Altered Serum Bile Acid Pattern as an Independent Factor for Covert and Overt Hepatic Encephalopathy in Patients With Cirrhosis

Aim Bile acid (BA) signaling plays an important role in the pathogenesis of hepatic encephalopathy (HE), including covert (CHE) and overt HE (OHE). However, few studies have examined its clinical impact in patients with cirrhosis. Methods This retrospective study included patients with cirrhosis who underwent CHE assessment using a computer‐aided neuropsychiatric test. BAs were quantified using liquid chromatography‐tandem mass spectrometry. Patients were divided into high and low groups according to their BA levels. Independent factors, namely CHE, OHE development, and mortality, were assessed using logistic, Fine–Gray competing risk, and Cox proportional hazards regression models. Results Among the 189 patients, the median age was 71 years, 74.1% were male, and 28.0% were diagnosed with CHE. During a median follow‐up period of 3.1 years, 15.9% ( n = 30) developed OHE, and 33.3% ( n = 63) died. Considering mortality as a competing risk, multivariable analysis identified a high conjugated primary BA level (subdistribution hazard ratio [HR] 3.44; 95% confidence interval [CI] 1.08–10.97) as an independent factor for OHE development. Additionally, a high non‐conjugated primary BA level (odds ratio 2.18; 95% CI 1.06–4.46) was an independent factor of CHE. Furthermore, a high conjugated primary BA level (HR 2.06; 95% CI 1.11–3.83) was an independent predictor of mortality. Conclusions Elevated serum conjugated primary BA levels are an independent factor for OHE development and mortality in patients with cirrhosis. Additionally, elevated non‐conjugated primary BA levels were an independent factor for CHE in these patients.