Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 6, 2023; 11(34): 8126-8138
Published online Dec 6, 2023. doi: 10.12998/wjcc.v11.i34.8126
Case-control analysis of venous thromboembolism risk in non-alcoholic steatohepatitis diagnosed by transient elastography
Mithil Gowda Suresh, Maya Gogtay, Yuvaraj Singh, Lekha Yadukumar, Ajay Kumar Mishra, George M Abraham
Mithil Gowda Suresh, Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
Maya Gogtay, Department of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE 68198, United States
Yuvaraj Singh, Department of Gastroenterology and Hepatology, University of Massachusetts, Worcester, MA 01605, United States
Lekha Yadukumar, Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, PA 18505, United States
Ajay Kumar Mishra, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
George M Abraham, Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
Author contributions: Suresh MG conceived the idea for the study, designed and undertook the literature review, performed the statistical analysis, figures, and appendix and analyzed and interpreted the data; Suresh MG, Singh Y, and Gogtay M collected data; Suresh MG, Singh Y, Gogtay M, Gogtay M, and Yadukumar L wrote the first draft of the manuscript; Suresh MG, Gogtay M, Singh Y, Yadukumar L, Mishra AK, and Abraham GM revised the subsequent manuscript drafts; and all authors reviewed and agreed on the final draft of the manuscript.
Institutional review board statement: The comprehensive investigation into the potential link between non-alcoholic steatohepatitis and venous thromboembolism was conducted in adherence to a well-defined protocol. This protocol was developed, reviewed, and sanctioned by the joint institutional review board at MetroWest Medical Center under Approval No. 2020-035.
Informed consent statement: The ethical requirement for individual informed consent was appropriately waived by the institutional review board due to the retrospective nature of this case-control study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at mithil58@gmail.com. Consent was not obtained, but the presented data are anonymized, and risk of identification is low.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mithil Gowda Suresh, MD, Academic Fellow, Department of Internal Medicine, Saint Vincent Hospital, 123 Summer Street, Worcester, MA 01608, United States. mithilgowda1.suresh@stvincenthospital.com
Received: October 30, 2023
Peer-review started: October 30, 2023
First decision: November 1, 2023
Revised: November 6, 2023
Accepted: November 24, 2023
Article in press: November 24, 2023
Published online: December 6, 2023
Abstract
BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Studies have shown a strong association between non-alcoholic steatohepatitis (NASH) cirrhosis and portal vein thrombosis. Specifically, there is paucity of data on the association of NASH and venous thromboembolism (VTE), with one such study predicting a 2.5-fold increased risk for VTE compared to other liver diseases in hospitalized patients. The mechanism is believed to be a hepatocellular injury, which causes a chronic inflammatory state leading to the unregulated activation of procoagulant factors. There has been no prior analysis of the degree of steatosis and fibrosis (measured using transient elastography, commonly known as FibroScan) in NASH and its association with VTE.

AIM

To examine the association between the degree of hepatic steatosis and fibrosis, quantified by transient elastography, and the incidence of VTE in patients with NASH.

METHODS

In our case-control study, we included patients with a documented diagnosis of NASH. We excluded patients with inherited thrombophilia, hemoglobinopathy, malignancy, alcohol use disorder, autoimmune hepatitis, and primary biliary cirrhosis. The collected data included age, demographics, tobacco use, recreational drug use, medical history, and vibration controlled transient elastography scores. VTE-specific data included the location, type of anticoagulant, need for hospital stay, and history of VTE recurrence. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate to severe) based on the controlled attenuation parameter score. Fibrosis was classified based on the kilopascal score and graded as F0-F1 (Metavir stage), F2, F3, and F4 (cirrhosis). χ2 and Mann-Whitney U tests were used for the qualitative and quantitative variable analyses, respectively. Furthermore, we performed a logistic regression using VTE as the dependent variable.

RESULTS

A total of 415 patients were analyzed, and 386 met the inclusion criteria. 51 and 335 patients were included in the VTE and non-VTE groups, respectively. Patients with VTE had a mean age of 60.63 years compared to 55.22 years in the non-VTE group (P < 0.014). Patients with VTE had a higher body mass index (31.14 kg/m² vs 29.30 kg/m²) and a higher prevalence of diabetes mellitus (29.4% vs 13.1%). The history of NASH was significantly higher in the VTE group (45.1% vs 30.4%, P < 0.037). Furthermore, moderate-to-severe steatosis was significantly higher in the VTE group (66.7% vs 47.2%, P < 0.009). Similarly, the F2-F4 fibrosis grade had a prevalence of 58.8% in the VTE group compared to 38.5% in the non-VTE group (P < 0.006). On logistic regression, using VTE as a dependent variable, diabetes mellitus had an odds ratio (OR) =1.702 (P < 0.015), and F2-F4 fibrosis grade had an OR = 1.5 (P < 0.033).

CONCLUSION

Our analysis shows that NASH is an independent risk factor for VTE, especially deep vein thrombosis. There was a statistically significant association between the incidence of VTE, moderate-to-severe steatosis, and fibrosis. All hospitalized patients should be considered for medical thromboprophylaxis, particularly those with NASH.

Keywords: Nonalcoholic fatty liver disease, Venous thromboembolism, Non-alcoholic steatohepatitis, Diabetes mellitus, Liver fibrosis, Steatosis, Deep vein thrombosis, Anticoagulation management

Core Tip: Our study delineates the intricate relationship between nonalcoholic fatty liver disease (NAFLD) and venous thromboembolism (VTE), highlighting the increased risk and prevalence of VTE in patients with NAFLD-related conditions. Notably, it demonstrates a significant correlation between advanced steatosis and fibrosis grades and the occurrence of VTE, suggesting that patients with more severe NAFLD characteristics require vigilant monitoring for potential thrombotic complications. These insights delineate the necessity for tailored clinical approaches in managing NAFLD patients to mitigate the risk of VTE, marking a substantial step forward in understanding NAFLD’s systemic impacts.