The association between familial Mediterranean fever and incident cirrhosis: A population-based matched cohort study

Objective: The association between FMF and incident liver cirrhosis is not widely studied. In this study, we aimed to examine the association between FMF and incident liver cirrhosis in a population-based cohort. Methods: Patients with FMF aged ≥ 18 in the Maccabi Healthcare Services (MHS) database were identified according to ICD-9 code 277.31 between January 1st, 2000 and December 31st, 2022. A control group was 1:1 age and gender-matched. Patients with chronic liver disease or cirrhosis were excluded, as well as patients who were treated with methotrexate, amiodarone or tamoxifen and patients with less than 12 months of follow-up. Incident cirrhosis was defined as a new diagnosis of cirrhosis according to ICD-9 code (571.5), newly diagnosed major cirrhotic complications or liver transplantation. The Cox proportional hazards models were used to examine the association between FMF and incident cirrhosis and the Kaplan-Meier curves to study the event-free survival. Results: Incident cirrhosis was detected among 2.1% and 0.4% in the study and control groups, respectively, P < 0.01. Being in the FMF group was associated with a significantly increased risk of incident cirrhosis (HR = 2.60, 95% CI: 1.54–4.38, P < 0.01). At 7 years, the cirrhosis-free survival rate was 98.2% in the study group and 99.6% in the control group (P < 0.01). Conclusion: FMF was associated with incident cirrhosis, irrespective of the traditional risk factors for metabolic syndrome, suggesting the contribution of the inflammatory state to the development of cirrhosis.