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1
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Hu J, Zhou G, Zhang L, Chen XM, Qi L, Sun L. Clinicopathological features of porto-sinusoidal vascular disorder with a novel GIMAP5 mutation in a pair of twin siblings. Dig Liver Dis 2025; 57:652-654. [PMID: 39818502 DOI: 10.1016/j.dld.2025.01.038] [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: 12/07/2024] [Revised: 01/01/2025] [Accepted: 01/02/2025] [Indexed: 01/18/2025]
Affiliation(s)
- Junke Hu
- Department of Pathology, Beijing Ditan Hospital, Captial Medical University, Beijing 100015, PR China
| | - Guiqin Zhou
- Department of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, PR China
| | - Liang Zhang
- Department of Pathology, Beijing Ditan Hospital, Captial Medical University, Beijing 100015, PR China
| | - Xiang-Mei Chen
- Department of Pathology, Beijing Ditan Hospital, Captial Medical University, Beijing 100015, PR China
| | - Liming Qi
- Department of Pathology, Beijing Ditan Hospital, Captial Medical University, Beijing 100015, PR China
| | - Lei Sun
- Department of Pathology, Beijing Ditan Hospital, Captial Medical University, Beijing 100015, PR China.
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2
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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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3
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Konkwo C, Chowdhury S, Vilarinho S. Genetics of liver disease in adults. Hepatol Commun 2024; 8:e0408. [PMID: 38551385 PMCID: PMC10984672 DOI: 10.1097/hc9.0000000000000408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 01/30/2024] [Indexed: 04/02/2024] Open
Abstract
Chronic liver disease stands as a significant global health problem with an estimated 2 million annual deaths across the globe. Combining the use of next-generation sequencing technologies with evolving knowledge in the interpretation of genetic variation across the human genome is propelling our understanding, diagnosis, and management of both rare and common liver diseases. Here, we review the contribution of risk and protective alleles to common forms of liver disease, the rising number of monogenic diseases affecting the liver, and the role of somatic genetic variants in the onset and progression of oncological and non-oncological liver diseases. The incorporation of genomic information in the diagnosis and management of patients with liver disease is driving the beginning of a new era of genomics-informed clinical hepatology practice, facilitating personalized medicine, and improving patient care.
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Affiliation(s)
- Chigoziri Konkwo
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
| | - Shanin Chowdhury
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Silvia Vilarinho
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
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4
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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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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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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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7
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Isidro RA, Zhao L. Evolving Understanding of Noncirrhotic Portal Hypertension. Surg Pathol Clin 2023; 16:549-563. [PMID: 37536888 DOI: 10.1016/j.path.2023.04.009] [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: 08/05/2023]
Abstract
Although cirrhosis is one of the most common causes of portal hypertension, noncirrhotic portal hypertension can result from hemodynamic perturbations occurring in the prehepatic, intrahepatic, and posthepatic circulation. Intrahepatic portal hypertension can be further subclassified relative to the hepatic sinusoids as presinusoidal, sinusoidal, and postsinusoidal. For many of these differential diagnoses, the etiology is known but the cause of idiopathic noncirrhotic portal hypertension, recently included in porto-sinusoidal vascular disease (PSVD), remains poorly understood. Herein, we discuss the diagnostic pathological features of noncirrhotic portal hypertension, with an emphasis on PSVD.
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Affiliation(s)
- Raymond A Isidro
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Lei Zhao
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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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; 43:1523-1536. [PMID: 37157951 DOI: 10.1111/liv.15603] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [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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Shan J, Megarbane A, Chouchane A, Karthik D, Temanni R, Romero AR, Hua H, Pan C, Chen X, Subramanian M, Saad C, Mbarek H, Mehawej C, Chouery E, Abuaqel SW, Dömling A, Remadi S, Yaghi C, Li P, Chouchane L. Genetic predisposition to porto-sinusoidal vascular disorder: A functional genomic-based, multigenerational family study. Hepatology 2023; 77:501-511. [PMID: 35989577 PMCID: PMC9869943 DOI: 10.1002/hep.32735] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 08/11/2022] [Accepted: 08/13/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND AIMS Porto-sinusoidal vascular disorder (PSVD) is a group of liver vascular diseases featuring lesions encompassing the portal venules and sinusoids unaccompanied by cirrhosis, irrespective of the presence/absence of portal hypertension. It can occur secondary to coagulation disorders or insult by toxic agents. However, the cause of PSVD remains unknown in most cases. Hereditary cases of PSVD are exceptionally rare, but they are of particular interest and may unveil genetic alterations and molecular mechanisms associated with the disease. APPROACH AND RESULTS We performed genome sequencing of four patients and two healthy individuals of a large multigenerational Lebanese family with PSVD and identified a heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 ( FCHSD1 ), an uncharacterized gene, in patients. This variant segregated with the disease, and its pattern of inheritance was suggestive of autosomal dominant with variable expressivity. RNA structural modelling of human FCHSD1 suggests that the C-to-T substitution at position 547, corresponding to FCHSD1R183W , may increase both messenger RNA (mRNA) and protein stability and its interaction with MTOR-associated protein, LST8 homolog, a key protein of the mechanistic target of rapamycin (mTOR pathway). These predictions were substantiated by biochemical analyses, which showed that FCHSD1R183W induced high FCHSD1 mRNA stability, overexpression of FCHSD1 protein, and an increase in mTORC1 activation. This human FCHSD1 variant was introduced into mice through CRISPR/Cas9 genome editing. Nine out of the 15 mice carrying the human FCHSD1R183W variant mimicked the phenotype of human PSVD, including splenomegaly and enlarged portal vein. CONCLUSIONS Aberrant FCHSD1 structure and function leads to mTOR pathway overactivation and may cause PSVD.
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Affiliation(s)
- Jingxuan Shan
- Genetic Intelligence Laboratory , Weill Cornell Medicine-Qatar , Qatar Foundation , Doha , Qatar.,Department of Genetic Medicine , Weill Cornell Medicine , New York , New York , USA
| | - André Megarbane
- Department of Human Genetics , Gilbert and Rose-Marie Chagoury School of Medicine , Lebanese American University , Beirut , Lebanon.,Institut Jérôme Lejeune , CRB BioJeL , Paris , France
| | - Aziz Chouchane
- Faculta di Medicina e Chirurgia , Universita Cattolica del Sacro Cuero , Rome , Italy.,Institute of Pathology , University of Bern , Bern , Switzerland
| | - Deepak Karthik
- Genetic Intelligence Laboratory , Weill Cornell Medicine-Qatar , Qatar Foundation , Doha , Qatar
| | | | - Atilio Reyes Romero
- Drug Design Group, Department of Pharmacy , University of Groningen , Groningen , Netherlands
| | - Huiying Hua
- Department of Pediatrics , Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China
| | - Chun Pan
- Department of Pediatrics , Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China
| | - Xixi Chen
- Department of Pediatrics , Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China
| | - Murugan Subramanian
- Genetic Intelligence Laboratory , Weill Cornell Medicine-Qatar , Qatar Foundation , Doha , Qatar
| | - Chadi Saad
- Genome Programme , Qatar Foundation Research, Development and Innovation , Qatar Foundation , Doha , Qatar
| | - Hamdi Mbarek
- Genome Programme , Qatar Foundation Research, Development and Innovation , Qatar Foundation , Doha , Qatar
| | - Cybel Mehawej
- Department of Human Genetics , Gilbert and Rose-Marie Chagoury School of Medicine , Lebanese American University , Beirut , Lebanon
| | - Eliane Chouery
- Department of Human Genetics , Gilbert and Rose-Marie Chagoury School of Medicine , Lebanese American University , Beirut , Lebanon
| | - Sirin W Abuaqel
- Genetic Intelligence Laboratory , Weill Cornell Medicine-Qatar , Qatar Foundation , Doha , Qatar
| | - Alexander Dömling
- Drug Design Group, Department of Pharmacy , University of Groningen , Groningen , Netherlands
| | | | - Cesar Yaghi
- Department of Gastroenterology , Hotel-Dieu de France Hospital , Faculty of Medicine, Saint Joseph University of Beirut , Beirut , Lebanon
| | - Pu Li
- Department of Pediatrics , Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China
| | - Lotfi Chouchane
- Genetic Intelligence Laboratory , Weill Cornell Medicine-Qatar , Qatar Foundation , Doha , Qatar.,Department of Genetic Medicine , Weill Cornell Medicine , New York , New York , USA.,Department of Microbiology and Immunology , Weill Cornell Medicine , New York , New York , USA
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De Gottardi A, Sempoux C, Berzigotti A. Porto-sinusoidal vascular disorder. J Hepatol 2022; 77:1124-1135. [PMID: 35690264 DOI: 10.1016/j.jhep.2022.05.033] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 05/15/2022] [Accepted: 05/23/2022] [Indexed: 12/04/2022]
Abstract
It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.
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Affiliation(s)
- Andrea De Gottardi
- Gastroenterology and Hepatology, Ente Ospedaliero Cantonale, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
| | - Christine Sempoux
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Annalisa Berzigotti
- Department for Visceral Medicine and Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
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Porto-Sinusoidal Vascular Disease: A Pediatric Study of 30 Patients. J Pediatr Gastroenterol Nutr 2022; 74:e132-e137. [PMID: 35258501 DOI: 10.1097/mpg.0000000000003445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Porto-sinusoidal vascular disease (PSVD) refers to a broad spectrum of histological lesions and phenotypic expressions. There are only a few reported pediatric cases in the literature. The primary outcomes of this study were to describe the phenotype of children with PSVD, to specify their mode of presentation and their clinical, biological, histological, and radiological characteristics as well as to identify their underlying etiologies. METHODS This is a descriptive, retrospective, and monocentric study of children followed at our reference center for rare vascular liver diseases. RESULTS Our study included 30 children ages 2months to 17.4years at the time of diagnosis. in most cases, the diagnosis was made incidentally without manifestation of any clinical symptom but rather on the finding of splenomegaly on physical examination (n = 9) or biological abnormalities (n = 13). In the other cases, the main presenting symptom was an upper gastrointestinal bleeding (n = 6). At the first visit, liver laboratory values were either normal (37%) or slightly disturbed. Anemia and/or thrombocytopenia associated with hypersplenism were found in 60% of patients. Liver biopsy was necessary for diagnosis. A total of 80% of cases had no identified etiology. After a median follow-up of 4.5 years, 33% had not developed portal hypertension (PHT) and we reported the first pediatric case of hepatocellular carcinoma in PSVD children. CONCLUSIONS PSVD is responsible for nonspecific symptomatology with variable evolution sometimes marked by serious complications requiring invasive treatments or even liver transplantation. Regular monitoring is essential to prevent, detect, and treat complications.
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12
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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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Hernández-Gea V, Campreciós G, Betancourt F, Pérez-Campuzano V, Seijo S, Díaz A, Gallego-Durán R, Olivas P, Orts L, Magaz M, Baiges A, Turon F, Sidorova J, Romero-Gómez M, Lozano JJ, García-Pagán JC. Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease. J Hepatol 2021; 75:924-934. [PMID: 34052252 DOI: 10.1016/j.jhep.2021.05.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND & AIMS Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD. METHODS We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group). RESULTS Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis. CONCLUSION PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. LAY SUMMARY Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.
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Affiliation(s)
- Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Genís Campreciós
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Fabián Betancourt
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
| | - Valeria Pérez-Campuzano
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
| | - Susana Seijo
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
| | - Alba Díaz
- Pathology Department, Biomedical Diagnostic Centre, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Catalonia, Spain
| | - Rocío Gallego-Durán
- Digestive Diseases Unit, Hospital Universitario Virgen del Rocío. SeLiver group, Instituto de Biomedicina de Sevilla/CSIC/Universidad de Sevilla, Sevilla, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Pol Olivas
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
| | - Lara Orts
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
| | - Marta Magaz
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain
| | - Anna Baiges
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Julia Sidorova
- Bioinformatic Platform, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Manuel Romero-Gómez
- Digestive Diseases Unit, Hospital Universitario Virgen del Rocío. SeLiver group, Instituto de Biomedicina de Sevilla/CSIC/Universidad de Sevilla, Sevilla, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Juan-José Lozano
- Bioinformatic Platform, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Juan Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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14
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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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15
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Slowik V, Hildreth A, Pacheco MC, Finn LS, King J, Shivaram G, Files M, Hsu EK, Horslen S. Hepatopulmonary Syndrome in an Adolescent With Insidious Hypoxia and Small Intrahepatic Portal Venous Shunts: Posttransplant Benefit From Sildenafil. Pediatr Dev Pathol 2020; 23:467-471. [PMID: 32813578 DOI: 10.1177/1093526620945951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We report a patient without known preexisting liver disease who presented with hepatopulmonary syndrome (HPS) due to aberrant intrahepatic portal venous development leading to portosystemic shunting. Liver transplantation resulted in resolution of portal hypertension and HPS and sildenafil was safely tolerated in the treatment of persistent fatigue and hypoxemia. Twelve months later, patient has normal allograft function and has returned to normal activity.
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Affiliation(s)
- Voytek Slowik
- Division of Gastroenterology Hepatology and Nutrition, Children's Mercy Kansas City, Kansas City, Missouri
| | - Amber Hildreth
- Division of Gastroenterology Hepatology and Nutrition, Presbyterian/St. Luke's Transplant Center, Rocky Mountain Hospital for Children, Denver, Colorado
| | - M Cristina Pacheco
- Department of Laboratories, Seattle Children's Hospital, Seattle, Washington
| | - Laura S Finn
- Department of Laboratories, Seattle Children's Hospital, Seattle, Washington
| | - Jeremy King
- Department of Pediatrics, Kapi'olani Medical Center for Women and Children, Honolulu, Hawaii
| | - Giridhar Shivaram
- Department of Radiology, Seattle Children's Hospital, Seattle, Washington
| | - Matthew Files
- Division of Pediatric Cardiology, Seattle Children's Hospital, Seattle, Washington
| | - Evelyn K Hsu
- Division of Gastroenterology Hepatology and Nutrition, Seattle Children's Hospital, Seattle, Washington
| | - Simon Horslen
- Division of Gastroenterology Hepatology and Nutrition, Seattle Children's Hospital, Seattle, Washington
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16
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Soret J, Debray D, Fontbrune FSD, Kiladjian JJ, Saadoun D, Latour RPD, Valla D, Hernandez-Gea V, Hillaire S, Dutheil D, Plessier A, Bureau C, De Raucourt E. Risk factors for vascular liver diseases: Vascular liver diseases: position papers from the francophone network for vascular liver diseases, the French Association for the Study of the Liver (AFEF), and ERN-rare liver. Clin Res Hepatol Gastroenterol 2020; 44:410-419. [PMID: 32651075 DOI: 10.1016/j.clinre.2020.03.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 02/04/2023]
Affiliation(s)
- Juliette Soret
- Center of Clinical Investigation, Saint-Louis Hospital APHP, 1, avenue Claude Vellefaux, 75010 Paris, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Dominique Debray
- Pediatric hepatology Unit, Necker Hospital APHP, 149, rue de Sèvres, 75015 Paris, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Flore Sicre de Fontbrune
- Service d'hématologie, French referral centre for Aplastic anemia and PNH and filière de santé maladies rares immunohématologiques, Saint-Louis Hospital APHP, ERN eurobloodnet, 75010 Paris, France
| | - Jean-Jacques Kiladjian
- Center of Clinical Investigation, Saint-Louis Hospital APHP, 1, avenue Claude Vellefaux, 75010 Paris, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - David Saadoun
- Departement of Internal Medecine, Médecine interne, La Pitié Salpêtrière Hospital APHP, CMR maladies auto_immunes systémiques rares ; CMR maladies auto inflammatoires et amylose, ERN RITA, 47-83, boulevard de l'Hôpital, 75651 Paris, France
| | - Régis Peffault de Latour
- Service d'hématologie, French referral centre for Aplastic anemia and PNH and filière de santé maladies rares immunohématologiques, Saint-Louis Hospital APHP, ERN eurobloodnet, 75010 Paris, France
| | - Dominique Valla
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Hepatology, Beaujon Hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) Rare-Liver
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Unit, Liver Unit. IMDIM. CIBERehd, Hospital Clinic, Barcelona, Spain
| | - Sophie Hillaire
- Department of Internal Medicine, Foch Hospital, 40, rue Worth, 92150 Suresnes, France
| | - Danielle Dutheil
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Association of patients with vascular liver diseases (AMVF), Beaujon Hospital, Department of Hepatology, 100, boulevard du Général-Leclerc, 92118 Clichy, France
| | - Aurélie Plessier
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Hepatology, Beaujon Hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) Rare-Liver
| | - Christophe Bureau
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Gastroenterology and Hepatology, Rangueil Hospital, University Hospital of Toulouse, 1, avenue du Professeur Jean-Poulhès, 31400 Toulouse, France
| | - Emmanuelle De Raucourt
- Department of Laboratory Hematology, Beaujon Hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Reference center of vascular liver diseases, European Reference Network (ERN) Rare-Liver
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17
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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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18
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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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19
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20
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Platzer A, Nussbaumer T, Karonitsch T, Smolen JS, Aletaha D. Analysis of gene expression in rheumatoid arthritis and related conditions offers insights into sex-bias, gene biotypes and co-expression patterns. PLoS One 2019; 14:e0219698. [PMID: 31344123 PMCID: PMC6657850 DOI: 10.1371/journal.pone.0219698] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 06/28/2019] [Indexed: 12/20/2022] Open
Abstract
The era of next-generation sequencing has mounted the foundation of many gene expression studies. In rheumatoid arthritis research, this has led to the discovery of important candidate genes which offered novel insights into mechanisms and their possible roles in the cure of the disease. In the last years, data generation has outstripped data analysis and while many studies focused on specific aspects of the disease, a global picture of the disease is not yet accomplished. Here, we analyzed and compared a collection of gene expression information from healthy individuals and from patients suffering under different arthritis conditions from published studies containing the following clinical conditions: early and established rheumatoid arthritis, osteoarthritis and arthralgia. We show comprehensive overviews of this data collection and give new insights specifically on gene expression in the early stage, into sex-dependent gene expression, and we describe general differences in expression of different biotypes of genes. Many genes that are related to cytoskeleton changes (actin filament related genes) are differently expressed in early rheumatoid arthritis in comparison to healthy subjects; interestingly, eight of these genes reverse their expression ratio significantly between men and women compared early rheumatoid arthritis and healthy subjects. There are some slighter changes between men and woman between the conditions early and established rheumatoid arthritis. Another aspect are miRNAs and other gene biotypes which are not only promising candidates for diagnoses but also change their expression grossly in average at rheumatoid arthritis and arthralgia compared to the healthy condition. With a selection of intersecting genes, we were able to generate simple classification models to distinguish between healthy and rheumatoid arthritis as well as between early rheumatoid arthritis to other arthritides based on gene expression.
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Affiliation(s)
- Alexander Platzer
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Nussbaumer
- Chair and Institute of Environmental Medicine, UNIKA-T, Technical University and Helmholtz Zentrum München, Augsburg, Germany
- Institute of Network Biology (INET), Helmholtz Center Munich, Neuherberg, Germany
| | - Thomas Karonitsch
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Josef S. Smolen
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Daniel Aletaha
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
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21
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Abstract
PURPOSE OF REVIEW Noncirrhotic portal hypertension represents a heterogeneous group of liver disorders that is characterized by portal hypertension in the absence of cirrhosis. The purpose of this review is to serve as a guide on how to approach a patient with noncirrhotic portal hypertension with a focus on recent developments. RECENT FINDINGS Recent studies pertaining to noncirrhotic portal hypertension have investigated aetiological causes, mechanisms of disease, noninvasive diagnostic modalities, clinical characteristics in the paediatric population and novel treatment targets. SUMMARY Noncirrhotic portal hypertension is an underappreciated clinical entity that can be difficult to diagnosis without a healthy suspicion. Diagnosis then relies on a comprehensive understanding of the causes and clinical manifestations of this disease, as well as a careful interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play a significant role moving forward in this disease. Treatment in NCPH remains largely targeted at the individual sequalae of portal hypertension.
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