FIB-4 and APRI for cirrhosis detection in a privately insured national cohort

Background and Aims: Non-invasive laboratory-based fibrosis indices have been proposed as a tool for population-based screening for advanced fibrosis. We aimed to examine the performance of fibrosis indices at the time of and prior to cirrhosis diagnosis.Methods: We included adult patients with cirrhosis diagnosis codes in a privately insured database (Optum) from 2010-2018 with 1:4 birth year-matched controls without cirrhosis diagnosis codes. We analyzed aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) up to 30 months prior to the entry of cirrhosis diagnosis codes. Cut-offs of <1 and >= 2 were used for APRI and <1.3 and >= 2.67 were used for FIB-4.Results: We included 10,650 patients with cirrhosis (median age 62 years), who were predominantly white (57.8%) and male (51.9%). The most common etiologies of cirrhosis were non-alcoholic steatohepatitis (23.8%), hepatitis C (23.0%), and alcohol related liver disease (20.5%). At the time of cirrhosis diagnosis (+/- 3 months), 9.3% of patients with cirrhosis had APRI >= 2 and 41.3% had a FIB-4 >= 2.67 compared to 1.2% and 8.9% in control patients, respectively. In the periods spanning 3-12, 12-21, and 21-30 months prior to cirrhosis diagnosis, APRI was >= 2 in 9.4%, 6.6%, and 6.5% of patients, respectively; FIB-4 was >= 2.67 in 42.1%, 37.1%, and 34.3% of patients, respectively. The sensitivity and specificity of APRI at the time of cirrhosis diagnosis were 9.3% and 98.8%, respectively, while the sensitivity and specificity of FIB-4 were 41.3% and 91.0%, respectively. Lower cut-off values for APRI and FIB-4 showed similar performance.Conclusions: Existing non-invasive fibrosis makers are suboptimal when used for advanced fibrosis identification, missing over half of patients with cirrhosis at the time of and prior to clinical diagnosis.Impact and implications: Commonly available laboratory-based indices, including APRI and FIB-4, have been proposed to rule in or rule out advanced fibrosis in the general population. In a study of a large privately insured cohort from the US, FIB-4 and APRI were not sufficient for screening for advanced fibrosis at the time of or prior to clinical diagnosis. While performance for screening out advanced fibrosis was better, a significant percentage of patients with cirrhosis have lab indices below threshold values. Future studies to develop laboratory-based algorithms to help stratify liver fibrosis for population-based screening are warranted.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

The commonly used liver fibrosis screening markers APRI and FIB-4 were found to be suboptimal for identifying advanced fibrosis at the time of and prior to clinical diagnosis, missing over half of patients with cirrhosis. Further research is needed to develop laboratory-based algorithms to aid in population-based screening for liver fibrosis.