Optimized Treatment of Peginterferon Alfa 2a in Treatment Experienced Patients With HBV Related Liver Fibrosis

An Open, Multi-center Clinical Study of Combination Therapy With Tenofovir Disoproxil Fumarate and Peginterferon Alpha 2a in Nucleos(t)Ide Analogs Experienced Patients With HBV Related Hepatic Fibrosis.

Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.

Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.

Main purpose: Comparing the improvement rate of liver fibrosis. Secondary purpose: Comparing the incidence of adverse events. Comparing the incidence of cirrhosis, hepatocellular carcinoma, and liver failure.

Comparing the rates of HBsAg and HBeAg serological conversion.

Inclusion Criteria:

1. Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year;
2. Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited;
3. Age from 18 to 55 years old;
4. Normal liver function(ALT<ULN,AST<ULN and TBil<ULN).
5. Undetectable hepatitis b virus DNA or less than 100IU/ml.
6. LSM between 6 and 12 kpa measured by fibroscan;
7. Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm.

Exclusion Criteria:

1. Decompensated cirrhosis, hepatocellular carcinoma or other malignancy;
2. Pregnancy, lactation or female has plan of pregnancy within 18 months;
3. Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)；
4. Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases;
5. Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions;
6. Patients who fail to comply with this research arrangement and sign an informed consent form
7. Patients can not follow-up;
8. Investigator considering inappropriate.