Abstract
The purpose of this study is to characterize the chronic liver disease (CLD) that may be associated with familial Mediterranean fever (FMF). Twenty-seven patients (mean age, 48 ± 18 years; F/M, 16:11) with FMF who were referred for assessment of CLD were studied. Data regarding FMF and CLD were obtained from patient medical files. Liver biopsy was performed in 21 of 27 patients and deferred in six (cirrhotic coagulopathy in five and one who improved after colchicine dose reduction). Patients with FMF and non-alcoholic fatty liver disease (NAFLD) were compared to matched controls from a cohort of 150 patients with NAFLD per liver biopsy but without FMF. The mean Tel Hashomer severity score was 1.7 ± 0.9. The mean daily dose of colchicine was 1.4 ± 0.4 mg over a mean duration of 21 years ± 10. Seven of ten patients who underwent mutation analysis for FMF were homozygous for M694V. In 15 patients, there was evidence of NAFLD: five with “simple” steatosis, three with non-alcoholic steatohepatitis (NASH), and seven with NASH-cirrhosis. An additional five patients had “cryptogenic” cirrhosis, which in most patients represents the end result of unrecognized NASH, and one had normal liver tissue. Comparing FMF patients with NAFLD to matched controls with NAFLD did not reveal excess of metabolic syndrome in FMF patients. Of our FMF patients, 74% had evidence of NAFLD, 75% of which with severe manifestation. The extremely high proportion of NAFLD in our cohort of FMF patients without overt metabolic syndrome may indicate an unappreciated novel association between FMF and NAFLD.
Similar content being viewed by others
References
Tweezer-Zaks N, Doron-Libner A, Weiss P, Ben-Horin S, Barshack I, Lidar M et al (2007) Familial Mediterranean fever and cryptogenic cirrhosis. Med Baltim 86(6):355–362
Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T et al (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40:1879–1885
Mor A, Shinar Y, Zaks N, Langevitz P, Chetrit A, Shtrasburg S et al (2005) Evaluation of disease severity in familial Mediterranean fever. Semin Arthritis Rheum 35(1):57–64
Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association, National Heart, Lung, and Blood Institute (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109(3):433–438
Pi-Sunyer FX (2000) Obesity: criteria and classification. Proc Nutr Soc 59(4):505–509
Brunt EM, Janney CJ, Di Bisceglie AM, Neuschwander-Tetti BA, Bacon BR (1999) Non-alcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroentrol 94:2467–2474
Lidar M, Tokov I, Chetrit A, Zaks N, Langevitz P, Livneh A (2005) Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps disclosed. Clin Exp Rheumatol 23(3):357–363
McCullough AJ (2006) Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 40(Suppl 1):S17–S29
Clark JM (2006) The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 40(Suppl 1):S5–S10
Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, Oren R (2006) Prevalence of primary nonalcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver Int 26(7):856–863
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R et al (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37(4):917–923
Radu C, Grigorescu M, Crisan D, Lupsor M, Constantin D, Dina L (2008) Prevalence and associated risk factors of non-alcoholic fatty liver disease in hospitalized patients. J Gastrointestin Liver Dis 17(3):255–260
Rossi L, Hentgen V, Hermeziu B, Koné-Paut I (2010) Familial Mediterranean fever and liver involvement: a case series from the French Reference Centre for Auto-inflammatory diseases. Poster no. L1.18, 6th International Congress on FMF and SAID, 2–6 September 2010, Amsterdam, Netherlands
Kasturi R, Joshi VC, Wakil SJ (1984) Colchicine inhibition of insulin induction of stearoyl-CoA desaturase and fatty acid synthetase in cultured avian liver explants. Arch Biochem Biophys 233(2):530–539
Reaven EP, Reaven GM (1980) Evidence that microtubules play a permissive role in hepatocyte very low density lipoprotein secretion. J Cell Biol 84(1):28–39
Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114(4):842–845
Notarnicola C, Didelot MN, Seguret F, Demaille J, Touitou I (2002) Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever. Genes Immun 3(1):43–45
Imirzalioglu N, Dursun A, Tastan B, Soysal Y, Yakicier MC (2005) MEFV gene is a probable susceptibility gene for Behçet's disease. Scand J Rheumatol 34(1):56–58
Ozçakar ZB, Yalçinkaya F, Cakar N, Acar B, Kasapçopur O, Ugüten D et al (2008) MEFV mutations modify the clinical presentation of Henoch-Schönlein purpura. J Rheumatol 35(12):2427–2429
Fidder H, Chowers Y, Ackerman Z, Pollak RD, Crusius JB, Livneh A et al (2005) The familial Mediterranean fever (MEVF) gene as a modifier of Crohn's disease. Am J Gastroenterol 100(2):338–343
Rozenbaum M, Rosner I (2004) Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol 22(4 Suppl 34):S75–S78
Disclosures
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rimar, D., Rosner, I., Rozenbaum, M. et al. Familial Mediterranean fever: an association with non-alcoholic fatty liver disease. Clin Rheumatol 30, 987–991 (2011). https://doi.org/10.1007/s10067-011-1718-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-011-1718-1