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Ozturk H, Sari S, Gurkan OE, Dalgic B. Prevalence of portal vein thrombosis in pediatric patients with cirrhosis and intrahepatic non-cirrhotic portal hypertension. Dig Liver Dis 2025:S1590-8658(25)00747-9. [PMID: 40350344 DOI: 10.1016/j.dld.2025.04.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 04/08/2025] [Accepted: 04/21/2025] [Indexed: 05/14/2025]
Abstract
INTRODUCTION Portal vein thrombosis (PVT) has been increasingly diagnosed in pediatric patients owing to the widespread use of non-invasive radiological techniques. Although the prevalence of PVT in adults with cirrhosis and intrahepatic non-cirrhotic portal hypertension ranges from 0.6 to 26 % and 13 to 46 %, respectively, no available data exist in the pediatric population. The prevalence of PVT in children with cirrhotic and intrahepatic non-cirrhotic portal hypertension was evaluated in this study. METHODS This retrospective study included children with cirrhosis and intrahepatic non-cirrhotic portal hypertension, which consisted of congenital hepatic fibrosis (CHF) and idiopathic noncirrhotic portal hypertension (INCPH). Patients with extrahepatic portal venous obstruction were excluded from the study. The presence of PVT was evaluated using abdominal Doppler ultrasonography and/or CT. Etiological, clinical, and laboratory findings were compared between the groups. RESULTS One hundred and forty-two patients with cirrhosis (mean admission age: 64.6 months ± 66.4, mean follow-up duration: 46.8 months ± 45.6) and 41 patients with non-cirrhotic patients (CHF=16, INCPH = 25, mean admission age: 126 months ± 64.2) were enrolled in this study. The prevalence of PVT was not significantly different between cirrhotic (8.5 %) and non-cirrhotic (9.7 %) patients. The incidence of PVT was significantly higher in patients with biliary atresia than in those with other etiologies in the cirrhotic group (p = 0.022). The frequency of PVT was higher in patients who had Child-Pugh score ≥7 in the cirrhotic group, but the difference was not statistically significant (p = 0066). The PVT group required more liver transplantations than the non-PVT group (p = 0.038). CONCLUSION The prevalence of PVT was similar in pediatric patients with cirrhosis and intrahepatic non-cirrhotic portal hypertension in our cohort, which is compatible with adult studies. Biliary atresia is found to be an important risk factor for PVT in our pediatric population. It might be associated with rapid progression of the disease, ascending cholangitis, and embryological abnormalities. These patients should be routinely evaluated to identify portal vein complications and early warning signs during follow-up.
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Affiliation(s)
- Hakan Ozturk
- Gazi University, Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara, Turkey.
| | - Sinan Sari
- Gazi University, Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara, Turkey
| | - Odul Egritas Gurkan
- Gazi University, Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara, Turkey
| | - Buket Dalgic
- Gazi University, Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara, Turkey
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Di Cola S, Gazda J, Fonte S, Lapenna L, Nardelli S, Cusi G, De Santis A, Merli M. The impact of bacterial infection on the risk of portal vein thrombosis development in patients with cirrhosis: A post-hoc analysis. Dig Liver Dis 2025:S1590-8658(25)00305-6. [PMID: 40204578 DOI: 10.1016/j.dld.2025.03.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 02/14/2025] [Accepted: 03/23/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Portal vein thrombosis (PVT) is a common complication in liver cirrhosis. Bacterial infections (BIs) may increase PVT risk through bacterial translocation, systemic inflammation, and coagulation dysfunction, but evidence is limited. AIMS This study investigates the 6-month risk of onset of PVT in patients hospitalized with BIs. METHODS This post-hoc analysis included 563 cirrhotic patients hospitalized between 2011 and 2021, with or without BIs diagnosis, and followed for 6 months post-discharge. Patients with HCC outside of Milan criteria were excluded. The main endpoint was the onset of PVT, diagnosed via abdominal ultrasound or CT/MRI. RESULTS BI was diagnosed in 146 patients (26 %). Forty-seven patients (8.5 %) experienced PVT events within 6 months, including 15 (10 %) with BIs and 32 (7.8 %) without (p = 0.4). Logistic regression showed no significant effect of BI on PVT occurrence (OR 1.35, 95 % CI 0.69-2.54), even after adjusting for confounding factors. However, urinary tract infections were independently associated with higher PVT risk (OR 3.17, 95 % CI 1.05-10.8, p = 0.048). Other infection sites (pneumonia, spontaneous bacterial peritonitis-SBP, spontaneous bacteremia) and isolated microbial strains (n = 77) were not associated with increased PVT risk. When analyzing the population excluding patients with HCC, the risk of developing PVT was significantly higher in patients with previous BI, regardless of the severity of liver disease (OR 2.92, 95 % CI 1.06-8.16). CONCLUSIONS In this large cohort, BIs did not significantly increase PVT risk within 6 months post-hospitalization in cirrhotic patients. However, when the cohort was reduced to patients without HCC, the risk of PVT appears to be significant.
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Affiliation(s)
- Simone Di Cola
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.
| | - Jakub Gazda
- 2nd Department of Internal Medicine, PJ Safarik University and L. Pasteur University Hospital in Kosice, 040 11 Kosice, Slovakia
| | - Stefano Fonte
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Giulia Cusi
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Adriano De Santis
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
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Premkumar M, Bhujade H, Sharma P, Nain J, Ahluwalia J, Sandhu A, Kumar Y, Rathi S, Taneja S, Duseja AK, Kulkarni AV, Singh C, Naseem S, Karki T, Gupta P, Chaluvashetty SB, Lad D, Reddy KR. Experience With Dabigatran on Rate of Portal Vein Thrombosis Recanalization, Disease Progression and Survival. Aliment Pharmacol Ther 2025; 61:971-987. [PMID: 39748673 DOI: 10.1111/apt.18474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/22/2024] [Accepted: 12/21/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND AND AIMS We assessed clinical, procoagulant and genetic risk factors and clinical outcomes in dabigatran-treated patients with non-tumoural acute and acute-on-chronic portal vein thrombosis (PVT). METHODS Patients with a new diagnosis of non-tumoural acute and acute-on-chronic PVT between January 2021 and January 2024 (aged ≥ 18 years) in those without/with cirrhosis (Child-Pugh (CP)-A/B/C ≤ 10) were started on dabigatran and followed and compared with those on vitamin K antagonist (VKA) and untreated individuals. RESULTS Dabigatran was prescribed in 119 patients with PVT type 1 (61, 51.3%), type 2 (34, 28.6%), type 3 (24, 20.2%); 72 (60.5%) with cirrhosis [CP-A (27, 37.5%), CP-B (43, 59.7%) and CP-C10 (2, 2.8%)]. Procoagulant factors noted were JAK2V617F (10.1%), CALR (2.5%) and factor V Leiden (1.6%) mutations, antiphospholipid syndrome (APS, 15.2%), isolated Protein C (14.3%) and Protein S (16.8%) deficiency. COMPARATORS 28 patients who declined anticoagulation/were unable to come for follow-up, and six with CP-C received VKA. Overall recanalization rate (RR) on dabigatran was 56 (47.1%); 25 (21%) complete recanalization, 31 (26%) partial recanalization and 63 (52.9%) stable PVT over median follow-up of 32 months. Patients not anticoagulated had a spontaneous RR in 21.4% (28 patients; p = 0.005 compared with dabigatran group) and none recanalized on VKA. On multivariable analysis, predictors of recanalization on dabigatran were Factor VIII Antigen level (FVIII:Ag, HR 0.6; 95% CI 0.3-0.9, p = 0.032), non-occlusive PVT (HR 3.5, 95% CI 1.9-5.6, p = 0.025) and acute PVT (HR 2.1; 95% CI 1.5-3.2, p = 0.003). Mortality was 14 (11.8%). CONCLUSION On dabigatran, 47% of 119 patients achieved portal vein recanalization over 32 months of follow-up which was higher than the spontaneous RR (21.4%) in an untreated cohort. High Factor VIII:Ag was a predictor of non-recanalization. Dabigatran was safe in cirrhosis (CP-A and B) while further work is needed in CP-C.
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Harish Bhujade
- Department of Radiodiagnosis and Interventional Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Prerna Sharma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jasvinder Nain
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jasmina Ahluwalia
- Department of Hematopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anchal Sandhu
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yogendra Kumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Kumar Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Charanpreet Singh
- Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shano Naseem
- Department of Hematopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Tanka Karki
- Department of Radiodiagnosis and Interventional Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pankaj Gupta
- Department of Radiodiagnosis and Interventional Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sreedhara B Chaluvashetty
- Department of Radiodiagnosis and Interventional Radiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Deepesh Lad
- Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, USA
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Lucatelli P, Krajina A, Loffroy R, Miraglia R, Pieper CC, Franchi-Abella S, Rocco B. CIRSE Standards of Practice on Transjugular Intrahepatic Portosystemic Shunts. Cardiovasc Intervent Radiol 2024; 47:1710-1726. [PMID: 39550753 DOI: 10.1007/s00270-024-03866-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 09/10/2024] [Indexed: 11/18/2024]
Abstract
BACKGROUND Proposed in the early 1980s as a solution for managing complications of portal hypertension, the percutaneous creation of transjugular intrahepatic portosystemic shunt has consistently gained a central role. Increasingly lower complication rates have been observed thanks to improvements in both technologies and the skills of interventional radiologists. PURPOSE This document is aimed at interventional radiologists and provides best practice recommendations for transjugular intrahepatic portosystemic shunt creation, describing patient selection, intraprocedural management and follow-up, in addition to recommendations in paediatric settings. METHODS The CIRSE Standards of Practice Committee established a writing group consisting of seven European clinicians with recognised expertise in the creation of transjugular intrahepatic portosystemic shunt. The writing group reviewed the existing literature performing a pragmatic evidence search using PubMed to select relevant publications in the English language and involving human subjects, preferably published from 2009 to 2024. The final recommendations were developed by consensus. RESULTS TIPS creation has an established role in the successful management of portal hypertension and its complications. This Standards of Practice document provides up-to-date recommendations for patient selection, materials, its safe performance, and follow-up with complications management.
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Affiliation(s)
- Pierleone Lucatelli
- Department of Diagnostic Medicine and Radiology, Interventional Radiology Unit, Azienda Policlinico Universitario Policlinico Umberto I, Rome, Italy
| | - Antonín Krajina
- Department of Radiology, University Hospital, Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic
| | - Romaric Loffroy
- Department of Vascular and Interventional Radiology, François-Mitterrand University Hospital, Dijon, France
| | | | - Claus Christian Pieper
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany
| | - Stéphanie Franchi-Abella
- Paris-Saclay University, Faculty of Medicine - AP-HP, Pediatric Radiology Department, Bicêtre Hospital, Reference Center for Vascular Diseases of the Liver, FSMR Filfoie, ERN Rare Liver, FHU Hepatinov - Biomaps UMR 9011, CNRS-INSERM-CEA, Le Kremlin-Bicêtre, France
| | - Bianca Rocco
- Department of Diagnostic Medicine and Radiology, Interventional Radiology Unit, Sapienza University of Rome, Rome, Italy.
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Hilscher MB, Wysokinski WE, Andrews JC, Simonetto DA, Law RJ, Kamath PS. Portal Vein Thrombosis in the Setting of Cirrhosis: Evaluation and Management Strategies. Gastroenterology 2024; 167:664-672. [PMID: 38801909 DOI: 10.1053/j.gastro.2024.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/10/2024] [Accepted: 05/18/2024] [Indexed: 05/29/2024]
Affiliation(s)
- Moira B Hilscher
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
| | | | - James C Andrews
- Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Ryan J Law
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
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Amjad W, Jiang ZG, Lai M. Metabolic dysfunction-associated steatotic liver disease related cirrhosis and incidence of portal vein thrombosis. Eur J Gastroenterol Hepatol 2024; 36:1038-1045. [PMID: 38829950 DOI: 10.1097/meg.0000000000002800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
BACKGROUND There is heterogeneous data on whether metabolic-associated steatohepatitis is an independent risk factor for portal vein thrombosis (PVT). We aim to compare the incidence of PVT in patients with cirrhosis with and without metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS This is a single-center retrospective study of patients with cirrhosis seen between 1 January 2016 and 31 January 2021. Patients with a history of hepatocellular cancer, liver transplant, Budd-Chiari syndrome, and intra-abdominal malignancies were excluded. Patients with cirrhosis were followed from their first hepatology visit for 180 days to determine the incidence of PVT. Cox proportional hazard regression was used to determine the relationship between MASLD with PVT. RESULTS We analyzed data from 2785 patients with cirrhosis who met inclusion and exclusion criteria [mean age: 61.0 ± 12.3 years, 44.3% female, 63.8% Whites and mean model for end-stage liver disease-sodium (MELD-Na) score: 11.7 ± 6.1]. MASLD was present in 21.7% of patients. A total of 89 patients developed PVT during the follow-up, which was fewer in patients with MASLD [2.0% vs. 3.5%, P = 0.04, unadjusted heart rate (HR): 0.60, 95% confidence interval (CI): 0.27-0.96, P = 0.04]. After adjusting for the demographics, MASLD-related comorbid conditions and MELD-Na score, MASLD was associated with a lower incidence of PVT as compared to non-MASLD cirrhosis (HR: 0.44, 95% CI: 0.21-0.92, P = 0.03). After adjusting for the indicators of Child-Pugh Turcotte score, the risk of PVT in patients with MASLD compared to non-MASLD was not statistically significant (HR: 0.50, 95% CI: 0.22-1.13, P = 0.096). CONCLUSION PVT incidence was lower in patients with MASLD cirrhosis as compared to non-MASLD cirrhosis. However, the difference was not significantly different after adjusting for liver decompensation.
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Affiliation(s)
- Waseem Amjad
- Liver Disease Department, Beth Israel Deaconess Medical Center
- Clinical Investigation, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Michelle Lai
- Liver Disease Department, Beth Israel Deaconess Medical Center
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Patidar Y, Babbar S, Mukund A, Sarin SK. Transjugular Intrahepatic Portosystemic Shunt (TIPS) Extension for Transhepatic Mesocaval Shunt Creation: A Case Series for Treating Refractory Upper Gastrointestinal Bleeding in Patients with Chronic Portal Vein Thrombosis. Indian J Radiol Imaging 2024; 34:335-341. [PMID: 38549885 PMCID: PMC10972657 DOI: 10.1055/s-0043-1777321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is known to benefit patients with decompensated liver disease by alleviating portal pressure. However, TIPS creation is technically difficult and challenging to perform in patients with chronic portal vein thrombosis (PVT) (4,5). Multiple endovascular techniques for portal vein recanalization with or without creating portosystemic shunt are available to decompress and alleviate portal hypertension in patients with PVT. In this case series, we represent TIPS extension to create an endovascular mesocaval shunt for the treatment of refractory upper gastrointestinal bleeding.
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Affiliation(s)
- Yashwant Patidar
- Department of Intervention Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sushant Babbar
- Department of Intervention Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amar Mukund
- Department of Intervention Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Cangemi R, Raparelli V, Talerico G, Basili S, Violi F. Hypoalbuminemia and Risk of Portal Vein Thrombosis in Cirrhosis. GASTRO HEP ADVANCES 2024; 3:646-653. [PMID: 39165413 PMCID: PMC11330931 DOI: 10.1016/j.gastha.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 03/08/2024] [Indexed: 08/22/2024]
Abstract
BACKGROUND AND AIMS Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. METHODS Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. RESULTS SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. CONCLUSION Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.
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Affiliation(s)
- Roberto Cangemi
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Valeria Raparelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
- Faculties of Nursing, Medicine and School of Public Health, University of Alberta, Edmonton, Alberta, Canada
| | - Giovanni Talerico
- Internal Medicine, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy
| | - Stefania Basili
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Francesco Violi
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
- Medicina Cardiocentro, Naples, Italy
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Wang PL, Ramalingam V, Yang LM. Portal Vein Thrombosis in Patients with Cirrhosis. CURRENT HEPATOLOGY REPORTS 2024; 23:64-72. [DOI: 10.1007/s11901-024-00636-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/07/2024] [Indexed: 01/04/2025]
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10
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Savic Z, Damjanov D, Latinovic-Bosnjak O, Janjic N, Dejanovic B, Krnetic Z, Vracaric V. Portal vein thrombosis in patients with liver cirrhosis. VOJNOSANIT PREGL 2024; 81:368-376. [DOI: 10.2298/vsp240116029s] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Background/Aim. Portal vein thrombosis (PVT) in patients with liver cirrhosis (LC) has a prevalence of 0.6?26%. It is most commonly discovered incidentally as part of the evaluation of LC or in the context of acute decompensation of LC due to portal hypertension. The aim of the study was to determine the prevalence of PVT in patients with LC in relation to the severity of the disease and individual elements of portal hypertension. Methods. A total of 326 patients treated for LC decompensation were included in a retrospective study. Standard laboratory analyses, abdominal ultrasonography and/or computed tomography, and esophagogastroduodenoscopy were performed. Results. The diameter of the portal vein (PV) differed between patients without esophageal varices (12.2 mm) and those with large varices (13.6 mm), p = 0.026. PVT was identified in 6.1% of patients with LC. The patients were classified according to the Child-Pugh scoring system, which has the A, B, and C categories used to assess the severity of liver disease. PVT was present in 3.0% of patients in class C and 12.0% in class B, while none of the patients in class A had PVT (p = 0.005). PVT was present in 4.4% of patients with small varices and 16.7% with large varices (p < 0.001). There was no difference in the presence of PVT between the groups of patients with and without variceal bleeding nor between groups with different degrees of ascites. A fatal outcome occurred in 29.4% of patients, but there was no difference between patients with and without PVT. Conclusion. PVT is present in more advanced stages of LC and predominantly in patients with large esophageal varices. There was no higher prevalence of PVT observed with the occurrence of variceal bleeding or with the death outcome in patients with LC.
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Affiliation(s)
- Zeljka Savic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia + University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
| | - Dimitrije Damjanov
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia + University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
| | - Olgica Latinovic-Bosnjak
- University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
| | - Nebojsa Janjic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia + University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
| | - Bozidar Dejanovic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia + University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
| | - Zarko Krnetic
- University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
| | - Vladimir Vracaric
- University Clinical Center of Vojvodina, Clinic for Gastroenterology and Hepatology, Novi Sad, Serbia
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Li Y, Gao J, Zheng X, Nie G, Qin J, Wang H, He T, Wheelock Å, Li CX, Cheng L, Li X. Diagnostic Prediction of portal vein thrombosis in chronic cirrhosis patients using data-driven precision medicine model. Brief Bioinform 2023; 25:bbad478. [PMID: 38221905 PMCID: PMC10788706 DOI: 10.1093/bib/bbad478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 11/16/2023] [Accepted: 12/01/2023] [Indexed: 01/16/2024] Open
Abstract
BACKGROUND Portal vein thrombosis (PVT) is a significant issue in cirrhotic patients, necessitating early detection. This study aims to develop a data-driven predictive model for PVT diagnosis in chronic hepatitis liver cirrhosis patients. METHODS We employed data from a total of 816 chronic cirrhosis patients with PVT, divided into the Lanzhou cohort (n = 468) for training and the Jilin cohort (n = 348) for validation. This dataset encompassed a wide range of variables, including general characteristics, blood parameters, ultrasonography findings and cirrhosis grading. To build our predictive model, we employed a sophisticated stacking approach, which included Support Vector Machine (SVM), Naïve Bayes and Quadratic Discriminant Analysis (QDA). RESULTS In the Lanzhou cohort, SVM and Naïve Bayes classifiers effectively classified PVT cases from non-PVT cases, among the top features of which seven were shared: Portal Velocity (PV), Prothrombin Time (PT), Portal Vein Diameter (PVD), Prothrombin Time Activity (PTA), Activated Partial Thromboplastin Time (APTT), age and Child-Pugh score (CPS). The QDA model, trained based on the seven shared features on the Lanzhou cohort and validated on the Jilin cohort, demonstrated significant differentiation between PVT and non-PVT cases (AUROC = 0.73 and AUROC = 0.86, respectively). Subsequently, comparative analysis showed that our QDA model outperformed several other machine learning methods. CONCLUSION Our study presents a comprehensive data-driven model for PVT diagnosis in cirrhotic patients, enhancing clinical decision-making. The SVM-Naïve Bayes-QDA model offers a precise approach to managing PVT in this population.
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Affiliation(s)
- Ying Li
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Jing Gao
- Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Heart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Xubin Zheng
- School of Computing and Information Technology, Great Bay University, Guangdong, China
| | - Guole Nie
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Jican Qin
- School of Computing and Information Technology, Great Bay University, Guangdong, China
| | - Haiping Wang
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Tao He
- Jilin Hepato-Biliary Diseases Hospital, Changchun, China
| | - Åsa Wheelock
- Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
| | - Chuan-Xing Li
- Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Lixin Cheng
- Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen, China
| | - Xun Li
- The First Hospital of Lanzhou University, Lanzhou, China
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12
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Zhang S, Zhong X, Zhong H, Zhong L, Li J, Zhu FS, Xia L, Yang CQ. Predicting the risk of variceal rehemorrhage in cirrhotic patients with portal vein thrombosis: A two-center retrospective study. J Dig Dis 2023; 24:619-629. [PMID: 37950606 DOI: 10.1111/1751-2980.13239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 11/06/2023] [Accepted: 11/09/2023] [Indexed: 11/12/2023]
Abstract
OBJECTIVES Although portal vein thrombosis (PVT) was thought to deteriorate portal hypertension and contribute to poor prognosis, risk stratification remains unclear. This study aimed to evaluate its effect on the risk of variceal rehemorrhage and to develop a competitive risk model in cirrhotic patients with PVT. METHODS Cirrhotic patients with and without PVT admitted for acute variceal hemorrhage were retrospectively included after matching (1:1) for age, gender and etiology of cirrhosis from two tertiary centers with 1-year follow-up. Those with PVT were subsequently divided into the training and validation cohorts. Cox regression analysis was performed to identify risk factors and develop a competitive risk model, of which the predictive performance and optimal decision threshold were evaluated by C-index, competitive risk curves, calibration curves and decision curve analysis. RESULTS Among 398 patients, PVT significantly increased the variceal rehemorrhage risk. Multivariate Cox regression analysis identified that the Child-Turcotte-Pugh score (P = 0.013), chronic PVT (P = 0.025), C-reactive protein (P < 0.001), and aspartate aminotransferase (P = 0.039) were independently associated with variceal rehemorrhage, which were incorporated into the competitive risk model, with high C-index (0.804 and 0.742 of the training and validation cohorts, respectively), risk stratification ability, and consistency. The optimal decision range of the threshold probability was 0.2-1.0. CONCLUSION We confirmed the adverse effect of PVT on variceal rehemorrhage and developed a competitive risk model for variceal rehemorrhage in cirrhotic patients with PVT, which might be conveniently used for clinical decision-making.
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Affiliation(s)
- Shuo Zhang
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xuan Zhong
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hui Zhong
- Department of Infectious Disease, Fengxian Guhua Hospital, Shanghai, China
| | - Lan Zhong
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jing Li
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Feng Shang Zhu
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Lu Xia
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chang Qing Yang
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
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13
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Lapenna L, Di Cola S, Gazda J, De Felice I, Gioia S, Merli M. New Indications for TIPSs: What Do We Know So Far? J Clin Exp Hepatol 2023; 13:794-803. [PMID: 37693277 PMCID: PMC10483008 DOI: 10.1016/j.jceh.2023.01.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 01/29/2023] [Indexed: 09/12/2023] Open
Abstract
Since 1988, transjugular intrahepatic portosystemic shunt (TIPS) has been an effective therapy for portal hypertension in many settings. Thanks to continuous technical improvements and a wiser selection of patients, excellent results have been achieved with this therapeutic strategy. The historical indications for TIPS placement, in the context of liver cirrhosis, such as refractory ascites and variceal bleeding are now well established and known. However, in recent years, new indications are emerging. These have been investigated and approved in some studies but are not yet included in guidelines and clinical practice. This review aims to highlight what is new for the role of TIPS in portal vein thrombosis (especially in patients awaiting liver transplantation), in recurrent ascites and not only refractory ascites, as a neoadjuvant therapy before abdominal surgery and, finally, in the setting of noncirrhotic portal hypertension. All these new aspects are addressed in this review with a critical approach based on the literature revision and clinical practice. Future research is needed to explore and validate the new role of TIPS in these scenarios.
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Affiliation(s)
- Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Simone Di Cola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Jakub Gazda
- 2nd Department of Internal Medicine, PJ Safarik University and L. Pasteur University Hospital in Kosice, Slovakia
| | - Ilaria De Felice
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
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14
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Primignani M, Tosetti G, Ierardi AM. Approach to different thrombolysis techniques and timing of thrombolysis in the management of portal vein thrombosis in cirrhotic patients. J Transl Int Med 2023; 11:198-202. [PMID: 37662891 PMCID: PMC10474884 DOI: 10.2478/jtim-2023-0113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023] Open
Abstract
Thrombolysis is not currently recommended in cirrhotic patients with acute portal vein thrombosis (PVT) in most guidelines, because of the exceedingly limited data and the perceived high risk of bleeding adverse events. However, in the few studies including patients with cirrhosis, the rate of success was high and that of adverse events was similar in patients with or without cirrhosis. Hence, thrombolysis might be a rescue therapeutic option in patients with cirrhosis and acute, symptomatic thrombosis of the portal venous system, unresponsive to anticoagulation, provided a suitable timing is kept, less than 30 days and, if possible, less than 14 days from the acute onset of portal vein thrombosis. In this review perspective article, I discuss the several potential approaches of thrombolysis, either local or systemic, alone or combined with mechanical procedures for thrombus removal, or as a complement to Transjugular Intrahepatic Portosystemic Shunt placement, with a focus on the more suitable timing of thrombolysis. However, the very limited available data preclude from performing firm recommendations, and decision to carry out thrombolysis must take into account both the occurrence of major contraindications and the current critical clinical setting. In the next future, large high-quality multicentre studies will hopefully be able to settle more firm indications and preferable techniques.
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Affiliation(s)
- Massimo Primignani
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan20122, Italy
| | - Giulia Tosetti
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan20122, Italy
| | - Anna Maria Ierardi
- Department of Radiology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan20122, Italy
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15
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Giuli L, Pallozzi M, Venturini G, Gasbarrini A, Ponziani FR, Santopaolo F. Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis. Int J Mol Sci 2023; 24:12754. [PMID: 37628933 PMCID: PMC10454315 DOI: 10.3390/ijms241612754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/07/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow's triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients.
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Affiliation(s)
- Lucia Giuli
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Maria Pallozzi
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Giulia Venturini
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Antonio Gasbarrini
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Francesco Santopaolo
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
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Guerrero A, Campo LD, Piscaglia F, Scheiner B, Han G, Violi F, Ferreira CN, Téllez L, Reiberger T, Basili S, Zamora J, Albillos A. Anticoagulation improves survival in patients with cirrhosis and portal vein thrombosis: The IMPORTAL competing-risk meta-analysis. J Hepatol 2023; 79:69-78. [PMID: 36858157 DOI: 10.1016/j.jhep.2023.02.023] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 01/19/2023] [Accepted: 02/13/2023] [Indexed: 03/03/2023]
Abstract
BACKGROUND & AIMS Previous meta-analyses demonstrated the safety and efficacy of anticoagulation in the recanalization of portal vein thrombosis in patients with cirrhosis. Whether this benefit translates into improved survival is unknown. We conducted an individual patient data (IPD) meta-analysis to assess the effect of anticoagulation on all-cause mortality in patients with cirrhosis and portal vein thrombosis. METHODS In this IPD meta-analysis, we selected studies comparing anticoagulation vs. no treatment in patients with cirrhosis and portal vein thrombosis from PubMed, Embase, and Cochrane databases (until June 2020) (PROSPERO no.: CRD42020140026). IPD were subsequently requested from authors. The primary outcome - the effect of anticoagulation on all-cause mortality - was assessed by a one-step meta-analysis based on a competing-risk model with liver transplantation as the competing event. The model was adjusted for clinically relevant confounders. A multilevel mixed-effects logistic regression model was used to determine the effect of anticoagulation on recanalization. RESULTS Individual data on 500 patients from five studies were included; 205 (41%) received anticoagulation and 295 did not. Anticoagulation reduced all-cause mortality (adjusted subdistribution hazard ratio 0.59; 95% CI 0.49-0.70), independently of thrombosis severity and recanalization. The effect of anticoagulation on all-cause mortality was consistent with a reduction in liver-related mortality. The recanalization rate was higher in the anticoagulation arm (adjusted odds ratio 3.45; 95% CI 2.22-5.36). The non-portal-hypertension-related bleeding rate was significantly greater in the anticoagulation group. CONCLUSIONS Anticoagulation reduces all-cause mortality in patients with cirrhosis and portal vein thrombosis independently of recanalization, but at the expense of increasing non-portal hypertension-related bleeding. PROSPERO REGISTRATION NUMBER CRD42020140026. IMPACT AND IMPLICATIONS Anticoagulation is effective in promoting recanalization of portal vein thrombosis in patients with cirrhosis, but whether this benefit translates into improved survival is controversial. Our individual patient data meta-analysis based on a competing-risk model with liver transplantation as the competing event shows that anticoagulation reduces all-cause mortality in patients with cirrhosis and portal vein thrombosis independently of recanalization. According to our findings, portal vein thrombosis may identify a group of patients with cirrhosis that benefit from long-term anticoagulation.
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Affiliation(s)
- Antonio Guerrero
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Salud Carlos III, Madrid, Spain
| | - Laura Del Campo
- Unidad de Bioestadística Clínica. Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero Universitaria di Bologna, Italy
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna. Rare Liver Disease (RALID) Center of the European Reference Network for Rare Hepatological Diseases (ERN RARE-LIVER), Medical University Vienna, Vienna, Austria
| | - Guohong Han
- Department of Liver Diseases and Digestive Interventional Radiology, Xi'an International Medical Center Hospital, Digestive Diseases Hospital, Northwest University, Xi'an, China; Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Francesco Violi
- Department of Internal Medicine, Anestesiology and Cardiovascular Sciences, Sapienza University, Roma, Italy
| | - Carlos-Noronha Ferreira
- Servico de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Clinica Universitaria de Gastrenterologia, Facultad de Medicina, Lisbon, Portugal
| | - Luis Téllez
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Salud Carlos III, Madrid, Spain
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna. Rare Liver Disease (RALID) Center of the European Reference Network for Rare Hepatological Diseases (ERN RARE-LIVER), Medical University Vienna, Vienna, Austria
| | - Stefania Basili
- Department of Internal Medicine, Anestesiology and Cardiovascular Sciences, Sapienza University, Roma, Italy
| | - Javier Zamora
- Unidad de Bioestadística Clínica. Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Institute of Metabolism and Systems Research, University of Birmingham, United Kingdom
| | - Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Salud Carlos III, Madrid, Spain.
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17
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Benevento F, Pecorelli A, Stefanescu H, Sparchez Z, Vukotic R, Pettinari I, Grigoras CA, Tovoli F, Ravaioli F, Stefanini B, Andreone P, Piscaglia F. Presence of Hepatocellular Carcinoma Does Not Affect Course and Response to Anticoagulation of Bland Portal Vein Thrombosis in Cirrhotic Patients. J Hepatocell Carcinoma 2023; 10:473-482. [PMID: 37007210 PMCID: PMC10065221 DOI: 10.2147/jhc.s390777] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins. AIM We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC. METHODS Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included. RESULTS A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109). CONCLUSION The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation.
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Affiliation(s)
- Francesca Benevento
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Horia Stefanescu
- Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Zeno Sparchez
- Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Ranka Vukotic
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Medicina Interna 4, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Irene Pettinari
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Crina-Anca Grigoras
- Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Francesco Tovoli
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federico Ravaioli
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Bernardo Stefanini
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Pietro Andreone
- Divisione di Medicina Interna a Indirizzo Metabolico-Nutrizionale, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Fabio Piscaglia
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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18
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Intraindividual variability over time of thrombin generation in patients with cirrhosis. J Thromb Haemost 2023; 21:1441-1452. [PMID: 36758726 DOI: 10.1016/j.jtha.2023.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 02/02/2023] [Accepted: 02/02/2023] [Indexed: 02/10/2023]
Abstract
BACKGROUND Patients with cirrhosis are at high risk of thrombotic events, including portal vein thrombosis and venous thromboembolism. In such patients, hypercoagulability is not detected by conventional coagulation tests, but only by the thrombin generation assay (TGA) that integrates the role of pro- and anticoagulant factors. However, TGA use to predict clinical events depends on thrombin generation variability over time. OBJECTIVES The aim of this study was to compare TGA intraindividual variability over time in patients with cirrhosis and in healthy controls. METHODS Blood samples were prospectively collected from 34 healthy controls and 52 patients with cirrhosis at week 0 (inclusion), 6, and 12. TGA was performed with the calibrated automated thrombogram method, tissue factor (5 pM), phospholipids, and with and without thrombomodulin (4 nM) or activated protein C (1 nM). RESULTS When TGA was performed with thrombomodulin, endogenous thrombin potential in patients with cirrhosis was higher compared with controls and increased with cirrhosis severity. Stability over time of all thrombin generation parameters was excellent in healthy controls, good in Child-Turcotte-Pugh (CTP)-A patients, and poor in CTP-B/C patients (severe cirrhosis). In CTP-B/C patients, the phenotype was more variable because one-third of patients switched to normal or hypercoagulability during the 3-month follow-up. CONCLUSION A study with longer monitoring is needed to correlate the hypercoagulable phenotype of patients with cirrhosis with the occurrence of thrombotic events.
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Caiano LM, Riva N, Ageno W. Anticoagulant therapy for splanchnic vein thrombosis: recent updates for patients with liver cirrhosis. Expert Rev Hematol 2023; 16:121-129. [PMID: 36820873 DOI: 10.1080/17474086.2023.2184340] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
INTRODUCTION Liver cirrhosis is accompanied by several hemostatic alterations, which contribute to the current theory of "rebalanced hemostasis." Splanchnic vein thrombosis (SVT) is a frequent complication of liver cirrhosis (17-26% of the cirrhotic patients), and liver cirrhosis is a common risk factor for SVT (24-28% of SVT cases). AREAS COVERED This narrative review aims to describe the current state of the art on the anticoagulant treatment of cirrhotic SVT, with a particular focus on the possible role of the direct oral anticoagulants (DOACs) and recent guidelines on this topic. EXPERT OPINION Early anticoagulant therapy is recommended in cirrhotic patients with acute SVT, to obtain vessel recanalization and decrease the rates of portal hypertension-related complications. Gastroesophageal varices do not represent a contraindication to anticoagulation, if adequate prophylaxis of variceal bleeding is established, and varices band ligation can be safely performed without the need to stop the anticoagulant treatment. The conventional treatment of cirrhotic SVT consisted of low molecular weight heparin, as initial treatment of choice, eventually followed by vitamin K antagonists, but the DOACs can be considered as a reasonable alternative in patients with compensated liver cirrhosis.
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Affiliation(s)
- Lucia M Caiano
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
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Xu X, Jin J, Liu Y, Li H. Analysis of related factors of portal vein thrombosis in liver cirrhosis. BMC Gastroenterol 2023; 23:26. [PMID: 36717769 PMCID: PMC9887918 DOI: 10.1186/s12876-022-02632-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 12/20/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND AND AIMS To investigate the usefulness of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), protein C (PC), and thromboelastography (TEG) to serve as a predictor of portal vein thrombosis (PVT) in patients with liver cirrhosis. Additionally, we examined the clinical significance of the above indicators in terms of disease progression. METHODS A total of 123 patients with liver cirrhosis were recruited from May 2021 to December 2021, according to the imaging findings. They were divided into the PVT group (n = 52) and the non-PVT group (n = 71). Furthermore, patients with PVT were divided into plasma transfusion groups (n = 13) and non-plasma transfusion groups (n = 39). The basic general information, past medical history, laboratory, and imaging examination data were collected and analyzed. RESULTS In univariate analysis, there was no significant difference between the two groups in IL-6, PC, reaction time (R), alpha angle (Angle), maximum amplitude, or coagulation index (CI) (P > 0.05). TNF-α in the PVT group was significantly lower than that in the non-PVT group (P = 0.001). K-time (K) in the PVT group was significantly higher than that in the non-PVT group (P = 0.031). There was no significant difference in IL-6, TNF-α, PC, or TEG between different Child-Pugh classification groups (P > 0.05). There were no significant differences in TEG between the plasma transfusion group and the non-plasma transfusion group. In Binary logistic regression analysis, TNF-α (OR = 0.9881, 95%CI = 0.971, 0.990, P < 0.001), K(OR = 1.28, 95% = 1.053, 1.569, P = 0.014), activate partial thromboplastin time (APTT) (OR = 0.753, 95%CI = 0.656, 0.865, P < 0.001), portal vein diameter (OR = 1.310, 95%CI = 1.108, 1.549, P = 0.002)and the history of splenectomy or embolism (OR = 7.565, 95%CI = 1.514, 37.799, P = 0.014)were related to the formation of PVT. CONCLUSIONS TNF-α, K, APTT, portal vein diameter, and splenectomy or embolism history were associated with PVT formation, but IL-6 was not.
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Affiliation(s)
- Xiaotong Xu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Jinglan Jin
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China.
| | - Yuwei Liu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Hang Li
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
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21
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Violi F, Pignatelli P, Castellani V, Carnevale R, Cammisotto V. Gut dysbiosis, endotoxemia and clotting activation: A dangerous trio for portal vein thrombosis in cirrhosis. Blood Rev 2023; 57:100998. [PMID: 35985881 DOI: 10.1016/j.blre.2022.100998] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 08/04/2022] [Accepted: 08/06/2022] [Indexed: 01/28/2023]
Abstract
Liver cirrhosis (LC) is associated with portal venous thrombosis (PVT) in roughly 20% of cirrhotic patients but the underlying mechanism is still unclear. Low-grade endotoxemia by lipopolysaccharides (LPS), a component of outer gut microbiota membrane, is detectable in the portal circulation of LC and could predispose to PVT. LPS may translocate into systemic circulation upon microbiota dysbiosis-induced gut barrier dysfunction, that is a prerequisite for enhanced gut permeability and ensuing endotoxemia. Experimental and clinical studies provided evidence that LPS behaves a pro-thrombotic molecule so promoting clotting and platelet activation. Experiments conducted in the portal circulation of cirrhotic patients showed the existence of LPS-related enhanced thrombin generation as well as endothelial dysfunction, venous stasis, and platelet activation. The review will analyze 1) the pro-thrombotic role of endotoxemia in the context of LC 2) the biological plausibility linking endotoxemia with PVT and 3) the potentially interventional tools to lower endotoxemia and eventually hypercoagulation.
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Affiliation(s)
- Francesco Violi
- Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, 155, Rome 00161, Italy; Mediterranea Cardiocentro-Napoli, Via Orazio, 2, 80122, Naples, Italy.
| | - Pasquale Pignatelli
- Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, 155, Rome 00161, Italy; Mediterranea Cardiocentro-Napoli, Via Orazio, 2, 80122, Naples, Italy
| | - Valentina Castellani
- Department of General and Specialized Surgery "Paride Stefanini", Sapienza University of Rome, Italy
| | - Roberto Carnevale
- Mediterranea Cardiocentro-Napoli, Via Orazio, 2, 80122, Naples, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 40100, Latina, Italy
| | - Vittoria Cammisotto
- Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, 155, Rome 00161, Italy
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22
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Garg P, Harrison B, Gane EJ. Incident portal vein thrombosis in liver transplant recipients in New Zealand: Predictors of risk and validation of portal vein thrombosis risk index calculator. FRONTIERS IN TRANSPLANTATION 2022; 1:1042684. [PMID: 38994395 PMCID: PMC11235241 DOI: 10.3389/frtra.2022.1042684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/20/2022] [Indexed: 07/13/2024]
Abstract
The risk of spontaneous portal vein thrombosis (PVT) is increased in patients on the waiting list for liver transplantation and increases perioperative risks. A predictive PVT risk-index (PVT-RI) calculator has been proposed to determine the risk of incident PVT. We performed a retrospective analysis on adult liver transplant recipients at the NZ Liver Transplant Unit between January 1998 and February 2020. Variables reviewed included age at listing and transplantation, wait time from listing to transplant, indication for listing, gender, ethnicity, etiology of liver disease, listing MELD score, hepatocellular carcinoma (HCC), moderate-to-severe ascites, hepatic encephalopathy (>grade 2), transjugular intrahepatic portosystemic shunt (TIPSS), spontaneous bacterial peritonitis (SBP), and diabetes. Incident PVT was determined by imaging of patients while on the waiting list and assessment at transplantation. A total of 553 out of 706 patients met the inclusion criteria. Of those 553, 18 (3.3%) patients had incident PVT. The PVT-RI calculator was not validated in our cohort with only one of those 18 (6%) patients having a score of >4.6 (high risk cut-off score). Longer waiting time for transplant and listing for liver failure rather than HCC were independent predictors of the risk of incident PVT. There was no statistically significant difference in the incidence of PVT in viral vs. non-viral and cholestatic vs. non-cholestatic etiology of chronic liver disease. Patients with longer waiting times on the transplant waiting list should be monitored regularly for PVT.
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Affiliation(s)
- Paras Garg
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - Barry Harrison
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - Edward J Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
- Faculty of Medicine, University of Auckland, Auckland, New Zealand
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23
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Wu W, Zhang H, Zeng Z, Wang X, Kong D. Comparison of transjugular intrahepatic portosystemic with endoscopic treatment plus anticoagulation for esophageal variceal bleeding and portal vein thrombosis in liver cirrhosis. Scand J Gastroenterol 2022; 57:1494-1502. [PMID: 35802771 DOI: 10.1080/00365521.2022.2094724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM The optimal management of esophageal variceal bleeding (EVB) and portal vein thrombosis (PVT) in liver cirrhosis has not been well-established. The aim of the present study was to compare the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic treatment (ET) plus anticoagulation in cirrhotic patients with EVB and PVT. PATIENTS AND METHODS A total of 66 cirrhotic patients with PVT and EVB (31 in the TIPS group and 35 in the ET plus anticoagulation group) were evaluated retrospectively between January 2016 and January 2022. RESULTS During the follow-up period, 85.5% of patients in the TIPS group achieved complete recanalization of the portal vein, as compared with 19.6% in the ET plus anticoagulation group (p < .001). The cumulative 5-year rate of variceal rebleeding in the TIPS group was significantly lower than that in the ET plus anticoagulation group (31.0 vs. 50.1%; p = .017). The TIPS group exhibited a significantly higher incidence of overt hepatic encephalopathy (HE) than the ET plus anticoagulation group (25.8 vs. 5.7%; p = .037). No difference in the 5-year survival rate (74.1 vs. 85.7%; p = .692) and probability of other complications was observed between the two groups. CONCLUSION TIPS was superior to ET plus anticoagulation in preventing variceal rebleeding and achieving recanalization of PVT but increased the incidence of overt HE without improving the survival rate.
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Affiliation(s)
- Wenyue Wu
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hejiao Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhuang Zeng
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xi Wang
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Derun Kong
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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24
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Zhao D, Huang YM, Liang ZM, Zhang KJ, Fang TS, Yan X, Jin X, Zhang Y, Tang JX, Xie LJ, Zeng XC. Reconstructing the portal vein through a posterior pancreatic tunnel: New choice for portal vein thrombosis during liver transplantation. World J Gastrointest Surg 2022; 14:1131-1140. [PMID: 36386397 PMCID: PMC9640334 DOI: 10.4240/wjgs.v14.i10.1131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/08/2022] [Accepted: 09/21/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Thrombectomy and anatomical anastomosis (TAA) has long been considered the optimal approach to portal vein thrombosis (PVT) in liver transplantation (LT). However, TAA and the current approach for non-physiological portal reconstructions are associated with a higher rate of complications and mortality in some cases.
AIM To describe a new choice for reconstructing the portal vein through a posterior pancreatic tunnel (RPVPPT) to address cases of unresectable PVT.
METHODS Between August 2019 and August 2021, 245 adult LTs were performed. Forty-five (18.4%) patients were confirmed to have PVT before surgery, among which seven underwent PV reconstruction via the RPVPPT approach. We retrospectively analyzed the surgical procedure and postoperative complications of these seven recipients that underwent PV reconstruction due to PVT.
RESULTS During the procedure, PVT was found in all the seven cases with significant adhesion to the vascular wall and could not be dissected. The portal vein proximal to the superior mesenteric vein was damaged in one case when attempting thrombolectomy, resulting in massive bleeding. LT was successfully performed in all patients with a mean duration of 585 min (range 491-756 min) and mean intraoperative blood loss of 800 mL (range 500-3000 mL). Postoperative complications consisted of chylous leakage (n = 3), insufficient portal venous flow to the graft (n = 1), intra-abdominal hemorrhage (n = 1), pulmonary infection (n = 1), and perioperative death (n = 1). The remaining six patients survived at 12-17 mo follow-up.
CONCLUSION The RPVPPT technique might be a safe and effective surgical procedure during LT for complex PVT. However, follow-up studies with large samples are still warranted due to the relatively small number of cases.
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Affiliation(s)
- Dong Zhao
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Yi-Ming Huang
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Zi-Ming Liang
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Kang-Jun Zhang
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Tai-Shi Fang
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Xu Yan
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Xin Jin
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Yi Zhang
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Jian-Xin Tang
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Lin-Jie Xie
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
| | - Xin-Chen Zeng
- Department of Liver Surgery and Organ Transplantation Center, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518000, Guangdong Province, China
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25
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Pan J, Wang L, Gao F, An Y, Yin Y, Guo X, Nery FG, Yoshida EM, Qi X. Epidemiology of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis. Eur J Intern Med 2022; 104:21-32. [PMID: 35688747 DOI: 10.1016/j.ejim.2022.05.032] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 05/23/2022] [Accepted: 05/30/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted. RESULTS Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis. CONCLUSION Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed.
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Affiliation(s)
- Jiahui Pan
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China; Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China; Postgraduate College, China Medical University, Shenyang 110122, PR China
| | - Fangbo Gao
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China; Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Yang An
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China; Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Yue Yin
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China
| | - Xiaozhong Guo
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China
| | - Filipe Gaio Nery
- Centro Hospitalar Universitário do Porto, Porto, Portugal; EpiUnit, Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal
| | - Eric M Yoshida
- Division of Gastroenterology, Vancouver General Hospital, Vancouver, BC, Canada
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China; Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Postgraduate College, China Medical University, Shenyang 110122, PR China.
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Abstract
Patients with cirrhosis of the liver are at high risk of developing portal vein thrombosis (PVT), which has a complex, multifactorial cause. The condition may present with a myriad of symptoms and can occasionally cause severe complications. Contrast-enhanced computed tomography (CT) is the gold standard for the diagnosis of PVT. There are uncertainties regarding the effect on PVT and its treatment outcome in patients with cirrhosis. The main challenge for managing PVT in cirrhosis is analyzing the risk of hemorrhage compared to the risk of thrombus extension leading to complications. All current knowledge regarding non-tumor PVT in cirrhosis, including epidemiology, risk factors, classification, clinical presentation, diagnosis, impact on natural history, and treatment, is discussed in the present article.
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Key Words
- ACLF, acute-on-chronic liver failure
- BCS, Budd–Chiari syndrome
- DOACs, direct-acting oral anticoagulants
- EASL, European Association for the Study of the Liver
- HCC, hepatocellular carcinoma
- HVPG, hepatic venous pressure gradient
- INR, international normalized ratio
- JAK2, Janus Kinase 2
- LMWH, low molecular weight heparin
- LT, liver transplant
- MELD, Model for End-Stage Liver Disease
- MTHFR, methyltetrahydrofolate reductase
- NASH, non-alcoholic steatohepatitis
- NO, nitric oxide
- NSBBs, non-selective beta-blockers
- PV, portal vein
- PVT, Portal vein thrombosis
- RCT, randomized controlled trial
- SMA, superior mesenteric artery
- SMV, superior mesenteric vein
- SVT, splanchnic vein thrombosis
- TIPS, Transjugular intrahepatic portosystemic shunt
- UNOS, United Network for Organ Sharing
- VEGF, vascular endothelial growth factors
- VKAs, vitamin K antagonists
- VKORC1, vitamin K epoxide reductase complex 1
- anticoagulation
- cirrhosis
- eNOS, endothelial nitric oxide synthase
- non-tumoral portal vein thrombosis
- portal hypertension
- rTPA, recombinant tissue plasminogen activator
- transjugular intrahepatic portosystemic shunt
- vWF, von Willebrand factor
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Affiliation(s)
- Akash Shukla
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Suprabhat Giri
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
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27
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Biolato M, Paratore M, Di Gialleonardo L, Marrone G, Grieco A. Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis: What is the evidence? World J Hepatol 2022; 14:682-695. [PMID: 35646264 PMCID: PMC9099104 DOI: 10.4254/wjh.v14.i4.682] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 09/22/2021] [Accepted: 04/03/2022] [Indexed: 02/06/2023] Open
Abstract
In recent years, the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved. Currently, it is known that in cirrhotic patients, the hemostatic system is rebalanced, which involves coagulation factors, fibrinolysis and platelets. These alterations disrupt homeostasis, skewing it toward a procoagulant state, which can lead to thromboembolic manifestations, especially when hemodynamic and endothelial factors co-occur, such as in the portal vein system in cirrhosis. Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease, prognosis of cirrhotic patients and success of liver transplantation. It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function. Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis. In chronic portal vein thrombosis, the role of anticoagulant therapy is still unclear. Traditional anticoagulants, vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis. In the last ten years, direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolic-related diseases, but evidence on their use in cirrhotic patients is very limited. The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.
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Affiliation(s)
- Marco Biolato
- Internal and Liver Transplant Medicine Unit, CEMAD, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy.
| | - Mattia Paratore
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Luca Di Gialleonardo
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Giuseppe Marrone
- Internal and Liver Transplant Medicine Unit, CEMAD, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Antonio Grieco
- Internal and Liver Transplant Medicine Unit, CEMAD, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
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28
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Dai CY, Chuang WL, Yu ML. Predicting portal thrombosis in cirrhosis: Some issues. J Hepatol 2022; 76:224-225. [PMID: 34461209 DOI: 10.1016/j.jhep.2021.08.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 12/27/2022]
Affiliation(s)
- Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Khayyat YM. Can we use non-invasive parameters to predict the development of gastroesophageal varices in cirrhotic patients with and without portal vein thrombosis? An observational study from the western region of Saudi Arabia. EGYPTIAN LIVER JOURNAL 2021; 11:25. [DOI: 10.1186/s43066-021-00095-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 03/30/2021] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The prevention of portal hypertensive complications, including upper gastrointestinal bleeding, is critically important and achieved only through the use of upper endoscopy for the management of oesophageal gastric varices (EGVs). There is a paucity of data and limited utilization of non-invasive predictive parameters to guide the selection of patients who may benefit from endoscopic surveillance, especially in cirrhotic patients with coexistent portal vein thrombosis.
Results
The study was conducted in eight hospitals in the western region of Saudi Arabia over the period of 2015–2017. Among 1349 chronic liver disease patients, eighty-five patients with complete endoscopic findings were included in the study. Twenty-eight patients were diagnosed with non-malignant PVT. Twenty-five patients (89%) developed oesophageal varices, compared with 57 patients with cirrhosis without PVT. A predictive factor for the development of oesophageal varices of statistical significance was hypoalbuminemia in PVT patients (p=0.04). No statistically significant differences were found in other biochemical markers (p<0.05) between the PVT and non-PVT groups.
Conclusions
The prevalence of oesophageal varices is increased in PVT patients. Serum albumin can be utilized as a predictor of varices development in cirrhosis patients.
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30
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Riva N, Attard LM, Vella K, Squizzato A, Gatt A, Calleja-Agius J. Diagnostic accuracy of D-dimer in patients at high-risk for splanchnic vein thrombosis: A systematic review and meta-analysis. Thromb Res 2021; 207:102-112. [PMID: 34600286 DOI: 10.1016/j.thromres.2021.09.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND D-dimer is included in the diagnostic algorithm for deep vein thrombosis and pulmonary embolism. However, its role in the diagnosis of splanchnic vein thrombosis (SVT) is still controversial. The aim of this study was to evaluate the diagnostic accuracy of D-dimer for SVT. METHODS We performed a systematic review of the literature with meta-analysis (PROSPERO protocol registration number: CRD42020184300). The electronic databases MEDLINE, EMBASE, and CENTRAL were searched from inception to March 2021 week 4. Studies which evaluated D-dimer accuracy for SVT in any category of patients were selected. The index test was any D-dimer assay; the reference standard was any radiological imaging. The QUADAS-2 checklist was used for the risk of bias assessment. A bivariate random-effects regression model was used to calculate summary estimates of sensitivity and specificity. RESULTS 12 studies (with a total of 1298 patients) evaluating the accuracy of D-dimer in patients at high risk of SVT (surgical patients, patients with liver cirrhosis or hepatocellular carcinoma) were included. None of the included studies was at low risk of bias. The weighted mean prevalence of SVT was 33.4% (95% CI, 22.5-45.2%, I2 = 94.8%). D-dimer accuracy was expressed by sensitivity 96% (95% CI, 72-100%); specificity 25% (95% CI, 5-67%); positive likelihood ratio 1.3 (95% CI, 0.9-1.9); negative likelihood ratio 0.16 (95% CI, 0.03-0.84); area under the ROC curve 0.80 (95% CI, 0.76-0.83). CONCLUSIONS D-dimer seems to have high sensitivity in the diagnosis of patients at high-risk for SVT. However, there is a strong need for more robust evidence on this topic.
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Affiliation(s)
- Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
| | - Laura Maria Attard
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
| | - Kevin Vella
- Coagulation Medicine Laboratory, Department of Pathology, Mater Dei Hospital, Msida, Malta.
| | | | - Alex Gatt
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Coagulation Medicine Laboratory, Department of Pathology, Mater Dei Hospital, Msida, Malta.
| | - Jean Calleja-Agius
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
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31
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Bos I, Blondeau M, Wouters D, Camus C, Houssel-Debry P, van der Plas WS, Nieuwenhuis LM, Bardou-Jacquet E, Lisman T, de Meijer VE, Porte RJ, Rayar M. Therapeutic anticoagulation after liver transplantation is not useful among patients with pre-transplant Yerdel-grade I/II portal vein thrombosis: A two-center retrospective study. J Thromb Haemost 2021; 19:2760-2771. [PMID: 34297481 DOI: 10.1111/jth.15472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/14/2021] [Accepted: 07/21/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT. OBJECTIVES The aim of our study was to evaluate the role of tAC post-LT in the prevention of PVT recurrence. PATIENTS/METHODS All adult LTs performed in two high-volume centers between 2003 and 2018 were retrospectively analysed. Only patients with PVT classified as Yerdel grade I or II and with standard portal reconstruction were included. PVT recurrence and tAC-associated morbidity within 1 year were compared between patients receiving tAC or not. RESULTS During the study period, of 2612 LTs performed, 235 (9%) patients with PVT were included; 113 patients (48.1%) received post-LT tAC (tAC group) while 122 (51.9%) did not (non-tAC group). The incidence of bleeding events was significantly higher in the tAC group (26 [23%] vs. 5 [4.1%], P < .01) and the initial hospitalization duration was longer (21 vs. 17.5 days, P < .01). Within the first year, PVT recurrence was observed for 9 (3.8%) patients without any difference between the tAC and non-tAC groups (6 [5.1%] vs. 3 [2.5%], P = .39). The only identified risk factor for PVT recurrence was the recipients' age (odds ratio= 0.94, P = .03). Graft (P = .11) and patient (P = .44) survival were similar between the two groups. CONCLUSION Therapeutic anticoagulation is not necessary in the prevention of grade I/II PVT recurrence and is associated with higher morbidity and longer hospital stay.
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Affiliation(s)
- Isabel Bos
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Marc Blondeau
- Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France
| | - Dune Wouters
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Christophe Camus
- Service de Maladies Infectieuses et Réanimation Médicale, CHU Rennes, Rennes, France
- INSERM, Rennes, France
| | | | - Willemijn S van der Plas
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Lianne M Nieuwenhuis
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | | | - Ton Lisman
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Vincent E de Meijer
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Robert J Porte
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Michel Rayar
- Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France
- INSERM, Rennes, France
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32
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Lopez-Gomez M, Llop E, Puente A, Hernández Conde M, Ruiz P, Alvárez S, Martínez JL, Abad J, Fernández N, Perelló C, Fernández-Carrillo C, Ferre C, Trapero M, Fraga E, Crespo J, Calleja Panero JL. Non-malignant portal vein thrombosis in a cohort of cirrhotic patients: Incidence and risk factors. Hepatol Res 2021; 51:1064-1072. [PMID: 34324766 DOI: 10.1111/hepr.13703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/06/2021] [Accepted: 07/21/2021] [Indexed: 01/04/2023]
Abstract
AIM Non-malignant portal vein thrombosis (PVT) is a complication of liver cirrhosis. The aim of this study was to evaluate the annual incidence of PVT and related risk factors. METHODS We retrospectively reviewed clinical, laboratory, and radiological data collected prospectively from September 2016 to September 2017. A follow-up of 36 months was performed in a subset of patients to determine the cumulative incidence of PVT and related complications. RESULTS The study included 567 patients. The incidence of PVT at 12, 24, and 36 months was 3.7%, 0.8%, and 1.4%, respectively. Patients with PVT were compared with patients without PVT, and showed differences in albumin (p = 0.04), aspartate aminotransferase (p = 0.04), hemoglobin (p = 0.01), and prothrombin activity (p = 0.01). The presence of hydropic decompensation (57.1% vs. 30.1%; p 0.004), gastroesophageal varices (76.2% vs. 39.5%; p = 0.05), variceal bleeding (52.4% vs. 22.7%; p < 0.001), hepatic encephalopathy (38.1% vs. 9.9%; p = 0.01), spontaneous bacterial peritonitis (9.5% vs. 1.7%; p < 0.001), and use of beta-blockers (71.4% vs. 27.7%; p < 0.001) were significantly associated. In the multivariate analysis, use of beta-blockers and hepatic encephalopathy appeared as risk factors, and high albumin levels a protective factor. CONCLUSIONS The incidence of PVT was 3.7%. Beta-blockers and hepatic encephalopathy were risks factors. High albumin levels were a protective factor.
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Affiliation(s)
- Marta Lopez-Gomez
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Elba Llop
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Angela Puente
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Marta Hernández Conde
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Patricia Ruiz
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Silvia Alvárez
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Jose Luis Martínez
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Javier Abad
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Natalia Fernández
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Christie Perelló
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Carlos Fernández-Carrillo
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Carlos Ferre
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Maria Trapero
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Enrique Fraga
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Javier Crespo
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Jose Luis Calleja Panero
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Madrid, Spain
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33
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Von Willebrand and Factor VIII Portosystemic Circulation Gradient in Cirrhosis: Implications for Portal Vein Thrombosis. Clin Transl Gastroenterol 2021; 11:e00123. [PMID: 32032127 PMCID: PMC7145026 DOI: 10.14309/ctg.0000000000000123] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Portal vein thrombosis seems to be dependent on local hypercoagulation and venous stasis; data regarding endothelial damage are lacking.
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34
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Costache RS, Dragomirică AS, Dumitraș EA, Mariana J, Căruntu A, Popescu A, Costache DO. Portal vein thrombosis: A concise review (Review). Exp Ther Med 2021; 22:759. [PMID: 34035856 DOI: 10.3892/etm.2021.10191] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 02/19/2021] [Indexed: 12/14/2022] Open
Abstract
Portal vein thrombosis (PVT) is a frequent complication in cirrhotic patients, but it may also exist as a basic vascular condition even without any liver damage. Local and systemic factors play a significant role in the pathogenesis of PVT; yet, in practice, more than one factor may be identified. PVT can be considered a result of liver fibrosis and hepatic insufficiency. The JAK2 mutation has been accepted as a factor producing PVT. In general, the anticoagulants are recommended but this therapy should be used carefully in treating patients that associate coagulopathy or thrombocytopenia and esophageal varices. Acute PVT without bowel infarction has a good prognosis. In liver cirrhosis, the mortality due to hemorrhage is higher than in chronic PVT. Therefore, for the patients with PVT, the survival rate is decreased by 55% in two years, due to hepatic insufficiency. Regarding the treatment, LMWH (low molecular weight heparine) is the most utilized in patients with cirrhosis, non-malignancies, infections, or those who are awaiting a liver transplant. DOACs (direct-acting oral anticoagulants) may be used in the rest of the medical conditions, being safe and equal to LMWH.
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Affiliation(s)
- Raluca S Costache
- Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania.,5th Clinical Department, Gastroenterology and Internal Medicine Discipline, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Andreea S Dragomirică
- Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Elena A Dumitraș
- Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Jinga Mariana
- Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania.,5th Clinical Department, Gastroenterology and Internal Medicine Discipline, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Ana Căruntu
- Department of Maxillofacial Surgery, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Andrada Popescu
- Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania.,5th Clinical Department, Gastroenterology and Internal Medicine Discipline, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Daniel O Costache
- Department of Research, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
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35
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Caiano LM, Riva N, Carrier M, Gatt A, Ageno W. Treatment of portal vein thrombosis: an updated narrative review. Minerva Med 2021; 112:713-725. [PMID: 33832217 DOI: 10.23736/s0026-4806.21.07526-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Portal vein thrombosis (PVT) is the most frequent among the splanchnic vein thrombosis, accounting for 90% of cases. More than half of PVT are provoked by liver cirrhosis, solid cancer or myeloproliferative neoplasms. The remaining cases are non-malignant non-cirrhotic PVT and include either unprovoked events or thrombosis secondary to other less common risk factors (e.g. abdominal surgery, intrabdominal inflammations/infections, or hormonal stimuli). Anticoagulant therapy in patients with acute symptomatic PVT should be started early after diagnosis, if no active bleeding, to obtain greater vessel recanalization and reduce the occurrence of portal-hypertension related complications. Gastroesophageal varices do not represent a contraindication to anticoagulant treatment, as long as adequate measures have been undertaken for the prophylaxis of gastroesophageal bleeding. Different treatment options (unfractionated or low molecular weight heparin, vitamin K antagonists and direct oral anticoagulants [DOACs]) can be considered. In this narrative review we will discuss the treatment of PVT in the three most common scenarios (cirrhosis-associated, cancer-associated and non-malignant non-cirrhotic PVT). We will also discuss the role of the DOACs and summarise recent guidelines on this topic.
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Affiliation(s)
- Lucia M Caiano
- Department of Medicine and Surgery, University of Insubria, Varese, Italy.,Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada
| | - Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta -
| | - Marc Carrier
- Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada
| | - Alex Gatt
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
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36
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Abstract
Portal vein thrombosis (PVT) is one of the common complications of liver cirrhosis, which can further increase portal vein pressure and aggravate liver function decompensation. However, due to the insidious onset and atypical symptoms, the importance of PVT has been neglected in clinical work for quite a long time. With the development of clinical diagnostic technology, the detection rate of PVT has increased year by year. At present, the well-established treatment methods for PVT include anticoagulant therapy, interventional therapy, and surgical treatment. However, the optimal choice for PVT treatment remains unclear. In this paper, we briefly review the recent progress in the diagnosis and treatment of PVT in order to provide a theoretical reference for the refined clinical management of patients with PVT.
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Affiliation(s)
- Wen-Yue Wu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 237000, Anhui Province, China
| | - De-Run Kong
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 237000, Anhui Province, China
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37
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Nacif LS, Zanini LY, Pinheiro RS, Waisberg DR, Rocha-Santos V, Andraus W, Carrilho FJ, Carneiro-D'Albuquerque L. Portal vein surgical treatment on non-tumoral portal vein thrombosis in liver transplantation: Systematic Review and Meta-Analysis. Clinics (Sao Paulo) 2021; 76:e2184. [PMID: 33503185 PMCID: PMC7811829 DOI: 10.6061/clinics/2021/e2184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 11/13/2020] [Indexed: 12/20/2022] Open
Abstract
Non-tumoral portal vein thrombosis (PVT) is associated with higher morbidity and mortality in liver transplantation (LT). In this study, we aimed to evaluate the impact of PVT in LT outcomes and analyze the types of surgical techniques used for dealing with PVT during LT. A systematic review was conducted in Cochrane, MEDLINE, and EMBASE databases, selecting articles from January 1990 to December 2019. The MESH-terms used were ("Portal Vein"[Mesh] AND "Thrombosis"[Mesh] NOT "Neoplasms"[Mesh]) AND ("Liver Transplantation"[Mesh]). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendation was used, and meta-analysis was performed with Review Manager Version 5.3 software. A total of 1,638 articles were initially found: 488 in PubMed, 289 in Cochrane Library, and 861 in EMBASE, from which 27 were eventually selected for the meta-analysis. Surgery time of LT in patients with PVT was longer than in patients without LT (p<0.0001). Intraoperative red blood cell (p<0.00001), fresh frozen plasma (p=0.01), and platelets (p=0.03) transfusions during LT were higher in patients with PVT. One-year (odds ratio [OR] 1.17; p=0.002) and 5-year (OR 1.12; p=0.01) patient survival after LT was worse in the PVT group. Total occlusive PVT presented higher mortality (OR 3.70; p=0.00009) and rethrombosis rates (OR 3.47 [1.18-10.21]; p=0.02). PVT Yerdel III/IV classification exhibited worse 1-year [2.04 (1.21-3.42); p=0.007] and 5-year [0.98 (0.59-1.62); p=0.93] patient survival. Thrombectomy with primary anastomosis was associated with better outcomes. LT in patients with non-tumoral PVT demands more surgical time, needs more intraoperative transfusion, and presents worse 1- and 5-year patient survival. Total occlusive PVT and Yerdel III/IV PVT classification were associated with higher mortality. (PROSPERO, registration number: CRD42020132915).
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Affiliation(s)
- Lucas S. Nacif
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Leonardo Y. Zanini
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Rafael S. Pinheiro
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Daniel R. Waisberg
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Vinicius Rocha-Santos
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Wellington Andraus
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Flair J. Carrilho
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Luiz Carneiro-D'Albuquerque
- Divisao de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
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38
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Bianchini M, Villa E. Future Directions. PORTAL VEIN THROMBOSIS 2021:165-171. [DOI: 10.1007/978-981-33-6538-4_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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39
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Lankarani KB. Risk Factors for Portal Vein Thrombosis. PORTAL VEIN THROMBOSIS 2021:29-37. [DOI: 10.1007/978-981-33-6538-4_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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40
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Northup PG, Garcia-Pagan JC, Garcia-Tsao G, Intagliata NM, Superina RA, Roberts LN, Lisman T, Valla DC. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:366-413. [PMID: 33219529 DOI: 10.1002/hep.31646] [Citation(s) in RCA: 358] [Impact Index Per Article: 89.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Patrick G Northup
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis in Liver Disease, University of Virginia, Charlottesville, VA
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.,Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver), Barcelona, Spain
| | - Guadalupe Garcia-Tsao
- Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT.,Veterans Administration Healthcare System, West Haven, CT
| | - Nicolas M Intagliata
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis in Liver Disease, University of Virginia, Charlottesville, VA
| | - Riccardo A Superina
- Department of Transplant Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Lara N Roberts
- Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Surgical Research Laboratory, Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Dominique C Valla
- Hepatology Service, Hospital Beaujon, Clichy, France.,Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver), Barcelona, Spain
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41
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Violi F, Loffredo L, Pastori D. Anticoagulation in patients with advanced liver disease: an open issue. Intern Emerg Med 2021; 16:61-71. [PMID: 33073317 DOI: 10.1007/s11739-020-02526-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 09/30/2020] [Indexed: 12/14/2022]
Abstract
Liver disease has been long considered as a risk factor for bleeding for the presence of prolongation of global tests of clotting activation and low platelet count. For this reason, the use of anticoagulants in patients with liver disease and an indication to anticoagulation, such as atrial fibrillation of venous thrombosis, has been poorly considered. Furthermore, recent studies underscored the fact that patients with chronic liver disease may experience thrombosis in portal as well as systemic circulation and treatment with anticoagulants should be considered. The introduction of direct oral anticoagulants has increased therapeutic options for thromboprophylaxis; however, evidence on their safety and efficacy in specific populations, such as patients with liver disease, is still scarce and needs further investigation. Thus, atrial fibrillation patients with coexistent liver disease have been excluded from clinical trials with direct oral anticoagulants. Here, we provide an overview on mechanisms of thrombosis in patients with advanced chronic liver disease and a summary of evidence on the use of oral anticoagulants in patients with liver disease and portal vein thrombosis or atrial fibrillation.
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Affiliation(s)
- Francesco Violi
- Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
- Mediterranea Cardiocentro, via Orazio 2, 80122, Naples, Italy.
| | - Lorenzo Loffredo
- Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Daniele Pastori
- Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
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42
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Ronca V, Podda GM, Cattaneo M. An "unmodifiable" risk factor that has been modified. Intern Emerg Med 2021; 16:157-159. [PMID: 31396923 DOI: 10.1007/s11739-019-02170-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 08/01/2019] [Indexed: 11/25/2022]
Affiliation(s)
- Vincenzo Ronca
- Divisione Di Epatologia E Gastroenterologia, ASST Santi Paolo E Carlo, Università Degli Studi Di Milano, Milano, Italy
| | - Gian Marco Podda
- U.O. Medicina III, ASST Santi Paolo e Carlo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via di Rudinì, 8, 20142, Milano, Italy.
| | - Marco Cattaneo
- U.O. Medicina III, ASST Santi Paolo e Carlo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via di Rudinì, 8, 20142, Milano, Italy
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43
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Rugivarodom M, Charatcharoenwitthaya P. Nontumoral Portal Vein Thrombosis: A Challenging Consequence of Liver Cirrhosis. J Clin Transl Hepatol 2020; 8:432-444. [PMID: 33447527 PMCID: PMC7782107 DOI: 10.14218/jcth.2020.00067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/27/2020] [Accepted: 10/18/2020] [Indexed: 12/13/2022] Open
Abstract
Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.
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Affiliation(s)
- Manus Rugivarodom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Correspondence to: Phunchai Charatcharoenwitthaya, Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Wang-Lang Road, Bangkoknoi, Bangkok 10700, Thailand. Tel: +662-419-7282, Fax: +662-411-5013, E-mail:
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Effects of Anticoagulants on Experimental Models of Established Chronic Liver Diseases: A Systematic Review and Meta-Analysis. Can J Gastroenterol Hepatol 2020; 2020:8887574. [PMID: 33381477 PMCID: PMC7749775 DOI: 10.1155/2020/8887574] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/09/2020] [Accepted: 11/28/2020] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE The role of anticoagulants in chronic liver diseases is inconclusive. A meta-analysis was thus undertaken to evaluate treatment-related survival and antifibrotic effects in animal models of chronic liver diseases. METHODS A systematic search of the literature took place (up to November 2020), screening for preclinical studies that evaluated anticoagulant effects in animal models of chronic liver diseases. We assessed the quality of methods and the certainty of evidence. Data on outcomes were extracted and pooled into random-effects models. RESULTS Sixteen studies proved eligible, each assessing anticoagulant use in animals with chronic liver diseases. Generally, the pooled evidence demonstrated that the administration of anticoagulants is preventive against fibrogenesis, as indicated by METAVIR fibrosis scores (risk ratio = 0.66, 95% confidence interval: 0.47 to 0.94), portal pressure determinations (mean difference = -1.39, 95% confidence interval: -2.33 to -0.44), inflammatory activity (mean difference = -169.69, 95% confidence interval: -257.64 to -81.74), and indices of hepatic injury, specifically alanine aminotransferase (mean difference = -82.7, 95% confidence interval: -107.36 to -58.04), aspartate aminotransferase (mean difference = -186.12, 95% confidence interval: -254.90 to -117.33), albumin (mean difference = 0.59, 95% confidence interval: 0.16 to 1.01), and total bilirubin (mean difference = -0.96, 95% confidence interval: -1.46 to -0.46), and it had no impact on animal survival (risk ratio = 1.03, 95% confidence interval: 0.94 to 1.13). CONCLUSIONS Our assessments indicate that in animal models of chronic liver diseases, anticoagulants may alleviate the degree of fibrosis evaluated by the METAVIR score system, portal pressure, inflammatory activity, and serum indices of hepatocellular injury, without impacting survival. High-quality experimental studies are still required.
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Talon L, Sinegre T, Lecompte T, Pereira B, Massoulié S, Abergel A, Lebreton A. Hypercoagulability (thrombin generation) in patients with cirrhosis is detected with ST-Genesia. J Thromb Haemost 2020; 18:2177-2190. [PMID: 32558351 DOI: 10.1111/jth.14963] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 05/06/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Thrombin generation assays (TGAs) performed with calibrated automated thrombography (CAT) in the presence of thrombomodulin (TM) indicate plasma hypercoagulability in cirrhosis. OBJECTIVE To evaluate, in the presence of TM, the new ST-Genesia automated device developed for improving TGA vs the previously used CAT method, with plasma samples of patients with cirrhosis. PATIENTS/METHODS Platelet-poor plasma samples were prepared from citrated blood samples of 52 healthy controls and 85 patients with cirrhosis (severity evaluated using the Child-Pugh score [CP]). TGAs were performed using CAT with PPP-Reagent and ST-Genesia with the STG-ThromboScreen reagent, in the presence of TM. Endogenous thrombin potential (ETP) was chosen as the main parameter. RESULTS Whatever the method, ETP values were higher in patients than in healthy controls. All patients identified as hypercoagulable with ST-Genesia and STG-ThromboScreen were found hypercoagulable with CAT and PPP-Reagent. Conversely, eight and ten patients in the CP-A and CP-B classes respectively were identified as hypercoagulable only with CAT. The use of ST-Genesia with the STG-ThromboScreen reagent with TM led to a bias, with higher ETP values for healthy controls and lower for patients compared with CAT. Crossover analysis (CAT with the STG-ThromboScreen reagent) evidenced a substantial effect of the STG-ThromboScreen reagent; the analyzer (including calibration and data analysis) plays a lesser role. CONCLUSION ST-Genesia evidences hypercoagulability in patients with cirrhosis when TG is studied in the presence of TM, but the results are not interchangeable with those obtained with CAT.
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Affiliation(s)
- Laurie Talon
- Service d'hématologie biologique, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Thomas Sinegre
- Service d'hématologie biologique, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Thomas Lecompte
- Hôpitaux Universitaires de Genève, Unité d'hémostase, Département de médecine, faculté de Médecine - GpG, Université de Genève, Geneva, Switzerland
| | - Bruno Pereira
- Unité de Biostatistiques (Direction de la recherche clinique et de l'innovation), CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Sylvie Massoulié
- Service d'Hépato-Gastro-Entérologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Armand Abergel
- Service d'Hépato-Gastro-Entérologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Aurélien Lebreton
- Service d'hématologie biologique, CHU Clermont-Ferrand, Clermont-Ferrand, France
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46
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Northup P, Davis J. Shortcomings in Design and Analysis of Clinical Studies on Bleeding and Thrombosis in Patients with Cirrhosis. Semin Thromb Hemost 2020; 46:665-672. [PMID: 32757183 DOI: 10.1055/s-0040-1714203] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Significant gains have been made in our understanding of bleeding and thrombosis in patients with liver disease in recent years, with concurrent exponential growth in the scientific literature published in this realm. Clinical studies of this population are challenging for multiple reasons including some hurdles unique to this population. Cirrhosis patients as a whole, especially those with decompensated cirrhosis, are a high-risk and heterogeneous population prone to serious adverse events. Outcomes of bleeding and thrombosis are relatively rare and lack standardized, validated definitions. Standard practices for clinical care have evolved rapidly and rendered some control data uninformative. We aim to highlight these challenges and make recommendations for best practices for future study design and implementation. Multidisciplinary collaboration with proceduralists, careful study design including attention to validated clinically relevant outcomes, and aggressive pursuit of all funding streams will be key to continued scientific success in this burgeoning field.
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Affiliation(s)
- Patrick Northup
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis and Coagulation Disorders in Liver Disease, University of Virginia, Charlottesville, Virginia
| | - Jessica Davis
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis and Coagulation Disorders in Liver Disease, University of Virginia, Charlottesville, Virginia
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Xu X, Xu S, Primignani M, De Stefano V, He Y, Yi F, Guo X, Valla D, Qi X. Nonselective β-Blockers May Progress the Thrombosis of Portal Venous System in Cirrhotic Patients: A Retrospective Observational Study. Adv Ther 2020; 37:1452-1463. [PMID: 32076942 PMCID: PMC7140745 DOI: 10.1007/s12325-020-01250-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Occlusive portal venous system thrombosis (PVT) is significantly associated with poor outcomes in cirrhotic patients. Nonselective β-blockers (NSBBs) may be associated with the development of PVT. However, the role of NSBBs in progressing thrombosis remains unclear. METHODS Forty-three patients on whom contrast-enhanced computed tomography or magnetic resonance imaging was performed twice, and for whom there was detailed information regarding NSBBs, were eligible in this study, including 16 in the NSBBs group and 27 in the no NSBBs group. A composite endpoint of progressing thrombosis included the development of PVT in patients without PVT and aggravation of PVT in patients with PVT. Logistic regression analysis was employed to identify the effect of NSBBs on the progression of PVT. RESULTS At the last admission, 13 patients had progressing thrombosis. The incidence of progressing thrombosis was significantly higher in the NSBBs group than in the no NSBBs group [50.0% (8/16) vs. 18.5% (5/27), P = 0.030]. The use of NSBBs (odds ratio 4.400, 95% confidence interval 1.107-17.482, P = 0.035) was significantly associated with progressing thrombosis in univariate logistic regression analyses, but not significant (odds ratio 4.084, 95% confidence interval 0.488-34.158, P = 0.194) in multivariate logistic regression analyses. CONCLUSIONS NSBBs may play a role in the progression of PVT in liver cirrhosis. The benefits and risks of NSBBs in the management of liver cirrhosis should be fully weighed.
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Affiliation(s)
- Xiangbo Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China
| | - Shixue Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China
| | - Massimo Primignani
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico Università degli Studi di Milano, Via F. Sforza 35, 20122, Milan, Italy
| | - Valerio De Stefano
- Fondazione Policlinico A. Gemelli IRCCS, Istituto di Ematologia, Università Cattolica, Rome, Italy
| | - Yanglan He
- Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China
| | - Fangfang Yi
- Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China
| | - Dominique Valla
- Service d'Hépatologie, Hôpital Beaujon, APHP, Clichy-la-Garenne, France
- CRI, UMR1149, Inserm and Université de Paris, Paris, France
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China.
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Riva N, Ageno W. Cerebral and Splanchnic Vein Thrombosis: Advances, Challenges, and Unanswered Questions. J Clin Med 2020; 9:E743. [PMID: 32164214 PMCID: PMC7141239 DOI: 10.3390/jcm9030743] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 03/03/2020] [Accepted: 03/08/2020] [Indexed: 02/07/2023] Open
Abstract
Cerebral vein thrombosis (CVT) and splanchnic vein thrombosis (SVT) are two manifestations of venous thromboembolism (VTE) at unusual sites. They have an incidence at least 25-50 times lower than usual site VTE, but represent true clinical challenges. Recent evidence on the epidemiology, risk factors, prognosis, and treatment of CVT and SVT has been published in the last two decades, thus contributing to a better understanding of these diseases. The improvement in imaging techniques and a higher degree of clinical suspicion may have led to the observed increased frequency, whereas a better knowledge of provoking mechanisms could have contributed to reducing the proportion of events classified as unprovoked or idiopathic (13%-21% of CVT, 15%-27% of SVT). Few small randomized clinical trials and a number of observational studies, although hampered by heterogeneous therapeutic approaches, shed light on the safety and effectiveness of anticoagulant therapy in these populations. However, there are still some grey areas that warrant future research. In this narrative review, we discuss recent advances and therapeutic challenges in CVT and SVT.
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Affiliation(s)
- Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida MSD2080, Malta;
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida MSD2080, Malta
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy
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Davis JPE, Intagliata NM. Anticoagulation in the Hospitalized Patient with Decompensated Cirrhosis: Management of a Delicate Balance. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:219-236. [DOI: 10.1007/978-3-030-24490-3_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Vizzutti F, Schepis F, Arena U, Fanelli F, Gitto S, Aspite S, Turco L, Dragoni G, Laffi G, Marra F. Transjugular intrahepatic portosystemic shunt (TIPS): current indications and strategies to improve the outcomes. Intern Emerg Med 2020; 15:37-48. [PMID: 31919780 DOI: 10.1007/s11739-019-02252-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 12/03/2019] [Indexed: 12/16/2022]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of complications of portal hypertension. Established indications to TIPS in cirrhotic patients include portal hypertensive bleeding and refractory ascites. Over the years additional indications have been proposed, such as the treatment of vascular disease of the liver, hepatic hydrothorax, hepatorenal syndrome and bleeding from ectopic varices. Indications under evaluation include treatment of portal hypertension prior to major abdominal surgery and treatment of portal vein thrombosis. In spite of these advances, there are still uncertainties regarding the appropriate workup for patients to be scheduled for TIPS. Moreover, prevention and management of post-TIPS complications including hepatic encephalopathy and heart failure are still suboptimal. These issues are particularly relevant considering aging in TIPS candidates in Western countries. Correct selection of patients is mandatory to prevent complications which may eventually frustrate the good hemodynamic results and worsen the patient's quality of life or even life expectancy. The possible role of small diameter TIPS to prevent post-procedural complications is discussed.
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Affiliation(s)
- Francesco Vizzutti
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy
| | - Filippo Schepis
- Department of Internal Medicine, University of Modena and Reggio, Modena, Italy
| | - Umberto Arena
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy
| | - Fabrizio Fanelli
- Department of Radiology, Interventional Radiology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy
| | - Silvia Aspite
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy
| | - Laura Turco
- Department of Internal Medicine, University of Modena and Reggio, Modena, Italy
| | - Gabriele Dragoni
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy
| | - Giacomo Laffi
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Viale Morgagni 85, 50134, Florence, Italy.
- Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy.
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