CHESS Criteria for Varices Screening in Compensated Advanced Chronic Liver Disease (CHESS2001/APPHA2001)

• Sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT04307264
• Collaborator: LanZhou University (Other), Tianjin Second People's Hospital (Other), The Sixth People's Hospital of Shenyang (Other), Ankang Central Hospital (Other), Guangxi Zhuang Autonomous Region (Other), Dalian Sixth People's Hospital (Other), Xingtai People's Hospital (Other), Shanghai Tongji Hospital, Tongji University School of Medicine (Other), Seventh Medical Center of PLA Army General Hospital (Other), Zhujiang Hospital (Other), The Fifth Affiliated Hospital of Zunyi Medical College (Other), Sir Run Run Shaw Hospital, Zhejiang University (Other), Beijing Tsinghua Changgeng Hospital (Other), The Central Hospital of Lishui City (Other), The Affiliated Third Hospital of Jiangsu University (Other)
• Enrollment: 150
• Locations: 15
• Anticipated Duration (Months): 12
• Patients Per Site: 10
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices in cACLD, esophagogastroduodenoscopy (EGD) should be performed. Once identified with medium-large varices, or small varices with red signs or Child-Pugh C class, defined as varices needing treatment (VNT), the patients with cACLD are recommended to receive the non-selective beta blockers or endoscopic variceal ligation per Baveno VI consensus. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria, which was validated by 310 patients dominant with hepatitis C virus (55.0%), recommended that EGD could be spared in patients with liver stiffness (LS) < 20kPa and platelet count > 150×10^{9 cells/L. Furthermore, the expanded-Baveno VI criteria (LS < 25kPa and platelet count > 110×10}9 cells/L), based on European cohort with hepatitis C virus (62.8%), was able to spare more unnecessary endoscopies than the Baveno VI criteria with VNT missed rate < 5%. Nevertheless, a recent Asian-pacific study indicated that though Baveno VI criteria was able to avoid screening endoscopy with 27.6%, it increased the odds of missing VNT in hepatitis B virus-related cACLD. Notably, this study also suggested that the expanded-Baveno VI criteria was not suited for Asian-pacific cohort with hepatitis B virus as the dominant cause with VNT missed rate > 5%. Our study aims to develop and validate an optimal cutoff value of LS and platelet count (CHESS criteria) to safely avoid more unnecessary endoscopies in patients with hepatitis B virus-dominated cACLD.

Condition or Disease	Intervention/Treatment	Phase
Compensated Advanced Chronic Liver Disease; Varices Needing Treatment	Procedure: Esophagogasrtoduodendoscopy, liver stiffness measurement

Detailed Description

Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices in cACLD, esophagogastroduodenoscopy (EGD) should be performed. Once identified with medium-large varices, or small varices with red signs or Child-Pugh C class, defined as varices needing treatment (VNT), the patients with cACLD are recommended to receive the non-selective beta blockers or endoscopic variceal ligation per Baveno VI consensus. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria, which was validated by 310 patients dominant with hepatitis C virus (55.0%), recommended that EGD could be spared in patients with liver stiffness (LS) < 20kPa and platelet count > 150×10^{9 cells/L. Furthermore, the expanded-Baveno VI criteria (LS < 25kPa and platelet count > 110×10}9 cells/L), based on European cohort with hepatitis C virus (62.8%), was able to spare more unnecessary endoscopies than the Baveno VI criteria (40.0% vs 21.5%, p < 0.001) with VNT missed rate < 5%. Nevertheless, a recent Asian-pacific study indicated that though Baveno VI criteria was able to avoid screening endoscopy with 27.6%, it increased the odds of missing VNT in hepatitis B virus-related cACLD. Notably, this study also suggested that the expanded-Baveno VI criteria was not suited for Asian-pacific cohort with hepatitis B virus as the dominant cause with VNT missed rate > 5%. Our study aims to develop and validate an optimal cutoff value of LS and platelet count (CHESS criteria) to safely avoid more unnecessary endoscopies in patients with hepatitis B virus-dominated cACLD.

Study Design

• Study Type: Observational
• Anticipated Enrollment: 150 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Development and Validation of CHESS Criteria for the Screening of Varices in Patients With Compensated Advanced Chronic Liver Disease (CHESS2001/APPHA2001)
• Actual Study Start Date: Mar 18, 2020
• Anticipated Primary Completion Date: Mar 17, 2021
• Anticipated Study Completion Date: Mar 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Overall eligible participants Eligible participants will receive standard esophagogasrtoduodendoscopy, liver stiffness measurement and serological examination (platelet count, alanine aminotransferase, aspartate aminotransferase, total bilirubin, Prothrombin time, albumin).	Procedure: Esophagogasrtoduodendoscopy, liver stiffness measurement; Time frame between liver stiffness measurement and esophagogastroduodendoscopy is less than 2 weeks.

Outcome Measures

Primary Outcome Measures

1. Accuracy of CHESS criteria [1 day]

   To assess the accuracy of Chinese Portal Hypertension Diagnosis and Monitoring Study Group (CHESS) criteria (optimal cutoff value of liver stiffness and platelet count) to avoid unnecessary endoscopies in patients with compensated advanced chronic liver disease

Secondary Outcome Measures

1. Accuracy of LSPS model [1 day]

   To assess the accuracy of LSPS model (liver stiffness * spleen diameter to platelet counts) for high-risk varices in patients with compensated advanced chronic liver disease

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• age 18-75 years;

• confirmed cirrhosis based on liver biopsy or clinical findings;

• without decompensated events (e.g. ascites, bleeding, or overt encephalopathy);

• scheduled to undergo esophagogastroduodenoscopy, and liver stiffness measurement;

• estimated survival time>24 months, and model for end-stage liver disease score<19, and without liver transplant;

• with written informed consent.

Exclusion Criteria:

• contradictions for esophagogastroduodenoscopy;

• accepted primary prevention (non-selective beta blockers or endoscopic variceal ligation);

• Child-Pugh score>9;

• time frame between liver stiffness and esophagogastroduodenoscopy>14 days;

• diagnosed as hepatocellular carcinoma or other hepatobiliary and pancreatic malignancies;

• splenectomy or hepatectomy;

• portal vein thrombosis or cavernous transformation of portal vein;

• pregnancy or unknown pregnancy status.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ankang Central Hospital	Ankang		China
2	Beijing Tsinghua Changgung Hospital	Beijing		China
3	the Seventh Medical Center of PLA General Hospital	Beijing		China
4	Dalian Sixth People's Hospital	Dalian		China
5	Zhujiang Hospital	Guangzhou		China
6	The First Hospital of Lanzhou University	Lanzhou		China
7	The Central Hospital of Lishui City	Lishui		China
8	Guangxi Zhuang Autonomous Region	Nanning		China
9	Shanghai Tongji Hospital	Shanghai		China
10	Sixth People's Hospital of Shenyang	Shenyang		China
11	Tianjin Second People's Hospital	Tianjin		China
12	Xingtai People's Hospital	Xingtai		China
13	Sir Run Run Shaw Hospital	Zhejiang		China
14	The Affiliated Third Hospital of Jiangsu University	Zhenjiang		China
15	the Fifth Affiliated Hospital of Zunyi Medical University	Zhuhai		China

Sponsors and Collaborators

• Hepatopancreatobiliary Surgery Institute of Gansu Province
• LanZhou University
• Tianjin Second People's Hospital
• The Sixth People's Hospital of Shenyang
• Ankang Central Hospital
• Guangxi Zhuang Autonomous Region
• Dalian Sixth People's Hospital
• Xingtai People's Hospital
• Shanghai Tongji Hospital, Tongji University School of Medicine
• Seventh Medical Center of PLA Army General Hospital
• Zhujiang Hospital
• The Fifth Affiliated Hospital of Zunyi Medical College
• Sir Run Run Shaw Hospital, Zhejiang University
• Beijing Tsinghua Changgeng Hospital
• The Central Hospital of Lishui City
• The Affiliated Third Hospital of Jiangsu University

Investigators

• Study Chair: Jiahong Dong, M.D., Beijing Tsinghua Changgeng Hospital
• Study Chair: Xiaolong Qi, M.D., LanZhou University
• Principal Investigator: Liting Zhang, M.D., LanZhou University
• Principal Investigator: Lin Zhang, M.D., Beijing Tsinghua Changgeng Hospital
• Principal Investigator: Fengmei Wang, M.D., Tianjin Second People's Hospital
• Principal Investigator: Ye Gu, M.D., The Sixth People's Hospital of Shenyang
• Principal Investigator: Zicheng Jiang, M.D., Ankang Central Hospital
• Principal Investigator: Guo Zhang, M.D., Guangxi Zhuang Autonomous Region
• Principal Investigator: Yong Zhang, M.D., Dalian Sixth People's Hospital
• Principal Investigator: Dengxiang Liu, M.D., Xingtai People's Hospital
• Principal Investigator: Li Yang, M.D., Shanghai Tongji Hospital, Tongji University School of Medicine
• Principal Investigator: Shuai Wang, M.D., Seventh Medical Center of PLA Army General Hospital
• Principal Investigator: Hua Mao, M.D., Zhujiang Hospital
• Principal Investigator: Chaohui He, M.D., The Fifth Affiliated Hospital of Zunyi Medical College
• Principal Investigator: Weiling Hu, M.D., Sir Run Run Shaw Hospital, Zhejiang University
• Principal Investigator: Shengqiang Zou, M.D., The Affiliated Third Hospital of Jiangsu University
• Principal Investigator: Chuxiao Shao, M.D., The Central Hospital of Lishui City

Study Documents (Full-Text)

None provided.

More Information

Publications

• Augustin S, Pons M, Maurice JB, Bureau C, Stefanescu H, Ney M, Blasco H, Procopet B, Tsochatzis E, Westbrook RH, Bosch J, Berzigotti A, Abraldes JG, Genescà J. Expanding the Baveno VI criteria for the screening of varices in patients with compensated advanced chronic liver disease. Hepatology. 2017 Dec;66(6):1980-1988. doi: 10.1002/hep.29363. Epub 2017 Oct 30.
• Bae J, Sinn DH, Kang W, Gwak GY, Choi MS, Paik YH, Lee JH, Koh KC, Paik SW. Validation of the Baveno VI and the expanded Baveno VI criteria to identify patients who could avoid screening endoscopy. Liver Int. 2018 Aug;38(8):1442-1448. doi: 10.1111/liv.13732. Epub 2018 Mar 25.
• Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, García-Pagán JC, Pinzani M, Bosch J. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 2013 Jan;144(1):102-111.e1. doi: 10.1053/j.gastro.2012.10.001. Epub 2012 Oct 8.
• de Franchis R; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015 Sep;63(3):743-52. doi: 10.1016/j.jhep.2015.05.022. Epub 2015 Jun 3.
• Ding NS, Nguyen T, Iser DM, Hong T, Flanagan E, Wong A, Luiz L, Tan JY, Fulforth J, Holmes J, Ryan M, Bell SJ, Desmond PV, Roberts SK, Lubel J, Kemp W, Thompson AJ. Liver stiffness plus platelet count can be used to exclude high-risk oesophageal varices. Liver Int. 2016 Feb;36(2):240-5. doi: 10.1111/liv.12916. Epub 2015 Sep 6.
• Maurice JB, Brodkin E, Arnold F, Navaratnam A, Paine H, Khawar S, Dhar A, Patch D, O'Beirne J, Mookerjee R, Pinzani M, Tsochatzis E, Westbrook RH. Validation of the Baveno VI criteria to identify low risk cirrhotic patients not requiring endoscopic surveillance for varices. J Hepatol. 2016 Nov;65(5):899-905. doi: 10.1016/j.jhep.2016.06.021. Epub 2016 Jul 5.
• Qi X, Berzigotti A, Cardenas A, Sarin SK. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):708-719. doi: 10.1016/S2468-1253(18)30232-2. Review.
• Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014 Dec;60(6):2099-108. doi: 10.1002/hep.27406. Epub 2014 Oct 29. Review.

• Responsible Party: Xiaolong Qi, Director, Institute of Portal Hypertension, Hepatopancreatobiliary Surgery Institute of Gansu Province
• ClinicalTrials.gov Identifier: NCT04307264
• Other Study ID Numbers: CHESS2001
• First Posted: Mar 13, 2020
• Last Update Posted: Mar 19, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Xiaolong Qi, Director, Institute of Portal Hypertension, Hepatopancreatobiliary Surgery Institute of Gansu Province: Varices needing treatment; Non-invasive; Liver stiffness; Platelet count
• Additional relevant MeSH terms: Liver Diseases; Varicose Veins

Study Results

No Results Posted as of Mar 19, 2020