{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:59:41Z","timestamp":1787979581645,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis is a common adverse event following gene therapy for haemophilia, often associated with a loss of transgene expression. Investigating the potential causes and implications of this is crucial for the overall success of treatment. Gene therapy trials using adeno\u2010associated virus (AAV) vectors have demonstrated promising results marked by increases in factor FVIII and FIX levels and reductions in episodes of bleeding. However, hepatocellular injury characterised by elevations in alanine aminotransferases (ALT) has been noted. This liver injury is typically transient and asymptomatic, posing challenges in determining its clinical significance. Proposed causes encompass immune\u2010mediated responses, notably T cell cytotoxicity in response to the AAV vector, direct liver injury from the viral capsid or transcribed protein via the unfolded protein response and pre\u2010existing liver conditions. Liver biopsy data conducted years post\u2010gene therapy infusion has shown sinusoidal infiltration without significant inflammation. The overall safety profile of gene therapy remains favourable with no evidence drug\u2010induced liver injury (DILI) based on Hy's Law criteria. Essential pre\u2010therapy monitoring and identifying patients at high risk of liver injury should involve liver function tests and non\u2010invasive fibroscans, while novel blood\u2010based biomarkers are under exploration. Further research is required to comprehend the mechanisms underlying transaminitis, loss of transgene expression and long\u2010term effects on the liver, providing insights for optimising gene therapy for haemophilia.<\/jats:p>","DOI":"10.1111\/jvh.13919","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:44:21Z","timestamp":1712925861000},"page":"14-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hepatitis after gene therapy, what are the possible causes?"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8603-0580","authenticated-orcid":false,"given":"Ann","family":"Maina","sequence":"first","affiliation":[{"name":"Barts Health NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham R.","family":"Foster","sequence":"additional","affiliation":[{"name":"Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-2513-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14530"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-043021-"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003777"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.517"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2022.11.026"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14545"},{"issue":"12","key":"e_1_2_7_9_1","first-page":"3891","article-title":"Immunotherapy and gene Therapy: new challenges in the diagnosis and management of drug\u2010induced liver injury","volume":"19","author":"Delire B","year":"2022","journal-title":"Front Pharmacol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211644"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119913"},{"key":"e_1_2_7_13_1","unstructured":"Peri\u2010operative Anesthetic Management in Liver Transplantation\u2013Google Books [Internet]. 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