Ab0033 Liver Disease Complicating Familial Mediterranean Fever: A Study on 57 Patients From the French Adult Jir Cohort

Background: When FMF patients with cirrhosis were compared with FMF patients without cirrhosis, those with cirrhosis had a significantly later diagnosis of hepatopathy: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease associated with a mutation in the MEFV gene. The liver may be involved in FMF, but data remain scarce; however, FMF patients may have cirrhosis 1. The usual metabolic risk factors are not the only explanation, as they were not associated with persistent hepatic cytolysis in a previous work in FMF patients while studying a score of steatosis 2. Objectives: Our aim was to evaluate liver involvement in FMF in a French tertiary centre for adult FMF. Methods: In this observational study, we included patients followed for FMF at the National Reference Centre for Adult Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA) in Paris, France. Heterozygous patients and patients with other identified causes of hepatopathy were not included. Sociodemographic data, underlying characteristics of FMF, laboratory, imaging and pathological features, and complications of cirrhosis, if present, were recorded. Among FMF patients with hepatopathy, we compared patients with and without cirrhosis. Statistical analysis was performed using EasyMedStat. Results: Of the 533 adult FMF patients followed, 57 (10.7%) had chronic liver function abnormalities, including 17 (30%) with cirrhosis. Hepatic features developed 47 24-58 years after FMF onset. All patients were receiving colchicine at a current median daily dose of 1.5 mg 1-2 mg, but 24 patients were colchicine-resistant (42%) and 23 (40%) were receiving interleukin-1 inhibitors, either anakinra (n=17) or canakinumab (n=8). Four patients also had AA amyloidosis. Thirty-five patients had active FMF with a CRP above 5 when liver abnormalities were detected. The median body mass index (BMI) was 26.3 22.3-29.7 kg/m2. When FMF patients with cirrhosis were compared with FMF patients without cirrhosis, those with cirrhosis had a significantly later diagnosis of hepatopathy, a longer delay in diagnosis of FMF and in starting treatment for their FMF. Patients with colchicine resistance and on interleukin-1 inhibitors were significantly more common in the cirrhosis group. BMI and AA amyloidosis were not significantly different between groups. Liver ultrasound was performed in all but fifteen patients. FibroScan was performed in 32 patients with a median controlled attenuation parameter (CAP) score of 257 226-303 dB/m and a median liver stiffness measurement (LSM) fibrosis stage score of 11.9 6-17. Nineteen patients underwent liver biopsy, including 14 with cirrhosis. The median SAF score was S1A3F4. Seventeen (90%) liver biopsies described inflammation with a variable infiltrate consisting of lymphocytes (n=8/13), neutrophils (n=3/13), monocytes and macrophages (n= 2/13), mononuclear cells (n=4/13) and fifteen had steatosis quantified as 15%, 11 patients had Mallory bodies and 11 patients had ballooning. Iron overload was found in 1 patient, vascular abnormalities in 4 patients and biliary abnormalities in 2 patients. Conclusion: FMF patients are at risk of chronic hepatopathy. This complication should be considered and sought because of its frequency in FMF patients, but also because of its morbidity with the risk of progression to cirrhosis and death. Liver function should be monitored in all FMF patients, especially those with uncontrolled inflammation. REFERENCES: 1 Fraisse T, Savey L, Hentgen V, Rossi-Semerano L, Koné-Paut I, Grateau G, et al. Non-amyloid liver involvement in familial Mediterranean fever: A systematic literature review. Liver Int. juin 2020;40(6):1269-77. 2 Deshayes S, Fraisse T, Fellahi S, Steichen O, Savey L, Turlin B, et al. Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis. Sci Rep. 5 oct 2022;12:16644. Acknowledgements: We wish to thank the following geneticians for performing MEFV sequencing at the diagnosis of FMF for French patients: Guilaine Boursier, Isabelle Touitou, Serge Amselem, Irina Giurgea, Isabelle Jeru, Laurence Cuisset. Disclosure of Interests: None declared.