Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis.
fatty liver
liver transplantation
venous thrombosis
Journal
BMJ open gastroenterology
ISSN: 2054-4774
Titre abrégé: BMJ Open Gastroenterol
Pays: England
ID NLM: 101660690
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
13
04
2021
accepted:
12
06
2021
entrez:
3
8
2021
pubmed:
4
8
2021
medline:
25
11
2021
Statut:
ppublish
Résumé
Non-alcoholic fatty liver disease is a prohaemostatic state with abnormal primary, secondary and tertiary haemostasis. Plasminogen activator inhibitor (PAI)-1 is the best-established marker for prohaemostasis in non-alcoholic fatty liver disease. While epidemiological studies demonstrate decompensated non-alcoholic steatohepatitis (NASH) cirrhosis patients have increased rates of venous thromboembolism, including portal vein thrombosis, mechanistic studies have focused exclusively on patients without or with compensated cirrhosis. We aimed to characterizecharacterise PAI-1 levels in decompensated NASH cirrhosis. PAI-1 level was measured in consecutive adult liver transplant recipients immediately prior to liver transplantation. Multivariable models were constructed using linear regression to assess factors related to PAI-1 level. Forty-six subjects with mean age 57 (IQR 53-62) years and Model for Endstage Liver Disease (MELD) score of 34 (IQR 30-40) were enrolled. Baseline characteristics were similar between NASH (n=10) and non-NASH (n=36) subjects except for rates of diabetes and hyperlipidaemia. Mean PAI-1 level was greater in NASH (53.9, 95% CI 33.3 to 74.5 mg/mL) when compared with non-NASH (36.1, 95% CI 28.7 to 43.5), p=0.040. NASH remained independently predictive of PAI-1 level prior to transplant on adjusted multivariable modelling (β 40.13, 95% CI 14.41 to 65.86, p=0.003). PAI-1 level is significantly elevated in decompensated NASH cirrhosis independent of other pro-haemostatic factors. This may explain the greater rates of venous thromboembolism in decompensated NASH cirrhosis. Future study focusing on prevention of venous thromboembolism in this population is paramount to improve patient-oriented outcomes given the high morbidity and mortality of venous thromboembolism and the significant impact it has on transplant candidacy.
Sections du résumé
BACKGROUND
Non-alcoholic fatty liver disease is a prohaemostatic state with abnormal primary, secondary and tertiary haemostasis. Plasminogen activator inhibitor (PAI)-1 is the best-established marker for prohaemostasis in non-alcoholic fatty liver disease. While epidemiological studies demonstrate decompensated non-alcoholic steatohepatitis (NASH) cirrhosis patients have increased rates of venous thromboembolism, including portal vein thrombosis, mechanistic studies have focused exclusively on patients without or with compensated cirrhosis. We aimed to characterizecharacterise PAI-1 levels in decompensated NASH cirrhosis.
METHODS
PAI-1 level was measured in consecutive adult liver transplant recipients immediately prior to liver transplantation. Multivariable models were constructed using linear regression to assess factors related to PAI-1 level.
RESULTS
Forty-six subjects with mean age 57 (IQR 53-62) years and Model for Endstage Liver Disease (MELD) score of 34 (IQR 30-40) were enrolled. Baseline characteristics were similar between NASH (n=10) and non-NASH (n=36) subjects except for rates of diabetes and hyperlipidaemia. Mean PAI-1 level was greater in NASH (53.9, 95% CI 33.3 to 74.5 mg/mL) when compared with non-NASH (36.1, 95% CI 28.7 to 43.5), p=0.040. NASH remained independently predictive of PAI-1 level prior to transplant on adjusted multivariable modelling (β 40.13, 95% CI 14.41 to 65.86, p=0.003).
CONCLUSIONS
PAI-1 level is significantly elevated in decompensated NASH cirrhosis independent of other pro-haemostatic factors. This may explain the greater rates of venous thromboembolism in decompensated NASH cirrhosis. Future study focusing on prevention of venous thromboembolism in this population is paramount to improve patient-oriented outcomes given the high morbidity and mortality of venous thromboembolism and the significant impact it has on transplant candidacy.
Identifiants
pubmed: 34341018
pii: bmjgast-2021-000683
doi: 10.1136/bmjgast-2021-000683
pmc: PMC8330585
pii:
doi:
Substances chimiques
Plasminogen Inactivators
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : L30 DK118601
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000127
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002014
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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