IFN) regimens during participation in this study;
• Willing and able to provide written informed consent.

Exclusion Criteria:

• Patients with Child-Turcotte-Pugh（CTP）score ≥ 7;
• Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or liver transplantation;
• Patients co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV), or alcoholic liver diseases, autoimmune liver disease, genetic liver disease, drug-induced liver injury, non-alcoholic fatty liver disease or other chronic liver diseases;
• Patients with evidence of hepatocellular carcinoma (HCC) by imaging with or without AFP;
• Patients with other uncured malignant tumors;
• Patients with organ or bone marrow transplantation;
• Patients currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion;
• Patients who are allergic to any component of TAF;
• Patients who recently or newly started bisphosphate (within 1 month);
• Patients with active alcohol or drug abuse or history of alcohol or drug abuse (hinder compliance with treatment, or participation in the study or interpretation of results considered by the Investigator);
• Patients with significant renal, cardiovascular, pulmonary, or neurological disease
• Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study;
• Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study;
• Not suitable for this study identified by researchers.