Clinical trial NCT06523608: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Liver Diseases
Hepatocellular Carcinoma
Hepatocarcinoma
Advanced Chronic Liver Disease
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
First posted: 2024-07-26
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients should be included in the study if they are hospitalized with suspected chronic liver liver disease of viral and/or steatotic origin.

Brief summary: 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.

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).

Primary outcomes:
measure: Mortality
timeFrame: 2 years
measure: Liver transplantation
timeFrame: 2 years
Secondary outcomes:
measure: De novo HCC
timeFrame: 2 years
measure: Acute liver decompensations
timeFrame: 2 years
measure: Therapy in patients who develop HCC during follow-up
timeFrame: 2 years
measure: Analysis of cost-effectiveness of the new algorithm compared to the routine follow-up
timeFrame: 2 years
measure: Analysis of proteome and metabolome in patients included into the study
timeFrame: 2 years
measure: Analysis of intestinal and circulating microbiome in patients included into the study
timeFrame: 2 years
measure: Influence of circulating immune cells in HCC development and progression
timeFrame: 2 years
measure: Influence of transcriptome and metagenome in HCC development and progression
timeFrame: 2 years
Other outcomes:
Locations:
city: Muenster
country: Germany
facility: University Hospital Muenster
state: North Rhine Westphalia
Study officials:
affiliation: Department of Internal Medicine B, University Hospital Muenster, Muenster, Germany
name: Jonel Trebicka, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: European Foundation for Study of Chronic Liver Failure, Barcelona, Spain
name: Jonel Trebicka, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Denmark
name: Jonel Trebicka, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
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