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Spleen Stiffness Combined With Liver Stiffness Measured by 2D-SWE for the Screening of High-risk Varices in Compensated Advanced Chronic Liver Disease (CHESS2004)

Recruiting
Conditions
Variceal Hemorrhage
Compensated Advanced Chronic Liver Disease
Interventions
Procedure: Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.
Registration Number
NCT04546360
Lead Sponsor
Hepatopancreatobiliary Surgery Institute of Gansu Province
Brief Summary

Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices, esophagogastroduodenoscopy (EGD) should be performed. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria recommended that EGD could be spared in patients with liver stiffness (LS) based on transient elastography (TE) \< 20 kPa and platelet count \>150000/mm3. However, only 30% of patients can spare EGD. In order to expand the screening criteria, Expanded-Baveno VI proposed that by using LS (TE)\<25 kPa and platelet count \>110000/mm3, 40% of patients can safely avoid EGD. It is worth noting that the Baveno VI criteria is based on the European and American compensatory cirrhosis cohort (55% for hepatitis C, 14% for non-alcoholic steatohepatitis, 13% for alcoholic hepatitis, 8% for hepatitis B), Expanded-Baveno VI is also of good diagnostic value for hepatitis C, alcoholic, and non-alcoholic steatohepatitis of cACLD. About 257 million people worldwide are infected with hepatitis B virus, and about 80 million people in China alone are infected with hepatitis B virus. Infected with hepatitis B virus is the main etiology of patients with cACLD in china. Hence, Baveno VI and Expanded-Baveno VI may not be suitable for patients with hepatitis B virus-dominant cACLD.

Previous studies have shown that LS has a significant correlation with the severity of portal hypertension. Nevertheless, LS only has a good correlation with portal pressure in the early stage of portal hypertension (hepatic vein pressure gradient ≤10mm Hg), because liver fibrosis is the main cause of portal hypertension in this period. In the late stage of liver cirrhosis, the involvement of hyperdynamic circulation and increased portal blood flow, spleen stiffness (SS) may have a better correlation with HVPG than that of LS. Therefore, SS provides a reliable basis for the hemodynamic changes that occur during the development of liver cirrhosis and avoids the limitations caused by the measurement of LS. Previous study has found that changes in SS before and after non-selective beta-blockers (NSBBs) as primary prophylaxis may be a promising non-invasive tool for predicting hemodynamic response in patients with high-risk varices.

Since SS is much higher than LS, the maximum threshold of 75 kPa measured with TE may not be sufficient to evaluate the hardness of the spleen. Meanwhile, numerous studies have found that the success rate of measuring SS and LS based on 2D-SWE is higher than that of TE. Hence, CHESS2004 study aims to establish a standard for predicting high-risk varices that is more suitable in patients with hepatitis B virus-dominant cACLD. In addition, non-invasive means of SS is used to evaluate the hemodynamic response of patients with high-risk varices receiving prophylaxis NSBBs therapy.

Detailed Description

Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices, esophagogastroduodenoscopy (EGD) should be performed. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria recommended that EGD could be spared in patients with liver stiffness (LS) based on transient elastography (TE) \< 20 kPa and platelet count \>150000/mm3. However, only 30% of patients can spare EGD. In order to expand the screening criteria, Expanded-Baveno VI proposed that by using LS (TE)\<25 kPa and platelet count \>110000/mm3, 40% of patients can safely avoid EGD. It is worth noting that the Baveno VI criteria is based on the European and American compensatory cirrhosis cohort (55% for hepatitis C, 14% for non-alcoholic steatohepatitis, 13% for alcoholic hepatitis, 8% for hepatitis B), Expanded-Baveno VI is also of good diagnostic value for hepatitis C, alcoholic, and non-alcoholic steatohepatitis of cACLD. About 257 million people worldwide are infected with hepatitis B virus, and about 80 million people in China alone are infected with hepatitis B virus. Infected with hepatitis B virus is the main etiology of patients with cACLD in china. Hence, Baveno VI and Expanded-Baveno VI may not be suitable for patients with hepatitis B virus-dominant cACLD.

Previous studies have shown that LS has a significant correlation with the severity of portal hypertension. Nevertheless, LS only has a good correlation with portal pressure in the early stage of portal hypertension (hepatic vein pressure gradient ≤10mm Hg), because liver fibrosis is the main cause of portal hypertension in this period. In the late stage of liver cirrhosis, the involvement of hyperdynamic circulation and increased portal blood flow, spleen stiffness (SS) may have a better correlation with HVPG than that of LS. Therefore, SS provides a reliable basis for the hemodynamic changes that occur during the development of liver cirrhosis and avoids the limitations caused by the measurement of LS. Previous study has found that changes in SS before and after non-selective beta-blockers (NSBBs) as primary prophylaxis may be a promising non-invasive tool for predicting hemodynamic response in patients with high-risk varices.

Since SS is much higher than LS, the maximum threshold of 75 kPa measured with TE may not be sufficient to evaluate the hardness of the spleen. Numerous studies have found that the success rate of measuring SS and LS based on two-dimensional shear wave elastography is higher than that of TE. Hence, CHESS2004 study in seven centers including LanZhou University, Tianjin Second People's Hospital, Sixth People's Hospital of Shenyang, Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region, The Central Hospital of Lishui City and Guangxi Zhuang Autonomous Region, aims to establish a standard for predicting high-risk varices that is more suitable in patients with hepatitis B virus-dominant cACLD. In addition, non-invasive means of SS is used to evaluate the hemodynamic response of patients with high-risk varices receiving prophylaxis NSBBs therapy.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
300
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, spleen stiffness measurement 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);
  • time frame between elastography measurement and esophagogastroduodenoscopy>14 days;
  • diagnosed as hepatocellular carcinoma;
  • absence of spleen or splenectomy.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Overall eligible participantsEsophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.Eligible participants will receive standard esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement based on two-dimensional shear wave elastography, gallbladder wall thickness, spleen thickness, spleen long diameter and serological examination (platelet count, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, albumin, prothrombin time, international normalized ratio).
Primary Outcome Measures
NameTimeMethod
Accuracy of combined model of spleen stiffness and liver stiffness1 day

To assess the accuracy of combined model of spleen stiffness and liver stiffness to avoid unnecessary esophagogasrtoduodendoscopy in patients with compensated advanced chronic liver disease

Secondary Outcome Measures
NameTimeMethod
Accuracy of LSPS model base on two-dimensional shear wave elastography1 day

To assess the accuracy of LSPS (liver stiffness-spleen size- to platelet ration risk score) base on two-dimensional shear wave elastography for high-risk varices in patients with compensated advanced chronic liver disease

Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy1 month

Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy assessed by spleen stiffness

Trial Locations

Locations (6)

Guangxi Zhuang Autonomous Region

🇨🇳

Guangxi, China

Lanzhou University

🇨🇳

Lanzhou, China

The Central Hospital of Lishui City

🇨🇳

Lishui, China

Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region

🇨🇳

Xi'zang, China

Sixth People's Hospital of Shenyang

🇨🇳

Shenyang, China

Tianjin Second People's Hospital

🇨🇳

Tianjin, China

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