AcceleRating the Translation of Virtual Twins Towards a pErsonalised Management of Steatotic Liver Patients
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 7,720
- 试验地点
- 1
- 主要终点
- Liver disease progression and regression in MASLD patients
研究概览
简要总结
The goal of this observational study is to create a detailed virtual model to better understand how Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) develops. This model will also help predict heart problem at different stage of the disease.
详细描述
- - Glossary CT : Computed Tomography CVD : Cardio-Vascular Disease HCC : Hepato Cellular Carcinoma MASH : Metabolic dysfunction-associated steatohepatitis MASLD : Metabolic dysfunction-Associated Steatotic Liver Disease MRI : Magnetic Resonance Imaging PET : Positron Emission Tomography SLD : Steatotic Liver Disease TACE : Trans-Arterial ChemoEmbolisation TARE : Trans-Arterial RadioEmbolisation TIPS : Transjugular Intrahepatic Portosystemic Shunt US : Ultrasound USE : Ultrasound elastography VCTE : Vibration-Controlled Transient Elastography
- - Description of the Clininical Study
ARTEMIs retrospective cohort responds to the definition of a "retrospective collection and analysis of health data obtained from individual patients or healthy persons in order to address scientific questions related to the understanding, prevention, diagnosis, monitoring or treatment of a disease, mental illness, or physical condition" as defined in the work programme of this call. In such, the definition of a clinical study as defined by Regulation 536/2014 (on medicinal products) is not applicable in the framework of our study.
The cohort will serve the following main objectives:
- To develop and validate machine-learning or mechanistic models that can predict the evolution of liver diseases, in particular MASLD at various stages (use cases 1 and 2), and the outcome of some intervention or therapies (use cases 3 and 4).
- To identify new correlations or validate suspected correlations between specific observations, interventions and outcomes, in particular cardiovascular complications.
- - Study rationale Metabolic dysfunction-associated steatotic liver disease (MASLD) is presently the most common chronic liver disease worldwide, accounting for a global prevalence of 25.24% (2). Its natural history remains unclear, given the multiple pathways through which disease progression takes place (3), as well as to the shortage of population-based studies addressing its long-term prognosis (4). As an attempt to alleviate the paucity of good quality data on MASLD's natural history (5) and to improve patient's care, the ARTEMIS project envisages to constitute a longitudinal cohort comprising patients at various stages of liver diseases, with emphasis on MASLD (use cases 1 and 2).
Given the remarkable heterogeneity underlying MASLD mechanisms, the deployment of computational models has increased in popularity among the scientific community, as an effective means to unravel this intricate subject (6). In particular, the understanding of the human liver metabolism plays a key role towards a deeper understanding of the main drivers that rule disease progression. In such, mechanistic models play a major role in the representation of the complexity that is inherent to the liver and the gastroenterology system. In a complementary way, machine learning models are expected to respond to more precise questions related to different stages of the disease and related comorbidities, therefore allowing the prediction of diagnosis and prognosis, as well as risk stratification, based upon parameters that are specific to each subpopulation.
In this light, the ARTEMIS cohort will be used to test new hypotheses, as well as to train, validate and evaluate the performance of computational models - including machine-learning models, mechanistic models and associations thereof - aimed to improve the management of MASLD patients. The ARTEMIs cohort will incorporate retrospective multisource data for MASLD patients along the spectrum of the disease, thus including MASH, cirrhosis and HCC patients. The cohort will include patients from 12 centres in 7 countries. The cohort will also incorporate data related to the most relevant comorbidities associated with these populations, most notably, cardiovascular events. 4. - Extent and evaluation of current knowledge directly linked to the scientific question(s) to be answered by the clinical study
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- Clinical Use Case 1: Liver disease staging in MASLD patients - Prediction model of fibrosis changes (progression and regression), with ability to distinguish between fast and non-fast fibrosis progression among MASLD patients.
- •Age ≥18 years
- •Diagnosis of MASLD confirmed by radiological imaging (any type: MR, CT, PET, VCTE, US, USE...) or histology (gold standard, following MASH SAF score)
- •With at least one follow-up of minimum 1 year after diagnosis of MASLD, with radiological imaging or histology
- •- Clinical Use case 2: MASLD and progression of cardiovascular diseases
- •Age ≥18 years MASLD patients regardless of disease stage of severity (from simple steatosis to cirrhosis)
- •Patients without known heart disease
- •Cardiovascular assessment available
- •3.1- Clinical Use case 3-TIPS: Patients with cirrhosis and portal hypertension who receive TIPS placement.
- •Age ≥18 years
- •TIPS indication (Baveno VII), except pre-emptive and salvage TIPS.
- •Recurrent variceal bleeding after failure of the usual pharmacological and endoscopic methods
- •Refractory or recurrent ascites or difficult to treat
- •Refractory Hydrothorax
- •Patients with diagnosis of liver cirrhosis (based on laboratory parameters, clinical, endoscopic, radiological or histological findings), of any aetiology.
- •3.2.- Clinical Use Case 3-LT: Patients with cirrhosis and portal hypertension who received liver transplantation.
- •Age ≥18 years
- •All patients with cirrhosis (all aetiologies) who were transplanted
- •4.- Clinical Use Case 4: Prediction of cardiac complications due to HCC treatments* (*Note: includes surgical interventions, ablation, TACE, TARE, SIRT and immunotherapies)
- •Age ≥18 years
- •Diagnosis of HCC (any aetiology)
- •Cross sectional imaging follow-up (any modality) of liver diseases 6 months after treatment
- •Non-cirrhotic or no more than Child-Pugh B cirrhosis.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients without history of prior HCC
- •Patients with a history of hypertension should be well controlled (< 140/90 mmHg) on a regimen of antihypertensive therapy.
- •With a minimum follow-up of two years or until death, after diagnosis of HCC
- •5.- Other populations (participation in control arms)
- •Age ≥18 years
- •Subjects presenting cardiac fibrosis, without a known MASLD diagnosis (as controls for use case 2)
排除标准
- •- Clinical Use Case 1: Liver disease staging in MASLD patients - Prediction model of fibrosis changes (progression and regression), with ability to distinguish between fast and non-fast fibrosis progression among MASLD patients.
- •Missing data on blood glucose, BMI and metabolic status.
- •Patients who have received systemic chemotherapy
- •Patients with hepatitis B (HBV) and hepatitis C (HCV), alcoholic liver disease (more than 5 years of drinking history, equivalent to alcohol volume ≥ 30g / D in male and ≥ 20g / D in female), drug-induced liver disease or autoimmune hepatitis.
- •Subjects having a significant risk of bleeding (platelet < 50x109 / L, prothrombin activity < 50%)
- •Presence of any other form of chronic liver, at the time of MASLD diagnosis.
- •- Clinical Use case 2: MASLD and progression of cardiovascular diseases
- •Association with another cause of liver disease
- •History of hepatitis B or C
- •Already known coronary artery disease
- •History of cardiovascular events
- •3.1- Clinical Use case 3-TIPS: Patients with cirrhosis and portal hypertension who receive TIPS placement.
- •Non-cirrhosis TIPS
- •Portosinusoidal vascular disease
- •Complete portal vein thrombosis
- •Patients with surgical porto-caval shunts.
- •Patients with evidence of current locally advanced or metastatic malignancy
- •Patients with acute or chronic heart failure (New York Heart Association [NYHA]).
- •Patients with chronic obstructive pulmonary disease GOLD grade III/IV
- •Patients with chronic kidney disease requiring renal replacement therapy
- •Patients with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection
- •Patients with previous liver transplantation
- •Patients lost to follow-up and therefore have an incomplete 1-year follow-up
- •3.2.- Clinical Use Case 3-LT: Patients with cirrhosis and portal hypertension who received liver transplantation.
- •Patients who were transplanted due to acute liver failure.
- •Patients who were already transplanted before (retransplant)
- •Patients who are lost to follow-up in the first 5 years after liver transplant.
- •4.- Clinical Use Case 4: Prediction of cardiac complications due to HCC treatments* (*Note: includes surgical interventions, ablation, TACE, TARE, SIRT and immunotherapies)
- •Mixed-tumor HCC based on radiological and/or pathological examination
- •Uncontrolled inter-current illness or psychiatric illness or social situations that would limit compliance with study requirements.
- •Subjects with history of another primary cancer
- •Fully recovered from any prior surgery and/or radiation and none within 2 weeks of initiating treatment.
- •Subjects with active hepatitis B or C on antiviral compounds may remain on such treatment, except for interferon.
- •Subjects with diagnosis of tumor of mixed origin, either from radiological or biopsy report.
- •5.- Other populations (participation in control arms)
- •Patients with diagnosis of MASLD
研究组 & 干预措施
ARTEMIs cohort
- Clinical Use Case #1& 2: Adult patients diagnosed with MASLD/MASH. Clinical Use Case #2, subgroup of patients with cardiovascular disease: Adult patients diagnosed with cardiac fibrosis, with or without MASLD.
- Clinical Use Case #3: Adult patients diagnosed with cirrhosis.
- Clinical Use Case #4: Adult patients diagnosed with HCC.
- Control group: Adult patients with neither liver conditions nor cardiovascular events, as healthy control for the ARTEMIs models.
干预措施: Data recollection (Other)
结局指标
主要结局
Liver disease progression and regression in MASLD patients
时间窗: From baseline assessment to last available follow-up (minimum 1 year, up to 5 years)
Probability rates of liver disease progression or regression in MASLD patients, including fibrosis stage changes and development of steatohepatitis (MASH), assessed using validated non-invasive tests, imaging techniques, and liver histology when available
次要结局
- Incidence of cardiovascular events in MASLD patients(Up to 5 years after baseline assessment)