Real-world data on the long-term use of trientine tetrahydrochloride in adults with Wilson’s disease: a retrospective multicentre Italian study

Background and aim: Wilson’s Disease (WD) is a rare inherited disorder of copper metabolism leading to toxic copper accumulation primarily in the liver and brain. Current first-line therapies, D-penicillamine (DPA) and zinc salts, are associated with numerous and sometimes severe adverse reactions and may therefore be substituted by trientine. This study aimed to evaluate the long-term safety and efficacy of trientine tetrahydrochloride (TETA-4HCl) in adults with WD. Methods: Retrospective cohort study of adults with WD (Leipzig score ≥ 4) and a minimum follow-up of 12 months after switching to TETA-4HCl. Efficacy and safety were assessed at 6, 12, 18, 24, 30, and 36 months with laboratory tests and imaging examinations, recorded adverse events (AE), and evaluation of major liver and neurological outcomes. Results: Data collection was performed between July 2025 and May 2026, and data analysis is still ongoing. Between October 2018 and November 2023, 74 patients (43 males; mean age 42 years) from three Italian reference centers were switched to TETA-4HCl from DPA (23), TETA-2HCl (38), or zinc salts (28), including combinations of chelators with zinc, and at least 12 months of follow-up. At switch, the majority (96%) were clinically stable; 20(27%) were cirrhotic, 2 (3%) decompensated cirrhotic, and 14 (19%) had neurological symptoms. Laboratory values remained stable. TETA-4HCl was generally well tolerated. Five patients (6.8%) reported non-severe gastrointestinal adverse events, none requiring either dose reduction or discontinuation. Three patients reported non-severe dermatological adverse events, none requiring either dose reduction or discontinuation. Three patients reported neurological adverse events, one discontinuing TETA-4HCl, and 2 managed with dose reduction. Two major liver outcomes were recorded: 1 cirrhotic decompensation, 1 hepatocellular carcinoma. Conclusions: Following a switch in therapy, TETA-4HCl was well tolerated over a period of 36 months with only 1/74 discontinuing due to neurological deterioration. Clinical efficacy and stability were maintained with a low rate (2/74) of major adverse liver outcomes secondary to progressive complications of cirrhotic liver disease.