Efficacy and Safety of Antiviral Therapy With Peg-interferon for Chronic Hepatitis B Complicated With Nonalcoholic Fatty Liver Disease（OCEAN PROJECT）

Обзор

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.

Вмешательства

• Препарат Peg-Interferon α
  Peg IFN-α injection was subcutaneously injected 180 μg weekly on the first day of the first week, and NAs was administered daily according to the standard dosage of each drug. For example, HBsAg sero-conversion is achieved within 48 weeks of treatment, Peg IFNα combined with NAs or PEG-IFNα monotherapy was continued for 12 weeks, with a maximum of 96 weeks, and follow-up up to 240 weeks after treatment. If HBsAg negative sero-conversion is not achieved within 48 weeks of treatment, the maximum d

Первичные конечные точки

• HBsAg clearance [Срок оценки: 48 weeks]

Вторичные конечные точки (4)

• HBsAg clearance at 96 weeks [Срок оценки: 96 weeks]
• Cumulative HBsAg clearance rate [Срок оценки: week 24、72、120、144、168、192、216、240]
• Liver Function Tests [Срок оценки: week 24、48、72、96、120、144、168、192、216、240]
• The incidence of liver cirrhosis and liver cancer [Срок оценки: week 24、48、72、96、120、144、168、192、216、240]

Критерии участия

Критерии включения

• Age of 18-60 years old, male or female (including 18 and 60 years old);
• 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).
• serum HBsAg positive >6 months;
• NAs treatment: baseline HBsAg≤1500 IU/ml, HBeAg negative, HBV DNA negative (not detected);
• 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);
• a negative serum pregnancy test within 24 hours before the first dose (for women of reproductive age);
• willing to receive treatment and signed informed consent.

Критерии исключения

• 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;
• Liver tumor was detected by liver imaging at the time of screening;
• 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 (< 35 g/L) and/or prolonged prothrombin time (prolonged > 3 seconds compared with the control); ⑤ Blood routine examination showed platelet count < 100×109/L;
• pregnant or lactating women or those who plan to become pregnant and do not want to use contraception during the study period;
• 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;
• 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;
• 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;
• patients with serious diseases of heart, lung, kidney, brain, blood and other important organs, and patients with other malignant tumors;
• 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;
• any history of organ transplantation and existing functional graft (except corneal or hair transplantation);
• patients who are allergic to interferon and its drug components, and who are not suitable for interferon according to the investigator's judgment;
• Patients deemed by the investigator to be ineligible for the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Ningbo No.2 Hospital — Ningbo
• Ruian People's Hospital — Rui’an
• The Second Affiliated Hospital of Wenzhou Medical University — Wenzhou
• Wenzhou People's Hospital — Wenzhou
• Yueqing People's Hospital — Yueqing

Идентификаторы

NCT: NCT06368882 · Yongping _Chen

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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