Efficacy and Safety Study of Tenofovir Disoproxil Fumarate (TDF) in Chinese Chronic Hepatitis B (CHB) Subjects With Advanced Fibrosis & Compensated Cirrhosis

Inclusion Criteria

• Age 18-60 years(inclusive);
• Presence of HBsAg in serum at screening and for at least 6 months before screening assessment;
• Serum HBV DNA>=2000 IU/mL if HBeAg positive at screening (with or without ALT elevation); or serum HBV DNA>=200IU/mL if HBeAg negative at screening (with or without ALT elevation);
• Clinically diagnosed as advanced fibrosis or compensated cirrhosis defined as both of following : liver stiffness measure (LSM) >12.4 kiloPascals (kpa) (ALT> Upper limit of normal [ULN]) or LSM>9.0 kpa (ALT =4, within the previous 6 months before screening and provided that no treatment likely to improve liver histology has been taken since). The slides must be available for review by an independent histopathologist; Endoscopy-proven gastroesophageal or gastric varices, non-cirrhotic portal hypertension excluded; Abdominal ultrasound or CT found changes indicating cirrhosis, irregular liver surface or nodularity, with/without splenomegaly (depth of spleen>4.0cm or spleen length>13cm); Blood platelets 50 nanograms (ng)/mL at screening.
• Serum ALT >10 times ULN at screening or history of acute exacerbation leading to transient decompensation;
• Documented co-infection with hepatitis A (HAV), hepatitis C (HCV), hepatitis delta virus (HDV), hepatitis E virus (HEV) or human immunodeficiency virus (HIV). For HCV co-infection, subjects who are anti-HCV positive and in whom HCV ribonucleic acid (RNA) is undetectable are considered to be not eligible for enrolment.
• Evidence of active liver disease due to autoimmune hepatitis (antinuclear antibody (ANA) titre >1:160).
• Decompensated liver disease as indicated by any of the following: serum bilirubin >1.5 xULN prothrombin time activity 1.5; serum albumin <32 grams per liter (g/L); history of previous clinical hepatic decompensation (e.g., ascites, variceal bleeding, or encephalopathy);
• Planned for liver transplantation or previous liver transplantation;
• Creatinine clearance less than 70 mL/minute (min);
• Haemoglobin <10 g/deciliter (dL), white blood cell (WBC) count <1.5 x 10^9/liter (L), platelets <=50 x 10^9/L;
• Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the Investigator, would interfere with subject treatment, assessment or compliance with the protocol. This would include any uncontrolled clinically significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, pathological fractures or cancer;
• Active alcohol or drug abuse or history of alcohol or drug abuse considered by the Investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results;
• A female who is breastfeeding or plan to breastfeed;
• Use of immunosuppressive therapy, immunomodulatory therapy (including IFN or thymosin alpha), systemic cytotoxic agents, chronic antiviral agents including Chinese herbal medicines known to have activity against HBV (e.g., lamivudine (LAM), adefovir, entecavir (ETV), telbivudine (LdT) or hepatitis B immunoglobulin (HBIg)) within the previous 6 months prior to screening into this study;
• Have ever received TDF or any medicinal products containing the above mentioned antiviral agents or any investigative anti-HBV treatments (e.g., emtricitabine (FTC), (2R,4R)-4-(2,6-Diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol (DAPD) and 1-(2-fluoro-5-methyl-beta, Larabinofuranosyl) uracil (L-FMAU));
• History of hypersensitivity to nucleoside and/or nucleotide analogues and/or any component of study medication;
• Therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotercin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid) within 2 months prior to study screening or the expectation that subject will receive any of these during the course of the study;
• Inability to comply with study r