A Blood-Based Prognostic Liver Secretome Signature Predicts Long-term Risk of Hepatic Decompensation in Cirrhosis

Abstract

Cirrhosis is the terminal stage of progressive liver fibrosis, affecting 1%-2% of the global population and accounting for 1.3 million deaths annually.^1,2 Median survival for persons with compensated cirrhosis is approximately 12 years, compared with only 2 years for those with hepatic decompensation. Accurate prediction of hepatic decompensation is an unmet need to enable identification of patients with cirrhosis who could benefit from close monitoring and timely medical interventions. Besides, risk stratification of patients with cirrhosis could help inform patient selection for trials evaluating therapies to prevent hepatic decompensation. Although various clinical scores, such as the albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) indices (ALBI-FIB4 score) have been proposed to predict long-term risk of hepatic decompensation,³ external validation has often shown suboptimal prognostic capability and revealed room for improvement.⁴.

Figure 1.

(A) Patten of PLSec protein abundance and associated clinical variables. (B) Association of PLSec with long-term risk of hepatic decompensation. (C) Association of PLSec with incident hepatic decompensation in various subgroups. The size of box is proportional to the number of patients. (D) Time-dependent AUROC of the PLAF, PLSec, ALBI-FIB-4, and MELD score. (E) Calibration plot of the PLAF score at 5 years. The grey dash line indicates ideal calibration. (F) Association of the PLAF score with long-term risk of hepatic decompensation. HCV, hepatitis C virus; PLSec, prognostic liver secretome signature; HR, hazard ratio; CI, confidence interval; ALBI, albumin-bilirubin; FIB-4, fibrosis-4; MELD, model for end-stage liver disease; PLAF, PLSec-ALBI-FIB4.