Long-term Outcomes of Anti-viral Therapies in Patients With Chronic Viral Hepatitis B

Recruiting

• Conditions: Chronic Hepatitis b
• Interventions: Drug: peginterferon alpha based regimen; Drug: nucleos(t)ide

• Registration Number: NCT04896255
• Lead Sponsor: Huashan Hospital

Brief Summary

The goal of this observational, multicenter , real-world study is to evaluate the long-term outcomes of different antiviral therapies in adults with chronic hepatitis B (CHB). The main questions it aims to answer are: What is the 5-year incidence of hepatocellular carcinoma (HCC) under various treatment regimens? How do rates of HBsAg seroclearance, decompensated cirrhosis, liver fibrosis progression, and other virological and clinical outcomes compare across regimens? Researchers will compare real-world treatment arms-including nucleos(t)ide analogue (NA) monotherapy (e.g., entecavir, tenofovir), PegIFN based regimen (e.g., PegIFN monotherapy, PegIFN plus NA combinations)-to identify optimal strategies for reducing HCC risk and improving functional cure rates.

Participants will undergo routine clinical care with no study-imposed interventions; data on demographics, medical history, symptoms, laboratory tests (e.g., HBsAg, HBV DNA, liver function), imaging (e.g., ultrasound, elastography), and clinical events will be collected prospectively (for up to 5 years in some cohorts) or retrospectively from medical records at baseline and scheduled follow-up visits (e.g., every 3-12 months initially, then annually).

Detailed Description

The OASIS study is a multicenter, observational, real-world cohort study designed to evaluate long-term outcomes of antiviral therapies for chronic hepatitis B (CHB). It compares nucleos(t)ide analogue (NA) monotherapy, pegylated interferon based regimen without randomization or blinding. Treatment decisions follow routine clinical guidelines, physician expertise, and patient-specific factors. The study includes three cohorts: Prospective (PS, 5-year follow-up post-consent), Retrospective-Prospective (RPS, retrospective from baseline ≥September 2020 to consent, then 5-year prospective), and Retrospective (RS, data from September 2020 to protocol implementation). The target of 33,000 patients was determined based on patient flow across sub-centers, ensuring sufficient power to detect differences in 5-year HCC incidence (primary endpoint) and secondary outcomes (e.g., HBsAg seroclearance rates).

Study Timeline

• Study Start: 2020-09-09
• Study First Submitted: 2021-05-14
• Study First Submitted QC: 2021-05-20
• Study First Posted: 2021-05-21
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-30
• Last Update Posted: 2025-10-06
• Primary Completion: 2026-11-01
• Study Completion: 2031-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 33000

Inclusion Criteria

• Male and female patients with age ≥18; subjects who are over 70 years of age must be in generally stable health conditions.
• There should be evidences that HBsAg has been positive for more than 6 months or HBV-related histological changes.
• Planned or currently receiving potent low-resistance NAs [entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or tenofovir amibufenamide (TMF)], or planned to receive PegIFNα-2b, either treated or treatment-naïve.
• Agree to participate in the study and sign the patient informed consent form.

Exclusion Criteria

• Hepatocellular carcinoma (diagnosed or planned for treatment) or liver failure at baseline
• Concurrently participating in other interventional clinical trials.
• Any other conditions deemed unsuitable by investigators or preventing compliance with study requirements.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Prospective	peginterferon alpha based regimen	CHB patients enrolled pre-Protocol v3.0 (Dec 2023), planned or on antiviral therapy, followed prospectively for 5 years post-consent. Treatments: routine NA monotherapy, or PegIFN based regimens, per clinical guidelines. Data: baseline and 5 -year follow-up via routine visits.
Prospective	nucleos(t)ide	CHB patients enrolled pre-Protocol v3.0 (Dec 2023), planned or on antiviral therapy, followed prospectively for 5 years post-consent. Treatments: routine NA monotherapy, or PegIFN based regimens, per clinical guidelines. Data: baseline and 5 -year follow-up via routine visits.
Retrospective-Prospective	peginterferon alpha based regimen	CHB patients with baseline (≥Sep 2020) pre-v3.0, consenting post-v3.0. Retrospective data from baseline to consent; prospective for 5 years from baseline. Treatments: NAs monotherapy, or PegIFN based regimens. Data: retrospective before consent; prospective from visit matching baseline-consent interval. Missing routine data noted.
Retrospective-Prospective	nucleos(t)ide	CHB patients with baseline (≥Sep 2020) pre-v3.0, consenting post-v3.0. Retrospective data from baseline to consent; prospective for 5 years from baseline. Treatments: NAs monotherapy, or PegIFN based regimens. Data: retrospective before consent; prospective from visit matching baseline-consent interval. Missing routine data noted.
Retrospective	peginterferon alpha based regimen	CHB patients with records from Sep 2020 to v3.0 (Dec 2023), collected retrospectively. Treatments: NAs monotherapy, or PegIFN based regimens, per historical practice. Data: extracted from the electronic healthcare record; missing routine data recorded.
Retrospective	nucleos(t)ide	CHB patients with records from Sep 2020 to v3.0 (Dec 2023), collected retrospectively. Treatments: NAs monotherapy, or PegIFN based regimens, per historical practice. Data: extracted from the electronic healthcare record; missing routine data recorded.

Primary Outcome Measures

Name	Time	Method
rate of hepatocellular carcinoma at 5 year from baseline	5 year from baseline	Rate of hepatocellular carcinoma will be evaluated as an end-stage liver disease event at 5 years from baseline

Secondary Outcome Measures

Name	Time	Method
rate of HBsAg loss	24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline	rate of HBsAg loss will be measured as a serological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively.
rate of decompensated cirrhosis	1year, 2 year, 3 year, 4 year and 5 year from baseline	Rate of decompensated cirrhosis will be evaluated as an end-stage liver disease event at 1year, 2 year, 3 year, 4 year, and 5 year from baseline
rate of fibrosis progression	24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline	rate of fibrosis progression will be measured as a histological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively.
rate of cirrhosis	1 year, 2 year, 3 year, 4year, and 5 year from baseline	rate of cirrhosis at 1 year, 2 year, 3 year, 4year, and 5 year from baseline
rate of HBeAg loss	24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline	rate of HBeAg loss will be measured as a serological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively.
rate of fibrosis regression	24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline	rate of fibrosis regression will be measured as a histological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively.
rate of liver transplantation	5 year from baseline	Rate of liver transplantation will be evaluated as an end-stage liver disease event at 5 year from baseline
HBsAg level	24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline	HBsAg level will be measured at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively, and kinetics will be described based on the results.
rate of HBeAg conversion	24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline	rate of HBeAg conversion will be measured as a serological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively.
rate of HBV DNA undetectable	1year, 2 year, 3 year, 4 year and 5 year from baseline	Rate of HBV DNA undetectable will be evaluated as an end-stage liver disease event at 1year, 2 year, 3 year, 4 year, and 5 year from baseline

Trial Locations

Locations (1)

Huashan Hospital; 🇨🇳 Shanghai, China