Hepatic Manifestations and Response to Treatment in Deficiency of Adenosine Deaminase 2

作者：Mohammed Rifat Shaik, Hawwa Alao, Nishat Anjum Shaik, Devika Kapuria, Harish Gopalakrishna, Ma Ai Thanda Han, Varun Takyar, Patrycja Hoffmann, Deborah Stone, Lorena Wilson, Ryan Videgar-Laird, Bernadette Redd, David E. Kleiner, Christopher Koh, Daniel L. Kastner, Dimana Dimitrova, Amanda K. Ombrello, Theo Heller · 发表于：Liver International · 年份：2026 · DOI：10.1111/liv.70660 · 被引用次数：1 · 研究领域：Adenosine and Purinergic Signaling、Folate and B Vitamins Research、Neurological Complications and Syndromes

BACKGROUND AND AIMS: Deficiency of adenosine deaminase 2 (DADA2) is caused by mutations in the ADA2 gene and results in an auto-inflammatory state. Hepatosplenomegaly, with or without abnormalities in liver enzymes, has been reported in DADA2. Anti-tumour necrosis factor (anti-TNF) 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-invasive tools for identifying liver disease and monitoring treatment response. METHODS: 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-to-height (SH) ratio. Liver biopsy and esophagogastroduodenoscopy were performed when indicated. RESULTS: 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-sinusoidal vascular disease (PSVD). Over a median follow-up of 4.5 years, 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-TNF therapy resulted in resolution of splenomegaly in 28% and a ...