Using Digital Twin Technology and Clinical Decision Support Systems to Improve the Early Detection, Personalised Treatment, and Long-term Monitoring of Patients Across the Full Spectrum of Metabolic-associated Fatty Liver Disease (MAFLD).

Prior treatment

• Patients with surgical porto-caval shunts.
• 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.
• Fully recovered from any prior surgery and/or radiation and none within 2 weeks of initiating treatment.

Other illness

• \- 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.
• Portosinusoidal vascular disease
• Complete portal vein thrombosis
• 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 who were transplanted due to acute liver failure.
• 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)
• Uncontrolled inter-current illness or psychiatric illness or social situations that would limit compliance with study requirements.
• Subjects with history of another primary cancer
• Subjects with active hepatitis B or C on antiviral compounds may remain on such treatment, except for interferon.

Lab values

• \- 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.

Other

• Non-cirrhosis TIPS
• Patients who were already transplanted before (retransplant)
• Mixed-tumor HCC based on radiological and/or pathological examination
• 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

• \- 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)