Long-term use of colchicine is associated with incident cirrhosis: a real-world cohort study

Introduction: Chronic effect of colchicine on the liver was not studied enough. We aimed to examine the association between long term colchicine use and incident cirrhosis among new colchicine initiators. Study: Using database of Maccabi Healthcare Services (MHS), we included all patients aged ≥18 years old who initiated colchicine between 1 January 2000 and 31 December 2018 and followed them until the earliest of the following: incident cirrhosis, leaving MHS, death or 31 December 2020. Incident cirrhosis was diagnosed according to ICD-9 code. We defined incident decompensated cirrhosis as the first presentation of cirrhosis, once ascites, encephalopathy and/or variceal bleeding were diagnosed within a period of 90 days before until 90 days after incident cirrhosis. Exposure to colchicine was evaluated in two manners: proportion of months covered (PMC) and mean daily dose (MDD). Results: A total of 21,773 eligible patients were included. We identified 129 incident cases of cirrhosis. Seventy-six (59%) had decompensated cirrhosis, as a first clinical presentation of cirrhosis. Familial Mediterranean Fever (FMF), BMI > 40, FIBROSIS-4 (FIB-4) score and colchicine PMC were all significantly associated with incident cirrhosis. Patients in ‘60–80%’ PMC group had the highest risk for developing cirrhosis (hazard ratio (HR) 3.68, 95% confidence interval (CI) 2.23–6.07). The risk was higher for patients on colchicine >60 months (HR 6.69, 95% CI 3.56–12.56). Conclusions: long term colchicine use is associated with incident cirrhosis, mainly with decompensation at the time of diagnosis. Long term colchicine treatment should be limited to diseases with no other alternative, such as FMF.