concurrence of more than one disease in the liver ( thereafter  overlap ) may have a significant impact on disease progression . due to a progressive increase in the prevalence of nonalcoholic fatty liver disease ( nafld ) associated with 
endemic obesity , overlapped nafld , especially in its necroinflammatory form of nonalcoholic steatohepatitis ( nash ) , has gained clinical relevance in the diagnosis and prognosis of chronic liver disease .
in fact , patients with chronic hepatitis c and nash have more advanced stages of fibrosis accompanied by more severe metabolic syndrome than those with chronic hepatitis c or chronic hepatitis c and nonalcoholic steatosis .
regarding overlap with other forms of chronic liver disease , nash - autoimmune hepatitis ( aih ) overlap syndrome has received special attention for several reasons .
first , histological diagnosis of nash - aih overlap is absolutely required , owing to previous reports that autoantibodies were present in about one quarter of patients with nafld   and that without liver biopsy , almost all the female patients were incorrectly diagnosed with aih .
second , the optimum treatment regimen to achieve biochemical remission has been difficult to standardize ; corticosteroids are likely to worsen nash   but improve aih - related necroinflammation .
third , the natural course and postintervention prognosis remain to be characterized . to our knowledge
, 8 cases of biopsy - proven nafld - aih overlap syndrome have been reported to date [ 2 , 3 , 6 ] , 3 with nash and 5 with nafld ( the latter without detailed information on the presence of steatohepatitis ) . among these ,
2 cases of nash - aih overlap were treated with corticosteroid , but histological changes as revealed by follow - up liver biopsies have not yet been reported . in this report
we describe a patient with nash - aih overlap who successfully achieved histological remission of aih as well as resolution of nash with a combination of prednisolone therapy and weight loss .
this is the first report demonstrating that corticosteroids improve the prognosis of nash - aih overlap .
a 57-year - old female patient was referred to our hospital with a 2-year history of low - grade but gradually progressing aminotransferase elevation . on admission ,
clinical examination was normal but blood tests revealed elevated liver enzymes , i.e. , ast 174 iu / l ( normal < 37
iu / l ) , and -gtp 120 iu / l ( normal < 75 iu / l ) .
her serum autoantibody profile was as follows : anti - nuclear antibody 1,280 ( speckled ) , anti - smooth muscle antibody 80 , and anti - ss - a 64 , but anti - mitochondria antibody was negative .
serum igg was increased to 2,370 mg / dl ( normal < 1,700 mg / dl ) and human leukocyte antigen was found to be dr3/dr4 .
elevated fasting blood glucose ( 123 mg / dl ) coupled with increased hba1c ( 7.3% ) indicated comorbid diabetes mellitus .
the homeostasis model assessment of insulin resistance ( homa - r ) was 11.4 , though the patient was not significantly obese ( body mass index was 23.6 ) .
as abdominal ct scan and ultrasonography both suggested the presence of fatty liver , subsequent liver biopsy was required to narrow down the differential diagnosis that included nafld , aih , and their concurrence .
steatosis and pericellular / bridging fibrosis were also prominent , accompanied by hepatocyte ballooning , implicating concurrence with the histological features of steatohepatitis .
a diagnosis of nash - aih overlap was made ( aih score was 18 , i.e. , definite , together with nash grade 2/stage 3 according to the blunt classification system ) , and 30 mg of prednisolone per day p.o . was initiated .
prednisolone exacerbated the patient 's diabetes during the 1st week of treatment , necessitating the administration of rapid - acting insulin .
as aminotransferase levels began to decrease shortly after the initiation of treatment , prednisolone was gradually tapered to 15 mg / day over 6 months until liver enzymes normalized .
prednisolone was further tapered to 5 mg / day over the next 12 months , without any hepatitis flare - up .
was then added to prednisolone as maintenance therapy , and rapid - acting insulin was subsequently replaced with an oral hypoglycemic agent .
follow - up liver tissue examination performed 40 months after diagnosis revealed only minimal inflammatory infiltrates in the portal area without any histological evidence of steatohepatitis ( fig .
the fibrosis score established by ishak et al .   decreased from 4 at diagnosis to 1 , while the nafld activity score   ( scale developed by the nash clinical research network ) decreased from 6 to 2 .
in this report we present a nash - aih overlap patient who successfully achieved histological remission of both aih and nash following prednisolone therapy . to our knowledge , this report is the first to document the detailed clinical course of nash - aih overlap during prednisolone therapy , accompanied by documentation of histological improvement .
information regarding treatment regimen was presented in 6 out of 8 nafld - aih overlap cases in the literature [ 2 , 3 , 6 ] : 2 patients were given prednisolone combined with diet therapy , resulting in a partial biochemical response .
on the other hand , 1 out of 2 patients treated with ursodeoxycholic acid and modified diet was reported to show normalized aminotransferases .
the remaining 2 cases were not treated , in 1 case due to coexisting diabetes and dyslipidemia despite the presence of definite aih . due to the anti - inflammatory action of glucocorticoid , fibrosis in aih commonly
improves or does not progress during therapy [ 9 , 10 , 11 ] . reflecting glucocorticoids cell- and tissue - specific mode of action through the glucocorticoid receptor ,
persistently elevated glucocorticoid levels have been associated with fatty liver development and their consequent phenotype in nafld . moreover , dose - dependent association of glucocorticoid with secondary nash was demonstrated in patients with systemic lupus erythematosus , and hepatic fat accumulation has been documented in patients with cushing 's syndrome . in accordance with clinical findings ,
lemke et al .   recently reported that liver - specific glucocorticoid receptor knock - down by shrna , through induction of transcriptional repressor hairy enhancer of split 1 ( hes1 ) , caused a pronounced decrease in hepatic triglyceride levels in the livers of obese db / db mice .
the above findings raise concerns about the use of glucocorticoids in the treatment of nafld - aih overlap . in our case the clinical benefit of prednisolone 's immunosuppressive and fibrolytic action clearly outweighed its steatogenic properties .
our findings thus emphasize the need of appropriate immunosuppressive treatment even in comorbid aih and nash , though interindividual differences and genetic susceptibility may affect the glucocorticoids steatogenic actions .
it should be noted that our study used a shorter duration and lower total dosage of prednisolone administration for aih compared to that for systemic lupus erythematosus , and this may not exacerbate concurrent nash if it is accompanied with appropriate diet therapy , the gold standard treatment for nash .
loria et al .   reported that 3 out of 84 nafld patients ( 3.6% ) were diagnosed with true nash - aih overlap after liver biopsy , whereas 1 out of 212 japanese nafld patients ( 0.5% ) had definite aih .
given ethnic differences in susceptibility to the development of nash - aih overlap , the increasing prevalence of nafld worldwide probably makes nash - aih overlap more clinically relevant .
obviously , the false diagnosis of overlapped aih in female nash patients who have not undergone liver biopsy should be avoided , but true diagnosis of nash - aih accompanied by appropriate corticosteroid induction is needed to prevent disease progression .
we presented a patient with nash - aih overlap who achieved histological remission as a result of prednisolone therapy .
future prospective studies and the accumulation of definite cases are needed to validate the effectiveness of corticosteroid therapy for nash - aih overlap .
 concurrence of nonalcoholic steatohepatitis ( nash ) with autoimmune hepatitis ( aih ) is a rare condition that is challenging to diagnosis , due to the relatively high prevalence of autoantibodies in nash . 
 it is also difficult to determine the most effective treatment as corticosteroids are likely to worsen nash despite being effective in the treatment of aih . in this case report , we present a female diagnosed with nash - aih overlap with accompanying diabetes mellitus , who successfully achieved normalization of serum alanine aminotransferase levels following prednisolone therapy and weight loss . 
 a follow - up liver biopsy performed 40 months after the initial diagnosis showed only minimal inflammatory infiltrates in the portal area without any nash histology . 
 resolution of nash , in conjunction with a reduction in hepatic fibrosis , might suggest that prednisolone itself does not aggravate steatohepatitis , but rather prevents disease progression . 
 appropriate immunosuppressive treatment may therefore be an important component of the optimum therapy for nash - aih overlap . 
Introduction
Case Report
Discussion