Antiviral therapy for chronic hepatitis B with nonalcoholic fatty liver disease

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

This study is testing if a new antiviral treatment can help people with chronic hepatitis B and fatty liver disease clear the virus better than the standard medication.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1500 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Wenzhou Medical University (Academic / other)
• Locations: 5 sites (Ningbo and 4 other locations)
• Trial ID: NCT06368882 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of peg-interferon α-based antiviral therapy in patients with chronic hepatitis B complicated by nonalcoholic fatty liver disease. It involves 1500 patients who are divided into a test group receiving peg-interferon therapy and a control group receiving nucleos(t)ide analogues. The primary goal is to assess HBsAg clearance at 48 weeks, with additional follow-up points to gather comprehensive data on treatment outcomes and adverse events. The study is designed to provide real-world evidence on the effectiveness of this treatment approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-60 with chronic hepatitis B and nonalcoholic fatty liver disease who meet specific diagnostic criteria.

Not a fit: Patients with co-infections of other hepatitis viruses or HIV, or those with drug-induced liver injury may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could lead to improved management of chronic hepatitis B and nonalcoholic fatty liver disease, potentially enhancing patient outcomes.

How similar studies have performed: Other studies have explored antiviral therapies for hepatitis B, but this specific combination with nonalcoholic fatty liver disease is less common, making this approach somewhat novel.

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 (\< 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;
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.

Where this trial is running

Ningbo and 4 other locations

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

Study contacts

• Study coordinator: Yongping Chen, Professor

Conditions Nonalcoholic Fatty Liver Disease; Chronic Hepatitis b; Chronic Hepatitis B; Peg-Interferon α; nucleotide analogues