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

LiverSeek addresses a well-recognised implementation gap: despite guideline recommendations to screen for liver fibrosis in high-risk metabolic patients, fewer than one-third of eligible patients are assessed in clinical practice. Encounter-triggered programmes (e.g., SOLID, PRELUDE1) require primary care clinicians to initiate the assessment process, creating a dependency on clinician awareness and workload capacity that limits scalability.

LiverSeek adopts a fundamentally different model: the screening process is initiated passively by the LIS infrastructure, triggered by existing routine blood test data, with zero additional burden on the primary care clinician. This passive architecture is the programme's principal conceptual innovation.

NIT pathway and pre-specified thresholds:

Step 1 (LIS-triggered): FIB-4 calculated automatically. Threshold: >1.30 (EASL 2024) Step 2 (reflex, same serum sample): ELF (threshold ≥9.8) and MASEF (threshold ≥0.33, Youden J-point) Step 2 alternative (VCTE-based): VCTE ≥8.0 kPa; FAST score ≥0.50 (Youden J-point) NIT-positive patients → Hepatology APN visit (VCTE, anthropometrics, clinical assessment, EQ-5D-5L, IEXPAC, MEDAS dietary questionnaire) NIT-positive patients with VCTE ≥8.0 kPa → Hepatology physician consultation ± liver biopsy per clinical criteria

Histological sub-study: Liver biopsy specimens are scored using the NAFLD Activity Score (Kleiner 2005). At-risk MASH is defined as NAS ≥4 + fibrosis stage ≥F2. A target of approximately 300 evaluable biopsies is projected.

Lifestyle intervention sub-study: NIT-positive patients receive a single structured APN-delivered visit with a personalised SMART lifestyle protocol, with 24-week reassessment. Outcomes include changes in LSM, CAP, ALT, AST, GGT, HbA1c, FIB-4, and body composition (BIA).

Data management: REDCap electronic case report form, pseudonymised, restricted access.

Statistical approach: Prevalence with 95% CI (primary endpoint); AUROC with DeLong test for head-to-head NIT comparisons; sensitivity, specificity, PPV, NPV, LR+ and LR- for sequential algorithms; kappa for concordance. Health-economic analysis via CIBERehd.

Inclusion criteria

• 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%

Exclusion criteria

• 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.