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Background: The exact pathophysiology of portal vein thrombosis (PVT), a common complication of cirrhosis, remains largely unknown. We previously found that cirrhotic PVT consists of fibrotic intimal thickening of the portal vein wall rather than of true fibrin-rich thrombus. We hypothesized that this portal vein intimal thickening is secondary to portal hypertension and/or to local inflammatory responses., Method: The intimal thickness of right and left portal branches was measured in hilar liver samples from 232 cirrhotic patients without PVT who underwent liver transplantation. The relation between intimal thickness and pre-transplant clinical variables was studied with linear regression. CT-scans of 25 patients prior to liver transplantation were reanalysed for portal vein and portal hypertension-related characteristics., Results: Median right intimal thickness was 129 (1 - 300 (IQR)) μm, median left intimal thickness was 112 (1 - 230) μm and there was correlation between intimal thickness in the right and left branches in individual patients (r = 0.30, P<.001). Intimal thickness of the portal vein was associated with a history of variceal bleeding, hepatic encephalopathy or ascites, etiology of disease and statin use. Other factors, including duration of liver disease, presence of infection, or radiological characteristics were not significantly associated with intimal thickness., Conclusion: Intrahepatic portal vein intimal thickness is highly variable in patients with cirrhosis, but relatively consistent between right and left portal branches. The association between intimal thickness and history of variceal bleeding suggests that portal hypertension may contribute to initiation of intimal thickening, and consequently to the development of PVT., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in patients with ESLD is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a proinflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development., Objectives: We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in patients with ESLD., Methods: Fecal samples, plasma samples, and data from patients with ESLD and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera Clinical Analyzer., Results: One hundred two patients with ESLD, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P = .18). Both ESLD groups had significantly lower alpha diversity than controls. Bacteroides fragilis and 3 Clostridiales species were increased in patients with PVT compared with without PVT. TMAO levels between the 3 groups were not significantly different., Conclusion: We observed profound differences in gut microbiota between patients with ESLD and controls, but minimal differences between patients with ESLD with or without PVT. In our cohort, a gut-derived proinflammatory state was not associated with presence of PVT in patients with ESLD., Competing Interests: Declaration of competing interests M.A.C. is an employee of LabCorp. M.A.C. assisted with the generation of the TMAO measurements. Labcorp was not involved in the study design, the data analysis, or the decision to publish the results. The rest of the authors declared they have no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)