Prediction of Decompensation and HCC Development in Advanced Chronic Liver Disease

Official title

Prediction of Decompensation and HCC Development in Patients With Advanced Chronic Liver Disease by the PLEASE and M10S20 Algorithms

Overview

The aim of this observational study is to predict the short- and long-term development of acute severe disease events, de novo hepatocarcinoma (HCC) and mortality in patients with advanced chronic liver disease using the M10S20 (Liver stiffness and Model for End-Stage Liver Disease Score \[MELD\] combined) and PLEASE (Platelet, Etiology, Age, Sex und Elastography) scores, as well as the validation of the cost-effectiveness of the algorithm. Patients in this study are randomly divided into two groups: * Control group: patients are examined according to the current clinical standard protocol (biannual follow-up). * Stratified surveillance program: * High-risk patients will receive an appointment for a hospital visit every 3 months. * Low-risk patients could receive an appointment in one year. When necessary, if decompensation develops or HCC occurs, patients could be followed-up more frequently.

Detailed description

Patients who are hospitalized with advanced chronic liver disease are randomly divided into two groups.

Patients in the control group are examined according to the current clinical standard protocol (biannual follow-up) or more frequently when decompensation or HCC develops.

Patients in the study group will be stratified for the risk of decompensation/mortality and de novo-HCC-risk, based on the M10S20 (\[Liver stiffness and MELD combined\]) and PLEASE (\[Platelet, Etiology, Age, Sex und Elastography\]) scores.

High-risk patients will be allocated for a further computer tomography (CT) or magnetic resonance imaging (MRI) examination and an alpha-fetoprotein (AFP) examination to exclude HCC and receive another appointment for a hospital visit within 3 months.

Low-risk patients could receive an appointment in one year. Patients in both arms, either outpatient or inpatient, will undergo at each visit an ultrasound examination with liver stiffness measurement and a routine blood test. Other examinations will be carried out according to standard medical care. Blood, urine and stool tests as well as instrumental diagnostics such as duplex ultrasound, CT, MRI, endoscopies, bone marrow punctures, elastographies, transjugular intrahepatic portosystemic shunt (TIPS) implantations, operations, etc. will be performed as part of the usual diagnostic clarification.

Hepatic encephalopathy is a decompensation event that will be diagnosed based on the West-Haven criteria, the number-connection test, the flicker frequency analysis and electroencephalogram. Written consent is required for every admitted patient. Data protection concept: When a patient is enrolled in the study, a center-specific study ID is first assigned for the purpose of pseudonymization.

The data collected is documented in an Excel spreadsheet. The assignment of the center-specific study ID to the respective patient is only possible for the respective investigator (Prof. Dr. Trebicka) and his staff (study nurse). For statistical evaluations, an analysis-specific data table will be created, which can be processed with an appropriate statistics program.

Patients cannot be identified with the data collected and the scientific research that derives from it.

Interventions

• Other Standard survillance protocol
  Patients will be followed every 6 months. They will undergo at each visit an ultrasound examination including liver stiffness and a routine blood test, including AFP. Other examinations are carried out according to the standard of medical care. Blood, urine and stool tests as well as instrumental diagnostics such as duplex ultrasound, computer tomography, MR-tomography, endoscopies, bone marrow punctures, elastographies, TIPS implantations, operations, etc. will be performed as part of the usual
• Other Stratified survillance protocol
  Based on PLEASE and M10LS20 scores, patients will be followed every 3 or 12 months. Low-risk patients will be followed once per year, and high-risk patients every 3 months. They will undergo at each visit an ultrasound examination including liver stiffness and a routine blood test, including AFP. Other examinations are carried out according to the standard of medical care. Blood, urine and stool tests as well as instrumental diagnostics such as duplex ultrasound, computer tomography, MR-tomogra

Primary outcome measures

• Mortality [Time frame: 2 years]
• Liver transplantation [Time frame: 2 years]

Secondary outcome measures (8)

• De novo HCC [Time frame: 2 years]
• Acute liver decompensations [Time frame: 2 years]
• Therapy in patients who develop HCC during follow-up [Time frame: 2 years]
• Analysis of cost-effectiveness of the new algorithm compared to the routine follow-up [Time frame: 2 years]
• Analysis of proteome and metabolome in patients included into the study [Time frame: 2 years]
• Analysis of intestinal and circulating microbiome in patients included into the study [Time frame: 2 years]
• Influence of circulating immune cells in HCC development and progression [Time frame: 2 years]
• Influence of transcriptome and metagenome in HCC development and progression [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• The patient admitted/referred to study center is hospitalized or is an outpatient with advanced chronic liver disease (based on the BAVENO criteria)

Exclusion criteria

• Pregnancy
• Age <18
• Evidence of current malignancy except for non-melanocytic skin cancer
• Presence or history of severe extra-hepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe heart disease (New York Heart Association (NYHA) > II); severe chronic pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) > III), severe neurological and psychiatric disorders).
• Human Immunodeficiency Virus (HIV) positive patients.
• Previous liver or other transplantation.
• Patients who decline to participate or who cannot provide prior written informed consent and when there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent.
• Physician's denial (e.g. the investigator considers that the patient will not follow the protocol scheduled).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Germany · 1 center

• University Hospital Muenster — Münster

Publications

• de Franchis R; Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2010 Oct;53(4):762-8. doi: 10.1016/j.jhep.2010.06.004. Epub 2010 Jun 27. No abstract available. PMID 20638742
• Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D'Amico G, Dickson ER, Kim WR. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001 Feb;33(2):464-70. doi: 10.1053/jhep.2001.22172. PMID 11172350
• Jansen C, Moller P, Meyer C, Kolbe CC, Bogs C, Pohlmann A, Schierwagen R, Praktiknjo M, Abdullah Z, Lehmann J, Thomas D, Strassburg CP, Latz E, Mueller S, Rossle M, Trebicka J. Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality. Hepatology. 2018 Apr;67(4):1472-1484. doi: 10.1002/hep.29612. Epub 2018 Feb 20. PMID 29059466
• Praktiknjo M, Book M, Luetkens J, Pohlmann A, Meyer C, Thomas D, Jansen C, Feist A, Chang J, Grimm J, Lehmann J, Strassburg CP, Abraldes JG, Kukuk G, Trebicka J. Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis. Hepatology. 2018 Mar;67(3):1014-1026. doi: 10.1002/hep.29602. Epub 2018 Jan 24. PMID 29059469
• Lehmann J, Praktiknjo M, Nielsen MJ, Schierwagen R, Meyer C, Thomas D, Violi F, Strassburg CP, Bendtsen F, Moller S, Krag A, Karsdal MA, Leeming DJ, Trebicka J. Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis. Liver Int. 2019 May;39(5):885-893. doi: 10.1111/liv.14070. Epub 2019 Mar 7. PMID 30739387
• Luo X, Leanza J, Massie AB, Garonzik-Wang JM, Haugen CE, Gentry SE, Ottmann SE, Segev DL. MELD as a metric for survival benefit of liver transplantation. Am J Transplant. 2018 May;18(5):1231-1237. doi: 10.1111/ajt.14660. Epub 2018 Feb 19. PMID 29316310
• Jansen C, Bogs C, Verlinden W, Thiele M, Moller P, Gortzen J, Lehmann J, Praktiknjo M, Chang J, Krag A, Strassburg CP, Francque S, Trebicka J. Algorithm to rule out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multicentre study. Gut. 2016 Jun;65(6):1057-8. doi: 10.1136/gutjnl-2016-311536. Epub 2016 Feb 19. No abstract available. PMID 26896458
• Herrmann E, de Ledinghen V, Cassinotto C, Chu WC, Leung VY, Ferraioli G, Filice C, Castera L, Vilgrain V, Ronot M, Dumortier J, Guibal A, Pol S, Trebicka J, Jansen C, Strassburg C, Zheng R, Zheng J, Francque S, Vanwolleghem T, Vonghia L, Manesis EK, Zoumpoulis P, Sporea I, Thiele M, Krag A, Cohen-Bacrie C, Criton A, Gay J, Deffieux T, Friedrich-Rust M. Assessment of biopsy-proven liver fibrosis by PMID 28370257

Identifiers

NCT: NCT06523608 · 2023-237-f-S

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗