type 1 autoimmune hepatitis ( aih ) is a progressive liver disorder predominantly affecting women that is characterized by the presence of circulating autoantibodies [ anti - nuclear antibody ( ana ) and/or anti - smooth muscle antibody ( asma ) ] , hypergammaglobulinemia , and a favorable response to immunosuppressive therapy ( 1 - 5 ) .
individuals affected with aih often have concurrent non - hepatic autoimmune disorders , such as chronic thyroiditis ( 9.2% ) , sjgren 's syndrome ( 7.2% ) , and rheumatoid arthritis ( 2.8% ) , but associations with immune thrombocytopenic purpura ( itp ) are rare ( 1.4% ) ( 5 ) . in the present report , we describe the clinical outcome of a patient with aih associated with itp who was successfully treated with prednisolone ( psl ) .
a 75-year - old japanese woman was admitted to the national hospital organization shinshu ueda medical center , japan , in july 2013 for further investigation of elevated serum aminotransferase levels and thrombocytopenia .
the laboratory data from her referring institution were aspartate aminotransferase ( ast ) 935 iu / l , alanine aminotransferase ( alt ) 913 iu / l , total bilirubin 7.7 mg / dl , and platelet count 2.810/l .
she had been diagnosed with essential hypertension three years prior and was taking a candesartan cilexetil / amlodipine besilate compound product .
her family history was negative for liver or autoimmune disease , and she denied exposure to agents relevant to hepatitis , such as blood transfusion or herbal ( kampo ) medicine .
the laboratory data on admission at our facility ( table 1 , 2 ) showed severe thrombocytopenia and increased levels of hepato - biliary enzymes and gamma - globulin .
platelet - binding igg ( pbigg ) was negative , but platelet - associated igg ( paigg ) was 894 ng/10 cells ( nl : 47 ) .
her thyroid - stimulating hormone and free - thyroxin levels were within normal ranges , although anti - thyroglobulin ( tg ) and anti - thyroperoxidase ( tpo ) antibodies were positive .
the diagnostic criteria for disseminated intravascular coagulation ( dic ) proposed by the japanese ministry of health , labor and welfare were not satisfied in this patient ( score : 4 ) .
tests for the hepatitis a , b , c , and e viruses , epstein - barr virus , cytomegalovirus , and herpes simplex virus were all negative . her human leukocyte antigen ( hla )
a bone marrow examination uncovered normoplastic marrow with platelet depletion and a megakaryocyte count of 30/l ( fig .
ret : reticulocyte , fdp : fibrin / fibrinogen degradation products laboratory findings on admission ( 2 ) .
ana : anti - nuclear antibody , asma : anti - smooth muscle antibody , ama : anti - mitochondria antibody , anti - lkm1 ab : anti - liver / kidney microsome type 1 antibody , paigg : platelet - associated igg , pbigg : platelet - binding igg , tg antibody : anti - thyroglobulin antibody , tpo antibody : anti - thyroperoxidase antibody , h. pylori ab : helicobacter pylori antibody , ebv : epstein - barr virus , cmv : cytomegalovirus , hsv : herpes simplex virus , hla : human leukocyte antigen the histological findings of a bone marrow examination .
magnification : ( a ) 40 , hematoxylin and eosin ( h&e ) staining ; ( b ) 400 , h&e staining .
a diagnosis of itp was made based on the above clinical and laboratory findings . according to the criteria of the international autoimmune hepatitis scoring system ( 6 ) ,
the patient 's pre - treatment clinical score without histology was 16 ( female : + 2 , alp ( alkaline phosphatase)/alt ratio : + 2 , igg level : + 2 , ana titer : + 2 , anti - mitochondrial antibody ( ama ) : 0 , viral markers : + 3 , drugs : + 1 , alcohol : + 2 and immune disease : + 2 ) , and indicative of definite aih .
the patient promptly began treatment with 30 mg / day ( 0.6 mg / kg / day ) of psl on day 5 of admission , which quickly restored her liver enzyme levels to within normal limits ( fig .
3a and c ) , infiltration of lymphocytic and plasma cells , and mild interface hepatitis around the portal vein ( fig .
( d ) the specimen showed infiltration of inflammatory cells consisting of lymphocytes and plasma cells , with mild interface hepatitis in the portal zone .
magnification : ( a ) 40 , hematoxylin and eosin ( h&e ) staining ; ( b ) 40 , azan - mallory staining ; ( c ) and ( d ) 400 , h&e staining . following an uneventful treatment course ,
the patient 's serum transaminase and igg levels became elevated without thrombocytopenia due to a recurrence of aih when psl was tapered to 5 mg / day . restoring the steroid dose to 20 mg / day normalized her laboratory findings , and the serum transaminase and igg levels and platelet count
have since remained normal for over 19 months with a maintenance dose of 10 mg / day psl ( fig .
aih is defined as a chronic liver disease with unknown etiological factors that is associated with aberrant auto - reactivity and a genetic predisposition ( 1 - 5 ) .
in contrast , itp is an acquired autoimmune disorder mediated by antibodies against platelet membrane glycoprotein ( gp ) ib or iib / iiia complexes and thrombopoietin receptor ( 8 - 10 ) .
the precise mechanism underlying itp remains elusive ( 11 ) , and itp complicating aih is rare and of uncertain pathogenesis ( 12 - 14 ) . in japan , given that type 1 aih represents the overwhelming majority ( 15 ) of aih cases , all reported cases of aih associated with itp have been type 1 .
summarized 16 cases of aih associated with itp appearing in the japanese literature ( 12 ) . while aih preceded itp in 5 cases , the disorders manifested simultaneously in the others . in agreement with these findings , wada et al .
reported on a patient with a six - year history of aih who developed itp ( 13 ) , and yamaike et al .
relapses of aih and/or itp were not found in any case . in our patient ,
either aih and itp developed simultaneously or aih shortly preceded itp , because liver histology ( biopsied 9 days after commencing steroid therapy ) showed very mild fibrosis ( fig .
3b ) . the first - line therapy for both aih and itp is corticosteroids ( 1 - 5 ) .
roughly 24 - 50% of aih patients experience relapse during steroid tapering or withdrawal ( 1,15 ) .
approximately 75% of patients with itp respond to corticosteroids , but only 5 - 30% achieve a sustained remission ( 16 ) . to our knowledge , the present case is the first of its kind , showing relapsing aih and non - relapsing itp during steroid tapering .
we suspected that the response thresholds of the two diseases to psl were different in our subject .
hla class ii molecules on antigen - presenting cells play a crucial role in triggering the immune response , which begins with the recognition of peptide antigens in the hla class ii groove by the t - cell receptor of cd4 t cells through direct contact of both molecules .
we previously reported that the most influential gene associated with type 1 aih susceptibility was hla - drb1 * 04:05 ( 17,18 ) , while drb1 * 15:01 conferred disease resistance ( 19 ) .
strong associations between anti - gp autoantibodies and hla class ii genes have been identified , as follows : anti - gpiib - iiia antibody association with drb1 * 04:05 and dqb*04:01 ; and anti - gpib - ix antibody with drb1 * 08:03 and dqb1 * 06:01 ( 20 ) .
the hla typing pattern in the present case was drb1 * 04:05 and drb1 * 15:01 .
thus , the drb1 * 04:05 allele may be linked to aih associated with itp .
however , it is difficult to explain the low frequency of aih with itp , although the immunologically different mechanisms of the two disorders , which remain unresolved , may be involved . since itp and aih manifest as autoimmune - mediated disorders , the treatment for both conditions is psl . here , aih recurred after psl tapering but itp did not .
this differential immunosuppressive effect is of clinical interest and may provide insights into the mechanisms and interplay of autoimmune diseases .
 although autoimmune hepatitis ( aih ) is frequently complicated with chronic thyroiditis or other autoimmune disorders , reports on its association with immune thrombocytopenic purpura ( itp ) are scarce . 
 we herein describe a case of aih associated with itp . a 75-year - old japanese woman was admitted to our hospital due to increased aminotransferase levels and severe thrombocytopenia . 
 elevated serum immunoglobulin g ( igg ) was detected , and tests for platelet - associated igg and anti - nuclear antibody were positive . following the diagnosis of aih - associated itp , prednisolone treatment of 0.6 mg / kg / day resulted in a decrease in the aminotransferase levels and an increased platelet count . 