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Background: The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus.Methods: From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP.Results: Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222-25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466-9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively.Conclusion: Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively.Trial Registration: We registered our research at https://www.Clinicaltrials: gov/ . The name of research registered is "Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection." The trial registration identifier at clinicaltrials.gov is NCT02247414. [ABSTRACT FROM AUTHOR]