Prediction of Decompensation and HCC Development in Advanced Chronic Liver Disease
- Conditions
- Hepatocellular CarcinomaHepatocarcinomaLiver DiseasesAdvanced Chronic Liver Disease
- Interventions
- Other: Stratified survillance protocolOther: Standard survillance protocol
- Registration Number
- NCT06523608
- Lead Sponsor
- University Hospital Muenster
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 600
- The patient admitted/referred to study center is hospitalized or is an outpatient with advanced chronic liver disease (based on the BAVENO 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).
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group with stratified surveillance Stratified survillance protocol 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 are allocated for a further CT/MRI examination and an AFP examination to exclude HCC and receive another appointment for a hospital visit within 3 months. Low-risk patients receive an appointment in one year. Control group Standard survillance protocol Patients in the control group are examined according to standard protocol (with a biannual follow-up) or more frequently when there is a development of decompensation or HCC.
- Primary Outcome Measures
Name Time Method Mortality 2 years All-cause mortality rate and liver-related mortality rate
Liver transplantation 2 years Incidence of liver transplantation during follow-up period and time until liver transplantation.
- Secondary Outcome Measures
Name Time Method Acute liver decompensations 2 years The acute occurrence of one or more complications of chronic portal hypertension, such as in patients with liver cirrhosis, a stable condition can develop into an acute decompensation. There is as well a new syndrome in patients with liver cirrhosis, which is characterized by a significantly increased hospitalization and a short-term (28-day) mortality rate. This syndrome is known as acute-on-chronic liver liver failure (ACLF).
Portal hypertension is the driving force behind acute decompensation, while in the course of further decompensation and development of ACLF, an increasing, severe systemic inflammatory reaction is added.Analysis of cost-effectiveness of the new algorithm compared to the routine follow-up 2 years This outcome will be measured using the Markov model, which compares effectiveness based on Quality-adjusted life-years (QALYs) to the costs of each algorithm.
Influence of circulating immune cells in HCC development and progression 2 years Extraction of 40 ml of blood (30ml EDTA blood and 10ml serum) will be performed at each visit to the patient in addition to the regular diagnostics.
From these blood samples circulating immune cells will be isolated, in order to investigate their influence on the disease.De novo HCC 2 years Prediction of the risk of de novo HCC in patients with advanced chronic liver disease, based on the stratified surveillance, which can lead to earlier detection and treatment.
Therapy in patients who develop HCC during follow-up 2 years Assesment in the electronic case report form of number and type of therapies used to treat HCC (liver ablation, liver resection, chemoembolization, radiation or systemic therapy) when the patients develop HCC during the follow-up period.
Analysis of proteome and metabolome in patients included into the study 2 years Extraction of 40 ml of blood (30ml EDTA blood and 10ml serum) will be taken at each visit to the patient in addition to the regular diagnostics.
This blood samples will be used to measure inflammatory markers (e.g. cytokines), components of the extracellular matrix components (e.g. collagens, matrix metalloproteinases), markers of bacterial translocation (e.g. LPS).Influence of transcriptome and metagenome in HCC development and progression 2 years Extraction 30ml EDTA blood for DNA analysis will be performed at each visit to the patient in addition to the regular diagnostics. DNA/RNA extraction is used for transcriptome and metagenome analyses.
Analysis of intestinal and circulating microbiome in patients included into the study 2 years Extraction of 40 ml of blood (30ml EDTA blood and 10ml serum) will be performed at each visit to the patient in addition to the regular diagnostics.
A measurement of metagenome and 16S rRNA sequencing analyses will be performed in blood as well in stool samples to determine the composition of the intestinal and circulating microbiome.
Trial Locations
- Locations (1)
University Hospital Muenster
🇩🇪Muenster, North Rhine Westphalia, Germany