Published online May 27, 2021. doi: 10.4254/wjh.v13.i5.543
Peer-review started: January 5, 2021
First decision: February 13, 2021
Revised: February 21, 2021
Accepted: March 31, 2021
Article in press: March 31, 2021
Published online: May 27, 2021
Most cholestatic diseases progress toward end stage liver failure, which likely requires liver transplantation. Numerous clinical and preclinical studies have shown up to a 100-fold increase in bile acids (BA) concentrations in urine with various hepatobiliary diseases. However, due to their high inter-and intra-individual variability, BA has not been used in clinic as markers for the diagnosis and prognosis of liver diseases. To this end, we have developed the concept of BA indices and utilized it to build a survival model to predict the prognosis of liver diseases.
Biomarkers currently used in the clinic for the diagnosis and prognosis of liver diseases are primarily serum liver enzymes. Model for end-stage liver disease (MELD) was developed to predict three-month mortality of patients with end-stage liver disease. MELD is based on three objective laboratory variables that are not necessarily liver specific. The potential use of BA as a marker for liver diseases has never translated into a widespread use in the clinic. To this end, we have developed the concept of BA indices and utilized it to build a survival model to predict the prognosis of liver diseases.
The objective of this project was to discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA profile. We investigated the use of the urinary BA profile to develop survival models to predict the prognosis of hepatobiliary diseases. One application for BAS could be to define the most seriously ill liver patients, who may need earlier intervention such as liver transplantation.
Sample analysis: Liquid chromatography-tandem mass spectrometry. Statistical analysis: univariate and multivariate Cox proportional hazards regression, testing proportional hazards assumption, receiver operating characteristic curve, survival probability, and Kaplan-Meier plots.
The bile-acid score (BAS) model (a survival model based on BA indices) was more accurate and results in higher true-positive and true-negative prediction of death compared to both non-BAS and MELD models. Both 3- and 5-year survival probabilities markedly decreased as a function of BAS. Patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low BAS. The increased risk of death with high vs low BAS was also 2-4-fold greater and the shortening of lifespan was 6-7-mo lower compared to MELD or non-BAS.
We have developed and validated a survival model (the BAS model) based on BA indices to predict the prognosis of cholestatic liver diseases.
BAS could be used to define the most seriously ill patients, who need earlier intervention such as liver transplant. This will help provide guidance for timely care for liver patients.