PMID- 35176084
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220228
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 2
DP  - 2022
TI  - Diagnostic and prognostic significance of cell death markers in patients with 
      cirrhosis and acute decompensation.
PG  - e0263989
LID - 10.1371/journal.pone.0263989 [doi]
LID - e0263989
AB  - BACKGROUND: The transition from compensated to decompensated liver cirrhosis is a 
      hallmark of disease progression, however, reliable predictors to assess the risk 
      of decompensation in individual patients from routine diagnostics are lacking. 
      Here, we characterize serum levels of cell death-associated markers and routine 
      biochemistry from patients with chronic liver disease with and without 
      decompensation. METHODS: A post-hoc analysis was based on prospectively collected 
      clinical data from 160 patients with chronic liver disease, stably compensated or 
      decompensated at baseline or during follow-up, over a median period of 721 days. 
      Serum levels of damage-associated molecular patterns (DAMPs) and routine 
      biochemistry are quantified at baseline (for all patients) and during follow-up 
      (for patients with acute decompensation). The panel of DAMPs assessed in this 
      study comprises high-mobility group-box protein 1 (HMGB1), cytochrome C (cyt C), 
      soluble Fas-ligand (sFasL), interleukin 6 (IL-6), soluble cytokeratin-18 
      (CK18-M65) and its caspase-cleaved fragment CK18-M30. RESULTS: In this cohort 
      study, 80 patients (50%) were diagnosed with alcoholic liver cirrhosis, 60 
      patients (37.5%) with hepatitis C virus- and 20 patients (13.5%) with hepatitis B 
      virus-related liver cirrhosis. At baseline, 17 patients (10.6%) showed 
      decompensated liver disease and another 28 patients (17.5%) developed acute 
      decompensation during follow-up (within 24 months). One hundred fifteen patients 
      showed stable liver disease (71.9%). We found DAMPs significantly elevated in 
      patients with decompensated liver disease versus compensated liver disease. 
      Patients with acute decompensation during follow-up showed higher baseline levels 
      of IL-6, sFasL, CK18-M65 and-M30 (P<0.01) compared to patients with stably 
      compensated liver disease. In multivariate analyses, we found an independent 
      association of baseline serum levels of sFasL (P = 0.02; OR = 2.67) and 
      gamma-glutamyl transferase (GGT) (P<0.001; OR = 2.1) with acute decompensation. 
      Accuracy of the marker combination for predicting acute decompensation was high 
      (AUC = 0.79). Elevated aminotransferase levels did not correlate with 
      decompensated liver disease and acute decompensation. CONCLUSIONS: DAMPs are 
      elevated in patients with decompensated liver disease and patients developing 
      acute decompensation. The prognostic value of a marker combination with soluble 
      Fas-ligand and GGT in patients with liver cirrhosis should be further evaluated.
FAU - Stoffers, Philipp
AU  - Stoffers P
AUID- ORCID: 0000-0001-6175-8315
AD  - Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 
      Frankfurt am Main, Germany.
FAU - Guckenbiehl, Sabrina
AU  - Guckenbiehl S
AD  - Department of Gastroenterology and Hepatology, University Hospital Essen and 
      University of Duisburg-Essen, Essen, Germany.
FAU - Welker, Martin Walter
AU  - Welker MW
AD  - Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 
      Frankfurt am Main, Germany.
FAU - Zeuzem, Stefan
AU  - Zeuzem S
AD  - Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 
      Frankfurt am Main, Germany.
FAU - Lange, Christian Markus
AU  - Lange CM
AD  - Department of Gastroenterology and Hepatology, University Hospital Essen and 
      University of Duisburg-Essen, Essen, Germany.
FAU - Trebicka, Jonel
AU  - Trebicka J
AD  - Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 
      Frankfurt am Main, Germany.
FAU - Herrmann, Eva
AU  - Herrmann E
AD  - Institute of Biostatistics and Mathematical Modelling, Faculty of Medicine, 
      Goethe-University, Frankfurt am Main, Germany.
FAU - Welsch, Christoph
AU  - Welsch C
AD  - Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 
      Frankfurt am Main, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220217
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Alarmins)
RN  - 0 (Biomarkers)
RN  - 0 (KRT18 protein, human)
RN  - 0 (Keratin-18)
SB  - IM
MH  - Aged
MH  - Alarmins/*blood
MH  - Biomarkers/*blood
MH  - Case-Control Studies
MH  - Cell Death
MH  - Disease Progression
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Keratin-18/blood
MH  - Liver Cirrhosis/blood/*pathology
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Prospective Studies
MH  - *Severity of Illness Index
PMC - PMC8853504
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/02/18 06:00
MHDA- 2022/03/01 06:00
PMCR- 2022/02/17
CRDT- 2022/02/17 17:14
PHST- 2021/11/25 00:00 [received]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/02/17 17:14 [entrez]
PHST- 2022/02/18 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2022/02/17 00:00 [pmc-release]
AID - PONE-D-21-37395 [pii]
AID - 10.1371/journal.pone.0263989 [doi]
PST - epublish
SO  - PLoS One. 2022 Feb 17;17(2):e0263989. doi: 10.1371/journal.pone.0263989. 
      eCollection 2022.