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

Official title

Long-term Outcomes of Anti-viral Therapies in Patients With Chronic Viral Hepatitis B: A Multicenter, Real-world Study

Overview

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).

Interventions

• Drug peginterferon alpha based regimen
  peginterferon alpha based regimen or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study
• Drug nucleos(t)ide
  peginterferon alpha based regimen or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study

Primary outcome measures

• rate of hepatocellular carcinoma at 5 year from baseline [Time frame: 5 year from baseline]

Secondary outcome measures (10)

• rate of HBsAg loss [Time frame: 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline]
• rate of decompensated cirrhosis [Time frame: 1year, 2 year, 3 year, 4 year and 5 year from baseline]
• rate of cirrhosis [Time frame: 1 year, 2 year, 3 year, 4year, and 5 year from baseline]
• rate of fibrosis progression [Time frame: 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 [Time frame: 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline]
• rate of liver transplantation [Time frame: 5 year from baseline]
• HBsAg level [Time frame: 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 [Time frame: 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 [Time frame: 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline]
• rate of HBV DNA undetectable [Time frame: 1year, 2 year, 3 year, 4 year and 5 year from baseline]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Huashan Hospital — Shanghai

Publications

• Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28. PMID 26231459
• Shin EC, Sung PS, Park SH. Immune responses and immunopathology in acute and chronic viral hepatitis. Nat Rev Immunol. 2016 Aug;16(8):509-23. doi: 10.1038/nri.2016.69. Epub 2016 Jul 4. PMID 27374637
• Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015 Dec;64(12):1972-84. doi: 10.1136/gutjnl-2015-309809. Epub 2015 Jun 5. PMID 26048673
• Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018 May 1;319(17):1802-1813. doi: 10.1001/jama.2018.3795. PMID 29715359
• Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Clin Liver Dis (Hoboken). 2018 Aug 22;12(1):33-34. doi: 10.1002/cld.728. eCollection 2018 Jul. No abstract available. PMID 30988907
• European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18. PMID 28427875
• Lim TH, Gane E, Moyes C, Borman B, Cunningham C. HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes. Hepatol Int. 2016 Sep;10(5):829-37. doi: 10.1007/s12072-016-9709-6. Epub 2016 Mar 8. PMID 26957439
• Hu P, Shang J, Zhang W, Gong G, Li Y, Chen X, Jiang J, Xie Q, Dou X, Sun Y, Li Y, Liu Y, Liu G, Mao D, Chi X, Tang H, Li X, Xie Y, Chen X, Jiang J, Zhao P, Hou J, Gao Z, Fan H, Ding J, Zhang D, Ren H. HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study. J Clin Transl Hepatol. 2018 Mar 28;6(1):25-34. doi: 10.14218/JCTH.2017. PMID 29577029

Identifiers

NCT: NCT04896255 · KY2020-911

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗