{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:03:59Z","timestamp":1790773439663,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Secondary to tumour necrosis factor\u2010alpha induced protein 3 (<jats:italic>TNFAIP3<\/jats:italic>) mutations, A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease with clinical features similar to those of Beh\u00e7et's and Crohn's diseases but with a constantly expanding clinical spectrum. Here, we describe HA20 liver involvement in three new patients from the same family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively assessed clinical, biological and\/or histological findings for eight patients over three generations of the same family with heterozygous mutations in the <jats:italic>TNFAIP3<\/jats:italic> gene (c.259C\u00a0&gt;\u00a0T, p.Arg87*).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The eight patients exhibited the following: aphthous ulcers (8\/8, bipolar in 7), autoimmune features (6\/8, including 5 with definitive autoimmune disease diagnoses, ie, type I diabetes, Hashimoto thyroiditis, pernicious anaemia, and\/or 5 with antinuclear antibodies \u2265320), pustulosis\/folliculitis (5\/8), abdominal pain (4\/8), arthralgia (3\/8), enlarged cervical lymph nodes (3\/8) and pericarditis (1\/8). In addition, three patients (twin sisters and their grandmother aged 23 and 70\u00a0years, respectively) exhibited persistent mild hepatic cytolysis associated with splenomegaly (n\u00a0=\u00a03), hepatomegaly (n\u00a0=\u00a01) and\/or liver atrophy (n\u00a0=\u00a01) on echography. We could not detect any other causes of chronic liver diseases. Liver biopsies from three patients displayed hepatic fibrosis, hepatocyte injury and\/or CD4<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> T lymphocyte infiltration, and patterns of inflammatory cells and NLRP3 or NF\u2010\u03baB immunostaining differed from the predominant neutrophil infiltration observed in skin or some digestive tract biopsies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study reinforces the dual involvement of innate and adaptive immunity in HA20 according to both acute and chronic injury and the organ involved and widens its clinical spectrum to include chronic hepatic involvement.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14935","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T13:34:58Z","timestamp":1620567298000},"page":"1894-1900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Chronic hepatic involvement in the clinical spectrum of A20 haploinsufficiency"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-3233","authenticated-orcid":false,"given":"Samuel","family":"Deshayes","sequence":"first","affiliation":[{"name":"Department of Internal Medicine CHU de Caen Normandie Caen France"},{"name":"Normandie Univ UNICAEN Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Bazille","sequence":"additional","affiliation":[{"name":"Department of Pathology CHU de Caen Normandie Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elma","family":"El Khouri","sequence":"additional","affiliation":[{"name":"Department of Genetics Sorbonne Universit\u00e9 UPMC University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Kone\u2010Paut","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology Bic\u00eatre Hospital AP\u2010HP University of Paris Sud Saclay CEREMAIA Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Giurgea","sequence":"additional","affiliation":[{"name":"Department of Genetics Sorbonne Universit\u00e9 UPMC University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-8854","authenticated-orcid":false,"given":"Sophie","family":"Georgin\u2010Lavialle","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Sorbonne Universit\u00e9 UPMC University CEREMAIA Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Martin Silva","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine CHU de Caen Normandie Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00ebl","family":"Dumont","sequence":"additional","affiliation":[{"name":"Department of 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