Prediction of Decompensation and HCC Development in Advanced Chronic Liver Disease
NCT Number: NCT06523608
Acronym: DETECT
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Liver Diseases|Hepatocellular Carcinoma|Hepatocarcinoma|Advanced Chronic Liver Disease
Interventions: DIAGNOSTIC_TEST: standard protocol
Sponsor: University Hospital Muenster
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 600
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09-01
Completion Date: 2027-09

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.

Primary Outcome Measures: Mortality, All-cause mortality rate and liver-related mortality rate, 2 years|Liver transplantation, Incidence of liver transplantation during follow-up period and time until liver transplantation., 2 years
Secondary Outcome Measures: De novo HCC, 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., 2 years|Acute liver decompensations, 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., 2 years|Therapy in patients who develop HCC during follow-up, 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., 2 years|Analysis of cost-effectiveness of the new algorithm compared to the routine follow-up, 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., 2 years|Analysis of proteome and metabolome in patients included into the study, 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)., 2 years|Analysis of intestinal and circulating microbiome in patients included into the study, 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., 2 years|Influence of circulating immune cells in HCC development and progression, 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., 2 years|Influence of transcriptome and metagenome in HCC development and progression, 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., 2 years