Autoimmune hepatitis associated with coagulation disorders and immunethyreopathy

Summary

We present the case of a 42-year-old female patient with the diagnoses of autoimmune hepatitis type I and autoimmunethyroiditis. Furthermore this patient had an unusual combination of coagulation disorders with homozygous Factor V Leiden mutation (APC resistance) and presence of antiphospholipid antibodies, leading to deep vein thromboses and miscarriages. Only few cases with the combination of autoimmune hepatitis and antiphospholipid antibodies have been described and almost all of them had become symptomatic with the antiphospholipid syndrome. As both autoimmune phenomenons furthermore share similar HLA-patterns, their coincidence is probably not as uncommon as the limited number of case reports suggests. Therefore attention in patients with autoimmune hepatitis should be focused on thrombophilia.

Autoimmunhepatitis kombiniert mit Gerinnungsdefekten und Immunthyreopathie

Vorgestellt wird der Fall einer 42-jährigen Patientin mit der Erstdiagnose einer Autoimmunhepatitis Typ I und Autoimmunthyreoiditis. Zusätzlich wies die Patientin mit der homozyogoten Mutation für den Faktor-V-Leiden (APC-Resistenz) sowie dem Vorhandensein von Phospholipidantikörpern eine ungewöhnlich schwere Kombination von Gerinnungsdefekten auf, die in der Vorgeschichte zu 3 tiefen Beinvenenthrombosen und 3 Spontanaborten geführt hatte. Die wenigen bislang beschriebenen Fälle mit gemeinsamem Auftreten von Autoimmunhepatitis und Phospholipidantikörpern waren fast immer mit einem Antiphospholipid-Syndrom symptomatisch geworden. Da beide Autoimmunphänomene außerdem gemeinsame HLA-Muster aufweisen, ist deren Koinzidenz möglicherweise größer als angenommen. Daher sollte bei Patienten mit Autoimmunhepatitis gezielte Aufmerksamkeit auf eine eventuelle Thromboseneigung gerichtet werden.

Autoimmune Hepatitis - Antiphospholipid - Anticardiolipin - Factor V Leiden - APC-Resistance - Thyroiditis - Thrombosis

Autoimmunhepatitis - Antiphospholipid - Kardiolipinantikörper - Faktor-V-Leiden - APC-Resistenz - Thyreoiditis - Thrombose

References

• 1 Krawitt E L. Medical Progress: Autoimmune hepatitis.  N Engl J Med . 1996;  334 897-903
• 2 Czaja A J, Manns M P, McFarlane I G, Hoofnagle J H. Autoimmune hepatitis: The investigational and clinical challenges.  Hepatology. 2000;  31 1194-1200
• 3 Desmet V J, Gerber M, Hoofnaagle J H, Manns M P, Scheuer P J. Classification of chronic hepatitis: Diagnosis, grading and staging.  Hepatology. 1994;  19 1513-1520
• 4 Johnson P J, McFarlane I G. Meeting report: International autoimmune hepatitis group.  Hepatology. 1993;  18 998-1005
• 5 Alvarez F, Berg P A, Bianchi F B. et al . International Autoimmune Hepatitis Group Report: Review of criteria for diagnosis of autoimmune hepatitis.  J Hepatol. 1999;  31 929-938
• 6 Obermayer-Straub P, Strassburg C P, Manns M P. Autoimmune hepatitis.  J Hepatol. 2000;  32 (Suppl. 1) 181-197
• 7 Betterle C, Greggio N A, Volpato M. Autoimmune polyglandular syndrome type 1.  J Clin Endocriol Metab. 1998;  83 1049-1055
• 8 Zeniya M. Thyroid disease in autoimmune liver diseases.  Nippon Rinsho. 1999;  57 1882-1887
• 9 Tsutsumi A, Takao K. Hepatic manifestations of the antiphospholipid syndrome.  Intern Med. 2000;  39 6-7
• 10 Bertina R M, Koeleman B P, Koster T. et al . Mutation in blood coagulation factor V associated with resistance to activated protein C.  Nature. 1994;  369 64-67
• 11 Alarcon-Segovia D, Ruiz-Arguelles G J, Garces-Eisele J, Ruiz Arguelles A. Inherited activated protein C resistance in a patient with familial primary antiphospholipid syndrome.  J Rheumatol. 1996;  23 2162-2165
• 12 Brenner B, Vulfsons S L, Lanir N, Nahir M. Coexistence of familial antiphospholipid syndrome and factor V Leiden: Impact on thrombotic diathesis.  Br J Haematol. 1996;  64 166-167
• 13 Simantov R, Lo S K, Salmon J E, Sammaritano L R, Silverstein R L. Factor V Leiden increases the risk of thrombosis in patients with antiphospholipid antibodies.  Thromb Res. 1996;  84 361-365
• 14 Schütt M, Klüter H, Hagedorn-Greiwe M, Fehm H L, Wiedemann G J. Familial coexistence of primary antiphospholipid syndrome and factor V Leiden.  Lupus. 1998;  7 176-182
• 15 Rosendaal F R, Koster T, Vandenbroucke J P, Reitsma P H. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance).  Blood. 1995;  85 1504-1508
• 16 Christiansen O B, Andersen E S, Lauritsen J G, Grunnet N. Treatment of habitual abortions associated with autoimmune abnormalities.  Acta Obstet Gynecol Scand. 1988;  67 663-664
• 17 Saeki R, Kaneko S, Terasaki S. et al . Mixed types of chronic active hepatitis and primary biliary cirrhosis associated with the anti-phospholipid antibody syndrome: A case report.  Hepatogastroenterology. 1993;  40 499-501
• 18 Nagayama K, Izumi N, Watanabe H. et al . A case of autoimmune hepatitis associated with anti-phospholipid antibody syndrome.  Nippon Shokakibyo Gakkai Zasshi. 1997;  94 695-699
• 19 Pathmakanthan S, Kay E W, Murray F E. Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies.  Eur J Gastroenterol Hepatol. 1998;  10 155-157
• 20 Kobayashi N, Sakai M, Ohta M. et al . A case of autoimmune hepatitis with anti-phospholipid syndrome.  Nippon Shokakibyo Gakkai Zasshi. 1998;  95 557-562
• 21 Tauchmanova L, Rossi R, Coppola A. et al . Antiphospholipid syndrome, adrenal failure, dilated cardiomyopathy and chronic hepatitis: An unusual manifestation of multiorgan autoimmune injury?.  Eur J Endocrinol. 1998;  139 641-645
• 22 Barak N, Orion Y, Schneider M, Bernheim J, Mekori Y A. Case report: Hepatic involvement in antiphospholipid syndrome.  J Gastroenterol Hepatol. 1999;  14 1124-1128
• 23 Katayama Y, Kohriyama K, Kirizuka K. et al . Sjogren’s syndrome complicated with autoimmune hepatitis and antiphospholipid antibody syndrome.  Intern Med. 2000;  39 73-76
• 24 Shapiro S S. The lupus anticoagulant/antiphospholipid syndrome.  Annu Rev Med. 1996;  47 533-553
• 25 Christiansen O B, Ulcova-Gallova Z, Mohapeloa H, Krauz V. Studies on associations between human leukocyte antigen (HLA) class II alleles and antiphospholipid antibodies in Danish and Czech women with recurrent miscarriages.  Hum Reprod. 1998;  13 3326-3331
• 26 Colucci A T, Di Lorenzo G, Ingrassia A. et al . Blood antiphospholipid antibody levels are influenced by age, sex and HLA-B8,DR3 phenotype.  Exp Clin Immunogenet. 1992;  9 72-79
• 27 Donaldson P T, Doherty D G, Hayllar K M. et al . Susceptibility to autoimmune chronic active hepatitis: Human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors.  Hepatology. 1991;  13 701-706

Address for correspondence