Diagnostic and prognostic performance of the LiverRisk score in tertiary care

Background & AimsThe LiverRisk score has been proposed as blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM≥10kPa) and liver-related events in subjects without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care.MethodsSubjects referred to two hepatology outpatient clinics (cohort-I: n=5897; cohort-II: n=1558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD compared to FIB-4/APRI. The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated.ResultsIn cohort-I/II, mean age was 48.3/51.8years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/ metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 [5.1-10.9]/ 5.8 [4.5-8.8]kPa, and 1690 (28.7%)/ 322 (20.7%) had cACLD.Despite a moderate correlation (Pearson's r: 0.325/0.422), the LiverRisk score systematically underestimated LSM ("bias": 2.93/1.80points/kPa lower) and range of agreement was wide, especially at higher values.The diagnostic accuracy of the LiverRisk score for cACLD (AUROC: 0.757/0.790) was comparable to FIB-4 (0.769/0.813) and APRI (0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9/93.4%), but low negative predictive value (76.6/84.5%, Cohen's κ=0.260/0.327).In cohort-I, 208 (3.5%) developed hepatic decompensation (median follow-up: 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1-5 years (AUROC: 0.778-0.832). However, it was inferior to LSM (0.847-0.901, p<0.001) and FIB-4 (0.898-0.913, p<0.001). Similar to the strata of other NIT, proposed LiverRisk groups had distinct risks of hepatic decompensation.ConclusionsThe LiverRisk score did not improve diagnosis of cACLD or prediction of hepatic decompensation in tertiary care setting.IMPACT AND IMPLICATIONThe LiverRisk score has been proposed as non-invasive tool to estimate liver stiffness measurement and thus, the risk of compensated advanced chronic liver disease and liver-related events. As automatic implementation into lab reports is being discussed, the question on its applicability outside of opportunistic screening in the general population arises.In two large cohorts of patients referred to hepatology outpatient clinics, the LiverRisk score did not accurately predict liver stiffness, did not improve cACLD identification, and had a lower predictive performance for hepatic decompensation as compared to FIB-4.While being a major step forward for screening patients without known liver disease in primary care, our findings indicate that the LiverRisk score does not improve patient management outside the primary care setting, i.e., in cohorts with a higher pre-test probability of cACLD.