Jun Xu<\/a>\u00a0<\/sup>,\u00a0Ya Wang<\/a>\u00a0<\/sup>,\u00a0Mina Khoshdeli<\/a>\u00a0<\/sup>,\u00a0Matt Peach<\/a>\u00a0<\/sup>,\u00a0Jen-Chieh Chuang<\/a>\u00a0<\/sup>,\u00a0Julie Lin<\/a>\u00a0<\/sup>,\u00a0Wen-Wei Tsai<\/a>\u00a0<\/sup>,\u00a0Sangeetha Mahadevan<\/a>\u00a0<\/sup>,\u00a0Wesley Minto<\/a>\u00a0<\/sup>,\u00a0Lauri Diehl<\/a>\u00a0<\/sup>,\u00a0Ruchi Gupta<\/a>\u00a0<\/sup>,\u00a0Michael Trauner<\/a>\u00a0<\/sup>,\u00a0Keyur Patel<\/a>\u00a0<\/sup>,\u00a0Mazen Noureddin<\/a>\u00a0<\/sup>,\u00a0Kris V Kowdley<\/a>\u00a0<\/sup>,\u00a0Aliya Gulamhusein<\/a>\u00a0<\/sup>,\u00a0Christopher L Bowlus<\/a>\u00a0<\/sup>,\u00a0Ryan S Huss<\/a>\u00a0<\/sup>,\u00a0Robert P Myers<\/a>\u00a0<\/sup>,\u00a0Chuhan Chung<\/a>\u00a0<\/sup>,\u00a0Andrew N Billin<\/a>\u00a0<\/sup><\/p>\n\n\n\n Background and aims: <\/strong>Pruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC).<\/p>\n\n\n\n Approach and results: <\/strong>Serum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31.<\/p>\n\n\n\n Conclusions:\u00a0<\/strong>IL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.<\/p>\n\n\n\n <\/p>\n\n\n\n IL-31 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is farnesoid X receptor responsive in NASH Jun Xu\u00a0,\u00a0Ya Wang\u00a0,\u00a0Mina Khoshdeli\u00a0,\u00a0Matt Peach\u00a0,\u00a0Jen-Chieh Chuang\u00a0,\u00a0Julie Lin\u00a0,\u00a0Wen-Wei Tsai\u00a0,\u00a0Sangeetha Mahadevan\u00a0,\u00a0Wesley Minto\u00a0,\u00a0Lauri Diehl\u00a0,\u00a0Ruchi Gupta\u00a0,\u00a0Michael Trauner\u00a0,\u00a0Keyur Patel\u00a0,\u00a0Mazen Noureddin\u00a0,\u00a0Kris V Kowdley\u00a0,\u00a0Aliya Gulamhusein\u00a0,\u00a0Christopher L Bowlus\u00a0,\u00a0Ryan S Huss\u00a0,\u00a0Robert P Myers\u00a0,\u00a0Chuhan Chung\u00a0,\u00a0Andrew N Billin\u00a0 Abstract Background and aims: Pruritus is associated with […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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