Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease
Open accessAbstract
BACKGROUND & AIMS: It is unclear whether the identification of individuals at risk of cirrhosis using non-invasive tests can be improved by repeated measurements. Herein, we tested whether repeated measurements of fibrosis-4 index (FIB-4) could improve the identification of individuals at risk of severe liver disease. METHODS: Data were derived from the population-based Swedish AMORIS cohort with baseline examinations from 1985-1996. FIB-4 was calculated at 2 time points within 5 years. Thereafter, we associated changes in FIB-4 with outcomes. Incident severe liver disease data was ascertained through linkage to Swedish national registers until 2011. Hazard ratios (HRs) and CIs for outcomes were calculated using Cox regression. RESULTS: Of 126,942 individuals with available FIB-4 data, 40,729 (32.1%) underwent a second test within 5 years (mean interval 2.4 years). During 613,376 person-years of follow-up, 581 severe liver disease events were documented (0.95/1,000 person-years). An increase of 1 unit in FIB-4 was associated with an elevated risk of severe liver disease (adjusted hazard ratio [aHR] 1.81; 95% CI 1.67-1.96). Transitioning from a low- or intermediate- to a high-risk group was associated with an increased risk of severe liver disease compared with those consistently in the low-risk group (aHR 7.99 and 8.64, respectively). A particularly increased risk of severe liver disease was found in individuals defined as high risk at both tests (aHR 17.04; 95% CI 11.67-24.88). However, almost half of all events occurred in those consistently in the low-risk group. CONCLUSIONS: Repeated testing of FIB-4 within 5 years improves the identification of individuals at an increased risk of severe liver disease in the general population. However, the sensitivity is comparatively low and improved tests are needed for screening in a general population or primary care setting. LAY SUMMARY: The fibrosis-4 scoring system is often used to estimate the risk of advanced fibrosis in liver diseases. Herein, we found that changes in this score over time are associated with the risk of future severe liver disease in a population-based cohort. However, even if the prediction is improved by repeated testing, the overall ability of the score to predict future events is relatively low.
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Only a very small proportion of individuals developed liver-related events, despite one third of the population having intermediate or high FIB-4 on more than one occasion.
“only a very small proportion of individuals developed liver-related events, despite one third of the population having intermediate or high FIB-4 on > -1 occasion. 191”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [191]
Up to 50% of individuals with liver events may have persistently low FIB-4.
“up to 50% of individuals with liver events may have persistently low FIB-4. 191”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [191]
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- Authors
- Hagström, H., Talbäck, M., Andreasson, A., Walldius, G., & Hammar, N.
- Affiliations
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Hagström, Hannes
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 73
- Issue
- 5
- Pages
- 1023-1029
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W3040545282
- Cited by
- 199
- References
- 23
- Citations by year
- 2026: 23 · 2025: 36 · 2024: 38 · 2023: 30 · 2022: 46 · 2021: 23 · 2020: 3
- FWCI
- 18.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Hepatology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Intercept Pharmaceuticals
- Stockholms Läns Landsting
- AstraZeneca
- Gilead Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- FIB-4, liver fibrosis, liver cirrhosis, severe liver disease, repeated measures, non-invasive risk prediction, liver disease screening, risk stratification, AMORIS cohort, general population screening, primary care screening
- MeSH terms
- Aged, Aged, 80 and over, Biopsy, Female, Follow-Up Studies, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Prognosis, Risk Factors, Severity of Illness Index, Sweden, Biomarkers, Comorbidity, Incidence, Disease Progression, Non-alcoholic Fatty Liver Disease
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