The liver dilemma in pediatric familial Mediterranean fever: colchicine toxicity or inflammatory activity? A cohort study of 179 patients

Liver enzyme elevations may occur during follow-up of children with familial Mediterranean fever [FMF], but their underlying mechanisms remain unclear. This study investigated associations between liver function test [LFT] abnormalities, colchicine exposure, inflammatory markers, genetic profile, and liver imaging findings. This multicenter retrospective cohort study included 179 pediatric FMF patients with at least one episode of elevated aminotransferases. Demographic, clinical, laboratory, genetic, treatment-related, and ultrasonographic data were collected. Liver enzyme elevations were classified according to multiples of the upper limit of normal. Correlations and group comparisons evaluated associations with disease-, treatment-, and imaging-related parameters. Aminotransferase elevations were generally mild and transient; 71.5% [ n = 128] experienced a single episode, whereas only 5.6% showed persistent elevation. Colchicine therapy was continued without modification in 53.6% [ n = 96] of patients, and permanent discontinuation was rare [4.5%]. In group comparisons, moderate-to-severe AST elevation was associated with higher CRP and ESR levels [ p = 0.037 and p = 0.020, respectively]. ALT levels correlated positively with FMF duration [ r = 0.256, p = 0.0006] and colchicine treatment duration [ r = 0.190, p = 0.011], while AST levels correlated with colchicine dose [ r = 0.228, p = 0.0024]; imported-colchicine subgroup analyses [ n = 18] were exploratory. In the complete-case subgroup with serial ultrasonography [ n = 27], liver-size percentile distributions changed significantly over time. Hepatosteatosis was detected in 26.1% [28/107] of imaged patients. Among pediatric FMF patients who developed liver enzyme elevation, aminotransferase abnormalities were generally self-limited and rarely required permanent colchicine discontinuation. The observed associations with inflammatory markers, disease duration, and colchicine exposure suggest that multiple factors may contribute to these abnormalities. However, in the absence of an FMF comparator group without liver enzyme elevation, these findings should be interpreted as associations within this selected cohort rather than determinants of hepatic involvement in FMF.