Clinical trial NCT05251272: A Combined Model Based on Spleen Stiffness, Liver Stiffness and Platelets for Assessing Portal Hypertension in Compensated Cirrhosis (CHESS2202)
Official title: A Combined Model Based on Spleen Stiffness, Liver Stiffness and Platelets for Assessing Portal Hypertension in Compensated Cirrhosis: A Prospective, Multicenter Study (CHESS2202)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Portal Hypertension
Keywords: compensated cirrhosis
spleen stiffness
liver stiffness
portal hypertension
hepatic venous pressure gradient
Lead sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province
Sponsor class: OTHER
Collaborators: name: LanZhou University
name: Shulan (Hangzhou) Hospital
name: The Third People's Hospital of Taiyuan
name: QuFu People's Hospital
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
First posted: 2022-02-22
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients was fulfilled the diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations.

Brief summary: Portal hypertension contributed to the main complications of liver cirrhosis. Currently, hepatic venous pressure gradient (HVPG) was the reference standard for evaluating portal pressure in patients with cirrhosis. However, the practice of HVPG is limited to require the extensive experience and highly specialized centers. In recent years, non-invasive methods were proposed to predict the degree of cirrhotic portal hypertension. Of them, liver stiffness measured by transient elastography had shown good performance for predicting clinically significant portal hypertension. However, liver stiffness only has a good correlation with portal pressure in the early stage of portal hypertension (HVPG\<10 mmHg), because liver fibrosis is the main cause of portal hypertension in this period. In the stage of clinically significant portal hypertension (CSPH) (HVPG≥10 mmHg), increased portal vein inflow due to splanchnic vasodilation and hyperdynamic circulation, spleen stiffness may have a better correlation with HVPG than that of liver stiffness. Several studies have explored the combination of liver stiffness, platelet count and spleen stiffness for varices screening. However, there are few studies to report the above parameters for assessing CSPH and unneeded HVPG avoiding.

Since the spleen was stiffer than the liver, the current vibration-controlled transient elastography examination is dedicated to the liver, rather than the spleen. Very recently, a novel spleen-dedicated stiffness measured by transient elastography was proposed. The prospective, multicenter study aims to add spleen stiffness as a supplementary parameter to establish new criteria for identify CSPH in patients with compensated cirrhosis, with a dedicated probe on transient elastography equipment to assess spleen stiffness and liver stiffness, and further develop a novel model based on spleen stiffness for predicting the liver decompensation in patients with compensated cirrhosis.

Detailed description: Portal hypertension contributed to the main complications of liver cirrhosis. Currently, hepatic venous pressure gradient (HVPG) was the reference standard for evaluating portal pressure in patients with cirrhosis. However, the practice of HVPG is limited to require the extensive experience and highly specialized centers. In recent years, non-invasive methods were proposed to predict the degree of cirrhotic portal hypertension. Of them, liver stiffness measured by transient elastography had shown good performance for predicting clinically significant portal hypertension. However, liver stiffness only has a good correlation with portal pressure in the early stage of portal hypertension (HVPG\<10 mmHg), because liver fibrosis is the main cause of portal hypertension in this period. In the stage of clinically significant portal hypertension (CSPH) (HVPG≥10 mmHg), increased portal vein inflow due to splanchnic vasodilation and hyperdynamic circulation, spleen stiffness may have a better correlation with HVPG than that of liver stiffness. Several studies have explored the combination of liver stiffness, platelet count and spleen stiffness for varices screening. However, there are few studies to report the above parameters for assessing CSPH and unneeded HVPG avoiding.

Since the spleen was stiffer than the liver, the current vibration-controlled transient elastography examination is dedicated to the liver, rather than the spleen. Very recently, a novel spleen-dedicated stiffness measured by transient elastography was proposed. The prospective, multicenter study (leaded by The First Hospital of Lanzhou University and Shulan (Hangzhou) Hospital) aims to add spleen stiffness as a supplementary parameter to establish new criteria for identify CSPH in patients with compensated cirrhosis, with a dedicated probe on transient elastography equipment to assess spleen stiffness and liver stiffness, and further develop a novel model based on spleen stiffness for predicting the liver decompensation in patients with compensated cirrhosis.

Eligibility criteria: Inclusion Criteria:

1. age above or equal to 18-year-old
2. fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations
3. without decompensated events (e.g. ascites, bleeding, or overt encephalopathy)
4. with spleen stiffness and liver stiffness by a dedicated probe on transient elastography examination and platelet count measurement
5. with HVPG measurement
6. signed informed consent

Exclusion Criteria:

1. non-cirrhotic portal hypertension
2. accepted primary prevention (non-selective beta blockers or endoscopic variceal ligation)
3. lactation or pregnancy
4. suspicious or confirmed hepatocellular carcinoma
5. asplenia or splenectomy
6. incomplete clinical information

Primary outcomes:
measure: Accuracy of a new model based on spleen stiffness (kPa), liver stiffness (kPa) or platelets (/L) for assessing portal hypertension in compensated cirrhosis.
timeFrame: 1 years
Secondary outcomes:
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
city: Jining
country: China
facility: Qufu People's Hospital
state: Shandong
city: Taiyuan
country: China
facility: The Third People's Hospital of Taiyuan
state: Shanxi
city: Hangzhou
country: China
facility: Shulan (Hangzhou) Hospital
state: Zhejiang
Study officials:
affiliation: Shulan (Hangzhou) Hospital
name: Lanjuan Li, M.D.
role: STUDY_CHAIR
affiliation: LanZhou University
name: Xiaolong QI, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shulan (Hangzhou) Hospital
name: Huadong Yan, M.D.
role: STUDY_DIRECTOR
References:
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.
citation: 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.
citation: Bureau C, Metivier S, Peron JM, Selves J, Robic MA, Gourraud PA, Rouquet O, Dupuis E, Alric L, Vinel JP. Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease. Aliment Pharmacol Ther. 2008 Jun;27(12):1261-8. doi: 10.1111/j.1365-2036.2008.03701.x. Epub 2008 Apr 4.
citation: Colecchia A, Montrone L, Scaioli E, Bacchi-Reggiani ML, Colli A, Casazza G, Schiumerini R, Turco L, Di Biase AR, Mazzella G, Marzi L, Arena U, Pinzani M, Festi D. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012 Sep;143(3):646-654. doi: 10.1053/j.gastro.2012.05.035. Epub 2012 May 27.
citation: Vizzutti F, Arena U, Romanelli RG, Rega L, Foschi M, Colagrande S, Petrarca A, Moscarella S, Belli G, Zignego AL, Marra F, Laffi G, Pinzani M. Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis. Hepatology. 2007 May;45(5):1290-7. doi: 10.1002/hep.21665.
citation: Colecchia A, Ravaioli F, Marasco G, Colli A, Dajti E, Di Biase AR, Bacchi Reggiani ML, Berzigotti A, Pinzani M, Festi D. A combined model based on spleen stiffness measurement and Baveno VI criteria to rule out high-risk varices in advanced chronic liver disease. J Hepatol. 2018 Aug;69(2):308-317. doi: 10.1016/j.jhep.2018.04.023. Epub 2018 May 3.
citation: Pons M, Augustin S, Scheiner B, Guillaume M, Rosselli M, Rodrigues SG, Stefanescu H, Ma MM, Mandorfer M, Mergeay-Fabre M, Procopet B, Schwabl P, Ferlitsch A, Semmler G, Berzigotti A, Tsochatzis E, Bureau C, Reiberger T, Bosch J, Abraldes JG, Genesca J. Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease. Am J Gastroenterol. 2021 Apr;116(4):723-732. doi: 10.14309/ajg.0000000000000994.
citation: Stefanescu H, Marasco G, Cales P, Fraquelli M, Rosselli M, Ganne-Carrie N, de Ledinghen V, Ravaioli F, Colecchia A, Rusu C, Andreone P, Mazzella G, Festi D. A novel spleen-dedicated stiffness measurement by FibroScan(R) improves the screening of high-risk oesophageal varices. Liver Int. 2020 Jan;40(1):175-185. doi: 10.1111/liv.14228. Epub 2019 Sep 11.
citation: Bastard C, Miette V, Cales P, Stefanescu H, Festi D, Sandrin L. A Novel FibroScan Examination Dedicated to Spleen Stiffness Measurement. Ultrasound Med Biol. 2018 Aug;44(8):1616-1626. doi: 10.1016/j.ultrasmedbio.2018.03.028. Epub 2018 May 3.