Recruiting
Not applicable
Screening At-risk Populations for Hepatic Fibrosis With Non-invasive Markers
Condition(s) studied
Liver Diseases, AlcoholicFibrosis
Investigational drug(s) / intervention(s)
transient elastographyEnhanced liver fibrosis testIndirect serum markers of liver fibrosisDirect serum markers of liver fibrosisLiverTRAILCytokeratin 18Omics markers
transient elastography: Ultrasound elastography using shear-wave elastography to measure liver stiffness as a marker of liver fibrosis. Patients with transient elastography above 8.0 kPa selected for liver biopsy to detect advanced liver fibrosis
Enhanced liver fibrosis test: Patented, commercially available algorithm of hyaluronic acid (HA), N-terminal propeptide of collagen type 3 (P3NP) and tissue inhibitor of metalloproteinase 1 (TIMP-1)
Indirect serum markers of liver fibrosis: Diagnostic markers using combination of routine liver biochemistry: age, AST, ALT, platelet count, cholesterol, GGT
Direct serum markers of liver fibrosis: Serum markers that reflect liver extracellular matrix turnover and -accumulation
LiverTRAIL: Software that contain 199 diagnostic algorithms, containing combinations of routine tests: age, AST, albumin, alkaline phosphatase, bilirubin, GGT, INR, platelet count, cholesterol and sodium, and specialist tests: transient elastography and direct serum markers of fibrosis.
Cytokeratin 18: Cytokeratin 18 from liver cell cytoskeleton; when cells undergo apoptosis, caspase-cleaved CK18 is released (M30), whereas full-length CK18 is realised during necrosis (M65)
Omics markers: Markers combining signatures of liver fibrosis and hepatic inflammation from many 'omics technologies
Study summary
Prospective screening study at Odense University Hospital to assess the effect of transient elastography and other serum and imaging markers of liver fibrosis to detect advanced fibrosis (Kleiner Fibrosis score F3-F4) in patients at risk of non-alcoholic fatty liver disease, alcoholic fatty liver disease, with a control group of participants recruited from the general population.
Eligibility
INCLUSION CRITERIA
Patients are eligible for screening if the following inclusion criteria are fulfilled:
* Age 30-75 years (except the general population, which should be aged 40-75)
* Informed consent to study investigations
* Ability to read and write Danish AND (only at-risk patients)
* Prior or current alcohol overuse, defined as an average intake of ≥24 grams/day (14 units/week) for women and ≥36 grams/day (21 units/week) for men, for at least 5 years; OR
* Presence of the metabolic syndrome defined by central obesity plus any two of the following four metabolic risk factors: (a) raised triglycerides, (b) reduced HDL cholesterol, (c) raised blood pressure and (d) raised fasting plasma glucose;\[38\] OR
* Type 2 diabetes mellitus defined by either fasting plasma glucose ≥7 mmol/L, HbA1c ≥48 mmol/mol, a random plasma glucose ≥11.1 mmol/L in the presence of classic diabetes or an oral glucose tolerance test with fasting plasma glucose ≥7.0 mmol/L and/or 2 hour plasma glucose ≥11.1 mmol/L.
EXCLUSION CRITERIA
We will exclude patients from screening in case of:
* Evidence of decompensated liver disease, defined by clinically obvious ascites, overt hepatic encephalopathy, jaundice or large esophageal varices with/without variceal bleeding.
* Known concurrent liver disease other than ALD and NAFLD.
* Cancer or other debilitating disease with an expected survival of less than 12 months.
* Inability to comply with the study protocol.
In screened patients with liver stiffness ≥8 kPa we will abstain from a liver biopsy in case of:
* Contraindications for a percutaneous liver biopsy
* Severe alcoholic hepatitis or other hepatic inflammation evidenced by transaminase elevation of more than three times the upper limit of normal.
* Hepatic congestion or bile duct dilation evidenced by ultrasound.
* Decrease of TE below 6.0 kPa from screening to time of planned liver biopsy.
Primary outcome measure(s)
- Biopsy-verified advanced fibrosis — 5 years
Number of patients with biopsy-verified, advanced fibrosis (Kleiner fibrosis score ≥F3) detected by screening
- Liver-related outcomes — 10 years
Number of liver-related clinical outcomes during 10 years of follow up after the first screened patient, compared to a matched, historical control group (The Inter99 study and the Copenhagen and Odense alcohol rehabilitation cohorts). Liver-related outcomes are defined as liver-related death, liver transplant, progression to liver-related complications (ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, jaundice, bleeding from esophagastric varices, hepatocellular carcinoma) or MELD-Na score \>15
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Department of Gastroenterology and Hepatology, Odense University Hospital |
Odense |
Denmark |
Recruiting |
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