Screening At-risk Populations for Hepatic Fibrosis With Non-invasive Markers

Not Applicable

Recruiting

• Conditions: Liver Diseases, Alcoholic; Fibrosis

• Registration Number: NCT03308916
• Lead Sponsor: Maja Thiele

Brief 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.

Detailed Description

This protocol describes a prospective screening study at Odense University Hospital, Department of Gastroenterology and Hepatology. The investigators will use liver stiffness measurements with transient elastography to screen 3000 participants from at-risk populations and 3500 participants from the general population for advanced liver fibrosis. At-risk is defined as either (A) a prior or current alcohol overuse (≥21 units/week for men and ≥14 units/week for women) for more than 5 years, or (B) presence of the metabolic syndrome with or without concomitant type 2 diabetes mellitus.

The study goal is to evaluate the aptitude of transient elastography as a screening tool for advanced liver fibrosis, based on analyses of benefit, harm, detection rate, technical applicability and prognostic potential. Secondary aims are to compare novel serum markers of liver fibrosis as potential screening tools against transient elastography: The Enhanced Liver Fibrosis test, neoepitope markers of extracellular matrix turnover, cytokeratin-18 based markers and indirect indices of fibrosis from algorithms combining routine liver blood test. Screened participants with elevated liver stiffness (≥8.0 kiloPascal; estimated 400 participants with alcoholic liver disease, 400 participants with non-alcoholic fatty liver disease and 280 participants from the general population) will be investigated with 2-dimensional shear-wave elastography and abdominal ultrasonography and a liver biopsy to confirm or reject presence of advanced fibrosis.

All participants with a positive screening elastography will be invited for repeated liver stiffness measurements and serum fibrosis markers after a minimum of one year from inclusion.

Participants at risk of alcoholic and non-alcoholic liver disease, independent of liver stiffness measurement at inclusion, will be invited for repeated liver stiffness measurements and serum fibrosis markers after a minimum of one year from inclusion. At-risk participants with elevated liver stiffness measurements at a follow-up visit (\>6.0 kiloPascal) will be offered a liver biopsy, however no earlier than two years after the index biopsy.

All participants will be followed for 10 years to assess liver-related outcomes and all-course mortality.

Study Timeline

• Study First Submitted: 2016-02-04
• Study Start: 2017-10-06
• Study First Submitted QC: 2017-10-11
• Study First Posted: 2017-10-13
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-29
• Last Update Posted: 2022-09-01
• Primary Completion: 2025-12-30
• Study Completion: 2035-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6500

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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
Biopsy-verified advanced fibrosis	5 years	Number of patients with biopsy-verified, advanced fibrosis (Kleiner fibrosis score ≥F3) detected by screening

Secondary Outcome Measures

Name	Time	Method
Mortality	10 years	Overall number of deaths 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	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 Locations

Locations (1)

Department of Gastroenterology and Hepatology, Odense University Hospital; 🇩🇰 Odense, Denmark