Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy

NUC is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required. Therefore, NUC resistance is an important clinical risk resulting from long-term therapy in chronic hepatitis B (CHB) management. Discontinuation of NUC is a feasible strategy to reduce resistance. However, the high rate of relapse after cessation of NUC treatment in CHB patients remains a big problem. NUC treatment of how to safely stop drug needs to be solved.

Peg-IFN can clear HBV by direct anti-viral and immune regulation mechanisms including enhancing natural killer cell response, increased cluster of differentiation 8(CD8 +) T lymphocytes and other mechanisms to restore and enhance the immune response in patients with CHB. Response to PEG-IFN is frequently sustained after a finite treatment course due to its immune modulating capacity.

Inclusion criteria

• HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment
• NUC monotherapy (including adefovir and entecavir) for more than 2.5 years,and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010):the patients who achieved undetectable HBV DNA (<300 copies/mL) with normal alanine aminotransferase (ALT) and the consolidation therapy reached 1.5 years ,total course of the treatment reached 2.5 years can stop NUC therapy
• Willing to stop the drug, and signed a written informed consent

Exclusion criteria

• HBsAb positive in screening period
• Compensated or Decompensated liver cirrhosis:with history of cirrhosis before NUC treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
• Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
• A history of immunoregulation drug therapy within one year before entry including IFN and so on.
• Coinfection with HAV、HCV、HDV、HEV 、HIV or with Other chronic liver diseases such as Alcoholic Liver Disease,Inherited Metabolic Liver Disease,Drug induced Liver Disease and nonalcoholic fatty liver
• Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on.
• Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months
• A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
• A serum creatinine level that was more than 1.5 times the upper limit of the normal range
• With other malignant tumors(exclude the cured ones)
• Severe organ dysfunction
• With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
• Uncontrolled diabetes, hypertension or thyroid disease
• Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
• Participate in other clinical studies at the same time
• Patients unsuitable for the research