efficacy and safety of antiviral therapy with peg-interferon for chronic hepatitis b complicated with nonalcoholic fatty liver disease（ocean project）

Conditions: Nonalcoholic Fatty Liver Disease; Chronic Hepatitis b

Summary: this is a prospective, multicenter, open-label, non-randomized controlled real-world study to explore the efficacy and safety and to accumulate more evidence-based medical data of an antiviral treatment programme for chronic viral hepatitis b with nonalcoholic fatty liver disease. a total of 1500 patients with chronic hepatitis b complicated with nonalcoholic fatty liver disease are divided into test group (1000 patients receiving peg-ifnα-based antiviral therapy (combined nas or peg-ifnα monotherapy) and control group（500 patients receiving nas monotherapy） according to their treatment intention. laboratory and medical data from specified follow-up points are collected, and adverse events and drug combinations are recorded detailly. the primary efficacy indicator is hbsag clearance at 48 weeks of treatment, and the secondary indicators included: (1) hbsag clearance at 96 weeks of treatment, (2) cumulative hbsag clearance at week 24、120、144、168、192、216 and 240; (3) the improvement of liver function level(alt, ast, tbil, etc.), blood lipid (tc, tg, ldl-c, hdl-c, etc.), fasting blood glucose, insulin resistance index (homa-ir), controlled attenuation parameter, body mass index , liver stiffness measurement, liver histological fibrosis, fib-4 index from baseline; (4)incidence of liver cirrhosis and hepatocellular carcinoma during follow-up. the security assessment includes adverse events, vital signs, and imaging.


Eligibility criteria:
inclusion criteria: 1. age of 18-60 years old, male or female (including 18 and 60 years old); 2. meet the diagnostic criteria for chronic hepatitis b in the guidelines for the prevention and treatment of chronic hepatitis b (2022 edition), and meet the imaging diagnostic criteria for fatty liver in the guidelines for the prevention and treatment of non-alcoholic fatty liver disease (2018 update edition). 3. serum hbsag positive \>6 months; 4. nas treatment: baseline hbsag≤1500 iu/ml, hbeag negative, hbv dna negative (not detected); 5. ihc initial treatment: baseline hbsag\<1000 iu/ml, hbeag negative, hbv dna negative (undetectable), alt and ast persistently normal (uln: \<50 iu/l in men, \<40 iu/l in women); 6. a negative serum pregnancy test within 24 hours before the first dose (for women of reproductive age); 7. willing to receive treatment and signed informed consent. exclusion criteria: 1. co-infection with active hepatitis a, c, d, e and/or hiv; or combined with drug-induced liver injury, inherited metabolic liver disease, autoimmune hepatitis, alcoholic liver disease; 2. liver tumor was detected by liver imaging at the time of screening; 3. patients diagnosed with hepatitis b cirrhosis, that is, those with liver biopsy pathology consistent with liver cirrhosis, or with two or more of the following five criteria, excluding non-cirrhotic portal hypertension: ① imaging examination showed signs of liver cirrhosis and/or portal hypertension; ② esophagogastric varices were found by endoscopy; ③ liver stiffness was consistent with cirrhosis; ④ blood biochemical examination showed decreased albumin level (\ 3 seconds compared with the control); ⑤ blood routine examination showed platelet count \< 100×109/l; 4. pregnant or lactating women or those who plan to become pregnant and do not want to use contraception during the study period; 5. neutrophil count \<1.5×109/l or platelet count \<90×109/l. patients with creatinine higher than 1.5 times the upper limit of normal; 6. the patients and their close relatives (parents, siblings, etc.) had a history of severe mental illness, especially depression. severe psychosis is defined as severe depression or psychosis, suicide attempt, hospitalization due to psychosis, or a period of incapacitation due to psychosis; 7. patients with a history of immune-mediated diseases (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis) or abnormally elevated levels of autoimmune antibodies; 8. patients with serious diseases of heart, lung, kidney, brain, blood and other important organs, and patients with other malignant tumors; 9. history of severe epilepsy or current use of antiepileptic drugs. control of unstable diabetes, hypertension, thyroid disease, etc. a history of severe retinopathy or other evidence of retinopathy; 10. any history of organ transplantation and existing functional graft (except corneal or hair transplantation); 11. patients who are allergic to interferon and its drug components, and who are not suitable for interferon according to the investigator's judgment; 12. patients deemed by the investigator to be ineligible for the study.

Keywords: nonalcoholic fatty liver disease chronic hepatitis b peg-interferon α nucleo(s)tide analogues