Diagnostic and prognostic performance of the LiverRisk score in tertiary care

Abstract

Background & aims: The LiverRisk score has been proposed as a blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM ≥10 kPa) and liver-related events in patients without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care.

Methods: Patients referred to two hepatology outpatient clinics (cohort I, n = 5,897; cohort II, n = 1,558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD was compared with that of fibrosis-4 (FIB-4)/aspartate aminotransferase-to-platelet ratio index (APRI). The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated.

Results: In cohort I/II, mean age was 48.3/51.8 years, 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 (IQR 5.1-10.9)/5.8 (IQR 4.5-8.8) kPa, and 1,690 (28.7%)/322 (20.7%) patients had cACLD.Despite a moderate correlation (Pearson's r = 0.325/0.422), the LiverRisk score systematically underestimated LSM (2.93/1.80 points/kPa lower), and range of agreement was wide, especially at higher values.The diagnostic accuracy of the LiverRisk score for cACLD (area under the receiver operator characteristics curve [AUROC] 0.757/0.790) was comparable to that of FIB-4 (AUROC 0.769/0.813) and APRI (AUROC 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%) patients 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 (AUROC 0.847-0.901, p <0.001) and FIB-4 (AUROC 0.898-0.913, p <0.001). Similar to the strata of other non-invasive tests, the proposed LiverRisk groups had distinct risks of hepatic decompensation.

Conclusions: The LiverRisk score did not improve the diagnosis of cACLD or prediction of hepatic decompensation in the tertiary care setting.

Impact and implications: The LiverRisk score has been proposed as a 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 of 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 with FIB-4. Although it represents 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, that is, in cohorts with a higher pre-test probability of cACLD.

Keywords: Chronic liver disease; FIB-4; LSM; Liver stiffness measurement; cACLD.

Graphical abstract

Fig. 1

Scatterplot of the LiverRisk score and LSM in (A) cohort I and (B) cohort II. The dashed black line represents the ‘identity line’, corresponding to perfect calibration between LSM and the LiverRisk score (i.e. predicted LSM); the red line represents the linear fit (see Table 2); and the yellow line represents a non-linear fit with natural splines and three degrees of freedom (df) for (more) flexible modeling of the relationship between LSM and the LiverRisk score. Figures were cut at 25 kPa/points for better interpretability; therefore, further outliers are not displayed. LSM, liver stiffness measurement.

Fig. 2

Modified Bland–Altman plot showing the mean of LSM and LiverRisk score within a patient (x-axis) and the difference (LSM - LiverRisk score, y-axis) in (A) cohort I and (B) cohort II. Dashed black lines represent the mean difference of both measurements (i.e. calibration in the large, ‘bias’) and the upper and lower limits of agreement, corresponding to the area of agreement within ±1.96 times the SD of the difference observed in the respective sample. Values close to 0 indicate no difference within the same subject (i.e. agreement). Red dashed lines represent quantile regression of the 95% CI of differences–means, modeled with natural splines (df = 3). The x-axis was log-transformed to increase interpretability in the clinically relevant range 5–15 kPa. df, degrees of freedom; LSM, liver stiffness measurement.

Fig. 3

Scatterplot of the LiverRisk score and LSM in (A) cohort I and (B) cohort II focusing on the distribution of disease etiologies (colored groups) and agreement/concordance for cACLD (cut-off ≥10 kPa/points). ALD, alcohol-related liver disease; cACLD, compensated advanced chronic liver disease; LSM, liver stiffness measurement; MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 4

Cumulative incidence curves of hepatic decompensation compared across categories of (A) LiverRisk score (<10, 10 to <15, and ≥15), (B) LSM (<10, 10–15, and >15 kPa), (C) FIB-4 (<1.3, 1.3–2.67, and >2.67), and (D) APRI (<0.5, 0.5–1.5, and >1.5) in cohort I. SHRs are given compared with the first group (Fine–Gray subdistribution hazard model). APRI, aspartate aminotransferase-to-platelet ratio index; CI, confidence interval; FIB-4, fibrosis-4; LSM, liver stiffness measurement; SHR, subdistribution hazard ratio.