Biomarker discovery

A possible role for FXR polymorphisms in the etiopathogenesis of acute decompensation of cirrhosis and ACLF: An observational study within CANONIC and PREDICT

The issue

Infections are the most common precipitants of acute-on-chronic liver failure (ACLF), but in more than 40% of patients, no precipitating event is identified. Numerous observations have substantiated a pivotal role for dysregulated systemic inflammation as the pacemaker in (multi-)organ failure and a dysfunctional gut–liver axis as a major instigator. The underlying molecular backbone remains largely unknown.

The approach

Recent translational and clinical research has suggested a central role for defective farnesoid X receptor (FXR) signaling in protracted hepatic inflammation and intestinal bacterial translocation, factors which are known to shape ACLF. The FRX is a bile acid activated nuclear receptor that regulates key genes in the metabolic process of bile acid synthesis and involved in the metabolism of carbohydrates and lipids, representing a promising therapeutic target for bile acid-related liver diseases. This study will explore FXR polymorphisms in the development of acute decompensation of cirrhosis and ACLF within the CANONIC and PREDICT study cohorts.

” The genetic risk of patients to decompensate has not been determined so far. Since FXR seems to play a role in development of cirrhosis and also its modulation may prevent complications, its genetic variants may also play a role. If the association is clear, then this helps to stratify care in the patients and probably with different monitoring and survellaince strategies in different genotypes. In addition, FXR-agonists may be then a strategy to treat these patients. Therefore, this project may open novel horizons in the care of patients. “

says Trebicka