HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet. In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, the drug metabolism characteristics of TAF will be explored in such severe liver injury population of HBV-ACLF.

Potent antivirals like entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF) and Tenofovir alafenamide (TAF) now are recommended as first-line therapy for patients with chronic HBV infection because of their significant suppression of viral replication and a high barrier to resistance. HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Only a limited number of medical treatments are available for ACLF. Although liver transplantation is a life-saving treatment for ACLF, the difficulty in finding a suitable donor and the high cost hinder its extensive clinical use.

The precise mechanism underlying the liver injury caused by HBV-related ACLF and the factors contributing to the progression of liver failure remain unknown. HBV DNA replication is one of the key factors causing the progression from liver damage to liver failure. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, the specific antiviral treatment for patients with liver failure remains unclear. In the past years, efficacy of nucleoside analogues, such as lamivudine, entecavir, telbivudine and tenofovir, for HBV-related liver failure has been reported. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet.

In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, pharmacokinetic properties of TAF tablets will be explored in the study subjects.

Inclusion Criteria:All of below

1. age 18-70 years, male or female.
2. HBsAg positive at least 6 months or more, HBeAg positive or negative.
3. Serum HBV DNA positive (Serum HBV DNA should be determined by the PCR assay at the local laboratory at screening for this study)
4. Recent development of increasing jaundice (a total serum bilirubin concentration of above 85μmol/L) and coagulopathy (INR ≥1.5 or prothrombin activity<40%)
5. Recent development of complications such as hepatic encephalopathy, or abrupt and obvious increase in ascites, or spontaneous bacterial peritonitis, or hepatorenal syndrome.
6. Patient is willing and able to comply with the study drug regimen and all other study requirements.
7. The patient is willing and able to provide written informed consent to participate in the study.

Exclusion Criteria: Any of below

1. Patient has concomitant other chronic viral infection (HCV or HIV)
2. Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL
3. Patient has medical condition that requires concurrent use of systemic prednisolone or other immunosuppressive agent (including chemotherapeutic agent)
4. Patient is pregnant or breastfeeding or willing to be pregnant
5. Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
6. A history of treated malignancy (other than hepatocellular carcinoma) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years.
7. Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, personality disorder that might interfere with participation in the study.
8. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.

All the patients received antivirals will be followed for at least 48 weeks and follow-up assessments were performed at week 1, 2, 3, 4, 12, 24 and 48.All the patients were detected Serum HBV DNA,HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb and HBcAb, routine biochemical tests mainly including ALT,AST,TB and ALB.