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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Compensated Advanced Chronic Liver Disease, Varices Needing Treatment

Intervention / Treatment
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* Procedure: Esophagogasrtoduodendoscopy, liver stiffness measurement


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Overall eligible participants<br>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<br>* Time frame between liver stiffness measurement and esophagogastroduodendoscopy is less than 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Varices needing treatment, Non-invasive, Liver stiffness, Platelet count