Factors Associated with Deep Vein Thrombosis in Type 2 Diabetics with Biopsy-Proven Non-alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) can lead to a prothrombotic stage increasing the risk of deep vein thrombosis (DVT). We aimed to assess the prevalence and factors associated with DVT in patients with type 2 diabetes (T2D) and biopsy-proven NAFLD. Using ICD-codes, all T2D patients who had liver biopsy done for suspected NAFLD were identified and assessed. Patients with secondary causes of hepatic steatosis (Hepatitis, excess alcohol, etc.) were excluded. Liver biopsy was staged as F0-4, advanced fibrosis (AF) being F3-4. A univariable and multivariate analysis was performed to assess factors associated with DVT. A total of 1295 patients were included in the final analysis. DVT was present in 5.5% of these patients. Our cohort consisted of 62% females, 90% were Caucasians, and 90% were obese or overweight (p = 0.59, 0.22, and 0.53, respectively). Mean platelet count was 200.1 ± 82.2 (p = 0.048) and mean HbA1c was 6.9 ± 1.7 (p = 0.71). On multivariate analysis, a 5-year increment in the age at time of T2D diagnosis was associated with 10% increase in likelihood of having DVT (OR {95% CI} 1.1 (1.01, 1.3), p = 0.031). Patients with IBD were 3-times more likely to have DVT than those without IBD and being on furosemide was associated with 2.5-times higher odds of DVT (OR {95% CI} 3.0 (1.3, 7.1), p = 0.012 and 2.5 (1.5, 4.1), p < 0.001, respectively). Our study suggests that older age, stricturing IBD disease, and use of furosemide in T2D with NAFLD increase the risk of DVT. Future prospective studies are required to confirm these findings. Clinical trial registration number: CCF 16-018 Keywords Non-alcoholic fatty liver disease (NAFLD). Deep vein thrombosis. Advanced fibrosis. Type 2 diabetes. Liver biopsy Abbreviations AF Advanced fibrosis AST Aspartate aminotransferase ALT Alanine aminotransferase ALP Alkaline phosphatase APRI AST to platelet ration index BMI Body mass index CDC Centers for Disease Control and Prevention CD Crohn's disease DVT Deep vein thrombosis FIB-4 Fibrosis-4 GGT γ-Glutamyl transpeptidase HDL High-density lipoprotein HbA1c Hemoglobin A1c This article is part of the Topical Collection on Medicine Electronic supplementary material The online version of this article (

Incidence and prevalence of venous thromboembolism in chronic liver disease: A systematic review and meta-analysis

“…Studentized residual tests, Buajat plot and r diagnostic tests for influential studies confirmed three studies [3,21,25] significantly influenced the incidence meta-analysis results (SP-Fig. 6), and two studies [28,48] prevalence meta-analysis results (SP-Fig.…”

“…After screening of titles and abstracts, 84 studies were selected for further search, 29 studies [3,12,14,17,[21][22][23][24][25][26][27][28][29][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] reporting incidence or prevalence of VTE in CLD were included (Fig. 1).…”

“…Mean age of participants was 56.1 years (SD ± 4.6), 60.1% were males and 65.3% were Caucasians (Table 1). Of the studies providing details of comorbidities, 0.10% (n = 14,003/13991921) had malignancy [3,17,21,28,44,47,48,54,56,58,59]; 0.84% (n = 11,832/ 1404948) hypertension [22,25,57,58], 0.59% (n = 82,109/13952904) diabetes [17,21,25,28,48,54,58,59], and 0.001% (n = 89/11225377) had history of major surgery in the past 3 months [3,17,21,54]. Singh et al only included patients with a diagnosis of type 2 diabetes mellitus and concomitant non-alcohol fatty liver disease (NAFLD) [25].…”

“…Eighteen studies reported cumulative incidence per year [3,17,21,22,24,25,27,[44][45][46][47][48]51,52,54,55,[57][58][59], comprising a total of 1,628,164 participants, and 17,424 new VTE events in hospitalised CLD patients. Three studies reported incidence rate (person-years) [51,57,58].…”

“…Moreover, since the publication of the above systematic reviews [2,20], there has been substantial new data examining epidemiology of VTE in CLD. Nine new studies [21][22][23][24][25][26][27][28][29] that were not included in the previous systematic reviews, comprising over seven million participants and sixty thousand VTE events (DVT and/or PE) have been published. We aim to systematically analyse published articles to evaluate the epidemiology of VTE in patients with CLD, and to compare relative risk of VTE in patients with CLD to those without CLD.…”