Portosinusoidal Vascular Disorder: When to Suspect and How to Manage?

Sarah Shalaby; Wagner Enrique Ramírez-Quesada; Asunción Ojeda; Valeria Perez-Campuzano; Anna Baiges; Fanny Turon; Carla Fuster; Alba Díaz; Virginia Hernández-Gea; Juan Carlos García-Pagán

doi:10.1055/a-2630-0848

Seminars in Liver Disease, Table of Contents

Semin Liver Dis
DOI: 10.1055/a-2630-0848

Review Article

Portosinusoidal Vascular Disorder: When to Suspect and How to Manage?

Sarah Shalaby

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

,

Wagner Enrique Ramírez-Quesada

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

,

Asunción Ojeda

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

,

Valeria Perez-Campuzano

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

,

Anna Baiges

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

³Departament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain

,

Fanny Turon

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

,

Carla Fuster

⁴Department of Pathology, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), University of Barcelona, Barcelona, Spain

,

Alba Díaz

⁴Department of Pathology, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), University of Barcelona, Barcelona, Spain

,

Virginia Hernández-Gea

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

³Departament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain

,

Juan Carlos García-Pagán

¹Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Barcelona, Spain

²Fundació de Recerca Clínic Barcelona (FRCB-IDIABPS), CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain

³Departament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain

› Author Affiliations

Abstract

Portosinusoidal vascular disorders (PSVD) represent a group of rare conditions characterized by abnormalities in the liver's vascular architecture, often manifesting with clinical features of portal hypertension (PH), in the absence of cirrhosis. The pathophysiology of PSVD remains unclear, but it is frequently linked to underlying immunological disorders, medications, hematological disorders, and thrombophilia. Laboratory tests typically show preserved liver function with or without slight alteration on the transaminase profile. A key diagnostic feature is the presence of clear signs of PH alongside normal or only slightly elevated liver stiffness and hepatic venous pressure gradient. Liver biopsy remains essential for confirming the diagnosis and excluding other causes of PH and cirrhosis. However, histological examination may reveal subtle or mild changes, making expert pathological analysis and high-quality specimens crucial for an accurate diagnosis. In some cases, characteristic histological findings may be identified in patients without overt PH, which could represent an early stage of the disease. The long-term prognosis for patients with PSVD is mainly influenced by severity of the underlying condition and development of PH. However, treatments that modify the disease's natural history are still lacking, and management primarily focuses on controlling complications related to PH. Further research into the pathogenesis and potential therapeutic strategies for PSVD is needed to improve patient outcomes.

Keywords

idiopathic noncirrhotic portal hypertension - noncirrhotic portal vein thrombosis - nodular regenerative hyperplasia - portal obliterative venopathy - incomplete septal fibrosis

Full Text

References

References
1 Khanna R, Sarin SK. Non-cirrhotic portal hypertension - diagnosis and management. J Hepatol 2014; 60 (02) 421-441
2 Sarin SK, Kapoor D. Non-cirrhotic portal fibrosis: current concepts and management. J Gastroenterol Hepatol 2002; 17 (05) 526-534
3 Okudaira M, Ohbu M, Okuda K. Idiopathic portal hypertension and its pathology. Semin Liver Dis 2002; 22 (01) 59-72
4 Schouten JNL, Garcia-Pagan JC, Valla DC, Janssen HLA. Idiopathic noncirrhotic portal hypertension. Hepatology 2011; 54 (03) 1071-1081
5 De Gottardi A, Rautou PE, Schouten J. et al; VALDIG group. Porto-sinusoidal vascular disease: proposal and description of a novel entity. Lancet Gastroenterol Hepatol 2019; 4 (05) 399-411
6 Sarin SK, Lohse AW, Kamath PS. Poor long-term outcome in patients with porto-sinusoidal vascular disease (PSVD): fact or disease misclassification?. J Hepatol 2025; 82 (01) 4-6
7 Shukla A, Rockey DC, Kamath PS. et al. Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management. Hepatol Int 2024; 18 (06) 1684-1711
8 Magaz M, Giudicelli-Lett H, Abraldes JG. et al. Porto-sinusoidal vascular liver disorder with portal hypertension: natural history and long-term outcome. J Hepatol 2025; 82 (01) 72-83
9 De Gottardi A, Sempoux C, Berzigotti A. Porto-sinusoidal vascular disorder. J Hepatol 2022; 77 (04) 1124-1135
10 Premkumar M, Anand AC. Porto-sinusoidal vascular disease: classification and clinical relevance. J Clin Exp Hepatol 2024; 14 (05) 101396
11 Tonutti A, Pugliese N, Ceribelli A. et al. The autoimmune landscape of porto-sinusoidal vascular disorder: what the rheumatologist needs to know. Semin Arthritis Rheum 2024; 67: 152467
12 Pugliese N, Giuli L, Mastrorocco E. et al. Exploring the link: porto-sinusoidal vascular disorder and inflammatory bowel disease - a comprehensive narrative review. Dig Liver Dis 2024; 56 (06) 964-970
13 Shalaby S, Ronzoni L, Hernandez-Gea V, Valenti L. The genetics of portal hypertension: recent developments and the road ahead. Liver Int 2023; 43 (12) 2592-2603
14 Zhang X, Durham KM, Garza AA, Murali AR. Portal vein thrombosis, hepatic decompensation, and survival in patients with porto-sinusoidal vascular disease and portal hypertension. J Gastroenterol 2023; 58 (03) 268-276
15 Wöran K, Semmler G, Jachs M. et al. Clinical course of porto-sinusoidal vascular disease is distinct from idiopathic noncirrhotic portal hypertension. Clin Gastroenterol Hepatol 2022; 20 (02) e251-e266
16 Sarin SK, Khanna R. Non-cirrhotic portal hypertension. Clin Liver Dis 2014; 18 (02) 451-476
17 Chawla Y, Dilawari JB. Anorectal varices–their frequency in cirrhotic and non-cirrhotic portal hypertension. Gut 1991; 32 (03) 309-311
18 Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 1992; 16 (06) 1343-1349
19 Sarin SK, Shahi HM, Jain M, Jain AK, Issar SK, Murthy NS. The natural history of portal hypertensive gastropathy: influence of variceal eradication. Am J Gastroenterol 2000; 95 (10) 2888-2893
20 Hillaire S, Bonte E, Denninger MH. et al. Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients. Gut 2002; 51 (02) 275-280
21 Siramolpiwat S, Seijo S, Miquel R. et al. Idiopathic portal hypertension: natural history and long-term outcome. Hepatology 2014; 59 (06) 2276-2285
22 Maruyama H, Kondo T, Sekimoto T, Yokosuka O. Differential clinical impact of ascites in cirrhosis and idiopathic portal hypertension. Medicine (Baltimore) 2015; 94 (26) e1056
23 Schouten JNL, Nevens F, Hansen B. et al. Idiopathic noncirrhotic portal hypertension is associated with poor survival: results of a long-term cohort study. Aliment Pharmacol Ther 2012; 35 (12) 1424-1433
24 Martinez-Palli G, Drake BB, Garcia-Pagan JC. et al. Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome. World J Gastroenterol 2005; 11 (43) 6858-6862
25 Babbs C, Warnes TW, Haboubi NY. Non-cirrhotic portal hypertension with hypoxaemia. Gut 1988; 29 (01) 129-131
26 Anand AC, Mukherjee D, Rao KS, Seth AK. Hepatopulmonary syndrome: prevalence and clinical profile. Indian J Gastroenterol 2001; 20 (01) 24-27
27 Sidali S, Spaes Y, El Husseini K. et al. Hepatopulmonary syndrome in patients with porto-sinusoidal vascular disorder: characteristics and outcome. JHEP Rep Innov Hepatol 2024; 7 (04) 101310
28 Gioia S, Nardelli S, Pasquale C. et al. Natural history of patients with non cirrhotic portal hypertension: comparison with patients with compensated cirrhosis. Dig Liver Dis 2018; 50 (08) 839-844
29 Chang PE, Miquel R, Blanco JL. et al. Idiopathic portal hypertension in patients with HIV infection treated with highly active antiretroviral therapy. Am J Gastroenterol 2009; 104 (07) 1707-1714
30 Naber AH, Van Haelst U, Yap SH. Nodular regenerative hyperplasia of the liver: an important cause of portal hypertension in non-cirrhotic patients. J Hepatol 1991; 12 (01) 94-99
31 Mahamid J, Miselevich I, Attias D, Laor R, Zuckerman E, Shaoul R. Nodular regenerative hyperplasia associated with idiopathic thrombocytopenic purpura in a young girl: a case report and review of the literature. J Pediatr Gastroenterol Nutr 2005; 41 (02) 251-255
32 Seiderer J, Zech CJ, Diebold J. et al. Nodular regenerative hyperplasia: a reversible entity associated with azathioprine therapy. Eur J Gastroenterol Hepatol 2006; 18 (05) 553-555
33 Rha SE, Lee MG, Lee YS. et al. Nodular regenerative hyperplasia of the liver in Budd-Chiari syndrome: CT and MR features. Abdom Imaging 2000; 25 (03) 255-258
34 Horita T, Tsutsumi A, Takeda T. et al. Significance of magnetic resonance imaging in the diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus: a case report and review of the literature. Lupus 2002; 11 (03) 193-196
35 Isobe Y, Yamasaki T, Yokoyama Y, Kurokawa F, Hino K, Sakaida I. Hepatocellular carcinoma developing six and a half years after a diagnosis of idiopathic portal hypertension. J Gastroenterol 2007; 42 (05) 407-409
36 Hidaka H, Ohbu M, Kokubu S, Shibuya A, Saigenji K, Okayasu I. Hepatocellular carcinoma associated with idiopathic portal hypertension: review of large nodules in seven non-cirrhotic portal hypertensive livers. J Gastroenterol Hepatol 2005; 20 (03) 493-494
37 Bernard PH, Le Bail B, Cransac M. et al. Progression from idiopathic portal hypertension to incomplete septal cirrhosis with liver failure requiring liver transplantation. J Hepatol 1995; 22 (04) 495-499
38 Isabel Fiel M, Thung SN, Hytiroglou P, Emre S, Schiano TD. Liver failure and need for liver transplantation in patients with advanced hepatoportal sclerosis. Am J Surg Pathol 2007; 31 (04) 607-614
39 Cazals-Hatem D, Hillaire S, Rudler M. et al. Obliterative portal venopathy: portal hypertension is not always present at diagnosis. J Hepatol 2011; 54 (03) 455-461
40 Pugliese N, De Nicola S, di Tommaso L, Aghemo A. Beyond portal hypertension: characterizing porto-sinusoidal vascular disorder in patients without signs of PH. J Hepatol 2025
41 Cerda Reyes E, González-Navarro EA, Magaz M. et al. Autoimmune biomarkers in porto-sinusoidal vascular disease: potential role in its diagnosis and pathophysiology. Liver Int 2021; 41 (09) 2171-2178
42 Semmler G, Petrenko O, Lozano JJ. et al. Metabolomic profiles differentiate between porto-sinusoidal vascular disorder, cirrhosis, and healthy individuals. JHEP Rep Innov Hepatol 2024; 6 (12) 101208
43 Seijo S, Lozano JJ, Alonso C. et al. Metabolomics discloses potential biomarkers for the noninvasive diagnosis of idiopathic portal hypertension. Am J Gastroenterol 2013; 108 (06) 926-932
44 Goel A, Ramakrishna B, Muliyil J. et al. Use of serum vitamin B12 level as a marker to differentiate idiopathic noncirrhotic intrahepatic portal hypertension from cryptogenic cirrhosis. Dig Dis Sci 2013; 58 (01) 179-187
45 Mackie I, Eapen CE, Neil D. et al. Idiopathic noncirrhotic intrahepatic portal hypertension is associated with sustained ADAMTS13 deficiency. Dig Dis Sci 2011; 56 (08) 2456-2465
46 Hernández-Gea V, Campreciós G, Betancourt F. et al. Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease. J Hepatol 2021; 75 (04) 924-934
47 Moga L, Paradis V, Ferreira-Silva J. et al; ERN RARE-LIVER; a study of VALDIG, an EASL consortium. Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder. Hepatology 2025; 81 (02) 546-559
48 Sarin SK, Sethi KK, Nanda R. Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis. Gut 1987; 28 (03) 260-266
49 Ohnishi K, Sato S, Nomura F, Iida S. Splanchnic hemodynamics in idiopathic portal hypertension: comparison with chronic persistent hepatitis. Am J Gastroenterol 1989; 84 (04) 403-408
50 Okuda K, Kono K, Ohnishi K. et al. Clinical study of eighty-six cases of idiopathic portal hypertension and comparison with cirrhosis with splenomegaly. Gastroenterology 1984; 86 (04) 600-610
51 Futagawa S, Fukazawa M, Musha H. et al. Hepatic venography in noncirrhotic idiopathic portal hypertension. Comparison with cirrhosis of the liver. Radiology 1981; 141 (02) 303-309
52 Vuppalanchi R, Mathur K, Pyko M, Samala N, Chalasani N. Liver stiffness measurements in patients with noncirrhotic portal hypertension-the devil is in the details. Hepatology 2018; 68 (06) 2438-2440
53 Seijo S, Reverter E, Miquel R. et al. Role of hepatic vein catheterisation and transient elastography in the diagnosis of idiopathic portal hypertension. Dig Liver Dis 2012; 44 (10) 855-860
54 Hernández-Gea V, Baiges A, Turon F, Garcia-Pagán JC. Idiopathic portal hypertension. Hepatology 2018; 68 (06) 2413-2423
55 de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C. Baveno VII Faculty. Baveno VII - renewing consensus in portal hypertension. J Hepatol 2022; 76 (04) 959-974
56 Lampichler K, Semmler G, Wöran K. et al. Imaging features facilitate diagnosis of porto-sinusoidal vascular disorder. Eur Radiol 2023; 33 (02) 1422-1432
57 Elkrief L, Lazareth M, Chevret S. et al; ANRS CO12 CirVir Group. Liver stiffness by transient elastography to detect porto-sinusoidal vascular liver disease with portal hypertension. Hepatology 2021; 74 (01) 364-378
58 Guido M, Sarcognato S, Sonzogni A. et al. Obliterative portal venopathy without portal hypertension: an underestimated condition. Liver Int 2016; 36 (03) 454-460
59 Noble S, Linz M, Correia E, Shalaby A, Bittencourt LK, Sclair SN. Porto-sinusoidal vascular disease and portal hypertension. Clin Liver Dis 2024; 28 (03) 455-466
60 Sarin SK, Gupta N, Jha SK. et al. Equal efficacy of endoscopic variceal ligation and propranolol in preventing variceal bleeding in patients with noncirrhotic portal hypertension. Gastroenterology 2010; 139 (04) 1238-1245
61 Noronha Ferreira C, Seijo S, Plessier A. et al. Natural history and management of esophagogastric varices in chronic noncirrhotic, nontumoral portal vein thrombosis. Hepatology 2016; 63 (05) 1640-1650
62 Shalaby S, Miraglia R, Senzolo M. Transjugular intrahepatic portosystemic shunt in nonmalignant noncirrhotic portal vein thrombosis and portosinusoidal vascular disorder. J Clin Med 2024; 13 (05) 1412
63 Bissonnette J, Garcia-Pagán JC, Albillos A. et al. Role of the transjugular intrahepatic portosystemic shunt in the management of severe complications of portal hypertension in idiopathic noncirrhotic portal hypertension. Hepatology 2016; 64 (01) 224-231
64 Sharma BC, Singh RP, Chawla YK. et al. Effect of shunt surgery on spleen size, portal pressure and oesophageal varices in patients with non-cirrhotic portal hypertension. J Gastroenterol Hepatol 1997; 12 (08) 582-584
65 Karagul S, Yagci MA, Tardu A. et al. Portosystemic shunt surgery in patients with idiopathic noncirrhotic portal hypertension. Ann Transplant 2016; 21: 317-320
66 Ozturk O, Eldem G, Peynircioglu B. et al. Outcomes of partial splenic embolization in patients with massive splenomegaly due to idiopathic portal hypertension. World J Gastroenterol 2016; 22 (43) 9623-9630
67 Magaz M, Giudicelli-Lett H, Nicoară-Farcău O. et al. Liver transplantation for porto-sinusoidal vascular liver disorder: long-term outcome. Transplantation 2023; 107 (06) 1330-1340