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

NCT ID: NCT04546360

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 381 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-08
• Study Completion Date: 2022-12-31

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.

Conditions

Compensated Advanced Chronic Liver Disease; Variceal Hemorrhage

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Overall eligible participants

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).

Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.

Intervention Type: PROCEDURE

Time frame between elastography measurement and esophagogastroduodendoscopy is within 2 weeks.

Interventions

Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.

Time frame between elastography measurement and esophagogastroduodendoscopy is within 2 weeks.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LanZhou University

OTHER

Sponsor Role: collaborator

Tianjin Second People's Hospital

OTHER

Sponsor Role: collaborator

The Sixth People's Hospital of Shenyang

OTHER

Sponsor Role: collaborator

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

UNKNOWN

Sponsor Role: collaborator

The Central Hospital of Lishui City

OTHER

Sponsor Role: collaborator

Guangxi Zhuang Autonomous Region

UNKNOWN

Sponsor Role: collaborator

Hepatopancreatobiliary Surgery Institute of Gansu Province

OTHER

Sponsor Role: lead

Responsible Party

Xiaolong Qi

Chief

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaolong Qi, MD

Role: STUDY_CHAIR

LanZhou University

Linxue Qian, MD

Role: STUDY_CHAIR

Beijing Friendship Hospital

Fengmei Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Tianjin Second People's Hospital

Ye Gu, MD

Role: PRINCIPAL_INVESTIGATOR

The Sixth People's Hospital of Shenyang

Chao Liu, MD

Role: PRINCIPAL_INVESTIGATOR

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

Chuxiao Shao, MD

Role: PRINCIPAL_INVESTIGATOR

The Central Hospital of Lishui City

Guo Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Guangxi Zhuang Autonomous Region

Sumei Ma, MD

Role: PRINCIPAL_INVESTIGATOR

LanZhou University

Locations

Guangxi Zhuang Autonomous Region

Guangxi, , China

Lanzhou University

Lanzhou, , China

The Central Hospital of Lishui City

Lishui, , China

Sixth People's Hospital of Shenyang

Shenyang, , China

Tianjin Second People's Hospital

Tianjin, , China

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

Xi'zang, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 30215362 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26047908 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27388923 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28696510 (View on PubMed)

Hirooka M, Ochi H, Koizumi Y, Kisaka Y, Abe M, Ikeda Y, Matsuura B, Hiasa Y, Onji M. Splenic elasticity measured with real-time tissue elastography is a marker of portal hypertension. Radiology. 2011 Dec;261(3):960-8. doi: 10.1148/radiol.11110156. Epub 2011 Sep 16.

Reference Type: BACKGROUND

PMID: 21926379 (View on PubMed)

Cooke GS, Andrieux-Meyer I, Applegate TL, Atun R, Burry JR, Cheinquer H, Dusheiko G, Feld JJ, Gore C, Griswold MG, Hamid S, Hellard ME, Hou J, Howell J, Jia J, Kravchenko N, Lazarus JV, Lemoine M, Lesi OA, Maistat L, McMahon BJ, Razavi H, Roberts T, Simmons B, Sonderup MW, Spearman CW, Taylor BE, Thomas DL, Waked I, Ward JW, Wiktor SZ; Lancet Gastroenterology & Hepatology Commissioners. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2019 Feb;4(2):135-184. doi: 10.1016/S2468-1253(18)30270-X.

Reference Type: BACKGROUND

PMID: 30647010 (View on PubMed)

Kim HY, So YH, Kim W, Ahn DW, Jung YJ, Woo H, Kim D, Kim MY, Baik SK. Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices. J Hepatol. 2019 Mar;70(3):412-422. doi: 10.1016/j.jhep.2018.10.018. Epub 2018 Oct 31.

Reference Type: BACKGROUND

PMID: 30389550 (View on PubMed)

Other Identifiers

CHESS2004

Identifier Type: -

Identifier Source: org_study_id