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

Compensated Advanced Chronic Liver Disease Clinical Trial

Official title:

Development and Validation of CHESS Criteria for the Screening of Varices in Patients With Compensated Advanced Chronic Liver Disease (CHESS2001/APPHA2001)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04307264
• Other study ID #: CHESS2001
• Status: Completed
• Start date: March 18, 2020
• Est. completion date: March 17, 2023

Study information

• Verified date: April 2023
• Source: Hepatopancreatobiliary Surgery Institute of Gansu Province
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2000
• Est. completion date: March 17, 2023
• Est. primary completion date: March 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Compensated Advanced Chronic Liver Disease
• Liver Diseases
• Varices Needing Treatment
• Varicose Veins

Intervention

Procedure:
• Esophagogasrtoduodendoscopy, liver stiffness measurement
Time frame between liver stiffness measurement and esophagogastroduodendoscopy is less than 2 weeks.

Locations

Country	Name	City	State
China	Ankang Central Hospital	Ankang
China	Beijing Tsinghua Changgung Hospital	Beijing
China	the Seventh Medical Center of PLA General Hospital	Beijing
China	Dalian Sixth People's Hospital	Dalian
China	Zhujiang Hospital	Guangzhou
China	The First Hospital of Lanzhou University	Lanzhou
China	The Central Hospital of Lishui City	Lishui
China	Guangxi Zhuang Autonomous Region	Nanning
China	Shanghai Tongji Hospital	Shanghai
China	Sixth People's Hospital of Shenyang	Shenyang
China	Tianjin Second People's Hospital	Tianjin
China	Xingtai People's Hospital	Xingtai
China	Sir Run Run Shaw Hospital	Zhejiang
China	The Affiliated Third Hospital of Jiangsu University	Zhenjiang
China	the Fifth Affiliated Hospital of Zunyi Medical University	Zhuhai

Sponsors (16)

Lead Sponsor

Collaborator

Hepatopancreatobiliary Surgery Institute of Gansu Province

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

Country where clinical trial is conducted

China, 

References & Publications (8)

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, Genesca 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. — View Citation

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. — View Citation

Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, Garcia-Pagan 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. — View Citation

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. No abstract available. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Accuracy of CHESS criteria	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	1 day
Secondary	Accuracy of LSPS model	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	1 day