it is characterized by autoantibodies that target against liver - specific and non - organ - specific antigens ( 1 ) .
corticosteroids , especially prednisone or prednisolone ( pd ) , have been the key drugs of initial antiinflammatory and immuno - suppressive therapy of autoimmune hepatitis in children ( 2 ) . however , it is well known that long - term use of corticosteroid is associated with the risk of steroid - induced toxicities , and this requires newer immunosuppressive agents for the treatment of autoimmune hepatitis , especially in growing children .
we report on the case of a 11-yr - old korean girl with type-1 autoimmune hepatitis who discontinued pd due to steroid - induced toxicities , but who remained in biochemical and clinical remission while undergoing deflazacort and ursodeoxycholic acid ( udca ) combination therapy .
a 9-yr - old girl was admitted to eul - ji hospital because of jaundice and right upper quadrant pain .
her height was 135 cm ( 75 - 90 percentile ) , and weight was 43 kg ( over 97 percentile ) . the sclera was icteric , and the liver edge descended 4 cm below the right costal margin .
the results of laboratory studies were as follows : aspartate aminotransferanse ( ast ) 1,106 iu / l , alanine aminotransferase ( alt ) 1,888
iu / l , total bilirubin 25.7 mg / dl , direct bilirubin 18.2 mg / dl , total protein 6.9 g / dl , albumin 4.2 g / dl , serum alkaline phosphatase 1,160 iu / l , ggtp 71 iu / l , inr 2.4 , aptt > 120 sec , antinuclear antibody ( ana ) ( + ) speckled pattern , with 1:320 titer , anti - smooth muscle antibody ( ab ) ( - ) , anti - mitochondrial ( ama ab ) ( - ) , igg 1,397 mg / dl , anti - hav igm ( - ) , anti - hbc igm ( - ) , hbsag ( - ) , ebv - vca igg / m ( -/- ) , and ceruloplasmin 28 mg / dl .
liver biopsy results showed piecemeal necrosis at the portal - lobular interface accompaning mild to moderate infiltration of lymphocytes , moderate centrilobular cholestasis , moderate lobular inflammation , and moderate fibrosis ( fig .
1 ) . according to the scoring system of international autoimmune hepatitis group ( 3 ) , she had definite autoimmune hepatitis ( score=16 ) .
initially , on 40 mg of pd and 300 mg of udca daily , she gradually recovered both clinically and biochemically .
pd was tapered gradually , and three months later , she was taking 15 mg of pd and 300 mg of udca daily . at eight months
, her aminotransferase level had elevated to 400 iu / l , but reduced rapidly when pd was increased to 40 mg / day . at nine months
, she was taking 15 mg / day of pd and 300 mg / day of udca , but she complained of hirsutism , striae , moon face , and buffalo hump , at ten months .
the results of a second round of laboratory studies conducted at this time were ; ast 21 iu / l , alt 52 iu / l , total bilirubin 0.7 mg / dl , total protein 7.2 g / dl , albumin 4.7 g / dl , glucose 86 mg / dl , ana ( + ) speckled pattern , with 1:160 titer .
accordingly , deflazacort ( calcort , handok pharm co. , ltd , eumseonggoon , chungcheongbuk - do , korea ) was administered at dose of 18 mg a day , instead of pd at dose of 18 mg a day , and udca was continued .
her biochemical test remained within normal ranges on this regimen , and the pd - associated complications improved rapidly .
fourteen months later , deflazacort was reduced at dose of 15 mg a day , and after 19 months of deflazacort treatment , a follow - up liver biopsy was performed .
this showed no lobular activity , no portal activity , near - normal periportal inflammation , and fibrosis ( fig .
. the girl has been in clinical and biochemical remission for two years now , without therapy .
there are few diseases to be differentiated from autoimmune hepatitis , overlap syndrome , in which the features of autoimmune hepatitis is combined with those of primary biliary cirrhosis , or primary sclerosing cholangitis , and autoimmune cholangitis . in overlap with primary biliary cirrhosis ,
serologic test of ama is usually positive and histologic study shows findings of cholangitis . in overlap with primary sclerosing cholangitis ,
serologic test of ama is negative , and histologic evidence suggests various forms of cholangitis . in autoimmune cholangitis ,
serologic test of ama is negative , and histologic examination shows bile duct injury , suggestive of primary biliary cirrhosis .
autoimmune cholangitis , also , is generally not steroid - responsive . in the present case , despite the cholestatic presentation , serum level of ggtp was not so high , histologic study showed no evidence of definite cholangitis , and response to steroid was excellent . according to the scoring system of international autoimmune hepatitis group ,
this case has definite autoimmune hepatitis ( pre - treatment score 16 , post - treatment score 18 ) .
the long - term use of corticosteroid is known to be associated with the risk of steroid - induced toxicities .
generally , there are several ways of reducing steroid - associated toxicities , i.e. , administering steroid on an alternate - day schedule , administering adjunctive agent to reduce the need for steroid , and finding a substitute agent .
however , of these three options in case of autoimmune hepatitis , the risk of relapse is higher if steroids are administered on an alternate - day schedule ( 4 ) , and thus this method is not recommended .
some authors add azathioprine to steroids if normalization of the liver function is not obtained by steroids alone or if too high a dose of steroids is required to maintain normal transaminase levels ( 4 ) .
initial combination therapy with steroid and azathioprine , is considered by some authors as standard therapy of autoimmune hepatitis in children , as in adults ( 1 ) .
however , there is concern about the oncogenecity associated with long - term azathioprine therapy ( 5 ) , and because of its hepatotoxicity , some authors do not recommend azathioprine as first line treatment , particularly in severely jaundiced patients ( 4 ) .
thus , udca was prescribed as an adjuvant medication with pd or deflazacort . in a clinical study on japanese adults ,
udca improved aminotransferase levels and reduced inflammation in liver biopsy ( 6 ) ; however , a clinical study on caucasian adults showed no significant difference in the results of biochemical tests or in histologic indices between a udca group and a placebo group ( 7 ) .
deflazacort is a synthetic steroid , an oxazoline derivative of pd , with potentially lower toxicities than prednisone or pd ( 8) , and has been widely used as an immunosuppressant in the field of pediatric nephrology ; nephrotic syndrome and renal transplantation ( 9 ) , and in duchenne dystrophy ( 10 ) .
only one case of adult study has indicated that deflazacort might be a suitable substitute for pd in the treatment of autoimmune hepatitis ( 11 ) . in clinical trials in spain , deflazacort was administered to patients with type-1 autoimmnune hepatitis who were in remission on a stable dose of pd .
only clinical and biochemical remission were maintained during the follow - up period without histologic examination . in the present case ,
deflazacort was substituted for pd as a therapeutic drug in a child who was in remission on pd and udca , but significant pd - associated toxicities occurred . after switching to deflazacort , these toxicities improved rapidly , and the patient remained in clinical and biochemical remission .
after 19 months on deflazacort , a follow - up liver biopsy showed near - normalization of auto - immune hepatitis .
this is the first known clinical report to show that deflazacort is a suitable substitute for pd in the treatment of autoimmune hepatitis .
a recent study showed the measurement of organ- and non - organ - specific auto - antibodies and igg levels correlated with disease activity in autoimmune hepatitis ( 12 ) .
the patient in the present case remained ana - positive with 1:160 titer , when on pd and udca , but became ana negative at about the time of the follow - up liver biopsy performed after 19 months on deflazacort and udca .
this may provide additional evidence that deflazacort is a possible substitute for pd in the treatment of autoimmune hepatitis .
this case poses the possibility that deflazacort can be a possible substitute for prednisone in type-1 autoimmune hepatitis in children , and demonstrates the need for further study .
 prednisone or prednisolone are the mainstay drug treatments for autoimmune hepatitis in children . however , long - term use of corticosteroid is associated with the risk of steroid - induced toxicities , and this situation requires newer immuno - suppressive agents for the treatment of autoimmune hepatitis , especially in growing children . an 11-yr - old korean girl with type-1 autoimmune hepatitis discontinued prednisolone due to toxicities , i.e. , hirsutism , buffalo hump , and skin striae , and remained clinical and biochemical remission under replacement of deflazacort and ursodeoxycholic acid combination therapy . 
 a follow - up liver biopsy after 19 months of deflazacort and ursodeoxycholic acid treatment showed histologic remission . 
INTRODUCTION
CASE REPORT
DISCUSSION