Risk of Hepatocellular Carcinoma in Patients Treated With ETV vs TDF for Chronic Hepatitis B With Compensated Cirrhosis

NCT04160897 | Unknown FDA Drug

• 1 other identifier: ISR-CN-9-10708
• Study Type: observational
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

The current first-line treatment for HBV is long-term oral antiviral drugs to inhibit HBV DNA replication. First-line antiviral drugs recommended by the Chinese 2015 Hepatitis B Guidelines include ETV and TDF. This study is based on a real-world clinical cohort to retrospectively analyze the effects of ETV and TDF on the long-term (5-year) incidence of HCC in Chinese patients with chronic hepatitis B with compensated cirrhosis. The results will guide the revision of the Chinese HBV guidelines.

Conditions

Hepatitis B, Chronic; Hepatocellular Carcinoma; Compensated Cirrhosis

Keywords

chronic hepatitis B; hepatocellular carcinoma; compensated cirrhosis; Chinese; entecavir; tenofovir disopropyl; multi-center; real-world; respective

Outcome Measures

Primary Outcomes (1)

• The 5-year cumulative incidence of hepatocellular carcinoma

  Compare the difference in the 5-year cumulative incidence of HCC in Chinese patients with chronic hepatitis B with cirrhosis in real world between ETV and TDF.

  5 years

Secondary Outcomes (3)

• The 5-year cumulative all-cause mortality rate

  5 years

• The 5-year cumulative liver transplantation rate

  5 years

• The 5-year cumulative liver disease-related mortality

  5 years

Study Arms (2)

ETV cohort

CHB patients with entecavir naive treatment

Drug: Entecavir

TDF cohort

CHB patients with naive tenofovir disopropyl naive treatment

Drug: Tenofovir Disoproxil

Interventions

Entecavir DRUG

entecavir naive for chronic hepatitis B patients

ETV cohort

Tenofovir Disoproxil DRUG

tenofovir disopropyl naive for chronic hepatitis B patients

TDF cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study was conducted in high-risk populations of HCC (patients with cirrhosis). According to the studies from Taiwan and Hongkong, the cumulative incidence of HCC in Chinese patients with cirrhosis in the ETV group was about 11.8-13.8% over 5 years, and we estimate it to be 12.8%; the 5-year incidence of HCC in the TDF group is estimated to be 8.0% according to the studies from Korea with the HR=0.55-0.75. Actual patients' use of ETV and TDF in China is about 3:1. We calculated that for this study to have 80% power to detect a 5% relative difference between the TDF and ETV groups, there would have to be 202 events and enroll 539 and 1616 patients at least in TDF and ETV treatment group based on log-rank (Lakatos) test. On the basis of these calculations, we planned to enroll 4,000 patients (1,000 patients in the TDF group, 3,000 patients in the ETV group).

You may qualify if:

• HBsAg+ \> 6 months
• age 18-80
• TDF or ETV Treatment Naive
• cirrhosis

You may not qualify if:

• TDF/ETV treatment duration\<12 m
• decompensated cirrhosis
• previous H/O organ or stem cell transplant
• IFN exposure or combination of IFN\>4 w
• HCC, death or OLT within 12 m after TDF or ETV treatment;
• previous HCC history;
• key data (such as key medical history, hematological and biochemical tests, HBV DNA and HBV antibody/antigen before treatment, et al) missing or error.

Sponsors & Collaborators

• Qing XIe: lead
• Shanghai MedSci Healthcare Co. Ltd: collaborator

Study Sites (1)

Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Related Publications (7)

• Zhang Q, Qi W, Wang X, Zhang Y, Xu Y, Qin S, Zhao P, Guo H, Jiao J, Zhou C, Ji S, Wang J. Epidemiology of Hepatitis B and Hepatitis C Infections and Benefits of Programs for Hepatitis Prevention in Northeastern China: A Cross-Sectional Study. Clin Infect Dis. 2016 Feb 1;62(3):305-12. doi: 10.1093/cid/civ859. Epub 2015 Oct 3.

  PMID: 26433720 BACKGROUND

• Su TH, Hu TH, Chen CY, Huang YH, Chuang WL, Lin CC, Wang CC, Su WW, Chen MY, Peng CY, Chien RN, Huang YW, Wang HY, Lin CL, Yang SS, Chen TM, Mo LR, Hsu SJ, Tseng KC, Hsieh TY, Suk FM, Hu CT, Bair MJ, Liang CC, Lei YC, Tseng TC, Chen CL, Kao JH; C-TEAM study group and the Taiwan Liver Diseases Consortium. Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients. Liver Int. 2016 Dec;36(12):1755-1764. doi: 10.1111/liv.13253. Epub 2016 Oct 4.

  PMID: 27634134 BACKGROUND

• Choi J, Kim HJ, Lee J, Cho S, Ko MJ, Lim YS. Risk of Hepatocellular Carcinoma in Patients Treated With Entecavir vs Tenofovir for Chronic Hepatitis B: A Korean Nationwide Cohort Study. JAMA Oncol. 2019 Jan 1;5(1):30-36. doi: 10.1001/jamaoncol.2018.4070.

  PMID: 30267080 BACKGROUND

• Kim SU, Seo YS, Lee HA, Kim MN, Lee YR, Lee HW, Park JY, Kim DY, Ahn SH, Han KH, Hwang SG, Rim KS, Um SH, Tak WY, Kweon YO, Kim BK, Park SY. A multicenter study of entecavir vs. tenofovir on prognosis of treatment-naive chronic hepatitis B in South Korea. J Hepatol. 2019 Sep;71(3):456-464. doi: 10.1016/j.jhep.2019.03.028. Epub 2019 Apr 6.

  PMID: 30959156 BACKGROUND

• Wong GL, Chan HL, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Lai JW, Lo AO, Chan HY, Wong VW. Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis. Hepatology. 2013 Nov;58(5):1537-47. doi: 10.1002/hep.26301. Epub 2013 Sep 30.

  PMID: 23389810 BACKGROUND

• Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association; Hou JL, lai W. [The guideline of prevention and treatment for chronic hepatitis B: a 2015 update]. Zhonghua Gan Zang Bing Za Zhi. 2015 Dec;23(12):888-905. doi: 10.3760/cma.j.issn.1007-3418.2015.12.002. No abstract available. Chinese.

  PMID: 26739464 BACKGROUND

• Chinese Foundation for Hepatitis Prevention and Control; Chinese Society of Infectious Disease and Chinese Society of Hepatology, Chinese Medical Association; Liver Disease Committee of Chinese Research Hospital Association. [Consensus on clinical application of transient elastography detecting liver fibrosis: a 2018 update]. Zhonghua Gan Zang Bing Za Zhi. 2019 Mar 20;27(3):182-191. doi: 10.3760/cma.j.issn.1007-3418.2019.03.004. Chinese.

  PMID: 30929334 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic; Carcinoma, Hepatocellular

Interventions

entecavir; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Qing Xie, MD

  Director of Department of Infectious Disease, Rui Jin Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Infectious Disease, Rui Jin Hospital

Study Record Dates

• First Submitted: November 10, 2019
• First Posted: November 13, 2019
• Study Start: October 22, 2019
• Primary Completion: October 31, 2020
• Study Completion: October 31, 2020
• Last Updated: November 13, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)