{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:31:07Z","timestamp":1784543467081,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Deficiency of adenosine deaminase 2 (DADA2) is caused by mutations in the ADA2 gene and results in an auto\u2010inflammatory state. Hepatosplenomegaly, with or without abnormalities in liver enzymes, has been reported in DADA2. Anti\u2010tumour necrosis factor (anti\u2010TNF) therapy is the standard of care for the prevention of recurrent ischemic strokes and reduction of inflammatory burden. However, little is known about the extent of hepatic involvement and the utility of non\u2010invasive tools for identifying liver disease and monitoring treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective analysis was performed on a prospective cohort of 70 patients with DADA2. Patients underwent baseline and annual laboratory testing, abdominal imaging and transient elastography. Hepatomegaly and splenomegaly were assessed on imaging, with splenomegaly defined using the spleen\u2010to\u2010height (SH) ratio. Liver biopsy and esophagogastroduodenoscopy were performed when indicated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, elevated ALT was uncommon (29%). Hepatomegaly and splenomegaly were present in 36% and 58%, respectively. Liver biopsies were performed in 12 patients, 8 of whom showed porto\u2010sinusoidal vascular disease (PSVD). Over a median follow\u2010up of 4.5\u2009years, 40% demonstrated persistently elevated ALT levels. Clinically evident portal hypertension was present in 14%, and decompensation events, such as ascites and variceal bleeding, occurred in 5%. Anti\u2010TNF therapy resulted in resolution of splenomegaly in 28% and a reduction in mean SH ratio across the entire cohort. Patients who underwent haematopoietic cell transplantation (HCT) appeared to be at risk for complications such as hepatic graft versus host disease and veno\u2010occlusive disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DADA2 vasculopathy appears to affect intrahepatic portal veins and result in PSVD. SH ratio shows significant promise in identifying liver involvement and monitoring treatment response. The improvement in SH suggests that PSVD may be reversible with treatment in this setting. Hepatic evaluation at baseline is encouraged for all patients, and pre\u2010HCT liver biopsy should be considered, as there can be clinically silent liver disease that could potentially cause transplant\u2010related complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70660","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:24:36Z","timestamp":1777955076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hepatic Manifestations and Response to Treatment in Deficiency of Adenosine Deaminase 2"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-5714","authenticated-orcid":false,"given":"Mohammed Rifat","family":"Shaik","sequence":"first","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawwa","family":"Alao","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishat Anjum","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine SSM Health\/Saint Louis University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Kapuria","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Gopalakrishna","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma Ai Thanda","family":"Han","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Takyar","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Stone","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Wilson","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Videgar\u2010Laird","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Redd","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3442-4453","authenticated-orcid":false,"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Koh","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kastner","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimana","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"Center for Immuno\u2010Oncology National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda K.","family":"Ombrello","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Heller","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109343(80)80008\u20108"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.02.081"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21524"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307361"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.182.4114.836"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926\u2010020\u201000944\u20101"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12722"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.935957"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0168\u20108278(99)80299\u20102"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/prrv.2001.0170"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010018\u20100525\u20108"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.811473"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1801927"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010021\u201001098\u20100"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23533"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29542"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.01.039"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.171.6.9843315"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.7863\/jum.2003.22.11.1155"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.09.056"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2311020963"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010013\u20109873\u20106"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29217"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medcli.2015.11.008"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010020\u201001385\u2010x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2018.01.005"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2005.12.013"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.152833"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201006286\u20103"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2023.101844"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010021\u201005711\u2010w"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1197361"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20140653"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.05.033"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010022\u201009132\u20104"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.11.042"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00489"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70019"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010025\u201002598\u2010y"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(11)61938\u20107"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.08.018"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70660","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70660","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:55:33Z","timestamp":1781182533000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/liv.70660"],"URL":"https:\/\/doi.org\/10.1111\/liv.70660","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"assertion":[{"value":"2025-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70660"}}