Identifying subjects at risk of liver cirrhosis via a range of thresholds for common fibrosis markers: A Welsh general population-based cohort study.

Abstract

Liver disease is on the increase worldwide, with cirrhosis and liver cancer accounting for around 3.5% of all deaths. Investigate the prognostic utility of three non-invasive liver fibrosis markers in the Welsh primary care population for identification of those at risk of cirrhosis or hepatocellular carcinoma (HCC). Using the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University (2000-2017), we identified people with liver blood tests allowing calculation of three commonly used liver fibrosis markers: aspartate transaminase to alanine transaminase (AST/ALT) ratio, AST to platelet ratio index (APRI) and fibrosis-4 index (FIB-4). We modelled 10-year risk of cirrhosis/HCC across a range of thresholds using competing risk survival analysis and compared their prognostic value using decision curve analysis (DCA). Blood tests enabling calculation of FIB-4, APRI and AST/ALT were available for 203,005 people. At commonly utilized cut-points to detect advanced fibrosis/cirrhosis of 3.25, 1.5 and 1.0 for FIB-4, APRI and AST/ALT, respectively, the 10-year risks of cirrhosis/HCC were 4.7%, 16% and <1%. DCA demonstrated the APRI has the greatest net benefit for estimating cirrhosis/HCC risk over 10 years, in a general population compared to AST/ALT or FIB-4. In higher risk subgroups, a greater proportion of at-risk patients were captured for fewer referrals. This was also observed in groups with combinations of risk factors. At risk thresholds often used for referral, liver fibrosis markers had prohibitively high false positive rates unless restricted to subgroups at increased risk of developing severe liver disease.