Disentangling the hepatic risks of familial Mediterranean Fever and colchicine: A propensity score-matched analysis of 19,231 patients.

BACKGROUND: Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease commonly treated with lifelong colchicine therapy. Although colchicine is considered safe, its long-term hepatic effects remain debated. Distinguishing liver injury attributable to FMF itself from that induced by colchicine is essential for guiding clinical management. OBJECTIVES: To determine whether FMF or colchicine exposure are independently associated with liver cirrhosis and fatty liver disease. METHODS: This retrospective cohort study utilized electronic medical records from a tertiary care centre in Israel. Patients diagnosed with FMF, gout, pseudogout, or pericarditis were included. Liver injury outcomes were assessed via ICD codes, imaging, and biopsy data. Propensity score matching was applied to isolate the effects of FMF diagnosis and colchicine treatment, and multivariate logistic regression models were constructed to adjust for relevant confounders. RESULTS: Among 19,231 patients, FMF diagnosis was significantly associated with increased risk of cirrhosis (OR = 4.00; 95% CI: 2.78-5.75) and fatty liver (OR = 2.03; 95% CI: 1.57-2.61), both in unmatched and matched cohorts. In contrast, colchicine treatment was not associated with elevated OR for either condition (Cirrhosis OR = 0.92 [95% CI: 0.69-1.22]; Fatty Liver OR = 1.01 [95% CI: 0.85-1.21]). CONCLUSIONS: FMF is independently associated with increased hepatic injury risk, while colchicine treatment does not appear to confer additional liver toxicity. These findings underscore the importance of controlling FMF-related inflammation to prevent hepatic complications, and support the continued use of colchicine as a safe therapeutic agent in this population.