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Magaz M, Giudicelli-Lett H, Abraldes JG, Nicoară-Farcău O, Turon F, Rajoriya N, Goel A, Raymenants K, Hillaire S, Téllez L, Elkrief L, Procopet B, Orts L, Nery F, Shukla A, Larrue H, Degroote H, Aguilera V, Llop E, Turco L, Indulti F, Gioia S, Tosetti G, Bitto N, Becchetti C, Alvarado E, Roig C, Diaz R, Praktiknjo M, Konicek AL, Olivas P, Fortea JI, Masnou H, Puente Á, Ardèvol A, Navascués CA, Romero-Gutiérrez M, Scheiner B, Semmler G, Mandorfer M, Damião F, Baiges A, Ojeda A, Simón-Talero M, González-Alayón C, Díaz A, García-Criado Á, De Gottardi A, Hernández-Guerra M, Genescà J, Drilhon N, Noronha Ferreira C, Reiberger T, Rodríguez M, Morillas RM, Crespo J, Trebicka J, Bañares R, Villanueva C, Berzigotti A, Primignani M, La Mura V, Riggio O, Schepis F, Verhelst X, Calleja JL, Bureau C, Albillos A, Nevens F, Hernández-Gea V, Tripathi D, Rautou PE, García-Pagán JC. Porto-sinusoidal vascular liver disorder with portal hypertension: Natural history and long-term outcome. J Hepatol 2025; 82:72-83. [PMID: 39181213 DOI: 10.1016/j.jhep.2024.07.035] [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: 10/30/2023] [Revised: 07/24/2024] [Accepted: 07/30/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND & AIMS Current knowledge of the natural history of patients with porto-sinusoidal vascular disorder (PSVD) is derived from small studies. The aim of the present study was to determine the natural history of PSVD and prognostic factors in a large multicenter cohort of patients. METHODS We performed a retrospective study on patients with PSVD and signs of portal hypertension (PH) prospectively registered in 27 centers. RESULTS A total of 587 patients were included, median age of 47 years and 38% were women. Four-hundred and one patients had an associated condition, which was graded as severe in 157. Median follow-up was 68 months. At diagnosis, 64% of patients were asymptomatic while 36% had a PH-related complication: PH-related bleeding in 112 patients, ascites in 117, and hepatic encephalopathy in 11. In those not presenting with bleeding, the incidence of first bleeding was 15% at 5 years, with a 5-year rebleeding rate of 18%. The 5-year cumulative incidence of new or worsening ascites was 18% and of developing portal vein thrombosis was 16%. Fifty (8.5%) patients received a liver transplantation and 109 (19%) died, including 55 non-liver-related deaths. Transplant-free survival was 97% and 83% at 1 and 5 years, respectively. Variables independently associated with transplant-free survival were age, ascites, serum bilirubin, albumin and creatinine levels at diagnosis and severe associated conditions. This allowed for the creation of a nomogram that accurately predicted prognosis. CONCLUSIONS The prognosis of PSVD is strongly determined by the severity of the associated underlying conditions and parameters of liver and renal function. IMPACT AND IMPLICATIONS Porto-sinusoidal vascular liver disorder (PSVD) is a rare entity that usually affects young people, frequently causes severe complications of portal hypertension, and may reduce life expectancy. To date, there is scarce information regarding its clinical manifestations, natural history and prognostic factors. The present study, including the largest number of patients with PSVD reported so far, shows that overall, when managed at centers of expertise, the prognosis of patients with PSVD is good, with LT-free survival rates of 83% and 72% at 5 and 10 years, respectively. Presence and severity of an underlying associated condition, presence of ascites, age and bilirubin, albumin and creatinine levels were associated with poor prognosis. These results are important to know for hepatologists. A final model combining these parameters enabled development of a nomogram that predicts prognosis with good discrimination and calibration capacity and can be easily applied in clinical practice.
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Affiliation(s)
- Marta Magaz
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Heloïse Giudicelli-Lett
- Université de Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France; AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Oana Nicoară-Farcău
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Neil Rajoriya
- The Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
| | - Ashish Goel
- The Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
| | - Karlien Raymenants
- Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven, Belgium
| | - Sophie Hillaire
- Université de Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France; AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Luis Téllez
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERehd, Universidad de Alcalá, Madrid, Spain
| | - Laure Elkrief
- Université de Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France; Service d'Hépato-Gastroentérologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland; Service d'Hépato-Gastroentérologie, CHU de Tours, France
| | - Bogdan Procopet
- Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Hepatology Department and "Iuliu Hatieganu" University of Medicine and Pharmacy, 3rd Medical Clinic, Cluj-Napoca, Romania
| | - Lara Orts
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Filipe Nery
- Immuno-Physiology and Pharmacology Department, School of Medicine and Biomedical Sciences, University of Porto, Portugal
| | - Akash Shukla
- Seth GS Medical College and KEM Hospital, Sion, Mumbai, India
| | - Hélène Larrue
- Department of Hepatology, Rangueil Hospital, CHU Toulouse, University Paul Sabatier of Toulouse, France
| | - Helena Degroote
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Victoria Aguilera
- Liver Transplantation and Hepatology Unit, Hospital Universitari i Politécnic La Fe, Valencia, Spain. CIBERehd (Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Valencia Spain), Instituto de Salud Carlos III, Spain
| | - Elba Llop
- Liver Unit, Hospital U, Puerta de Hierro. Universidad Autònoma de Madrid, CIBEREHD, IDIPHISA, Madrid, Spain
| | - Laura Turco
- Department of Gastroenterology and Hepatology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
| | - Federica Indulti
- Department of Gastroenterology and Hepatology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giulia Tosetti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine -Hemostasis and Thrombosis, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Niccolò Bitto
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine -Hemostasis and Thrombosis, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Chiara Becchetti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Edilmar Alvarado
- Liver Unit, Department of Gastroenterology Hospital Sant Pau, Barcelona, Autonomous University, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Cristina Roig
- Liver Unit, Department of Gastroenterology Hospital Sant Pau, Barcelona, Autonomous University, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Raquel Diaz
- Department of Gastroenterology and Hepatology, University Gregorio Marañón Hospital, liSGM, CIBERehd, Barcelona, Spain; Facultad de Medicina. Universidad Complutense de Madrid, Madrid, Spain
| | - Michael Praktiknjo
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Anna-Lena Konicek
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Pol Olivas
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - José Ignacio Fortea
- Liver Unit, Digestive Disease Department, Marqués de Valdecilla University Hospital, Santander, Cantabria University, Spain
| | - Helena Masnou
- Liver Unit, University Hospital Germans Trias i Pujol, Badalona, Spain. Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Spain
| | - Ángela Puente
- Liver Unit, Digestive Disease Department, Marqués de Valdecilla University Hospital, Santander, Cantabria University, Spain
| | - Alba Ardèvol
- Liver Unit, University Hospital Germans Trias i Pujol, Badalona, Spain. Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Spain
| | - Carmen A Navascués
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Marta Romero-Gutiérrez
- Liver Unit, Department of Gastroenterology and Hepatology, Complejo Hospitalario Universitario de Toledo, Spain
| | - Bernhard Scheiner
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Filipe Damião
- Department of Gastroenterology and Hepatology, Hospital de Santa Maria - Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Anna Baiges
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Asunción Ojeda
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Macarena Simón-Talero
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebrón, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBERehd, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Carlos González-Alayón
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario de Canarias. Tenerife, Spain
| | - Alba Díaz
- Department of Histopathology, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | | | - Andrea De Gottardi
- Dept. of Gastroenterology and Hepatology, Cantonal Hospital Lucerne, University of Lucerne, Switzerland
| | - Manuel Hernández-Guerra
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario de Canarias. Tenerife, Spain
| | - Joan Genescà
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebrón, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBERehd, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Nicolas Drilhon
- Université de Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France; AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Carlos Noronha Ferreira
- Department of Gastroenterology and Hepatology, Hospital de Santa Maria - Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Manuel Rodríguez
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Rosa María Morillas
- Liver Unit, University Hospital Germans Trias i Pujol, Badalona, Spain. Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Spain
| | - Javier Crespo
- Liver Unit, Digestive Disease Department, Marqués de Valdecilla University Hospital, Santander, Cantabria University, Spain
| | - Jonel Trebicka
- Hepatology, Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany; European Foundation for Study of Chronic Liver Failure, Barcelona, Spain
| | - Rafael Bañares
- Department of Gastroenterology and Hepatology, University Gregorio Marañón Hospital, liSGM, CIBERehd, Barcelona, Spain
| | - Càndid Villanueva
- Liver Unit, Department of Gastroenterology Hospital Sant Pau, Barcelona, Autonomous University, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Massimo Primignani
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine -Hemostasis and Thrombosis, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Vincenzo La Mura
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine -Hemostasis and Thrombosis, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Filippo Schepis
- Department of Gastroenterology and Hepatology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - José Luis Calleja
- Liver Unit, Hospital U, Puerta de Hierro. Universidad Autònoma de Madrid, CIBEREHD, IDIPHISA, Madrid, Spain
| | - Christophe Bureau
- Department of Hepatology, Rangueil Hospital, CHU Toulouse, University Paul Sabatier of Toulouse, France
| | - Agustín Albillos
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERehd, Universidad de Alcalá, Madrid, Spain
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven, Belgium
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain
| | - Dhiraj Tripathi
- The Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
| | - Pierre-Emmanuel Rautou
- Université de Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France; AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Juan Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Barcelona, Spain.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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Nie Q, Liang Q, Li M, Zhu R, Ren J, Jiang K, Li J. Idiopathic non-cirrhotic portal hypertension: A case report. Medicine (Baltimore) 2024; 103:e40642. [PMID: 39705493 DOI: 10.1097/md.0000000000040642] [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: 12/22/2024] Open
Abstract
RATIONALE Idiopathic noncirrhotic portal hypertension (INCPH) is a rare liver disorder with elevated portal pressure without cirrhosis, making diagnosis challenging. This case report presents a 46-year-old Chinese male with INCPH, highlighting the crucial role of liver biopsy. PATIENT CONCERNS A 46-year-old male presented with persistent fatigue that lasted for 2 months and significantly worsened over the last 3 days. The patient described his fatigue as a profound lack of energy that persisted throughout the day, which progressively impaired his ability to perform daily activities and maintain his usual work responsibilities. He reported feeling exhausted even after light physical exertion, such as walking or standing for short periods. The severity of the fatigue also led to frequent short rests during the day, and he experienced difficulty concentrating and carrying out routine tasks. In addition, he noted a loss of appetite and mild discomfort in the upper abdomen. Given his previous history of abnormal liver function tests and a liver biopsy showing mild chronic liver damage, the patient was initially diagnosed with cirrhosis at a local hospital. This initial diagnosis caused significant emotional distress, as the patient experienced a state of panic and anxiety over the implications of having a progressive liver disease. The psychological burden was evident in his reported difficulty sleeping and persistent worry about his health and future. DIAGNOSES Initial imaging suggested portal hypertension and cirrhosis, but a liver biopsy ruled out cirrhotic changes, confirming INCPH by excluding other causes such as chronic hepatitis. INTERVENTIONS The patient received symptomatic treatment (acid suppression, gastric and liver protection) and underwent a liver biopsy. Histological analysis confirmed INCPH, ruling out cirrhosis. OUTCOMES After the definitive diagnosis, the patient's anxiety lessened. Fatigue and weakness improved with ongoing symptomatic treatment, and psychological support enhanced his overall well-being. His follow-up plan includes regular liver function monitoring, imaging for portal pressure changes, and potential anticoagulation therapy for thrombosis risks. LESSONS This case highlights the diagnostic difficulty of INCPH and underscores the importance of liver biopsy. Further research is needed to develop specific diagnostic tools and treatments for INCPH.
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Affiliation(s)
- Qilong Nie
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Qiuyan Liang
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Mingyang Li
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Ronghuo Zhu
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Jian Ren
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Kaiping Jiang
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Jianhong Li
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
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Shukla A, Rockey DC, Kamath PS, Kleiner DE, Singh A, Vaidya A, Koshy A, Goel A, Dökmeci AK, Meena B, Philips CA, Sharma CB, Payawal DA, Kim DJ, Lo GH, Han G, Qureshi H, Wanless IR, Jia J, Sollano JD, Al Mahtab M, Muthiah MD, Sonderup MW, Nahum MS, Merican MIB, Ormeci N, Kawada N, Reddy R, Dhiman RK, Gani R, Hameed SS, Harindranath S, Jafri W, Qi X, Chawla YK, Furuichi Y, Zheng MH, Sarin SK. Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management. Hepatol Int 2024; 18:1684-1711. [DOI: https:/doi.org/10.1007/s12072-024-10739-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 09/28/2024] [Indexed: 04/13/2025]
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Shukla A, Rockey DC, Kamath PS, Kleiner DE, Singh A, Vaidya A, Koshy A, Goel A, Dökmeci AK, Meena B, Philips CA, Sharma CB, Payawal DA, Kim DJ, Lo GH, Han G, Qureshi H, Wanless IR, Jia J, Sollano JD, Al Mahtab M, Muthiah MD, Sonderup MW, Nahum MS, Merican MIB, Ormeci N, Kawada N, Reddy R, Dhiman RK, Gani R, Hameed SS, Harindranath S, Jafri W, Qi X, Chawla YK, Furuichi Y, Zheng MH, Sarin SK. Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management. Hepatol Int 2024; 18:1684-1711. [PMID: 39546143 DOI: 10.1007/s12072-024-10739-6] [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: 06/17/2024] [Accepted: 09/28/2024] [Indexed: 11/17/2024]
Abstract
Since the Asian Pacific Association for the Study of the Liver (APASL) published guidelines on non-cirrhotic portal fibrosis/idiopathic portal hypertension in 2007, there has been a surge in new information, especially with the introduction of the term porto-sinusoidal vascular disorder (PSVD). Non-cirrhotic intra-hepatic causes of portal hypertension include disorders with a clearly identifiable etiology, such as schistosomiasis, as well as disorders with an unclear etiology such as non-cirrhotic portal fibrosis (NCPF), also termed idiopathic portal hypertension (IPH). This entity is being increasingly recognized as being associated with systemic disease and drug therapy, especially cancer therapy. An international working group with extensive expertise in portal hypertension was assigned with formulating consensus guidelines to clarify the definition, diagnosis, histological features, natural history, and management of NCPF/IPH, especially in the context of PSVD. The guidelines were prepared based on evidence from existing published literature. Whenever there was paucity of evidence, expert opinion was included after detailed deliberation. The goal of this manuscript, therefore, is to enhance the current understanding and help create global consensus on the issues surrounding NCPF/IPH.
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Affiliation(s)
- Akash Shukla
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 803, MSC 623, Charleston, SC, 29425, USA
| | | | | | - Ankita Singh
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Arun Vaidya
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Abraham Koshy
- Department of Gastroenterology, VPS Lakeshore Hospital, Kochi, Kerala, India
| | - Ashish Goel
- Department of Hepatology, CMC, Vellore, India
| | - A Kadir Dökmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Babulal Meena
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Cyriac Abby Philips
- Department of Clinical and Translational Hepatology, The Liver Institute, Rajagiri Hospital, Aluva, Kerala, India
| | - Chhagan Bihari Sharma
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Diana A Payawal
- Fatima University Medical Center Manila, Manila, Philippines
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea
| | - Gin-Ho Lo
- Department of Medical Research, E-Da Hospital, Kaohsiung, School of Medicine for International Students, I-Shou University, 1, Yi-Da Road, Kaohsiung, 824, Taiwan
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | | | - Ian R Wanless
- Department of Pathology, Dalhousie University, Halifax, Canada
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Beijing, Mainland, China
| | - Jose D Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Mendez Sanchez Nahum
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Necati Ormeci
- İstanbul Health and Technology University, Istanbul, Turkey
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Rajender Reddy
- Division of Gastroenterology and Hepatology, 2 Dulles, Liver Transplant Office, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - R K Dhiman
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Rino Gani
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Saeed S Hameed
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Sidharth Harindranath
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Wasim Jafri
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
| | - Yogesh Kumar Chawla
- Department of Hepatology and Gastroenterology, Kalinga Institute of MedicalSciences, KIIT University, Bhubaneshwar, India
| | - Yoshihiro Furuichi
- Department of Clinical Laboratory and Endoscopy, Tokyo Women's Medical University, Adachi Medical Center, Tokyo, Japan
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, 325000, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
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Premkumar M, Anand AC. Porto-sinusoidal Vascular Disease: Classification and Clinical Relevance. J Clin Exp Hepatol 2024; 14:101396. [PMID: 38601747 PMCID: PMC11001647 DOI: 10.1016/j.jceh.2024.101396] [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: 12/10/2023] [Accepted: 03/05/2024] [Indexed: 04/12/2024] Open
Abstract
Non-cirrhotic portal hypertension (NCPH) is a well-recognized clinico-pathological entity, which is associated with clinical signs and symptoms, imaging, and endoscopic features of portal hypertension (PHT), in absence of cirrhosis. In patients with NCPH without known risk factors of PHT or extrahepatic portal vein thrombosis, the condition is called idiopathic non-cirrhotic portal hypertension (INCPH). There are multiple infectious, immune related causes, systemic diseases, drug and toxin exposures, haematological disorders, and metabolic risk factors that have been associated with this INCPH. However, the causal pathogenesis is still unclear. The Vascular liver disorders interest group group recently proposed porto-sinusoidal vascular disease (PSVD) as a syndromic entity, which provides definite histopathological criteria for diagnosis of NCPH (table 1). The three classical histo-morphological lesions specific for PSVD include obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. The PSVD definition includes patients with portal vein thrombosis, PVT, and even those without PHT, thus broadening the scope of diagnosis to include patients who may have presented early, prior to haemodynamic changes consistent with PHT. However, this new diagnosis has pros and cons. The cons include mandating invasive liver biopsy to assess the PSVD histological triad in all patients with NCPH, an erstwhile clinical diagnosis in Asian patients. In addition, the natural history of the subclinical forms of PSVD without PHT and linear progression to develop PHT is unknown yet. In this review, we discuss the diagnosis and treatment of INCPH/PSVD, fallacies and strengths of the old and new schema, pathobiology of this disease, and clinical correlates in an Asian context. Although formulation of standardised diagnostic criteria is useful for comparison of clinical cohorts with INCPH/PSVD, prospective clinical validation in global cohorts is necessary to avoid misclassification of vascular disorders of the liver.
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anil C. Anand
- Department of Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, Odisha, India
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Yamamoto H, Taniguchi Y. Idiopathic portal hypertension as a cause of hepatic dysfunction and ascites in antisynthetase syndrome. Int J Rheum Dis 2024; 27:e15249. [PMID: 39078100 DOI: 10.1111/1756-185x.15249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/17/2024] [Accepted: 06/21/2024] [Indexed: 07/31/2024]
Affiliation(s)
- Hirotaka Yamamoto
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Kochi University, Nankoku, Kochi, Japan
| | - Yoshinori Taniguchi
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Kochi University, Nankoku, Kochi, Japan
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9
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Noble S, Linz M, Correia E, Shalaby A, Bittencourt LK, Sclair SN. Porto-sinusoidal Vascular Disease and Portal Hypertension. Clin Liver Dis 2024; 28:455-466. [PMID: 38945637 DOI: 10.1016/j.cld.2024.03.004] [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] [Indexed: 07/02/2024]
Abstract
Porto-sinusoidal vascular disease (PSVD) is the medical diagnosis for a patient who has portal hypertension in the absence of cirrhosis on liver biopsy. There are several specific histologic findings for PSVD, including obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. Epidemiologic reports vary widely among regions; PSVD comprises less than 10% of causes of portal hypertension in Western countries but incidence has been found to be as high as 48% in India. There is an expansive list of etiologies that have been reported to cause PSVD.
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Affiliation(s)
- Sarah Noble
- Digestive Health Institute, University Hospitals, Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Marguerite Linz
- Department of Internal Medicine, University Hospitals, Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Eduardo Correia
- Department of Radiology, University Hospitals, Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Akram Shalaby
- Department of Pathology, University Hospitals, Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Leonardo Kayat Bittencourt
- Department of Radiology, University Hospitals, Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Seth N Sclair
- Digestive Health Institute, University Hospitals, Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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10
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Malik A, Malik S, Farooq A, Malik MI, Javaid S. Histopathological features of idiopathic portal hypertension: A systematic review and meta-analysis. Sci Prog 2024; 107:368504241264996. [PMID: 39053026 PMCID: PMC11282518 DOI: 10.1177/00368504241264996] [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] [Indexed: 07/27/2024]
Abstract
BACKGROUND Portal hypertension (PH) is a clinically significant entity that could present with life-threatening gastrointestinal bleeding. Cirrhosis is the most common cause of PH, with well-documented histopathology and etiology. However, in idiopathic portal hypertension (IPH), no single histopathologic finding is associated with PH. Our systematic review aims to identify and summarize the prevalence of the common histological findings of IPH. METHODS We systematically searched PubMed, Cochrane CENTRAL, Web of Science, and Scopus till 1ST March 2022 for studies describing the histopathological features of IPH. Data were extracted from eligible studies and pooled as events rate and 95% confidence interval (CI) using binary random-effects model by open meta-analyst software. RESULTS We included 23 retrospective studies with a total sample size of 813 patients. The overall incidence of nodular regenerative hyperplasia was 38.6%, 59.8% for portal fibrosis, 51.3% for periportal fibrosis, 39.3% for perisinusoidal fibrosis, 89.8% for portal vein sclerosis, 42.2% for portal inflammation, 53.3% for mega-sinusoids, 39.5% for thickening of portal vein branches, 93.8% for narrowing of portal veins, 53.3% for hepatic veins/venous outflow obstruction, 51.4% for aberrant portal/periportal vessels, 42.4% for shunt vessel, 50.9% for ductular proliferation, and 16.3% for steatosis. CONCLUSION Due to the relatively non-pathognomonic and non-specific nature of IPH, a combination of different histological features such as the portal and periportal fibrosis, portal vein sclerosis, mega-sinusoids, narrowing of portal veins, hepatic venous outflow obstruction, aberrant portal or periportal vessels, and ductular proliferation may be of value in diagnosing IPH as the incidence rate of these features was at approximately 50%.
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Affiliation(s)
- Adnan Malik
- Mountain Vista Medical Center, Midwestern University Program, Mesa AZ, USA
| | - Sohira Malik
- Penn State College of Medicine, Hershey, PA, USA
| | - Ahsan Farooq
- Penn State College of Medicine, Hershey, PA, USA
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11
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Büyük M, Berker N, Bakkaloğlu DV, Şenkal İV, Önal Z, Güllüoğlu M. Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH). Hepatol Int 2024; 18:1011-1019. [PMID: 38536628 PMCID: PMC11126445 DOI: 10.1007/s12072-024-10654-w] [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: 12/06/2023] [Accepted: 01/26/2024] [Indexed: 05/25/2024]
Abstract
AIM Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. MATERIALS AND METHODS Hematoxylin-eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. RESULTS In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). CONCLUSION In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.
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Affiliation(s)
- Melek Büyük
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey.
| | - Neslihan Berker
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
| | - Doğu Vurallı Bakkaloğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
| | - İbrahim Volkan Şenkal
- Department of Gastroenterology and Hepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Zerrin Önal
- Department of Pediatric Gastroenterology, Hepatology and Nutrition Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
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12
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Miyazawa M, Yanagi M, Chiba T, Kido H, Matsuo T, Nishitani M, Orita N, Takata N, Hayashi T, Seki A, Nakagawa H, Nio K, Terashima T, Iida N, Yamada S, Takatori H, Shimakami T, Arai K, Yamashita T, Mizukoshi E, Honda M, Yamashita T. Post-allogeneic Hematopoietic Stem Cell Transplantation Portal Hypertension Not Associated with Liver Cirrhosis, Veno-occlusive Disease, or Graft-versus-host Disease. Intern Med 2024; 63:1563-1568. [PMID: 37839881 PMCID: PMC11189707 DOI: 10.2169/internalmedicine.2489-23] [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: 06/26/2023] [Accepted: 08/30/2023] [Indexed: 10/17/2023] Open
Abstract
We herein report a rare case of idiopathic portal hypertension (IPH)-like disease that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A 53-year-old woman who underwent allo-HSCT for acute myeloid leukemia showed portal hypertension with radiological and histopathological findings consistent with IPH, distinct from veno-occlusive disease (VOD) and graft-versus-host disease (GVHD) of the liver. This case highlights the importance of considering IPH-like disease as a potential cause of portal hypertension after allo-HSCT. Awareness of this complication can aid in the early diagnosis and appropriate management of patients post allo-HSCT.
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Affiliation(s)
- Masaki Miyazawa
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Masahiro Yanagi
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Tomoyoshi Chiba
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Hidenori Kido
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Toshiki Matsuo
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Masaki Nishitani
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Noriaki Orita
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Noboru Takata
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Tomoyuki Hayashi
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Akihiro Seki
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | | | - Kouki Nio
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | | | - Noriho Iida
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Shinya Yamada
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Hajime Takatori
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | | | - Kuniaki Arai
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | | | | | - Masao Honda
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Taro Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Japan
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13
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Gioia S, De Santis A, d'Amati G, Nardelli S, Spagnoli A, Rocco AD, Ridola L, Riggio O. Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis. Hepatobiliary Pancreat Dis Int 2024; 23:20-24. [PMID: 37468349 DOI: 10.1016/j.hbpd.2023.07.001] [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: 11/19/2022] [Accepted: 07/05/2023] [Indexed: 07/21/2023]
Abstract
BACKGROUND Porto-sinusoidal vascular disease (PSVD) and portal vein thrombosis (PVT) are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system. As PVT may be a consequence of PSVD, in PVT patients at presentation, a pre-existing PSVD should be suspected. In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management, but it could be challenging. In this setting ultrasonography may be valuable in differential diagnosis. The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and "pure" PVT and then to suspect PVT secondary to a pre-existing PSVD. METHODS Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse (ARFI). RESULTS ARFI was higher and superior mesenteric vein (SMV) diameter was wider in PSVD patients than in PVT patients. Thus, a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT (the area under the curve = 0.780; 95% confidence interval: 0.690-0.869). CONCLUSIONS A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.
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Affiliation(s)
- Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
| | - Adriano De Santis
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giulia d'Amati
- Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Alessandra Spagnoli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Arianna Di Rocco
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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14
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Campreciós G, Vilaseca M, Tripathi DM, Montironi C, Díaz A, Aguilar D, García-Calderó H, Montañés R, Anton A, Hernández-Gea V, García-Pagán JC. Interspecies transcriptomic comparison identifies a potential porto-sinusoidal vascular disorder rat model suitable for in vivo drug testing. Liver Int 2024; 44:180-190. [PMID: 37872644 DOI: 10.1111/liv.15765] [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: 06/29/2023] [Revised: 09/21/2023] [Accepted: 10/09/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND Porto-sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life-threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease. METHODS We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium-enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data. RESULTS All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD-specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model. CONCLUSIONS The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition.
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Affiliation(s)
- Genís Campreciós
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Marina Vilaseca
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Dinesh M Tripathi
- Liver Physiology & Vascular Biology Group, Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences (ILBS), Vasant Kunj, New Delhi, India
| | - Carla Montironi
- Pathology Department & Molecular Biology Core, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Alba Díaz
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Pathology Department, Biomedical Diagnostic Centre, Hospital Clínic Barcelona, Barcelona, Catalonia, Spain
| | - Daniel Aguilar
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Héctor García-Calderó
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Rosa Montañés
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Aina Anton
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Medicine Department, Faculty of Medicine, University of Barcelona, Barcelona, Catalonia, Spain
| | - Joan Carles García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Medicine Department, Faculty of Medicine, University of Barcelona, Barcelona, Catalonia, Spain
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15
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Jafari P, Evaristo G, Du XA, Sharma AE, Marcus V, Liu X, Zhao L, Westerhoff M, Hart J. Portosinusoidal Vascular Disorder: A Heretofore Unrecognized Manifestation of Sickle Cell Disease? Mod Pathol 2024; 37:100351. [PMID: 37820763 DOI: 10.1016/j.modpat.2023.100351] [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: 07/09/2023] [Revised: 09/10/2023] [Accepted: 10/04/2023] [Indexed: 10/13/2023]
Abstract
Portosinusoidal vascular disorder (PSVD) is a recently proposed histopathologic entity that encompasses a spectrum of often subtle hepatic microvascular lesions and related microarchitectural abnormalities. Clinical manifestations may arise years after histologic diagnosis and include extrahepatic portal vein thrombosis and portal hypertension. While the histopathologic features of PSVD have been associated with numerous clinical conditions, most notably prothrombotic/vasculopathic disorders, PSVD has not yet been described in sickle cell disease. This gap is striking given the central role of microvascular dysfunction in sickle cell disease and well-described patterns of hepatic injury and dysfunction in this population. This case series is the first to explore the prevalence and pathogenesis of PSVD in sickle cell disease. Forty-one diagnostically adequate liver biopsies from patients with sickle cell disease were identified across the archives of 5 tertiary medical centers. All biopsies exhibited at least 1 histopathologic feature associated with PSVD (mean 3.8 features/case). Overall, 90.2% of patients met the criteria for a diagnosis of PSVD based on the presence of specific histopathologic and/or clinical findings. Immunohistochemical stains for von Willebrand factor, CD34, and glutamine synthetase were performed on 36 cases (87.8%). Aberrant (centrilobular sinusoidal) CD34 and von Willebrand factor staining was present in 97.2% and 86.1% of cases, respectively. Glutamine synthetase reactivity was at least mildly decreased in zone 3 hepatocytes in 52.8% of cases. We posit that chronic erythrocyte sickling results in dysfunction and remodeling of the portal microvasculature, culminating in regression of zone 3 hepatocytes. The presence of PSVD may explain, at least in part, the hepatic dysfunction observed in this patient population. These patients may also benefit from extended clinical surveillance for portal hypertension and other complications. While subtle and prone to overdiagnosis, the features of PSVD should be carefully considered when interpreting liver biopsies from patients with sickle cell disease.
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Affiliation(s)
- Pari Jafari
- Department of Pathology, University of Chicago Medicine, The University of Chicago, Chicago, Illinois.
| | - Gertruda Evaristo
- Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Xiaotang Alison Du
- Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Aarti E Sharma
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Victoria Marcus
- Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Xiuli Liu
- Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri
| | - Lei Zhao
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Maria Westerhoff
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
| | - John Hart
- Department of Pathology, University of Chicago Medicine, The University of Chicago, Chicago, Illinois
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16
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17
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Campreciós G, Bartrolí B, Montironi C, Belmonte E, García-Pagán JC, Hernández-Gea V. Porto-sinusoidal vascular disorder. SINUSOIDAL CELLS IN LIVER DISEASES 2024:445-464. [DOI: 10.1016/b978-0-323-95262-0.00022-x] [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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18
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Shalaby S, Ronzoni L, Hernandez-Gea V, Valenti L. The genetics of portal hypertension: Recent developments and the road ahead. Liver Int 2023; 43:2592-2603. [PMID: 37718732 DOI: 10.1111/liv.15732] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/07/2023] [Accepted: 09/02/2023] [Indexed: 09/19/2023]
Abstract
Portal hypertension (PH), defined as a pathological increase in the portal vein pressure, has different aetiologies and causes. Intrahepatic PH is mostly secondary to the presence of underlying liver disease leading to cirrhosis, characterized by parenchymal changes with deregulated accumulation of extracellular matrix and vascular abnormalities; liver sinusoidal endothelial cells and hepatic stellate cells are key players in PH progression, able to influence each other. However, PH may also develop independently of parenchymal damage, as occur in portosinusoidal vascular disorder (PSVD), a group of clinical and histological entities characterized by portal vasculature dysfunctions. In this particular group of disorders, the pathophysiology of PH is still poorly understood. In the last years, several genetic studies, based on genome-wide association studies or whole-exome sequencing analysis, have highlighted the importance of genetic heritability in PH pathogenesis, both in cirrhotic and non-cirrhotic cases. The common PNPLA3 p.I148M variant, one of the main determinants of the susceptibility to steatotic liver disease, has also been associated with decompensation in patients with PH. Genetic variations at loci influencing coagulation, mainly the ABO locus, may directly contribute to the pathogenesis of PH. Rare genetic variants have been associated with familiar cases of progressive PSVD. In this review, we summarize the recent knowledges on genetic variants predisposing to PH development, contributing to better understand the role of genetic factors in PH pathogenesis.
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Grants
- Commissioner for Universities and Research from the Department of Economy and Knowledge" of the "Generalitat de Catalunya" (AGAUR SGR2017_517) (VHG)
- Fondazione Patrimonio Ca' Granda, "Liver BIBLE" (PR-0361) (LV)
- Gilead_IN-IT-989-5790 (LV)
- Innovative Medicines Initiative 2 joint undertaking of European Union's Horizon 2020 research and innovation programme and EFPIA European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS (LV)
- Instituto de Salud Carlos III" FIS PI20/00569 FEDER from the European Union (Fondos FEDER, "Una manera de hacer Europa") (VHG)
- Italian Ministry of Health (Ministero della Salute), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Ricerca Corrente (LV)
- Italian Ministry of Health (Ministero della Salute), Rete Cardiologica "CV-PREVITAL" (LV)
- Italian Ministry of Health (Ministero della Salute), Ricerca Finalizzata 2016, RF-2016-02364358 ("Impact of whole exome sequencing on the clinical management of patients with advanced nonalcoholic fatty liver and cryptogenic liver disease"), Ricerca Finalizzata 2021 RF-2021-12373889, Italian Ministry of Health, Ricerca Finalizzata PNRR 2022 "RATIONAL: Risk strAtificaTIon Of Nonalcoholic fAtty Liver" PNRR-MAD-2022-12375656 (LV)
- Italian Ministry of Health (Ministero della Salute). PNRR PNC-E3-2022-23683266 PNC-HLS-DA, INNOVA (LV)
- The European Union, H2020-ICT-2018-20/H2020-ICT-2020-2 programme "Photonics" under grant agreement No. 101016726 - REVEAL (LV)
- The European Union, HORIZON-MISS-2021-CANCER-02-03 programme "Genial" under grant agreement "101096312" (LV)
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Affiliation(s)
- Sarah Shalaby
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, CIBEREHD, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain
- Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Padua, Italy
| | - Luisa Ronzoni
- Precision Medicine Lab, Biological Resource Center Unit, Department of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, CIBEREHD, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain
| | - Luca Valenti
- Precision Medicine Lab, Biological Resource Center Unit, Department of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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19
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Barisic-Jaman M, Milosevic M, Pastrovic F, Skrtic A, Grgurevic I. Porto-sinusoidal vascular disease: a new definition of an old clinical entity. Clin Exp Hepatol 2023; 9:297-306. [PMID: 38774199 PMCID: PMC11103802 DOI: 10.5114/ceh.2023.133107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/23/2023] [Indexed: 05/24/2024] Open
Abstract
Porto-sinusoidal vascular disease (PSVD) is defined as a vascular liver disease characterized by the absence of cirrhosis and the presence of characteristic histological features, with or without the presence of portal hypertension (PH). Half of the patients with PSVD also have associated disease that may contribute to the development of PSVD. Patients usually remain asymptomatic until complications of PH arise. Variceal bleeding and portal vein thrombosis are major complications associated with PSVD. The treatment is focused on managing complications of PH, mainly through primary prophylaxis of variceal bleeding and treatment of portal vein thrombosis. Currently, there is insufficient evidence to support the use of anticoagulants for thrombosis prevention in these patients. Despite the increase of recognition of PSVD, further research is needed to enable early disease diagnosis, establish optimal screening methods, and develop strategies to slow down disease progression.
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Affiliation(s)
- Mislav Barisic-Jaman
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
| | - Marko Milosevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
| | - Frane Pastrovic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
| | - Anita Skrtic
- Department of Pathology, University Hospital Merkur, Zagreb, Croatia
- University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
- University of Zagreb, School of Medicine, Zagreb, Croatia
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20
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Kagihara JE, Goyes D, Rabiee A. Diagnosis and Management of Noncirrhotic Portal Hypertension. CURRENT HEPATOLOGY REPORTS 2023; 22:252-262. [DOI: 10.1007/s11901-023-00619-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/10/2023] [Indexed: 01/04/2025]
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21
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Baumert LS, Shih A, Chung RT. Management of liver disease and portal hypertension in common variable immunodeficiency (CVID). JHEP Rep 2023; 5:100882. [PMID: 37869072 PMCID: PMC10585302 DOI: 10.1016/j.jhepr.2023.100882] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/30/2023] [Accepted: 07/22/2023] [Indexed: 10/24/2023] Open
Abstract
Patients with common variable immunodeficiency (CVID) frequently develop liver disease and associated complications, which represent an increasingly prevalent unmet medical need. The main hepatic manifestation of CVID is nodular regenerative hyperplasia (NRH), resulting in non-cirrhotic portal hypertension (NCPH). Liver disease is often underdiagnosed, leading to poor outcomes and decreased survival. The increasing numbers of patients with CVID who are diagnosed late with progressive liver disease underscores the importance of appropriate clinical management and treatment of liver complications. At the same time, specific guidelines for the clinical management of CVID-related liver disease are still lacking. Here, we review the epidemiology of CVID-related liver disease, reveal new insights into NRH and NCPH biology and highlight recently uncovered opportunities for NCPH diagnostics in CVID. Finally, we focus on current management of liver disease, portal hypertension and its complications - the key challenge in patients with CVID. Specifically, we review recent data regarding the role of transjugular intrahepatic portosystemic shunt and liver transplantation in clinical management. The role for anticoagulants and immunosuppressants targeting the pathogenesis of NRH will also be discussed. We propose an updated algorithm for the diagnostic work-up and treatment of NCPH in CVID. Finally, we consider future needs and therapeutic opportunities for CVID-related liver disease.
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Affiliation(s)
- Lukas S. Baumert
- Liver Center, Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Faculty of Medicine, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Angela Shih
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raymond T. Chung
- Liver Center, Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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22
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Fiordaliso M, Marincola G, Pala B, Muraro R, Mazzone M, Di Marcantonio MC, Mincione G. A Narrative Review on Non-Cirrohotic Portal Hypertension: Not All Portal Hypertensions Mean Cirrhosis. Diagnostics (Basel) 2023; 13:3263. [PMID: 37892084 PMCID: PMC10606323 DOI: 10.3390/diagnostics13203263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/17/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.
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Affiliation(s)
- Michele Fiordaliso
- Department of Medicine and Ageing Sciences, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy;
| | - Giuseppe Marincola
- Bariatric and Metabolic Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy;
| | - Barbara Pala
- Division of Cardiology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035/1039, 00189 Rome, Italy;
| | - Raffaella Muraro
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Mariangela Mazzone
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Maria Carmela Di Marcantonio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Gabriella Mincione
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
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23
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Lesmana CRA. Endoscopic ultrasound-guided portal pressure gradient measurement in managing portal hypertension. World J Gastrointest Surg 2023; 15:1033-1039. [PMID: 37405096 PMCID: PMC10315130 DOI: 10.4240/wjgs.v15.i6.1033] [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: 10/28/2022] [Revised: 11/30/2022] [Accepted: 04/24/2023] [Indexed: 06/15/2023] Open
Abstract
Portal hypertension (PH) is still a challenging clinical condition due to its silent manifestations in the early stage and needs to be measured accurately for early detection. Hepatic vein pressure gradient measurement has been considered as the gold standard measurement for PH; however, it needs special skill, experience, and high expertise. Recently, there has been an innovative development in using endoscopic ultrasound (EUS) for the diagnosis and management of liver diseases, including portal pressure measurement, which is commonly known as EUS-guided portal pressure gradient (EUS-PPG) measurement. EUS-PPG measurement can be performed concomitantly with EUS evaluation for deep esophageal varices, EUS-guided liver biopsy, and EUS-guided cyanoacrylate injection. However, there are still major issues, such as different etiologies of liver disease, procedural training, expertise, availability, and cost-effectiveness in several situations with regard to the standard management.
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Affiliation(s)
- Cosmas Rinaldi Adithya Lesmana
- Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta 10430, DKI, Indonesia
- Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta 12950, DKI, Indonesia
- Gastrointestinal Cancer Center, MRCCC Siloam Semanggi Hospital, Jakarta 12930, DKI, Indonesia
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24
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Poddar U, Reddy DVU. Non-Cirrhotic Portal Hypertension in Children: Current Management Strategies. CURRENT HEPATOLOGY REPORTS 2023; 22:158-169. [DOI: 10.1007/s11901-023-00608-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/08/2023] [Indexed: 01/05/2025]
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25
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Di Giorgio A, Matarazzo L, Sonzogni A, Nicastro E, Pietrobattista A, Cananzi M, Gaio P, Sciveres M, Di Leo G, Iorio R, Marseglia A, Carioli G, Maggiore G, Guido M, D'Antiga L. Paediatric porto-sinusoidal vascular disease: Two different clinical phenotypes with subtle histological differences. Liver Int 2023. [PMID: 37157951 DOI: 10.1111/liv.15603] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 04/13/2023] [Accepted: 04/23/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND AND AIMS In paediatrics, porto-sinusoidal vascular disease (PSVD) is relatively unknown and probably underdiagnosed. We aimed to describe clinical phenotypes, histology and outcome of children diagnosed with PSVD. METHODS Retrospective multicentre study of children diagnosed with PSVD. Diagnosis of PSVD was based on histopathology reports; liver specimens were re-evaluated by two expert liver pathologists. RESULTS Sixty two children diagnosed with PSVD (M/F = 36/26, median age 6.6 years, range 3.3-10.6), from 7 centres, were included. Thirty-six presented with non-cirrhotic portal hypertension, PH, (PH-PSVD Group = 58%) while 26 had a liver biopsy because of chronic elevation of transaminases without PH (noPH-PSVD Group = 42%). On histology review, the two groups differed for the prevalence of obliterative portal venopathy (more prevalent in PH-PSVD, p = 0.005), and hypervascularised portal tracts (more common in noPH-PSVD, p = 0.039), the other histological changes were equally distributed. At multivariate analysis, platelet count ≤185 000/mm3 was the only independent determinant of PH (p < 0.001). After a median follow-up of 7 years (range 3.0-11.2), in PH-PSVD group 3/36 (8%) required TIPS placement, 5/36 (14%) developed pulmonary vascular complications of PH, and 7/36 (19%) required liver transplantation. In noPH-PSVD none progressed to PH nor had complications. CONCLUSIONS Paediatric patients with PSVD present with two different clinical phenotypes, one characterised by PH and one by chronic elevation of transaminases without PH. PSVD should be included among the conditions causing isolated hypertransaminasaemia. On histology, the differences between the two groups are subtle. Medium-term outcome is favourable in patients without PH; progression of the disease is observed in those with PH.
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Affiliation(s)
- Angelo Di Giorgio
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Lorenza Matarazzo
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | | | - Emanuele Nicastro
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Andrea Pietrobattista
- Hepatology, Gastroenterology, Digestive Endoscopy, Nutrition, and Liver Transplantation Unit, IRCCS Bambino Gesù, Pediatric Hospital, Rome, Italy
| | - Mara Cananzi
- Unit of Gastroenterology, Digestive Endoscopy, Hepatology and Care of the Child with Liver Transplantation, University Hospital of Padova, Padova, Italy
| | - Paola Gaio
- Unit of Gastroenterology, Digestive Endoscopy, Hepatology and Care of the Child with Liver Transplantation, University Hospital of Padova, Padova, Italy
| | - Marco Sciveres
- Paediatric Department and Transplantation, ISMETT, Palermo, Italy
| | | | - Raffaele Iorio
- Department of Translational Medical Science, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Antonio Marseglia
- Fondazione IRCCS Casa Sollievo della Sofferenza, Division of Pediatrics, San Giovanni Rotondo, Italy
| | - Greta Carioli
- FROM Research Foundation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Giuseppe Maggiore
- Hepatology, Gastroenterology, Digestive Endoscopy, Nutrition, and Liver Transplantation Unit, IRCCS Bambino Gesù, Pediatric Hospital, Rome, Italy
| | - Maria Guido
- Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Lorenzo D'Antiga
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
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26
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Ferronato M, Molo CD, Bakken SM, Leoni FG, Vizioli L, Donato RD, Serra C, Dietrich CF. Porto-Sinusoidal Vascular Disorder, report of a novel association with POEMS syndrome. Future challenge for the hepatologist. Clin Res Hepatol Gastroenterol 2023; 47:102126. [PMID: 37068710 DOI: 10.1016/j.clinre.2023.102126] [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: 01/19/2023] [Revised: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 04/19/2023]
Abstract
Porto-Sinusoidal Vascular Disorder (PSVD) is a recently introduced clinical entity. Since it is rare and often underrecognized, there is growing interest in identifying patients at increased risk. We present a case of a 59-year-old male with refractory ascites, pleural effusion, and high-risk varices meeting the diagnostic criteria for PSVD with a concomitant diagnosis of POEMS syndrome. The possible association between PSVD and POEMS syndrome has been described only in eight reports in literature, but it may be underrecognized due to the clinical manifestations overlap. To gain a wider comprehension of PSVD, it is fundamental to cooperate using international networks.
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Affiliation(s)
- Marco Ferronato
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Chiara De Molo
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Sofia M Bakken
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | - Luca Vizioli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | - Carla Serra
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Christoph F Dietrich
- Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem und Permanence, Bern, Switzerland
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27
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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; 58:268-276. [PMID: 36692825 DOI: 10.1007/s00535-023-01957-0] [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: 11/30/2022] [Accepted: 01/07/2023] [Indexed: 01/25/2023]
Abstract
BACKGROUND Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. METHODS A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. RESULTS Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96 months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan-Meier survival estimates at 1, 5, and 10 years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson-Aalen cumulative risk estimate for PVT at 1, 5 and 10 years were 16%, 25% and 48%. The median model for end-stage liver disease and Child-Pugh score at initial presentation were 8 (IQR [7-12]) and 5 [5-6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100 months. CONCLUSIONS PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH.
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Affiliation(s)
- Xiaocen Zhang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Katelin Marie Durham
- Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Alexander Austin Garza
- Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Arvind R Murali
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA.
- Liver Center, Orlando Health Digestive Health Institute, 89 W. Copeland Dr., Orlando, FL, USA.
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Nodular Regenerative Hyperplasia Is Not a Rare Condition After Liver Transplantation: Incidence, Predictive Factors, and Impact on Survival. Transplantation 2023; 107:410-419. [PMID: 36117256 DOI: 10.1097/tp.0000000000004303] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND The objectives of this study were to evaluate incidence and to identify the risk factors of occurrence and the predictive factors of symptomatic forms of nodular regenerative hyperplasia (NRH) after liver transplantation (LT). METHODS To identify risk factors of NRH following LT, we included 1648 patients transplanted from 2004 to 2018 and compared the patients developing NRH after LT to those who did not. To identify predictive factors of symptomatic NRH, we selected 115 biopsies displaying NRH and compared symptomatic to asymptomatic forms. Symptomatic NRH was defined as the presence of ascites, esophageal varices, hepatic encephalopathy, portal thrombosis, retransplantation, or death related to NRH. RESULTS The incidence of NRH following LT was 5.1%. In multivariate analysis, the independent factor of developing NRH after LT was the donor's age (odds ratio [OR] = 1.02; confidence interval, 1.01-1.03; P = 0.02). Symptomatic forms occurred in 29 (25.2%) patients: 19 (16.5%) patients presented with ascites, 13 (11.3%) with esophageal varices, 4 (3.5%) with hepatic encephalopathy, and 8 (7%) with portal thrombosis. The median period before the onset of symptoms was 8.4 (1.5-11.3) y after LT. The spleen size at diagnosis/before LT ratio (OR = 12.5; 114.17-1.37; P = 0.0252) and thrombectomy during transplantation (OR = 11.17; 1.48-84.11; P = 0.0192) were associated with symptomatic NRH in multivariate analysis. CONCLUSIONS NRH following LT is frequent (5.1%) and leads to symptomatic portal hypertension in 25.2% of patients. Using older grafts increases the risk of developing NRH after LT. Clinicians should screen for signs of portal hypertension, particularly in measuring spleen size.
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29
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Jin SJ, Choi WM. Porto-Sinusoidal Vascular Disease: A Concise Updated Summary of Epidemiology, Pathophysiology, Imaging, Clinical Features, and Treatments. Korean J Radiol 2023; 24:31-38. [PMID: 36606618 PMCID: PMC9830138 DOI: 10.3348/kjr.2022.0668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/06/2022] [Accepted: 10/26/2022] [Indexed: 01/03/2023] Open
Affiliation(s)
- Su Jin Jin
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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30
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Penrice DD, Thakral N, Kezer CA, Lennon R, Moreira RK, Graham RP, Kamath PS, Simonetto DA. Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases. Liver Int 2022; 42:1379-1385. [PMID: 35187783 DOI: 10.1111/liv.15202] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 12/11/2021] [Accepted: 12/29/2021] [Indexed: 02/13/2023]
Abstract
BACKGROUND Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. METHODS A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. RESULTS One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1-306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. CONCLUSIONS The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.
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Affiliation(s)
- Daniel D Penrice
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nimish Thakral
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Camille A Kezer
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Ryan Lennon
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Roger K Moreira
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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31
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Tang S, Bai L, Zhang W, Song W, Liu H, Li L, Liang C, Duan Z, Zheng S. A HRG novel mutation associated with idiopathic portal hypertension: Case report and literature review. ILIVER 2022; 1:90-95. [DOI: 10.1016/j.iliver.2022.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/20/2025]
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32
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Wöran K, Semmler G, Jachs M, Simbrunner B, Bauer DJM, Binter T, Pomej K, Stättermayer AF, Schwabl P, Bucsics T, Paternostro R, Lampichler K, Pinter M, Trauner M, Mandorfer M, Stift J, Reiberger T, Scheiner B. Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension. Clin Gastroenterol Hepatol 2022; 20:e251-e266. [PMID: 33279774 DOI: 10.1016/j.cgh.2020.11.039] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/08/2020] [Accepted: 11/25/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. METHODS Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. RESULTS 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). CONCLUSION Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.
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Affiliation(s)
- Katharina Wöran
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - David Josef Maria Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Teresa Binter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Katharina Pomej
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
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Primignani M, Tripodi A. Antithrombotic Therapy and Liver Disease. VASCULAR DISORDERS OF THE LIVER 2022:249-265. [DOI: 10.1007/978-3-030-82988-9_16] [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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Ashraf MF, Trifonova R, Batool A. Obliterative Portal Venopathy Caused by Oral Contraceptive Pills: A Case Report. J Med Cases 2021; 12:446-450. [PMID: 34804304 PMCID: PMC8577609 DOI: 10.14740/jmc3779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 09/22/2021] [Indexed: 11/20/2022] Open
Abstract
Oral contraceptive pills (OCPs) have a known prothrombotic effect. Obliterative portal venopathy (OPV) can be seen in patients with underlying hypercoagulability. We present a case of a 19-year-old female patient taking OCPs who presented with obstructive jaundice. Her main concern was pruritis. An extensive workup was done to reach a diagnosis but it came back negative. A liver biopsy showed OPV. This was thought secondary to her OCP use. Her OCPs were discontinued which resulted in a complete resolution of her symptoms and laboratory abnormalities. Cases with a direct relationship between OPV and OCP use are extremely rare. More studies are required to establish a correlation between OPV and OCPs. OPV should be considered in the differential diagnosis among patients with obstructive jaundice without an obvious cause, especially in patients taking OCPs. Treatment is stopping the OCPs with close follow-up to confirm disease resolution.
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Affiliation(s)
| | | | - Asra Batool
- Division of Gastroenterology, Albany Medical Center, NY, USA
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35
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Gioia S, Riggio O, Nardelli S, d'Amati G, Ridola L. Identifying Patients at High Risk of Developing Non-Cirrhotic Portal Hypertension. Hepat Med 2021; 13:105-111. [PMID: 34764704 PMCID: PMC8572743 DOI: 10.2147/hmer.s282674] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/27/2021] [Indexed: 12/23/2022] Open
Abstract
The term porto-sinusoidal vascular disease (PSVD) has been recently proposed to replace the term idiopathic non-cirrhotic portal hypertension (INCPH) to describe patients with or without signs of portal hypertension and typical histological lesions involving the portal venules or sinusoids in the absence of cirrhosis. According to the new definition, the presence of known causes of liver disease as well as of portal vein thrombosis does not rule out PSVD. Therefore, the patients in whom the diagnosis of PSVD is possible are much more than the patients strictly fulfilling the diagnostic criteria for INCPH. In this setting, the clinical challenge for the hepatologist is to identify patients at risk of developing PSVD and to indicate liver biopsy to confirm the diagnosis. We describe some possible scenarios in which PSVD should always be suspected, and we provide some tools useful to reach the diagnosis of PSVD.
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Affiliation(s)
- Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giulia d'Amati
- Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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36
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Sarma MS, Seetharaman J. Pediatric non-cirrhotic portal hypertension: Endoscopic outcome and perspectives from developing nations. World J Hepatol 2021; 13:1269-1288. [PMID: 34786165 PMCID: PMC8568571 DOI: 10.4254/wjh.v13.i10.1269] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/27/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
Non-cirrhotic portal hypertension (NCPH) forms an important subset of portal hypertension in children. Variceal bleed and splenomegaly are their predominant presentation. Laboratory features show cytopenias (hypersplenism) and preserved hepatic synthetic functions. Repeated sessions of endoscopic variceal ligation or endoscopic sclerotherapy eradicate esophageal varices in almost all cases. After variceal eradication, there is an increased risk of other complications like secondary gastric varices, cholangiopathy, colopathy, growth failure, especially in extra-hepatic portal vein obstruction (EHPVO). Massive splenomegaly-related pain and early satiety cause poor quality of life (QoL). Meso-Rex bypass is the definitive therapy when the procedure is anatomically feasible in EHPVO. Other portosystemic shunt surgeries with splenectomy are indicated when patients present late and spleen-related issues predominate. Shunt surgeries prevent rebleed, improve growth and QoL. Non-cirrhotic portal fibrosis (NCPF) is a less common cause of portal hypertension in children in developing nations. Presentation in the second decade, massive splenomegaly and patent portal vein are discriminating features of NCPF. Shunt surgery is required in severe cases when endotherapy is insufficient for the varices. Congenital hepatic fibrosis (CHF) presents with firm palpable liver and splenomegaly. Ductal plate malformation forms the histological hallmark of CHF. CHF is commonly associated with Caroli’s disease, renal cysts, and syndromes associated with neurological defects. Isolated CHF has a favourable prognosis requiring endotherapy. Liver transplantation is required when there is decompensation or recurrent cholangitis, especially in Caroli’s syndrome. Combined liver-kidney transplantation is indicated when both liver and renal issues are present.
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Affiliation(s)
- Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Jayendra Seetharaman
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Kmeid M, Liu X, Ballentine S, Lee H. Idiopathic Non-Cirrhotic Portal Hypertension and Porto-Sinusoidal Vascular Disease: Review of Current Data. Gastroenterology Res 2021; 14:49-65. [PMID: 34007347 PMCID: PMC8110235 DOI: 10.14740/gr1376] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 03/30/2021] [Indexed: 12/29/2022] Open
Abstract
Idiopathic non-cirrhotic portal hypertension (INCPH) is a clinicopathologic disease entity characterized by the presence of clinical signs and symptoms of portal hypertension (PH) in the absence of liver cirrhosis or known risk factors accountable for PH. Multiple hematologic, immune-related, infectious, hereditary and metabolic risk factors have been associated with this disorder. Still, the exact etiopathogenesis is largely unknown. The recently proposed porto-sinusoidal vascular disease (PSVD) scheme broadens the spectrum of the disease by also including patients without clinical PH who are found to have similar histopathologic findings on core liver biopsies. Three histomorphologic lesions have been identified as specific for PSVD to include obliterative portal venopathy, nodular regenerative hyperplasia and incomplete septal cirrhosis/fibrosis. However, these findings are often subtle, under-recognized and subjective with low interobserver agreement among pathologists. Additionally, the natural history of the subclinical forms of the disease remains unexplored. The clinical course is more favorable compared to cirrhosis patients, especially in the absence of clinical PH or liver dysfunction. There are no universally accepted guidelines in regard to diagnosis and treatment of INCPH/PSVD. Hence, this review emphasizes the need to raise awareness of this entity by highlighting its complex pathophysiology and clinicopathologic associations. Lastly, formulation of standardized diagnostic criteria with clinical validation is necessary to avoid misclassifying vascular diseases of the liver and to develop and implement targeted therapeutic strategies.
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Affiliation(s)
- Michel Kmeid
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - Xiuli Liu
- Department of Pathology and Laboratory Medicine, University of Florida at Gainesville, FL, USA
| | - Samuel Ballentine
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
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Imabayashi K, Nakano K, Iwata S, Tanaka Y. A case of systemic lupus erythematosus with marked ascites due to idiopathic non-cirrhotic portal hypertension. Mod Rheumatol Case Rep 2021; 5:285-291. [PMID: 33783333 DOI: 10.1080/24725625.2021.1904607] [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: 11/09/2022]
Abstract
A 43-year-old-woman admitted to our department because of abdominal pain, abdominal distension, pain on both inner thighs and blurred vision lasting for 3 months. Pancytopenia and positive anti-double stranded DNA (dsDNA) antibodies were noted 5 years prior to her hospitalisation. On admission, the patient was diagnosed with systemic lupus erythematosus (SLE) with retinal vasculitis, panniculitis, cholecystitis and enteritis. The ultrasound test revealed a large amount of ascites, splenomegaly, a hypoechoic band in the liver, and portal hypertension with mildly elevated hepatic venous wedge pressure (15 mmHg). Liver biopsy showed no evidence of hepatitis, cholangitis or liver cirrhosis, leading to the diagnosis of idiopathic non-cirrhotic portal hypertension (INCPH). Prednisolone (PSL) at a daily dose of 50 mg and intravenous cyclophosphamide pulse therapy (IVCY) were initiated for SLE, while diuretics were administered for transudative ascites associated with INCPH. Although these symptoms temporarily improved, 2 months later, SLE and ascites effusion aggravated again, and portal vein thrombosis was confirmed by computed tomography. After increasing the dose of IVCY and adding an anticoagulant agent, all symptoms improved, allowing a reduction of the PSL dose. In the present case, the exacerbation of INCPH was associated with the exacerbation of SLE and the occurrence of portal thrombosis, suggesting an autoimmune and thrombotic mechanism of INCPH. On the other hand, splenomegaly, oesophageal varices, the hypoechoic band remained unchanged, suggesting the established organised INCPH was refractory to immunosuppressive agents.
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Affiliation(s)
- Keisuke Imabayashi
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.,Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuhisa Nakano
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Shigeru Iwata
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yoshiya Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
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Liang J, Shi C, Dupont WD, Salaria SN, Huh WJ, Correa H, Roland JT, Perri RE, Washington MK. Key histopathologic features in idiopathic noncirrhotic portal hypertension: an interobserver agreement study and proposal for diagnostic criteria. Mod Pathol 2021; 34:592-602. [PMID: 32958831 DOI: 10.1038/s41379-020-00676-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/21/2020] [Accepted: 08/25/2020] [Indexed: 12/16/2022]
Abstract
Histologic features of idiopathic noncirrhotic portal hypertension (INCPH), loosely termed as obliterative portal venopathy (OPV), are heterogenous, often subtle, and overlap with other entities. To this date, no consensus histopathologic diagnostic criteria have been established for INCPH. For these reasons, rendering a reproducible consensus histologic diagnosis of OPV on a liver biopsy may often be challenging even for experienced hepatopathologists. We report herein a two-phase interobserver agreement study on the diagnosis of OPV and assessed the relative value of histologic features in 104 liver biopsies in distinguishing between INCPH and non-INCPH with the goal to obtain a consensus on specific practical diagnostic criteria. Six hepatopathologists blinded to clinical information and original pathologic diagnosis reviewed internet-based case study sets with high-resolution whole-slide images. The initial interobserver agreement on OPV was expectedly low, but significantly improved (moderate agreement in most categories) upon adopting a consensus view recognizing portal vein sclerosis as the only strong independent histologic predictor for INCPH, and that contrary to the conventional view, aberrant portal/periportal vessels does not significantly contribute to the positive assignment of OPV status. We propose a three-tiered classification with diagnostic criteria to facilitate the histologic assignment of OPV status for the evaluation of INCPH. Furthermore, we have validated the performance of the proposed criteria either based on histology alone or coupled with clinicopathologic correlation. This classification may aid in practical histologic assessment of liver biopsies with or without portal hypertension and help to improve diagnostic consistency and accuracy.
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Affiliation(s)
- Jiancong Liang
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Chanjuan Shi
- Department of Pathology, Duke University Medical Center, Durham, NC, USA
| | - William D Dupont
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Safia N Salaria
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Won Jae Huh
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Hernan Correa
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Joseph T Roland
- Epithelial Biology Center and Department of Surgery, Vanderbilt University School of Medicine and the Nashville VA Medical Center, Nashville, TN, USA
| | - Roman E Perri
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Mary Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
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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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Abstract
Short telomere syndrome is a genetically inherited syndrome resulting in premature telomere shortening. This premature shortening of telomeres can result in hematologic, pulmonary, vascular, gastrointestinal, and hepatic manifestations of disease. Identifying patients with short telomere syndrome can be a clinical challenge due to the multitude of potential manifestations and lack of widely available diagnostic tests. In this review, we will highlight hepatic manifestations of short telomere syndrome with a focus on diagnosis, testing, and potential treatments.
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Affiliation(s)
- Daniel D Penrice
- Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
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Kmeid M, Zuo C, Lagana SM, Choi WT, Lin J, Yang Z, Liu X, Westerhoff M, Fiel MI, Affolter K, Choi EYK, Lee H. Interobserver study on histologic features of idiopathic non-cirrhotic portal hypertension. Diagn Pathol 2020; 15:129. [PMID: 33097074 PMCID: PMC7583235 DOI: 10.1186/s13000-020-01049-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 10/15/2020] [Indexed: 02/08/2023] Open
Abstract
Background Histologic features of idiopathic non-cirrhotic portal hypertension (INCPH) may overlap with those without INCPH. Recently, these features have been recognized as part of the larger spectrum of porto-sinusoidal vascular disease (PSVD). We assessed interobserver agreement on histologic features that are commonly associated with INCPH and studied whether a provision of relevant clinical history improves interobserver agreement. Methods The examined histologic features include lobular (such as anisocytosis, nodular regeneration, sinusoidal dilatation, increased parenchymal draining veins, and incomplete fibrous septa) and portal tract changes (such as paraportal shunting vessel(s), portal tract remnant, increased number of portal vessels, and obliterative portal venopathy). Thirty-four archived liver samples from patients with (group A) and without (group B) INCPH were retrieved. A total of 90 representative images of lobules (L) and portal tracts (P) were distributed among 9 liver pathologists blinded to true clinical history. Each pathologist answered multiple choice questions based on the absence (Q1) or presence (Q2) of clinical history of portal hypertension. Fleiss’ kappa coefficient analysis (unweighted) was performed to assess interobserver agreement on normal versus abnormal diagnosis, in L and P, based on Q1 and Q2. Results The kappa values regarding normal versus abnormal diagnosis were 0.24, 0.24, 0.18 and 0.18 for L-Q1, L-Q2, P-Q1, and P-Q2, respectively. With true clinical history provided, the kappa values were L- 0.32, P-0.17 for group A and L-0.12, P-0.14 for group B. Four pathologists changed their assessments based on the provided history. Interobserver agreement on the interpretation of L and P as normal versus abnormal was slight to fair regardless of provision of clinical history. Conclusions Our findings indicate that the histologic features of INCPH/PSVD are not limited to patients with portal hypertension and are subject to significant interobserver variation. Supplementary information The online version contains supplementary material available at 10.1186/s13000-020-01049-0.
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Affiliation(s)
- Michel Kmeid
- Department of Pathology, Albany Medical Center, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA
| | - Chunlai Zuo
- Department of Pathology, Albany Medical Center, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA
| | - Stephen M Lagana
- Department of Pathology, Columbia University, New York, NY, 10032, USA
| | - Won-Tak Choi
- Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA
| | - Jingmei Lin
- Department of Pathology, Indiana University, Indianapolis, IN, 46202, USA
| | - Zhaohai Yang
- Department of Pathology, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Xiuli Liu
- Department of Pathology, University of Florida at Gainesville, Gainesville, FL, 32608, USA
| | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - M Isabel Fiel
- Department of Pathology, Mount Sinai Medical Center, New York, NY, 10029, USA
| | - Kajsa Affolter
- Department of Pathology, University of Utah, Salt Lake City, UT, 84132, USA
| | - Eun-Young K Choi
- Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Hwajeong Lee
- Department of Pathology, Albany Medical Center, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA.
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Tanwar A, Gupta GK, Chauhan V, Sharma D, Jain MK, Bhardwaj H, Jhajharia A, Nijhawan S. Celiac Disease and Portal Hypertension: A Causal Association or Just a Coincidence? J Clin Exp Hepatol 2020; 10:290-295. [PMID: 32655231 PMCID: PMC7335706 DOI: 10.1016/j.jceh.2019.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Celiac disease (CD) has been linked to portal hypertension (PHT) of varied etiology, but the causality association has never been proved. We aim to study the prevalence of CD in patients of PHT of different etiology. METHODS A prospective observational study was conducted from June 2017 to December 2018 involving all the cases of PHT of varied etiology. Consecutive patients of PHT with chronic liver disease (CLD) of defined etiology like ethanol, viral hepatitis (B or C), Budd-Chiari syndrome (BCS), autoimmune-related cirrhosis, and cryptogenic CLD (cCLD) (group A) and those with noncirrhotic PHT (NCPHT), which included noncirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO) (group B), were screened for CD by IgA anti-tTG antibody followed by duodenal biopsy in serology-positive patients. RESULTS Out of a total of 464 patients, group A constituted 382 patients, CLD related to ethanol (155), cCLD (147), hepatitis B (42), hepatitis C (21), autoimmune (10), and BCS (7), whereas 82 patients were in group B with NCPF (64) and EHPVO (18). Total 29 patients were diagnosed with CD in both groups, 17 in group A (4.5%) and 12 in group B (14.6%). In group A, 13 patients with cCLD, two with HBV-related CLD, one with BCS, and one with autoimmune-related CLD were concomitantly diagnosed as CD. In group B, CD was diagnosed in 12 patients of NCPF (11) and EHPVO (1). Liver histology showed chronic hepatitis in two patients and was normal in three patients. CONCLUSION CD is common in PHT of different etiology, especially in cCLD, NCPH and autoimmune hepatitis; however, the etiological basis for this association is still to be defined. The likelihood of CD is higher in liver disease than the general population, and these patients should be screened for CD.
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Key Words
- AIH, autoimmune hepatitis
- ANA, anti-nuclear antibody
- ASMA, anti-smooth muscle antibody
- Anti LKM, anti-liver kidney microsome antibody
- BCS, Budd–Chiari syndrome
- CD, celiac disease
- CLD, chronic liver disease
- EHPVO, extrahepatic portal vein obstruction
- HBV, hepatitis B virus
- HBs Ag, hepatitis B surface antigen
- HLA, human leukocyte antigen
- Ig G, immunoglobulin G
- NCIPH, noncirrhotic idiopathic portal hypertension
- NCPF, noncirrhotic portal fibrosis
- NCPH, noncirrhotic portal hypertension
- PHT, portal hypertension
- c CLD, cryptogenic chronic liver disease
- celiac disease
- chronic liver disease
- noncirrhotic portal hypertension
- portal hypertension
- tTG antibody, tissue transglutaminase antibody
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Affiliation(s)
- Amit Tanwar
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Gaurav K. Gupta
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Virender Chauhan
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Deepak Sharma
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Mukesh K. Jain
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Hemendra Bhardwaj
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Ashok Jhajharia
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
| | - Sandeep Nijhawan
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, India
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Nicoară-Farcău O, Rusu I, Stefănescu H, Tanțău M, Badea RI, Procopeț B. Diagnostic challenges in non-cirrhotic portal hypertension - porto sinusoidal vascular disease. World J Gastroenterol 2020; 26:3000-3011. [PMID: 32587444 PMCID: PMC7304099 DOI: 10.3748/wjg.v26.i22.3000] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/31/2020] [Accepted: 05/27/2020] [Indexed: 02/06/2023] Open
Abstract
Non-cirrhotic portal hypertension consists of a group of diseases characterized by signs and complications of portal hypertension, which differ from cirrhosis through histological alterations, hemodynamic characterization and, clinical outcome. Because of the similarities in clinical presentation and imaging signs, frequently these patients, and particularly those with porto-sinusoidal vascular disease (PSVD), are misdiagnosed as having liver cirrhosis and thus raising difficulties in their diagnosis. The most challenging differentiation to be considered is between PSVD and cirrhosis and, although not pathognomonic, liver biopsy is still the standard of diagnosis. Although they still require extended validation before being broadly used, new non-invasive methods for the diagnosis of porto-sinusoidal vascular disease, like transient elastography, contrast-enhanced ultrasound or metabolomic profiling, have shown promising results. Another issue is the differentiation between PSVD and chronic extrahepatic portal vein obstruction, especially now when it is known that 40% of patients suffering from PSVD develop portal vein thrombosis. In this particular case, once the portal vein thrombosis occurred, the diagnosis of PSVD is impossible according to the current guidelines. Moreover, so far, the differentiation between PSVD and sinusoidal obstruction syndrome has not been clear so far in particular circumstances. In this review we highlighted the diagnostic challenges regarding the PSVD, as well as the current techniques used in the evaluation of these patients.
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Affiliation(s)
- Oana Nicoară-Farcău
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Ioana Rusu
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Pathology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Horia Stefănescu
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Marcel Tanțău
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Radu Ion Badea
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Imagistic Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Bogdan Procopeț
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
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De Gottardi A, Rautou PE, Schouten J, Rubbia-Brandt L, Leebeek F, Trebicka J, Murad SD, Vilgrain V, Hernandez-Gea V, Nery F, Plessier A, Berzigotti A, Bioulac-Sage P, Primignani M, Semela D, Elkrief L, Bedossa P, Valla D, Garcia-Pagan JC. Porto-sinusoidal vascular disease: proposal and description of a novel entity. Lancet Gastroenterol Hepatol 2020; 4:399-411. [PMID: 30957754 DOI: 10.1016/s2468-1253(19)30047-0] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/16/2019] [Accepted: 01/17/2019] [Indexed: 12/14/2022]
Abstract
Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.
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Affiliation(s)
- Andrea De Gottardi
- University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Pierre-Emmanuel Rautou
- Service d'Hépatologie, Hôpital Beaujon, Clichy, France; Centre de Recherche de l'Inflammation, Inserm and Université Paris Diderot, Paris, France
| | | | - Laura Rubbia-Brandt
- Service de Pathologie Clinique, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Frank Leebeek
- Department of Haematology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Jonel Trebicka
- Department of Internal Medicine I, University of Bonn, Bonn, Germany; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
| | | | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; CIBER Hepatic and Digestive Diseases, Instituto de Salud Carlos III, Madrid, Spain
| | - Filipe Nery
- Centro Hospitalar Universitário and EpiUnit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
| | - Aurélie Plessier
- Service d'Hépatologie, Hôpital Beaujon, Clichy, France; Centre de Recherche de l'Inflammation, Inserm and Université Paris Diderot, Paris, France
| | - Annalisa Berzigotti
- University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
| | | | - Massimo Primignani
- Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - David Semela
- Gastroenterology and Hepatology, Kantonsspital, St Gallen, Switzerland
| | - Laure Elkrief
- Hepatology, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | | | - Dominique Valla
- Service d'Hépatologie, Hôpital Beaujon, Clichy, France; Centre de Recherche de l'Inflammation, Inserm and Université Paris Diderot, Paris, France
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; CIBER Hepatic and Digestive Diseases, Instituto de Salud Carlos III, Madrid, Spain.
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Varma A, Abraham SC, Mehta RS, Saini NY, Honhar M, Rashid M, Chen J, Srour SA, Bashir Q, Rondon G, Oran B, Hosing CM, Nieto Y, Kebriaei P, Alousi AM, Ahmed S, Marin D, Khouri IF, Ciurea SO, Qazilbash MH, Rezvani K, Anderlini P, Andersson BS, Shpall EJ, Champlin RE, Popat UR. Idiopathic refractory ascites after allogeneic stem cell transplantation: a previously unrecognized entity. Blood Adv 2020; 4:1296-1306. [PMID: 32236526 PMCID: PMC7160275 DOI: 10.1182/bloodadvances.2019000638] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 02/27/2020] [Indexed: 11/20/2022] Open
Abstract
At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)-related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients' median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.
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Affiliation(s)
- Ankur Varma
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
- Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL
| | - Susan C Abraham
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Rohtesh S Mehta
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Neeraj Y Saini
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Medhavi Honhar
- Department of Pediatrics, Comer Children's Hospital, Chicago, IL; and
| | - Munazza Rashid
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Julianne Chen
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Samer A Srour
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Qaiser Bashir
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gabriela Rondon
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Betul Oran
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Chitra M Hosing
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yago Nieto
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Partow Kebriaei
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Amin M Alousi
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sairah Ahmed
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - David Marin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Issa F Khouri
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Stefan O Ciurea
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Muzaffar H Qazilbash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Katy Rezvani
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Paolo Anderlini
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Borje S Andersson
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Elizabeth J Shpall
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Richard E Champlin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Uday R Popat
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
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Tseng Y, Ma L, Li S, Luo T, Luo J, Zhang W, Wang J, Chen S. Application of CT-based radiomics in predicting portal pressure and patient outcome in portal hypertension. Eur J Radiol 2020; 126:108927. [PMID: 32146345 DOI: 10.1016/j.ejrad.2020.108927] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 02/25/2020] [Accepted: 02/28/2020] [Indexed: 12/13/2022]
Abstract
PURPOSE Portal venous pressure (PVP) measurement is of clinical significance, especially in patients with portal hypertension. However, the invasive nature and associated complications limits its application. The aim of the study is to propose a noninvasive predictive model of PVP values based on CT-extracted radiomic features. METHODS Radiomics PVP (rPVP) models based on liver, spleen and combined features were established on an experimental cohort of 169 subjects. Radiomics features were extracted from each ROI and reduced via the LASSO regression to achieve an optimal predictive formula. A validation cohort of 62 patients treated for gastroesophageal varices (GOV) was used to confirm the utility of rPVP in predicting variceal recurrence. The association between rPVP and response to treatment was observed. RESULTS Three separate predictive formula for PVP were derived from radiomics features. rPVP was significantly correlated to patient response to endoscopic treatment for GOV. Among which, the model containing both liver and spleen features has the highest predictability of variceal recurrence, with an optimal cut-off value at 29.102 mmHg (AUC 0.866). A Kaplan Meier analysis further confirmed the difference between patients with varying rPVP values. CONCLUSION PVP values can be accurately predicted by a non-invasive, CT derived radiomics model. rPVP serves as a non-invasive and precise reference for predicting treatment outcome for GOV secondary to portal hypertension.
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Affiliation(s)
- Yujen Tseng
- Department of Gastroenterology,Zhongshan Hosptial, Fudan University, China; Department of Digestive Diseases, Huashan Hospital, Fudan University, China
| | - Lili Ma
- Department of Endoscopy Center, Zhongshan Hospital, Fudan University, China
| | - Shaobo Li
- Shanghai Medical College, Fudan University, China
| | - Tiancheng Luo
- Department of Gastroenterology,Zhongshan Hosptial, Fudan University, China
| | - Jianjun Luo
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, China
| | - Wen Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, China
| | - Jian Wang
- Department of Gastroenterology,Zhongshan Hosptial, Fudan University, China
| | - Shiyao Chen
- Department of Gastroenterology,Zhongshan Hosptial, Fudan University, China; Department of Endoscopy Center, Zhongshan Hospital, Fudan University, China; Evidence-Based Medicine Center, Fudan University, China.
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El Jabbour T, McHugh KE, Patil DT, Zuo C, Koo BH, Kim S, Lee H. Histologic Lesions of Porto-Sinusoidal Vascular Disease Following Phlebotomy in Hemochromatosis. Gastroenterology Res 2020; 13:32-39. [PMID: 32095171 PMCID: PMC7011912 DOI: 10.14740/gr1236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 11/12/2019] [Indexed: 12/19/2022] Open
Abstract
Background Phlebotomy induces regression of liver fibrosis in genetic hemochromatosis. We assessed the histologic changes in pre-phlebotomy and post-phlebotomy liver biopsies from patients with HFE mutation as a model to study regression of fibrosis. We aimed to show that phlebotomy-induced histologic lesions overlap with porto-sinusoidal vascular disease (PSVD, also known as idiopathic non-cirrhotic portal hypertension), histologically. Methods A total of 51 biopsies (22 pre-phlebotomy and 29 post-phlebotomy) were reviewed, and three variables were studied: iron index indicative of the amount of accumulated iron (range 0 to 18), the combined score of vascular changes reflecting the presence of histological lesions that are described in PSVD (range 0 to 9) and the high-grade shunt vessel by calculating the proportion of portal tracts with shunt vessels, with a cutoff of 50%. Two-tailed Student's t-test and Fisher's exact test were performed to compare the means of two variables and frequencies of the histologic lesions in two groups, respectively. A P-value < 0.05 was considered statistically significant. Results The iron index was higher in the pre-phlebotomy compared to post-phlebotomy group (P = 0.01). Compared to the pre-phlebotomy group, the combined score was higher in the post-phlebotomy group when the cases of advanced fibrosis were excluded (P = 0.023) and remained higher when patients with risk factors for PSVD were further excluded (P = 0.034). The high-grade shunt vessel tended to be more common in the post-phlebotomy group when advanced fibrosis was excluded; however, the statistical significance was marginal (P = 0.056). Conclusions Phlebotomy reduces hepatic iron load and induces histologic lesions of PSVD in patients with HFE mutation. Our data support a postulation that some of the histologic lesions of PSVD represent vascular remodeling following a regression of fibrosis and may not be reflective of risk factors or etiopathogenesis of PSVD. Regressed fibrosis and PSVD may not be reliably distinguished in a limited sample, therefore warranting cautious interpretation in the right clinical context.
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Affiliation(s)
| | | | - Deepa T Patil
- Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.,Pathology, Brigham and Women's hospital, Boston, MA, USA
| | - Chunlai Zuo
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
| | | | - Sungeun Kim
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
| | - Hwajeong Lee
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
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Goel A, Ramakrishna B, Zachariah U, Sajith KG, Burad DK, Kodiatte TA, Keshava SN, Balasubramanian KA, Elias E, Eapen CE. What makes non-cirrhotic portal hypertension a common disease in India? Analysis for environmental factors. Indian J Med Res 2020; 149:468-478. [PMID: 31411170 PMCID: PMC6676844 DOI: 10.4103/ijmr.ijmr_1405_17] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.
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Affiliation(s)
- Ashish Goel
- Department of Hepatology, Division of GI Sciences, Christian Medical College, Vellore, India
| | - Banumathi Ramakrishna
- Department of Pathology, Division of GI Sciences, Christian Medical College, Vellore, India
| | - Uday Zachariah
- Department of Hepatology, Division of GI Sciences, Christian Medical College, Vellore, India
| | - K G Sajith
- Department of Hepatology, Division of GI Sciences, Christian Medical College, Vellore, India
| | - Deepak K Burad
- Department of Pathology, Division of GI Sciences, Christian Medical College, Vellore, India
| | - Thomas A Kodiatte
- Department of Pathology, Division of GI Sciences, Christian Medical College, Vellore, India
| | - Shyamkumar N Keshava
- Department of Radio-diagnosis, Division of GI Sciences, Christian Medical College, Vellore, India
| | - K A Balasubramanian
- Department of Wellcome Research Laboratory, Division of GI Sciences, Christian Medical College, Vellore, India
| | - Elwyn Elias
- Department of Hepatology, Division of GI Sciences, Christian Medical College, Vellore, India; Liver Unit, University Hospitals, Birmingham, UK
| | - C E Eapen
- Department of Hepatology, Division of GI Sciences, Christian Medical College, Vellore, India
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50
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Hepatobiliary Involvement in Cystic Fibrosis. Respir Med 2020. [DOI: 10.1007/978-3-030-42382-7_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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