SSM Predicts Outcomes of CLD Inpatients With Acute Liver Injury

Portal Hypertension Clinical Trial

Official title:

Spleen Stiffness Measurement Predicts Short-term Outcomes of Chronic Liver Disease Inpatients With Acute Liver Injury: a Prospective, Observational and Single-centre Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06173947
• Other study ID #: NFEC-2023-495
• Status: Recruiting
• Start date: January 1, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: March 2024
• Source: Nanfang Hospital, Southern Medical University
• Contact: Jinjun Chen, PHD
• Phone: 86-18588531001
• Email: chjj[@]smu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In this study, a single non-invasive tool, spleen stiffness measurement (SSM), was used to monitor the disease regression of inpatients with chronic liver disease (CLD) and acute liver injury. The present study aimed to establish an early diagnosis warning model for acute-on-chronic liver failure (ACLF) by SSM and investigate the effect of dynamic changes in SSM on the short-term prognosis (28-day, 90-day morbidity and mortality) of inpatients with CLD and acute liver injury.

Description:

Portal hypertension is a major complication of cirrhosis and can lead to serious clinical manifestations such as ascites, hepatic encephalopathy, variceal bleeding, etc. Colecchia et al. proposed the use of spleen stiffness measurement (SSM) to dynamically monitor portal pressure and to predict the risk of oesophageal varices. Studies have now demonstrated the utility of SSM in assessing portal hypertension, ruling out high-risk varices, and predicting clinical complications in cirrhotic patients. Furthermore, the Baveno VII consensus of portal hypertension has included SSM in its recommendations for non-invasive screening. Pathogenic triggers, important clinical events (ascites, encephalopathy, etc.), and short-term prognosis in compensated advanced chronic liver disease are associated with portal pressure. Exploring the relationship between portal hypertension and liver failure development would be of great clinical and scientific value. The present study is mainly based on a single non-invasive tool, SSM, to monitor the disease regression of chronic liver disease (CLD) inpatients with acute liver injury, to establish an early warning model for early diagnosis of acute-on-chronic liver failure, and to investigate the effect of dynamic changes in SSM on the short-term prognosis of inpatients with CLD and acute liver injury.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 411
• Est. completion date: September 30, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age between 18 years and 80 years

2. Chronic liver diseases regardless of etiology

3. Acute liver injury with total bilirubin = 3 mg/dl regardless of inducement

Exclusion Criteria:

1. Prior surgery of liver diseases before enrollment such as liver transplantation, transjugular intrahepatic portosystemic shunt (TIPS), splenectomy and partial splenic embolization

2. Severe extrahepatic diseases such as chronic obstructive pulmonary disease level IV, chronic kidney disease with end-stage renal failure, myocardial infarction within 3 months before admission

3. Receiving Immunosuppressive drugs for reasons rather than chronic liver diseases

4. Diagnosis of hepatocellular carcinoma or other non-liver malignancies during screening period

5. Serious mental illnesses such as anxiety, depressive disorders to obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD)

6. The pregnant

7. Jaundice due to biliary obstruction or cholestasis

8. Unsuitable to participate in this study judging by investigators

Related Conditions & MeSH terms

• End Stage Liver Disease
• Hypertension
• Hypertension, Portal
• Jaundice
• Liver Diseases
• Liver Dysfunction
• Portal Hypertension

Intervention

Device:
• FibroScan® Expert 630
The SSM by FibroScan 630 was first performed after admission, repeated at the day 5±2 as soon as feasible, and finally evaluated before discharge.

Locations

Country	Name	City	State
China	Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital, Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (19)

Berzigotti A, Bosch J, Boyer TD. Use of noninvasive markers of portal hypertension and timing of screening endoscopy for gastroesophageal varices in patients with chronic liver disease. Hepatology. 2014 Feb;59(2):729-31. doi: 10.1002/hep.26652. Epub 2013 — View Citation

Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol. 2017 Aug;67(2):399-411. doi: 10.1016/j.jhep.2017.02.003. Epub 2017 Feb 14. — View Citation

Colecchia A, Colli A, Casazza G, Mandolesi D, Schiumerini R, Reggiani LB, Marasco G, Taddia M, Lisotti A, Mazzella G, Di Biase AR, Golfieri R, Pinzani M, Festi D. Spleen stiffness measurement can predict clinical complications in compensated HCV-related c — View 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 esophage — View 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 — View Citation

de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. doi: 10.1016/j.jhep.2021.12.022. Epub 2021 Dec 30. Erratum In: J Hepatol. 2022 Apr — View Citation

de Franchis R, Pascal JP, Ancona E, Burroughs AK, Henderson M, Fleig W, Groszmann R, Bosch J, Sauerbruch T, Soederlund C, et al. Definitions, methodology and therapeutic strategies in portal hypertension. A Consensus Development Workshop, Baveno, Lake Mag — View 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. — View Citation

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 — View Citation

Karagiannakis DS, Voulgaris T, Siakavellas SI, Papatheodoridis GV, Vlachogiannakos J. Evaluation of portal hypertension in the cirrhotic patient: hepatic vein pressure gradient and beyond. Scand J Gastroenterol. 2018 Oct-Nov;53(10-11):1153-1164. doi: 10.1 — View Citation

Li J, Liang X, You S, Feng T, Zhou X, Zhu B, Luo J, Xin J, Jiang J, Shi D, Lu Y, Ren K, Wu T, Yang L, Li J, Li T, Cai Q, Sun S, Guo B, Zhou X, Chen J, He L, Li P, Yang H, Hu W, An Z, Jin X, Tian J, Wang B, Chen X, Xin S, Li J; Chinese Group on the Study o — View Citation

Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium. Acute — View Citation

Reiberger T. The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in Compensated Cirrhosis. Hepatol Commun. 2022 May;6(5):950-964. doi: 10.1002/hep4.1855. Epub 2021 Dec 14. — View Citation

Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, Saigal S, Saraf N, Soin AS, Devarbhavi H, Kim DJ, Dhiman RK, Duseja A, Taneja S, Eapen CE, Goel A, Ning Q, Chen T, Ma K, Duan Z, Yu C, Treeprasertsuk S, Hamid SS, Butt AS, Jafri W, Shukla — View 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 — View 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. Hepatolo — View Citation

Wang H, Wen B, Chang X, Wu Q, Wen W, Zhou F, Guo Y, Ji Y, Gu Y, Lai Q, He Q, Li J, Chen J, Hou J. Baveno VI criteria and spleen stiffness measurement rule out high-risk varices in virally suppressed HBV-related cirrhosis. J Hepatol. 2021 Mar;74(3):584-592 — View Citation

Wu T, Li J, Shao L, Xin J, Jiang L, Zhou Q, Shi D, Jiang J, Sun S, Jin L, Ye P, Yang L, Lu Y, Li T, Huang J, Xu X, Chen J, Hao S, Chen Y, Xin S, Gao Z, Duan Z, Han T, Wang Y, Gan J, Feng T, Pan C, Chen Y, Li H, Huang Y, Xie Q, Lin S, Li L, Li J; Chinese G — View Citation

Zhang X, Song J, Zhang Y, Wen B, Dai L, Xi R, Wu Q, Li Y, Luo X, Lan X, He Q, Luo W, Lai Q, Ji Y, Zhou L, Qi T, Liu M, Zhou F, Wen W, Li H, Liu Z, Chen Y, Zhu Y, Li J, Huang J, Cheng X, Tu M, Hou J, Wang H, Chen J. Baveno VII algorithm outperformed other — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90-day mortality	The primary end point was 90-day mortality, defined as all-cause death within 90 days, including deaths within the initial hospitalization, after discharge, after transfer to other acute care facilities, and requiring readmission.	Day 90
Primary	28-day mortality	The primary end point was 28-day mortality, defined as all-cause death within 28 days, including deaths within the initial hospitalization, after discharge, after transfer to other acute care facilities, and requiring readmission.	Day 28
Secondary	Incidence of new onset complications	Development of ascites, bleeding from gastro-oesophageal varices and hepatic encephalopathy.	From admission to Day 90
Secondary	Incidence of acute kidney injury (AKI)	AKI is defined as a change in SCr of = 0.3 mg/dl (26.5 µmol/L) in = 48 h, or a 50% increase in SCr from a baseline that is known or presumed to have occurred in the past 7 days.	From admission to Day 90
Secondary	Rate of progression to acute-on-chronic liver failure (ACLF)	ACLF was defined according to the European Association for the Study of Liver-Chronic Liver Failure (EASL-CLIF) criteria. ACLF grade-1 includes three subgroups: 1) patients with single kidney failure; 2) patients with single failure of the liver, coagulation, circulation or respiration, who had serum creatinine ranging from 1.5 to 1.9 mg/dl and/or mild-to-moderate hepatic encephalopathy; and 3) patients with single cerebral failure who had serum creatinine ranging from 1.5 and 1.9 mg/dl. ACLF grade-2: patients with two organs failure. ACLF grade-3: patients with three organ failures or more. ACLF development: patients with absence of ACLF on admission and progression to ACLF within 28 days. The severity of liver disease was evaluated by the model of end-stage liver disease (MELD) score, Child-Pugh score and CLIF-AD score (in those without ACLF).	From admission to Day 90
Secondary	Rates for re-admissionin of patients hospitalized with acute liver injury	Re-admission was defined as the first admission for any cause at any ward to any hospital in following discharge from the index admission with acute liver injury.	From discharge to Day 90
Secondary	Number of Participants with bacterial infection	All kinds of infection, including pneumonia, SBP, urine tract infection and so on.	From admission to Day 90