Automated Passive Case-Finding for Advanced Liver Fibrosis in MASLD: The LiverSeek Programme

NCT07658755 | Recruiting

• 1 other identifier: HEP-OSF2024
• Study Type: observational
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

LiverSeek is a fully automated, passive case-finding programme for advanced liver fibrosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD) in primary care. The programme operates through the Laboratory Information System (LIS; Modulab/Biwer Analytics) of the Clinical Biochemistry Laboratory at Hospital General Universitario Gregorio Marañón (HGUGM), covering approximately 350,000 inhabitants across 11 peri-urban primary care centres affiliated to SERMAS (Servicio Madrileño de Salud) in Madrid, Spain. When a high-risk patient (age 50-75 years with ≥1 of: ALT above ULN + HbA1c ≥6.5%; ALT above ULN + BMI \>30; BMI \>30 + HbA1c ≥6.5%) undergoes a routine blood test in primary care, the LIS automatically calculates FIB-4. If FIB-4 \>1.30, the system reflexively orders ELF and MASEF from the same serum sample, without any action required from the primary care clinician. Patients with a positive second-step NIT (ELF ≥9.8 or MASEF ≥0.33) receive an automatic alert directing them to the Hepatology Advanced Practice Nurse for VCTE (FibroScan) and clinical evaluation. The primary objective is to evaluate the prevalence of hepatic fibrosis in the high-risk population using this single-step automated strategy. Secondary objectives include head-to-head diagnostic comparison of FIB-4+ELF vs FIB-4+MASEF vs FIB-4+FAST for histologically-confirmed endpoints (significant fibrosis ≥F2, advanced fibrosis ≥F3, at-risk MASH), evaluation of the Liver Risk Score, and a health-economic analysis. A sub-study evaluates a nurse-led structured lifestyle intervention in NIT-positive patients.

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease; Liver Fibrosis; Non-alcoholic Fatty Liver Disease NAFLD; Type 2 Diabetes Mellitus; Obesity; Obesity Type 2 Diabetes Mellitus

Keywords

MASLD; MAFLD; NAFLD; liver fibrosis; FIB-4; ELF; MASEF; screening; passive screening; advanced practice nurse; lifestyle intervention

Outcome Measures

Primary Outcomes (1)

• Prevalence of hepatic fibrosis detected by the automated single-step case-finding strategy

  Proportion of high-risk patients with a positive result on at least one confirmatory NIT (ELF ≥9.8, MASEF ≥0.33, or VCTE ≥8.0 kPa) among all patients in whom FIB-4 was automatically calculated by the LIS

  Within 3 months of index blood test

Secondary Outcomes (3)

• Diagnostic accuracy of FIB-4+ELF versus FIB-4+MASEF for histologically-confirmed significant fibrosis (≥F2)

  At time of liver biopsy

• Diagnostic accuracy of sequential NIT algorithms for at-risk MASH

  At time of liver biopsy

• Cost-effectiveness of the automated single-step strategy versus standard of care

  At study completion (September 2027)

Study Arms (2)

NIT-Negative Cohort

High-risk patients (age 50-75 years with ≥1 metabolic risk criterion) in whom FIB-4 was automatically calculated by the LIS and found to be ≤1.30. These patients do not undergo further NIT evaluation and are followed as the non-exposed reference cohort.

NIT-Positive Cohort

High-risk patients with FIB-4 \>1.30 in whom ELF and MASEF were reflexively determined from the same serum sample. Patients with ELF ≥9.8 or MASEF ≥0.33 are referred to the Hepatology Advanced Practice Nurse for VCTE (FibroScan) and clinical assessment.

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients attending primary care in peri-urban Madrid (SERMAS network) with metabolic risk factors for liver fibrosis, identified passively through routine laboratory data

You may qualify if:

• Age between 50 and 75 years (inclusive)
• Routine blood test processed in the Clinical Biochemistry Laboratory of Hospital General Universitario Gregorio Marañón, ordered by a primary care physician in one of the 11 affiliated SERMAS primary care centres
• Presence of at least one of the following metabolic risk factor combinations:
• ALT above the upper limit of normal AND HbA1c ≥6.5%
• ALT above the upper limit of normal AND BMI \>30 kg/m²
• BMI \>30 kg/m² AND HbA1c ≥6.5%

You may not qualify if:

• Age \<50 years or \>75 years
• Known pre-existing liver disease (significant or advanced fibrosis, cirrhosis, hepatocellular carcinoma, prior liver transplantation)
• Prior fibrosis assessment within the preceding 12 months.

Sponsors & Collaborators

• Hospital General Universitario Gregorio Marañon: lead
• Instituto de Investigación Sanitaria Gregorio Marañón: collaborator
• Consorcio Centro de Investigación Biomédica en Red (CIBER): collaborator

Study Sites (1)

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Related Publications (5)

• Graupera I, Thiele M, Castera L, Pera G, Piano S, Soria A, Fabrellas N, Toran P, Chacon C, Bech KT, Schnefeld HL, Tonon M, Incicco S, Moussy J, Levy V, Madir A, Kukic S, Jan Havaj D, Adamcova-Selcanova S, Pustjens J, van Kleef LA, Jimenez-Masip A, Pages L, Zoncape M, Weber SN, Galle PR, Harris R, Ibanez-Samaniego L, Morillas RM, Diaz A, Detlefsen S, Serra-Burriel M, Arslanow A, Andersen P, Pich J, Bonfill E, Korenjak M, Fournier-Poizat C, Llorca A, Gourmelon MC, de Koning HJ, Perez-Guasch M, Thu Ma A, Juanola A, Pose E, Arteaga I, Villesen I, Hansen JK, Calvino V, Gagliardi R, Boutouria B, Pastrovic F, Kujundzic PD, Zilincanova D, Sulejova KK, Rojo D, de Knegt RJ, Melo MD, Torrejon A, Hernandez-Ibanez R, Hoyo J, Munoz L, Lopez-Martos R, Griffin SJ, Manns M, Karlsen TH, Newsome PN, Kamath PS, Banares R, Guha IN, Schattenberg JM, Lammert F, Tsochatzis E, Brouwer WP, Pericas JM, Skladany L, Grgurevic I, Roulot D, Angeli P, Krag A, Caballeria L, Gines P; LiverScreen Consortium Investigators. Prevalence of liver fibrosis in the general population (the LiverScreen project): a multinational European cohort study. Lancet. 2026 Apr 11;407(10537):1448-1458. doi: 10.1016/S0140-6736(26)00354-5.

  PMID: 41969010 BACKGROUND

• Serra-Burriel M, Juanola A, Serra-Burriel F, Thiele M, Graupera I, Pose E, Pera G, Grgurevic I, Caballeria L, Piano S, van Kleef L, Reichert M, Roulot D, Pericas JM, Schattenberg JM, Tsochatztis EA, Guha IN, Garcia-Retortillo M, Hernandez R, Hoyo J, Fuentes M, Exposito C, Martinez A, Such P, Madir A, Detlefsen S, Tonon M, Martini A, Ma AT, Pich J, Bonfill E, Juan M, Soria A, Carol M, Gratacos-Gines J, Morillas RM, Toran P, Navarrete JM, Torrejon A, Fournier C, Llorca A, Arslanow A, de Koning HJ, Cucchietti F, Manns M, Newsome PN, Hernaez R, Allen A, Angeli P, de Knegt RJ, Karlsen TH, Galle P, Wong VW, Fabrellas N, Castera L, Krag A, Lammert F, Kamath PS, Gines P; LiverScreen Consortium Investigators. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. Lancet. 2023 Sep 16;402(10406):988-996. doi: 10.1016/S0140-6736(23)01174-1. Epub 2023 Aug 9.

  PMID: 37572680 BACKGROUND

• European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7.

  PMID: 38851997 BACKGROUND

• Kjaergaard M, Lindvig KP, Thorhauge KH, Andersen P, Hansen JK, Kastrup N, Jensen JM, Hansen CD, Johansen S, Israelsen M, Torp N, Trelle MB, Shan S, Detlefsen S, Antonsen S, Andersen JE, Graupera I, Gines P, Thiele M, Krag A. Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease. J Hepatol. 2023 Aug;79(2):277-286. doi: 10.1016/j.jhep.2023.04.002. Epub 2023 Apr 21.

  PMID: 37088311 BACKGROUND

• Noureddin M, Truong E, Mayo R, Martinez-Arranz I, Minchole I, Banales JM, Arrese M, Cusi K, Arias-Loste MT, Bruha R, Romero-Gomez M, Iruzubieta P, Aller R, Ampuero J, Calleja JL, Ibanez-Samaniego L, Aspichueta P, Martin-Duce A, Kushner T, Ortiz P, Harrison SA, Anstee QM, Crespo J, Mato JM, Sanyal AJ. Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF). Hepatology. 2024 Jan 1;79(1):135-148. doi: 10.1097/HEP.0000000000000542. Epub 2023 Jul 24.

  PMID: 37505221 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Diabetes Mellitus, Type 2; Obesity; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Fatty Liver

Study Officials

• Rafael Bañares, Full-Professor of Medicine

  Universidad Complutense de Madrid, President of Spanish Association for the Study of the Liver (AEEH)

  STUDY CHAIR

• Magdalena Salcedo, MD, PhD

  President of the Spanish Society of Liver Transplantation (SETH)

  STUDY CHAIR

Central Study Contacts

Luis Ibáñez-Samaniego, MD, PhD

CONTACT

+34 91 586 8308; luis.ibanez@salud.madrid.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Luis Ibáñez-Samaniego MD, PhD - Senior Consultant in Hepatology

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: June 22, 2026
• Study Start: October 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)