Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease

Hannes Hagström,Mats Talbäck,Anna Andreasson,Göran Walldius,Niklas Hammar

doi:10.1016/j.jhep.2020.06.007

Hannes Hagström, Mats Talbäck + Show 3 more

Open Access

https://doi.org/10.1016/j.jhep.2020.06.007

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Abstract

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. 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. 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. 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. 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.

Highlights

Advanced fibrosis is the major predictor of clinically significant liver-related outcomes.[1,2,3] defining the presence or absence of advanced fibrosis is key in determining prognosis in individuals with known or suspected chronic liver disease
An increase of 1 unit in fibrosis-4 index (FIB-4) was associated with an elevated risk of severe liver disease
A increased risk of severe liver disease was found in individuals defined as high risk at both tests

Summary

Introduction

Advanced fibrosis (stage 3-4 by liver biopsy) is the major predictor of clinically significant liver-related outcomes.[1,2,3] defining the presence or absence of advanced fibrosis is key in determining prognosis in individuals with known or suspected chronic liver disease. We showed that the capacity of 5 non-invasive scores to predict incident severe liver disease in a general population setting was modest.[8]. It is unclear whether the identification of individuals at risk of cirrhosis using non-invasive tests can be improved by repeated measurements. 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. We found that changes in this score over time are associated with the risk of future severe liver disease in a population-based cohort.

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