Clinical trial NCT05100485: Algorithm to Stratify Clinical Decompensation Risk in Patients With Compensated Advanced Chronic Liver Disease (CHESS2108)
Official title: A Novel Algorithm to Stratify Clinical Decompensation Risk in Patients With Compensated Advanced Chronic Liver Disease (CHESS2108)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Compensated Advanced Chronic Liver Disease
Keywords: liver stiffness
platelets
portal hypertension
varices
compensated advanced chronic liver disease
Lead sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province
Sponsor class: OTHER
Collaborators: name: Tianjin Second People's Hospital
name: The Third People's Hospital of Taiyuan
name: Ehime University Graduate School of Medicine
name: Korea University Ansan Hospital
name: Hyogo Medical University
name: Zagazing University Faculty of Medicine
name: Institute of Liver and Biliary Sciences (ILBS)
name: Changi General Hospital
name: Ruijin Hospital
First posted: 2021-10-29
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is an international, multicenter cohort study initialed by Portal Hypertension Alliance in China (CHESS) and eligible patients will enroll from China, Japan, Southern Korea, Egypt, Singapore, and India.

Brief summary: Compensated advanced chronic liver disease (cACLD) commonly indicates severe fibrosis and compensated cirrhosis at risk of developing clinically significant portal hypertension (CSPH) and hepatic decompensation. The presence of CSPH (defined as hepatic venous pressure gradient \[HVPG\] ≥ 10 mmHg) is the strongest predictor of hepatic decompensation. However, HVPG measurement is invasive, operator dependent, and not widely available. According to the 2021 updated EASL Clinical Practice Guidelines, cACLD patients who did not meet the Baveno VI criteria but had any of the two variables (LSM \> 20 kPa or PLT \< 150 × 109/L) were suggested to perform screening endoscopy and HVPG measurement. However, the number of cACLD patients with unfavorable Baveno VI status is huge, no detailed risk stratifications existed at this timepoint. This study intended to investigate a novel algorithm to stratify the decompensation risk in patients with cACLD.

Detailed description: Compensated advanced chronic liver disease (cACLD) commonly indicates severe fibrosis and compensated cirrhosis at risk of developing clinically significant portal hypertension (CSPH) and hepatic decompensation. The presence of CSPH (defined as hepatic venous pressure gradient \[HVPG\] ≥ 10 mmHg) is the strongest predictor of hepatic decompensation. However, HVPG measurement is invasive, operator dependent, and not widely available. According to the 2021 updated EASL Clinical Practice Guidelines, cACLD patients who did not meet the Baveno VI criteria but had any of the two variables (LSM \> 20 kPa or PLT \< 150 × 109/L) were suggested to perform screening endoscopy and HVPG measurement. However, the number of cACLD patients with unfavorable Baveno VI status is huge, no detailed risk stratifications existed at this timepoint. This international multicenter cohort study intended to investigate a novel algorithm to stratify the decompensation risk in patients with cACLD.

Eligibility criteria: Training and Validation cohort

Inclusion Criteria:

1. age above or equal to 18-year-old,
2. fulfilled diagnosis of cACLD based on radiological, histological features of severe fibrosis or cirrhosis according to the Baveno VI consensus.

Exclusion Criteria:

1. prior hepatic decompensation,
2. hepatocellular carcinoma,
3. prior liver transplantation,
4. portal vein thrombosis,
5. antiplatelet or anticoagulation,
6. without screening endoscopy within six months of transient elastography,
7. alcoholic cirrhosis with significant ongoing alcohol intake,
8. presence of gastric varix,
9. incomplete follow-up data.

HVPG cohort.

Inclusion Criteria:

1. age above or equal to 18-year-old,
2. fulfilled diagnosis of cACLD based on radiological, histological features of severe fibrosis or cirrhosis according to the Baveno VI consensus.

Exclusion Criteria:

1. prior hepatic decompensation,
2. hepatocellular carcinoma,
3. prior liver transplantation,
4. portal vein thrombosis,
5. antiplatelet or anticoagulation,
6. without screening endoscopy within six months of transient elastography,
7. alcoholic cirrhosis with significant ongoing alcohol intake,
8. presence of gastric varix,
9. non-sinusoidal portal hypertension.

Primary outcomes:
measure: Accuracy of a novel algorithm for predicting liver decompensation.
timeFrame: 3 years
Secondary outcomes:
measure: The accuracy of the novel alogrithm for predicting clinically significant portal hypertension.
timeFrame: 1 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital
state: Jiangsu
Study officials:
affiliation: Lanzhou University First Affiliated Hospital
name: Xiaolong Qi, MD
role: STUDY_CHAIR
affiliation: Shanghai Jiao Tong university affiliated Ruijin Hospital
name: Qing Xie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Second People's Hospital
name: Jia Li, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Changi General Hospital
name: Yu Jun Wong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ehime University Graduate School of Medicine
name: Masashi Hirooka, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hyogo Medical University
name: Hirayuki Enomoto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea UniversityAnsan Hospital
name: Tae Hyung Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zagazig University
name: Amr Shaaban Hanafy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Third People's Hospital of Taiyuan
name: Ying Guo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Liver and Biliary Sciences (ILBS)
name: Shiv Sarin, MD
role: PRINCIPAL_INVESTIGATOR
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: Villanueva C, Albillos A, Genesca J, Garcia-Pagan JC, Calleja JL, Aracil C, Banares R, Morillas RM, Poca M, Penas B, Augustin S, Abraldes JG, Alvarado E, Torres F, Bosch J. beta blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2019 Apr 20;393(10181):1597-1608. doi: 10.1016/S0140-6736(18)31875-0. Epub 2019 Mar 22.
citation: European Association for the Study of the Liver. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol. 2021 Sep;75(3):659-689. doi: 10.1016/j.jhep.2021.05.025. Epub 2021 Jun 21.
citation: Albilllos A, Garcia-Tsao G. Classification of cirrhosis: the clinical use of HVPG measurements. Dis Markers. 2011;31(3):121-8. doi: 10.3233/DMA-2011-0834.
citation: Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, Escorsell A, Garcia-Pagan JC, Makuch R, Patch D, Matloff DS, Bosch J; Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007 Aug;133(2):481-8. doi: 10.1053/j.gastro.2007.05.024. Epub 2007 May 21.
citation: Bosch J, Abraldes JG, Berzigotti A, Garcia-Pagan JC. The clinical use of HVPG measurements in chronic liver disease. Nat Rev Gastroenterol Hepatol. 2009 Oct;6(10):573-82. doi: 10.1038/nrgastro.2009.149. Epub 2009 Sep 1.
citation: Thabut D, Bureau C, Layese R, Bourcier V, Hammouche M, Cagnot C, Marcellin P, Guyader D, Pol S, Larrey D, De Ledinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Goria O, Cales P, Peron JM, Alric L, Bourliere M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grange JD, Attali P, Bacq Y, Wartelle-Bladou C, Dao T, Pilette C, Silvain C, Christidis C, Capron D, Bernard-Chabert B, Hillaire S, Di Martino V, Sutton A, Audureau E, Roudot-Thoraval F, Nahon P; ANRS CO12 CirVir group. Validation of Baveno VI Criteria for Screening and Surveillance of Esophageal Varices in Patients With Compensated Cirrhosis and a Sustained Response to Antiviral Therapy. Gastroenterology. 2019 Mar;156(4):997-1009.e5. doi: 10.1053/j.gastro.2018.11.053. Epub 2019 Feb 13.
citation: Abraldes JG, Bureau C, Stefanescu H, Augustin S, Ney M, Blasco H, Procopet B, Bosch J, Genesca J, Berzigotti A; Anticipate Investigators. Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: The "Anticipate" study. Hepatology. 2016 Dec;64(6):2173-2184. doi: 10.1002/hep.28824. Epub 2016 Oct 27.
citation: Chen RC, Cai YJ, Wu JM, Wang XD, Song M, Wang YQ, Zheng MH, Chen YP, Lin Z, Shi KQ. Usefulness of albumin-bilirubin grade for evaluation of long-term prognosis for hepatitis B-related cirrhosis. J Viral Hepat. 2017 Mar;24(3):238-245. doi: 10.1111/jvh.12638. Epub 2016 Nov 14.