The Nijmegen-Leiden-Amsterdam 2-tiered Care Path Study

NCT05712603 | Completed DMC

• 1 other identifier: NL81357.018.22
• Study Type: observational
• Target: 655
• Locations: 1 country
• Sites: 3

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is a liver disease, caused by storage of fat in the liver. The most-important risk-factors are being overweight, and disorders in sugar and cholesterol handling of the body. On average does around 30% of the population worldwide have any signs of fatty liver. Most people will not get severe complaints as a result of their fatty liver. But in some of them, the fat storage will lead to hepatitis. This causes damage to the liver which can eventually lead to scarring of the liver, and in some patients to cirrhosis. This possibly can cause liver failure, liver cancer, an several complaints which reduce the quality of life. There are several tests which can help in detecting scarring of the liver. However, the scientific world still does not know well enough which test works best and if they perhaps might work better if they are used together. In this study these questions will be investigated in order to design a care path which does several tests consecutively. The goal is that this will make it possible to easily detect a severely diseased liver and that this will eventually help to detect patients earlier so they can be treated earlier and complications of the disease might be reduced. Moreover, is the goal that this study will lead to a decrease in unnecessary referrals to a hepatologist, resulting in a reduction in invasive diagnostic interventions. Hospital specialists who think that their patient might be at risk for advanced liver disease, can refer a patient to this study. Participants will go to the hospital for one study visit where several tests will be done which are designed to detect liver scarring. Depending on the results, a participant will be referred to a hepatologist for more extensive diagnostics or referred back to the referring specialist with advice for management of the disease.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

Care path; Non-alcoholic Fatty Liver Disease; FIB4; FibroScan; ELF-test

Outcome Measures

Primary Outcomes (2)

• Diagnostic accuracy of the three different care paths to detect advanced fibrosis.

  The diagnostic accuracy of the three different sequential care path algorithms to detect underlying advanced (≥F3) liver fibrosis, assessed using sensitivity, specificity, predictive values and area under the receiver characteristics (AUROC) curve

  The time frame is based on the time between the study visit and the subsequent read-outs of the EHR, up to 24 months later

• Diagnostic performance of the three different care paths to increase correct and decrease incorrect referrals.

  The diagnostic performance of the three different sequential care path algorithms, defined as the increase in correct and the decrease in unnecessary referrals when using these care paths to detect underlying advanced (≥F3) NAFLD-fibrosis compared to regular care.

  The time frame is based on the time between the study visit and the subsequent read-outs of the EHR, up to 24 months later

Secondary Outcomes (8)

• Cost effectiveness of the different diagnostic modalities/care path algorithms

  The time frame is based on the time between the study visit and the subsequent read-outs of the EHR, up to 24 months later.

• Number of patients coded for NAFLD before and after the study

  through study completion, an average of 1 year

• The diagnostic accuracy of the FIB4-score for detecting advanced fibrosis

  The time frame is based on the time between the study visit and the subsequent read-outs of the EHR, up to 24 months later.

• The diagnostic accuracy of the ELF-test for detecting advanced fibrosis

  The time frame is based on the time between the study visit and the subsequent read-outs of the EHR, up to 24 months later.

• The diagnostic accuracy of VCTE for detecting advanced fibrosis

  The time frame is based on the time between the study visit and the subsequent read-outs of the EHR, up to 24 months later.

Study Arms (3)

Prospective care path arm

Participants who enter the care path will make up the prospective care path arm. In patients entering the care path three diagnostic tests for liver fibrosis will be performed. FIB4-score, Vibration controlled transient elastography and Enhanced Liver Fibrosis test

Diagnostic Test: FIB4-score; Diagnostic Test: Vibration controlled transient elastography; Diagnostic Test: Enhanced Liver Fibrosis test

Prospective arm of 'regular care'

Patients who are referred to the hepatologist in participating centers during the study period without using the care path (e.g. because of altered liver function tests for instance), will be the prospective 'regular care' arm

Retrospective arm of 'regular care'

The investigators will do an data extraction of the electronic health records of patients referred to the hepatologist in the five years prior to the study. They will make up the retrospective comparative arm of regular care

Interventions

FIB4-score DIAGNOSTIC_TEST

A score which estimates the risk for advanced liver fibrosis, based on: age, ALT, AST and thrombocytes

Prospective care path arm

Vibration controlled transient elastography DIAGNOSTIC_TEST

VCTE measures the speed of a mechanically generated shear wave across the liver to derive a liver stiffness measurement (LSM), a marker of hepatic fibrosis

Also known as: VCTE

Prospective care path arm

Enhanced Liver Fibrosis test DIAGNOSTIC_TEST

The ELF-test is a non-invasive blood test that measures three direct markers of liver fibrosis: hyaluronic acid (HA), procollagen III amino-terminal peptide (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1).

Also known as: ELF-test

Prospective care path arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from three different academic medical centres in the Netherlands, namely Radboudumc, LUMC and Amsterdam UMC. Patients who are suspected of underlying severe NAFLD-fibrosis by their treating physician are eligible for inclusion in the study. This suspection will most often arise because of risk factors as obesity, diabetes type 2, hypercholesterolemia or metabolic syndrome, or proven heaptic steatosis because of an conventional ultrasound. Patients are referred from hospital specialists

You may qualify if:

• Age ≥ 18 years;
• Suspected by treating physician to suffer from a severe stage of NAFLD-fibrosis.

You may not qualify if:

• Previous diagnosis of advanced (≥F3) liver fibrosis;
• Any other known chronic liver disease (alcoholic steatohepatitis, hepatitis B, hepatitis C, autoimmune hepatitis, hemochromatosis, Wilsons disease, alpha-1-antitrypsin deficiency);
• Drugs that may cause drug-induced hepatic steatosis, (table provided elsewhere)
• Present excessive alcohol use, defined as \> 2 units/day for women and \> 3 units/day for men;
• A psychiatric, addictive or any other disorder that compromises the subject's ability to understand the study content and to give written informed consent for the participation in the study.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Maag Lever Darm Stichting: collaborator
• Radboud University Medical Center: collaborator
• Leiden University Medical Center: collaborator

Study Sites (3)

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Amsterdam UMC, location AMC

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Leiden universitair medisch centrum

Leiden, South Holland, 2333 ZA, Netherlands

Location

Related Publications (22)

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  PMID: 28930295 BACKGROUND

• Ruissen MM, Mak AL, Beuers U, Tushuizen ME, Holleboom AG. Non-alcoholic fatty liver disease: a multidisciplinary approach towards a cardiometabolic liver disease. Eur J Endocrinol. 2020 Sep;183(3):R57-R73. doi: 10.1530/EJE-20-0065.

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  PMID: 32027911 BACKGROUND

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• Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014 Jan 14;20(2):475-85. doi: 10.3748/wjg.v20.i2.475.

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• Alexander M, Loomis AK, van der Lei J, Duarte-Salles T, Prieto-Alhambra D, Ansell D, Pasqua A, Lapi F, Rijnbeek P, Mosseveld M, Avillach P, Egger P, Dhalwani NN, Kendrick S, Celis-Morales C, Waterworth DM, Alazawi W, Sattar N. Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ. 2019 Oct 8;367:l5367. doi: 10.1136/bmj.l5367.

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• Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW. Nonalcoholic Fatty Liver Disease in Adults: Current Concepts in Etiology, Outcomes, and Management. Endocr Rev. 2020 Jan 1;41(1):bnz009. doi: 10.1210/endrev/bnz009.

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Biospecimen

Retention: SAMPLES WITH DNA

Serum of the participants will be retained if they give permission for that. buffy coats will be stored as well, for future DNA research.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Onno Holleboom, MD PhD

  Amsterdam UMC, location AMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vascular internist and endocrinologist, Assistant professor, Principal investigator

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: February 3, 2023
• Study Start: October 1, 2022
• Primary Completion: June 30, 2024
• Study Completion: October 15, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)