A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study

Abstract

Introduction: In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD.

Methods: Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network. Baseline variables from a Japanese cohort of 197 patients with cACLD were examined and fitted a Cox hazard regression model to develop a specific score for predicting hepatic decompensation. The novel score was validated in an external cohort (n = 770) from 5 centers in China, Singapore, Korea, and Egypt, and was further assessed for the ability of predicting clinically significant portal hypertension in a hepatic venous pressure gradient cohort (n = 285).

Results: In the derivation cohort, independent predictors of hepatic decompensation were identified including Stiffness of liver, Albumin, Varices, and platElets and fitted to develop the novel score, termed "SAVE" score. This score performed significantly better (all P < 0.05) than other assessed methods with a time-dependent receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.83-0.94) and 0.83 (95% CI: 0.73-0.92) in the derivation and validation cohorts, respectively. The decompensation risk was best stratified by the cutoff values at -6 and -4.5. The 5-year cumulative incidences of decompensation were 0%, 24.9%, and 69.0% in the low-risk, middle-risk, and high-risk groups, respectively ( P < 0.001). The SAVE score also accurately predicted clinically significant portal hypertension (AUC, 0.85 95% CI: 0.80-0.90).

Discussion: The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD.

Trial registration: ClinicalTrials.gov NCT04975477.

Figure 1.

Flowchart of patient recruitment in the derivation and validation cohorts. cACLD, compensated advanced chronic liver disease; EGD, esophagogastroduodenoscopy; LSM, liver stiffness measurement; PLT, platelet.

Figure 2.

Summary time-dependent receiver operating characteristic curve for the Stiffness of liver, Albumin, Varices, and platElets (SAVE) score and other models to predict hepatic decompensation within the 5-year follow-up in the derivation (a) and validation (b) cohorts. ALBI, albumin‐bilirubin; MELD, Model of End‐stage Liver Disease; PLT, platelet; RESIST‐HCV, Rete Sicilia Selezione Terapia–hepatitis C virus.

Figure 3.

Cumulative incidence of first decompensation in patients with compensated advanced chronic liver disease stratified by the Stiffness of liver, Albumin, Varices, and platElets score in the derivation (a) and validation (b) cohorts. Cumulative incidence curves were calculated by competing risks regression taking death as a competing event. Comparison across different cumulative incidence curves was performed with the Gray test.

Figure 4.

Exploratory analysis of the SAVE score in association with hepatic venous pressure gradient and prediction of clinically significant portal hypertension. (a) Flowchart of patient recruitment in the HVPG cohort, (b) comparisons of the SAVE score with other methods in predicting the presence of clinically significant portal hypertension, and (c) the distribution of HVPG in low‐risk, middle-risk, and high‐risk groups, respectively. ALBI, albumin‐bilirubin; FIB‐4, fibrosis; MELD, Model of End‐stage Liver Disease; PLT, platelet; RESIST‐HCV, Rete Sicilia Selezione Terapia–hepatitis C virus; SAVE, Stiffness of liver, Albumin, Varices, and platElets.