PMID- 35686937
OWN - NLM
STAT- MEDLINE
DCOM- 20230112
LR  - 20240113
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 77
IP  - 1
DP  - 2023 Jan 1
TI  - IL-31 levels correlate with pruritus in patients with cholestatic and metabolic 
      liver diseases and is farnesoid X receptor responsive in NASH.
PG  - 20-32
LID - 10.1002/hep.32599 [doi]
AB  - BACKGROUND AND AIMS: 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). APPROACH AND RESULTS: 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. CONCLUSIONS: 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.
CI  - Copyright (c) 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
FAU - Xu, Jun
AU  - Xu J
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Wang, Ya
AU  - Wang Y
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Khoshdeli, Mina
AU  - Khoshdeli M
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Peach, Matt
AU  - Peach M
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Chuang, Jen-Chieh
AU  - Chuang JC
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Lin, Julie
AU  - Lin J
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Tsai, Wen-Wei
AU  - Tsai WW
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Mahadevan, Sangeetha
AU  - Mahadevan S
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Minto, Wesley
AU  - Minto W
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Diehl, Lauri
AU  - Diehl L
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Gupta, Ruchi
AU  - Gupta R
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Trauner, Michael
AU  - Trauner M
AD  - Division of Gastroenterology and Hepatology , Department of Internal Medicine III 
      , Medical University of Vienna , Vienna , Austria.
FAU - Patel, Keyur
AU  - Patel K
AD  - University of Toronto , Toronto , Ontario , Canada.
FAU - Noureddin, Mazen
AU  - Noureddin M
AD  - Fatty Liver Program , Cedars-Sinai Medical Center , Los Angeles , California , 
      USA.
FAU - Kowdley, Kris V
AU  - Kowdley KV
AUID- ORCID: 0000-0002-8553-3652
AD  - Liver Institute Northwest , Seattle , Washington , USA.
FAU - Gulamhusein, Aliya
AU  - Gulamhusein A
AD  - University of Toronto , Toronto , Ontario , Canada.
FAU - Bowlus, Christopher L
AU  - Bowlus CL
AD  - University of California Davis , Davis , California , USA.
FAU - Huss, Ryan S
AU  - Huss RS
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Myers, Robert P
AU  - Myers RP
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Chung, Chuhan
AU  - Chung C
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
FAU - Billin, Andrew N
AU  - Billin AN
AD  - Gilead Sciences, Inc. , Foster City , California , USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220717
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Non-alcoholic Fatty Liver Disease/complications/drug therapy
MH  - *Cholestasis/complications/drug therapy
MH  - Biomarkers
MH  - *Metabolic Diseases/complications
MH  - Pruritus/drug therapy/etiology
MH  - *Liver Cirrhosis, Biliary/complications/drug therapy
PMC - PMC9970017
COIS- Andrew N. Billin owns stock in and is employed by Gilead. Christopher L. Bowlus 
      consults for and received grants from Cymabay, GSK, and Mirum. He received grants 
      from Intercept, Takeda, BMS, BiomX, Gilead, Novartis, and Pliant. Chuhan Chung 
      owns stock in and is employed by Inipharm. He owns stock in Gilead. Jen-Chieh 
      Chuang owns stock in and is employed by TLC Inc. Jun Xu owns stock in and is 
      employed by Gilead. Keyur Patel consults for Gilead. He advises Intercept. Kris 
      V. Kowdley consults for, is on the speakers' bureau for, and received grants from 
      Gilead and Intercept. He consults for and received grants from Hightide, Mirum, 
      NGM, and 89 Bio. He consults for Madrigal, PTG, and Genfit. He is on the 
      speakers' bureau for AbbVie. He received grants from GSK, Pliant, Hanmi, Viking, 
      and Pfizer. Lauri Diehl owns stock in and is employed by Gilead. Michael Trauner 
      consults for, is on the speakers' bureau for, and received grants from Falk, 
      Intercept, Gilead, and MSD. He consults for and received grants from Alberio. He 
      consults for BiomX, Boehringer Ingelheim, Genfit, Janssen, Novartis, Shire, 
      Phenex, and Regulus. He received grants from Cymabay, Takeda, Alnylam, 
      Ultragenyx, and AbbVie. He is the coinventor of patents on the medical use of 
      24-norursodesoxycholic acid. Matt Peach owns stock in and is employed by Gilead. 
      Mazen Noureddin owns stock in Anaetos, Chrownwell, Ciema, Rivus Pharma, and 
      Viking. He advises and received grants from Gilead, Pfizer, and Madrigal. He 
      advises 89BIO, Altimmune, cohBar, Cytodyn, Intercept, Novo Nordisk, Blade, 
      EchoSens, Fractyl, NorthSea, Perspecturm, Terns, Siemens, and Roche. He received 
      grants from Allergan, BMS, Galmed, Galectin, Genfit, Shire, Zydus, Conatus, 
      Enanta, and Novartis. Mina Khoshdeli owns stock in and is employed by Gilead. 
      Robert P. Myers owns stock in and is employed by The Liver Company. He receives 
      stock from Gilead. Ryan S. Huss owns stock in and is employed by The Liver 
      Company. He receives stock from Gilead. Wiley Minto owns stock in and is employed 
      by Gilead.
EDAT- 2022/06/11 06:00
MHDA- 2023/01/13 06:00
PMCR- 2023/02/27
CRDT- 2022/06/10 09:22
PHST- 2022/02/17 00:00 [received]
PHST- 2022/05/12 00:00 [accepted]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2023/01/13 06:00 [medline]
PHST- 2022/06/10 09:22 [entrez]
PHST- 2023/02/27 00:00 [pmc-release]
AID - 01515467-202301010-00008 [pii]
AID - 10.1002/hep.32599 [doi]
PST - ppublish
SO  - Hepatology. 2023 Jan 1;77(1):20-32. doi: 10.1002/hep.32599. Epub 2022 Jul 17.