Clinical trial NCT04307264: CHESS Criteria for Varices Screening in Compensated Advanced Chronic Liver Disease (CHESS2001/APPHA2001)
Official title: Development and Validation of CHESS Criteria for the Screening of Varices in Patients With Compensated Advanced Chronic Liver Disease (CHESS2001/APPHA2001)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Compensated Advanced Chronic Liver Disease
Varices Needing Treatment
Keywords: Varices needing treatment
Non-invasive
Liver stiffness
Platelet count
Lead sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province
Sponsor class: OTHER
Collaborators: name: LanZhou University
name: Tianjin Second People's Hospital
name: The Sixth People's Hospital of Shenyang
name: Ankang Central Hospital
name: Guangxi Zhuang Autonomous Region
name: Dalian Sixth People's Hospital
name: Xingtai People's Hospital
name: Shanghai Tongji Hospital, Tongji University School of Medicine
name: Seventh Medical Center of PLA Army General Hospital
name: Zhujiang Hospital
name: The Fifth Affiliated Hospital of Zunyi Medical College
name: Sir Run Run Shaw Hospital
name: Beijing Tsinghua Changgeng Hospital
name: The Central Hospital of Lishui City
name: The Affiliated Third Hospital of Jiangsu University
First posted: 2020-03-13
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with compensated advanced chronic liver disease

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Accuracy of CHESS criteria
timeFrame: 1 day
Secondary outcomes:
measure: Accuracy of LSPS model
timeFrame: 1 day
Other outcomes:
Locations:
city: Ankang
country: China
facility: Ankang Central Hospital
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
city: Beijing
country: China
facility: the Seventh Medical Center of PLA General Hospital
city: Dalian
country: China
facility: Dalian Sixth People's Hospital
city: Guangzhou
country: China
facility: Zhujiang Hospital
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
city: Lishui
country: China
facility: The Central Hospital of Lishui City
city: Nanning
country: China
facility: Guangxi Zhuang Autonomous Region
city: Shanghai
country: China
facility: Shanghai Tongji Hospital
city: Shenyang
country: China
facility: Sixth People's Hospital of Shenyang
city: Tianjin
country: China
facility: Tianjin Second People's Hospital
city: Xingtai
country: China
facility: Xingtai People's Hospital
city: Zhejiang
country: China
facility: Sir Run Run Shaw Hospital
city: Zhenjiang
country: China
facility: The Affiliated Third Hospital of Jiangsu University
city: Zhuhai
country: China
facility: the Fifth Affiliated Hospital of Zunyi Medical University
Study officials:
affiliation: Beijing Tsinghua Changgeng Hospital
name: Jiahong Dong, M.D.
role: STUDY_CHAIR
affiliation: LanZhou University
name: Xiaolong Qi, M.D.
role: STUDY_CHAIR
affiliation: LanZhou University
name: Liting Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tsinghua Changgeng Hospital
name: Lin Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Second People's Hospital
name: Fengmei Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Sixth People's Hospital of Shenyang
name: Ye Gu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ankang Central Hospital
name: Zicheng Jiang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangxi Zhuang Autonomous Region
name: Guo Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Dalian Sixth People's Hospital
name: Yong Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Xingtai People's Hospital
name: Dengxiang Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Tongji Hospital, Tongji University School of Medicine
name: Li Yang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Seventh Medical Center of PLA Army General Hospital
name: Shuai Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhujiang Hospital
name: Hua Mao, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Affiliated Hospital of Zunyi Medical College
name: Chaohui He, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sir Run Run Shaw Hospital
name: Weiling Hu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Third Hospital of Jiangsu University
name: Shengqiang Zou, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Central Hospital of Lishui City
name: Chuxiao Shao, M.D.
role: PRINCIPAL_INVESTIGATOR
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