Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Carcinoma

Liver Cirrhosis

Carcinoma, Hepatocellular

Hemochromatosis

Hemosiderosis

Fibrosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hemochromatosis Type 3

Anti-Infective Agents

Central Nervous System Depressants

All Drugs and Chemicals

Ethanol

Ultrasonographic screening

Jean-Claude Trinchet, Pr, MD, PhD

Liver carcinoma is becoming the main complication of cirrhosis. Treatment of symptomatic or large tumors is disappointing. Regular ultrasonographic screening of small (curable) tumors is currently recommended, but the best periodicity is unknown.This randomized trial is aimed to compare 6-month (current recommendation) and 3-month ultrasonographic screenings.

Patients: All consecutive patients with compensated HBV, HCV, alcohol or hemochromatosis-related cirrhosis (without any previous clinical complication including liver cancer).

Randomization: factorial: ultrasonography (3-month versus 6-month); serum alfa-fetoprotein assay (none versus 6-month).

End points: rate of small tumors (first main criteria); survival (second main criteria).

Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis

Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis. A Randomized Trial Comparing Two Periodicities of Ultrasonographic Surveillance: 3-month vs 6-month

Ministry of Health, France

UNICANCER

Assistance Publique - Hôpitaux de Paris

Sylla KHAOUSSOU

Infections

Hepatitis A

Hepatitis

Hepatitis B

Hepatitis B, Chronic

Hepatitis, Chronic

Hepatitis, Viral, Human

Virus Diseases

Communicable Diseases

Enterovirus Infections

Picornaviridae Infections

RNA Virus Infections

Blood-Borne Infections

Hepadnaviridae Infections

DNA Virus Infections

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Tenofovir

Entecavir

Antiviral Agents

Reverse Transcriptase Inhibitors

Enzyme Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

CHB patients with entecavir naive treatment

CHB patients with naive tenofovir disopropyl naive treatment

entecavir naive for chronic hepatitis B patients

tenofovir disopropyl naive for chronic hepatitis B patients

Tenofovir Disoproxil

Qing Xie, MD

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.

HBV infection is a global problem, and China has a heavy disease burden with approximately 86 million people infected with HBV. According to the epidemiological survey of nearly 230,000 people in Northeast China in 2010-2013, the positive rate of HBsAg reached 6.1%, of which 10.7% had cirrhosis.

According to the latest authoritative guidelines, including the guidelines published in 2018 by American Association for the Study of Liver Diseases (AASLD) and in 2017 by European Association for the Study of Liver Diseases (EASL), entecavir (ETV) and tenofovir diisopropyl (TDF) are recommended as first-line antiviral drugs. ETV is a guanosine nucleoside analog that inhibits HBV polymerase and inhibits the synthesis of HBV DNA. TDF is a cyclic nucleoside phosphorylated diester structural analog of adenosine monophosphate, and its hydrolysis and phosphorylation products can inhibit the activity of HBV reverse transcriptase and also inhibit the synthesis of HBV DNA. In 2005, ETV was listed in China Mainland and TDF was listed in 2014. Over the years, clinical studies have shown that both have good antiviral effects and low drug resistance rates, so they are chosen as first-line antiviral drugs.

HBV infection is one of the risk factors for hepatocellular carcinoma (HCC). Previous studies based on the Chinese patients have shown that antiviral therapy (such as ETV) can significantly reduce the incidence of HCC in patients with cirrhosis (the 4-year cumulative incidence of HCC decreased from 17.5% to 9.4%). However, a study from South Korea published online in September 2018 in JAMA Oncology showed that TDF significantly reduced the incidence of HCC compared to ETV (HR 0.68, 95% CI 0.46-0.99) . In contrast, another multicenter study in Korea, published in March 2019 in The JOURNAL OF HEPATOLOGY showed no significant difference between ETV and TDF (HR 0.975, p=0.852) \[4\]. In the latter study, there was a problem with the small sample size, and the sample size was not sufficient to test the difference between the two antiviral drugs, and the sample size needed to be expanded to verify the result.

Compared with Koreans, the incidence of HCC in Chinese is significantly lower (in patients with cirrhosis, the 5-year cumulative incidence of HCC is about: China vs Korea: 12% vs 20%), showing the differences between countries. There is at present no similar study based on Chinese patients, especially in patients with cirrhosis to compare the effects of ETV and TDF on the incidence of HCC.

China has a huge disease burden and a high incidence of HCC. The ETV and TDF both have generic drugs marketing in China Mainland which through quality consistency evaluation and entering the 4+7 drug procurement (the centralized drug procurement in "4+7 Cities": Beijing, Tianjin, Shanghai, Chongqing, Shenyang, Dalian, Xiamen, Guangzhou, Shenzhen, Chengdu and Xian), bringing good antiviral effect to patients at preferential prices. If we can detect the difference in the occurrence of HCC between ETV and TDF, rational selection of drugs will reduce the incidence of HCC in Chinese patients with chronic hepatitis B (Korean studies showed that cumulative HCC patients can reduce 32% in 5 years), greatly reducing the burden on Chinese patients and health care.

This research is a real-world, multi-center, retrospective, and observational study.

Patient data are collected from 5-10 research centers in mainland China, including basic demographic information, antiviral regimen, time of stating antivirus, endpoint event, time of endpoint event, last follow-up time, important testing data, etc.

Patients with the time of last follow-up (or the time of the endpoint event) between 2013-1-1 and 2019-12-31 are included in this study.

Based on the data we collect, the Propensity Score Matching and Inverse Probability Multiple Weighted methods and the Competing Risk Model are utilized to correct the confounding factors to calculate the impact of TDF and ETV on HCC events.

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

Risk of Hepatocellular Carcinoma in Patients Treated With ETV vs TDF for Chronic Hepatitis B With Compensated Cirrhosis: A Multicenter, Real-world and Respective Study

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.

Compare the difference in the 5-year cumulative all-cause mortality rate in Chinese patients with chronic hepatitis B with cirrhosis in real world between ETV and TDF.

Compare the difference in the 5-year cumulative liver transplantation rate in Chinese patients with chronic hepatitis B with cirrhosis in real world between ETV and TDF.

Compare the difference in the 5-year cumulative liver disease-related mortality in Chinese patients with chronic hepatitis B with cirrhosis in real world between ETV and TDF.

Shanghai MedSci Healthcare Co. Ltd

Qing XIe

Director of Department of Infectious Disease, Rui Jin Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis	NCT00190385	Compensated Cir...	Ultrasonographi...	30 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
Risk of Hepatocellular Carcinoma in Patients Treated With ETV vs TDF for Chronic Hepatitis B With Compensated Cirrhosis	NCT04160897	Hepatitis B, Ch... Hepatocellular ... Compensated Cir...	Entecavir Tenofovir Disop...	18 Years - 80 Years	Ruijin Hospital

Spots Global Cancer Trial Database for compensated cirrhosis