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

[BACKGROUND] Liver disease is on the increase worldwide, with cirrhosis and liver cancer accounting for around 3.5% of all deaths.

[OBJECTIVES] 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).

[METHODS] 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).

[RESULTS] 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.

[CONCLUSION] 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.