Clinical trial NCT04546360: Spleen Stiffness Combined With Liver Stiffness Measured by 2D-SWE for the Screening of High-risk Varices in Compensated Advanced Chronic Liver Disease (CHESS2004)
Official title: Spleen Stiffness Combined With Liver Stiffness Measured by Two-dimensional Shear Wave Elastography for the Screening of High-risk Varices in Patients With Compensated Advanced Chronic Liver Disease (CHESS2004)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Compensated Advanced Chronic Liver Disease
Variceal Hemorrhage
Keywords: Spleen stiffness
Liver stiffness
Two-dimensional shear wave elastography
High-risk varices
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: Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region
name: The Central Hospital of Lishui City
name: Guangxi Zhuang Autonomous Region
First posted: 2020-09-14
Enrollment: 381
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, 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.

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, 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.

Primary outcomes:
measure: Accuracy of combined model of spleen stiffness and liver stiffness
timeFrame: 1 day
Secondary outcomes:
measure: Accuracy of LSPS model base on two-dimensional shear wave elastography
timeFrame: 1 day
measure: Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy
timeFrame: 1 month
Other outcomes:
Locations:
city: Guangxi
country: China
facility: Guangxi Zhuang Autonomous Region
city: Lanzhou
country: China
facility: Lanzhou University
city: Lishui
country: China
facility: The Central Hospital of Lishui City
city: Shenyang
country: China
facility: Sixth People's Hospital of Shenyang
city: Tianjin
country: China
facility: Tianjin Second People's Hospital
city: Xi'zang
country: China
facility: Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region
Study officials:
affiliation: LanZhou University
name: Xiaolong Qi, MD
role: STUDY_CHAIR
affiliation: Beijing Friendship Hospital
name: Linxue Qian, MD
role: STUDY_CHAIR
affiliation: Tianjin Second People's Hospital
name: Fengmei Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Sixth People's Hospital of Shenyang
name: Ye Gu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region
name: Chao Liu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Central Hospital of Lishui City
name: Chuxiao Shao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangxi Zhuang Autonomous Region
name: Guo Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: LanZhou University
name: Sumei Ma, MD
role: PRINCIPAL_INVESTIGATOR
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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.
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