Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul;8(1):e000683.
doi: 10.1136/bmjgast-2021-000683.

Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis

Gloriany Rivas  1 , Breianna Hummer-Bair  1 , Dmitri Bezinover  1 , Zakiyah Kadry  1 , Jonathan Stine  2
Affiliations

Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis

Gloriany Rivas et al. BMJ Open Gastroenterol. 2021 Jul.

Abstract

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.

Keywords: fatty liver; liver transplantation; venous thrombosis.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Mean PAI-1 (mg/mL) (+SD) of patients at the time of liver transplantation. N=10 with decompensated NASH cirrhosis and N=36 non-NASH. NASH, non-alcoholic steatohepatitis; PAI, plasminogen activator inhibitor.
Figure 2
Figure 2
Mean PAI-1 (mg/mL) (+SD) of patients on the postoperative day 5. N=10 with decompensated NASH cirrhosis and N=36 Non-NASH. NASH, non-alcoholic steatohepatitis; PAI, plasminogen activator inhibitor.
See this image and copyright information in PMC

References

    1. Ng M, Fleming T, Robinson M, et al. . Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014;384:766–81. 10.1016/S0140-6736(14)60460-8 - DOI - PMC - PubMed
    1. Younossi ZM, Stepanova M, Rafiq N, et al. . Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 2011;53:1874–82. 10.1002/hep.24268 - DOI - PubMed
    1. Rinella M, Charlton M. The globalization of nonalcoholic fatty liver disease: prevalence and impact on world health. Hepatology 2016;64:19–22. 10.1002/hep.28524 - DOI - PubMed
    1. Bhala N, Angulo P, van der Poorten D, et al. . The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54:1208–16. 10.1002/hep.24491 - DOI - PMC - PubMed
    1. Stine JG, Rinella ME. Editorial: age and non-invasive markers of fibrosis in patients with nonalcoholic fatty liver disease: time to adjust the clock? Am J Gastroenterol 2017;112:752–4. 10.1038/ajg.2017.60 - DOI - PubMed

Publication types

Substances