PMID- 38015590
OWN - NLM
STAT- MEDLINE
DCOM- 20231129
LR  - 20240212
IS  - 2471-254X (Electronic)
IS  - 2471-254X (Linking)
VI  - 7
IP  - 12
DP  - 2023 Dec 1
TI  - Altered profiles of circulating cytokines in chronic liver diseases (NAFLD/HCC): 
      Impact of the PNPLA3I148M risk allele.
LID - 10.1097/HC9.0000000000000306 [doi]
LID - e0306
AB  - BACKGROUND: Individuals carrying the risk variant p.I148M of patatin-like 
      phospholipase domain-containing protein 3 (PNPLA3) have a higher susceptibility 
      to fatty liver diseases and associated complications, including HCC, a cancer 
      closely linked to chronic inflammation. Here, we assessed circulating cytokine 
      profiles for patients with chronic liver diseases genotyped for PNPLA3. METHODS: 
      Serum concentrations of 22 cytokines were measured by multiplex sandwich-ELISA. 
      The cohort comprised 123 individuals: 67 patients with NAFLD without cirrhosis 
      (57 steatosis, 10 NASH), 24 patients with NAFLD with cirrhosis, 21 patients with 
      HCC (15 cirrhosis), and 11 healthy controls. Receiver operator characteristic 
      analyses were performed to assess the suitability of the cytokine profiles for 
      the prediction of steatosis, cirrhosis, and HCC. RESULTS: HGF, IL-6, and IL-8 
      levels were increased in patients, with  approximately 2-fold higher levels in patients with 
      cirrhosis versus healthy, while platelet derived growth factor-BB (PDGF-BB) and 
      regulated on activation, normal T cell expressed and secreted (RANTES) showed 
      lower concentrations compared to controls. Migration inhibitory factor and 
      monocyte chemoattractant protein-1 (MCP-1) were found at higher levels in NAFLD 
      samples (maximum: NAFLD-cirrhosis) versus healthy controls and HCC samples. In 
      receiver operator characteristic analyses, migration inhibitory factor, IL-8, 
      IL-6, and monocyte chemoattractant protein-1 yielded high sensitivity scores for 
      predicting noncirrhotic NAFLD (vs. healthy). The top combination to predict 
      cirrhosis was HGF plus PDGF-BB. Migration inhibitory factor performed best to 
      discriminate HCC from NAFLD; the addition of monokine induced gamma (MIG), 
      RANTES, IL-4, macrophage colony-stimulating factor (M-CSF), or IL-17A as second 
      parameters further increased the AUC values (> 0.9). No significant impact of the 
      PNPLA3I148M allele on cytokine levels was observed in this cohort. CONCLUSIONS: 
      Cytokines have biomarker potential in patients with fatty liver, possibly suited 
      for early HCC detection in patients with fatty liver. Patients carrying the 
      PNPLA3 risk allele did not present significantly different levels of circulating 
      cytokines.
CI  - Copyright (c) 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Association for the Study of Liver Diseases.
FAU - Kirchmeyer, Melanie
AU  - Kirchmeyer M
AUID- ORCID: 0009-0007-6588-3261
AD  - Department of Life Sciences and Medicine, University of Luxembourg, Luxembourg.
FAU - Gaigneaux, Anthoula
AU  - Gaigneaux A
AUID- ORCID: 0000-0003-0465-3773
AD  - Department of Life Sciences and Medicine, University of Luxembourg, Luxembourg.
FAU - Servais, Florence A
AU  - Servais FA
AD  - Department of Life Sciences and Medicine, University of Luxembourg, Luxembourg.
FAU - Arslanow, Anita
AU  - Arslanow A
AUID- ORCID: 0000-0002-8231-274
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
AD  - Fundacio de Recerca Clinic Barcelona-Institut d'Investigacions Biomediques August 
      Pi i Sunyer, Barcelona, Spain.
FAU - Casper, Markus
AU  - Casper M
AUID- ORCID: 0000-0002-1146-288
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
FAU - Krawczyk, Marcin
AU  - Krawczyk M
AUID- ORCID: 0000-0002-0113-0777
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
FAU - Lammert, Frank
AU  - Lammert F
AUID- ORCID: 0000-0003-4450-7201
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
AD  - Health Sciences, Hannover Medical School MHH, Hannover, Germany.
FAU - Behrmann, Iris
AU  - Behrmann I
AUID- ORCID: 0000-0003-3688-3645
AD  - Department of Life Sciences and Medicine, University of Luxembourg, Luxembourg.
LA  - eng
PT  - Journal Article
DEP - 20231122
PL  - United States
TA  - Hepatol Commun
JT  - Hepatology communications
JID - 101695860
RN  - 0 (Cytokines)
RN  - 0 (Chemokine CCL2)
RN  - 1B56C968OA (Becaplermin)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
SB  - IM
MH  - Humans
MH  - *Non-alcoholic Fatty Liver Disease/genetics
MH  - Cytokines/genetics
MH  - Chemokine CCL2/genetics
MH  - Becaplermin
MH  - Alleles
MH  - *Carcinoma, Hepatocellular/genetics
MH  - Interleukin-6/genetics
MH  - Interleukin-8/genetics
MH  - *Liver Neoplasms/genetics
MH  - Liver Cirrhosis/diagnosis/genetics
PMC - PMC10667005
COIS- The authors have no conflicts to report.
EDAT- 2023/11/28 12:41
MHDA- 2023/11/29 06:42
PMCR- 2023/11/22
CRDT- 2023/11/28 11:53
PHST- 2023/06/02 00:00 [received]
PHST- 2023/09/02 00:00 [accepted]
PHST- 2023/11/29 06:42 [medline]
PHST- 2023/11/28 12:41 [pubmed]
PHST- 2023/11/28 11:53 [entrez]
PHST- 2023/11/22 00:00 [pmc-release]
AID - 02009842-202312010-00003 [pii]
AID - HEP4-23-0473 [pii]
AID - 10.1097/HC9.0000000000000306 [doi]
PST - epublish
SO  - Hepatol Commun. 2023 Nov 22;7(12):e0306. doi: 10.1097/HC9.0000000000000306. 
      eCollection 2023 Dec 1.