Prevalence of Pruritus and Association with Anxiety and Depression in Patients with Nonalcoholic Fatty Liver Disease

Abstract

Patient-reported outcomes are important in nonalcoholic fatty liver disease (NAFLD). Pruritus is of special interest for evolving therapies with farnesoid X receptor (FXR) agonists. The aim of this study was to investigate the prevalence of pruritus in a real-life NAFLD cohort and analyze associations with anxiety and depression. Pruritus was assessed using a visual analogue- (VAS) and 5-D itch-scale (5-D). Anxiety and depression were evaluated by Beck’s-Depression-Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS-A, HADS-D). An optimal logistic regression model was found with a stepwise procedure to investigate variables associated with pruritus. In total, 123 NAFLD patients were recruited. VAS and 5-D were highly correlated (Spearman’s correlation coefficient 0.89). Moderate/severe pruritus was reported in 19% (VAS) and 21% (5-D) of patients. Anxiety and depression were present in 12% and 4% (HADS-A and HADS-D, respectively) and 12% (BDI) of cases. There was a significant association between VAS and BDI (p = 0.019). The final multivariate model for 5-D included diabetes mellitus (OR 4.51; p = 0.01), BDI (OR 5.98; p = 0.024), and HADS-A (OR 7.75; p = 0.011). One-fifth of NAFLD patients reported moderate or severe pruritus. 5-D was significantly associated with diabetes mellitus, depression, and anxiety. These findings should be tested in larger populations and considered in candidates for treatment with FXR agonists.

EDP‐297: A novel, farnesoid X receptor agonist—Results of a phase I study in healthy subjects

“…Pruritus is an important tolerability concern with FXR agonists resulting in treatment discontinuation in 9% of patients in a large, 18‐month trial of obeticholic acid 21 . However, pruritus occurs commonly in patients with NASH with reports of a 20% incidence at baseline 22,30 . Even within clinical studies of FXR agonists, the incidence of pruritus at baseline and in placebo treatment groups is ~20% 22 .…”

“… 21 However, pruritus occurs commonly in patients with NASH with reports of a 20% incidence at baseline. 22 , 30 Even within clinical studies of FXR agonists, the incidence of pruritus at baseline and in placebo treatment groups is ~20%. 22 Phase I studies in healthy volunteers have shown similar pruritus effects at higher multiple dose cohorts, including MET409 at 100 mg and 150 mg MAD (14 days), EDP‐305 20 mg, and 10 mg MAD (14 days), and HPG1860 at 20 mg MAD (14 days).…”

Bile acid signalling and its role in anxiety disorders

“…Clinical studies have reported that in patients with anxiety disorders, certain metabolically abnormal bile acids excessively activate FXR and promote the secretion of FGF19 in intestinal cells. The latter enters the brain through systemic circulation and participates in the neuroinflammatory process, thereby promoting anxiety ( 49 ). A large number of studies have consistently demonstrated that anxiety related to abnormal bile acid metabolism is frequently accompanied by intestinal diseases ( 7 , 8 , 10 , 50 ), particularly irritable bowel syndrome (IBS).…”