{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:25:19Z","timestamp":1789694719019,"version":"4.0.1"},"reference-count":98,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018712","name":"University of Medicine and Pharmacy of Cluj-Napoca","doi-asserted-by":"publisher","award":["32153\/16.12.2024"],"award-info":[{"award-number":["32153\/16.12.2024"]}],"id":[{"id":"10.13039\/501100018712","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Romanian Ministry of Research, Innovation and Digitalization","award":["PNRR\/2022\/C9\/MCID\/I8"],"award-info":[{"award-number":["PNRR\/2022\/C9\/MCID\/I8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency or inborn error of immunity (IEI) encountered in clinical practice. Characterized by a remarkably broad clinical spectrum, CVID presents with phenotypes spanning from \u201cinfection only\u201d to significant non-infectious complications. The frequent overlap between these classifications underscores that their distinction is more accurately viewed as a continuous spectrum, rather than a binary categorization. CVID-associated liver disease is a significant source of morbidity, yet often poses diagnostic challenges due to its insidious and clinically silent nature, typically becoming apparent only upon the development of complications. Manifestations range from abnormal liver tests to irreversible organ damage, with reports including granulomas, autoimmune hepatitis, fibrosis, and porto-sinusoidal vascular disorder (PSVD). Regenerative nodular hyperplasia (RNH), commonly associated with PSVD, is a frequent histopathological finding. Management requires a multidisciplinary approach, including cause-directed immunosuppression and supportive treatment for non-cirrhotic portal hypertension. Despite significant advances in comprehending CVID-associated liver involvement, substantial gaps persist concerning its pathogenesis, its optimal management, and the correlation between histological findings and clinical outcomes. A heightened awareness of CVID-associated liver disease is paramount for multidisciplinary teams across IEI centers. Furthermore, given its prevalence, its insidious clinical phenotype until advanced complications, and the significant diagnostic delay and underdiagnosis, such awareness is critical across a broader range of medical specialties. In this paper, we aim to consolidate current knowledge regarding CVID-related liver disease, examining its clinical presentation, recent genetic and pathogenetic advancements along with current diagnostic methodologies, and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27031518","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:46:28Z","timestamp":1770137188000},"page":"1518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liver Disease in Common Variable Immunodeficiency: Current Evidence and Knowledge Gaps"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3822-7273","authenticated-orcid":false,"given":"Irena","family":"Nedelea","sequence":"first","affiliation":[{"name":"Allergy and Immunology Discipline, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Allergy and Clinical Immunology Outpatient Clinic, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Nicoara-Farcau","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Discipline, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Hepatology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Procopet","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Discipline, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Hepatology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-5471","authenticated-orcid":false,"given":"Horia","family":"Stefanescu","sequence":"additional","affiliation":[{"name":"Hepatology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Radu","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Discipline, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Hepatology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Balan","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Discipline, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Fit","sequence":"additional","affiliation":[{"name":"Pathology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Rusu","sequence":"additional","affiliation":[{"name":"Pathology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Deleanu","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Outpatient Clinic, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"},{"name":"Pathology Department, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1182\/blood-2007-11-124545","article-title":"Common variable immunodeficiency disorders: Division into distinct clinical phenotypes","volume":"112","author":"Chapel","year":"2008","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e20250003","DOI":"10.70962\/jhi.20250003","article-title":"Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee","volume":"1","author":"Poli","year":"2025","journal-title":"J. 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