Since the first description by Ludwig[1-2] in 1988,
several cases of IAD have been reported abroad, and this is the first case reported in China.

Etiology of IAD
Numerous previous studies have been implicated in the pathogenesis of intrahepatic biliary destruction, including develop-mental biliary atresia (secondary to infection or α1-antitrypsin deficiency), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), graft versus. host disease, ischemia, infection, sarcoidosis, lymphoma, chemical injuries (such as injection of scolicidal solution or formaldehyde), as well as a variety of therapeutic drugs (including chlorpromazine, prochlorperazine, organic arsenicals, and tolbutamide). If these causes are systematically excluded, IAD should be considered as the possible diagnosis in young to middle-aged adults, who manifest cholestatic liver disease without history of infantile cholangiopathy. Ludwig[1-2] reported the causes of small duct biliary diseases in 2082 cases diagnosed between 1988 and 1994. These were: 65% PBC; 28% PSC; 3% chronic ductopenic rejection; 1.6% paucity of intrahepatic bile ducts; 1.2% idiopathic adult ductopenia; 0.7% chronic cholestasis of sarcoidosis, and 0.5% drug-induced ductopenia.
Although a distinct cause of IAD has not been determined, several hypotheses have been raised. ①IAD may be related to the late expression of a nonsyndromic form of Alagille syndrome[3-7]: infantile scarcity of interlobular bile ducts, sharing few characteristics with the nonsyndromic form of Alagille syndrome and lacking the relatively poor prognosis; ②Small-duct PSC, without large duct involvement and without evidence of inflammatory bowel disease. The clinical appearance of patients with IAD bears similarities to that of patients with PSC. In fact, pericholangitis is frequently observed surrounding the remaining bile ducts in liver biopsy specimens from patients with IAD. Patients with Alagille’s syndrome have cholestasis that is most severe in infancy and tends to improve as they grow, it is conceivable that IAD could be considered a form of isolated, atypical, or limited variant of small-duct PSC; ③Nonsuppurative viral cholangitis, some viral hepatitis may cause nonsuppurative viral cholangitis, leading to disappearance of interlobular. Dural et al[8] reported an old hepatitis C virus (HCV) patient without clinical characters was diagnosed as IAD; ④PBC, in the absence of typical autoantibodies (cryptogenic chronic hepatitis), which is a normal cholangiogram and no evidence of inflammatory bowel disease; ⑤Genes: Garcia studied 22 Caucasian patients with mild idiopathic adulthood ductopenia (MIAD), found that a different pattern of HLA-DRB1 increased in MIAD, and positions 25 and 32 of the beta chain of the HLA- DR associated with MIAD respectively[8-10]. Kelly et al[9] reported five cases in three generations with one IAD Family, suggesting that genetic factors may play an important role in IAD.

Clinical characteristics of IAD
Nearly one third of the IAD patients started with jaundice, pruritus, which attacked recurrently and were gradually progressive and severe; A few patients, first manifested esophageal varices resulted from portal hypertension or upper gastrointestinal bleeding; some had no symptoms, and only serum biochemical tests of liver function showed a predominantly cholestatic pattern. Medical check-up found xanthochromia, pigmentation and splenohepatomegalia in various degrees. Laboratory studies showed GGT level and ALP level increased, simultaneously with hyperbilirubinemia and hypercholesteremia, which manifested bilirubin rising up mostly. In addition, for most patients AST level and ALT level were abnormal too, in advanced stage, hypoproteinemia happened probably. Imageology-scopy: retrogressive pancreatocholangiography showed intrahepatic and extrahepatic biliary ducts were normal, and normal colonoscopy excluding inflammatory bowel disease-related cholangiopathy, which would help to distinct to IAD and PSC[1-5, 11-15].

Diagnosis of IAD
Diagnostic criteria of IAD was proposed by Ludwig et al[1-2]: ① Entity in adults, including anaphase of puberty; ②Biochemical tests of liver function showed a predominantly cholestatic pattern, and ALP level increased; ③Showed the disappearance of interlobular and septal bile ducts in at least 50% of the portal tracts; ④Cholangiography and duplex contrasting retrogressive colon opacification or colonoscope had no abnormality seen. Exclusion criteria: ①History of infantile cholangiopathy, contacting history of drug or poison and evidence of inflammatory bowel disease; ②Serum AMA was positive; ③Having granulomatous cholangitis, neutrophilia purulent cholangitis or non-neutrophilia cholangitis, histiocytosis X, lymphoma or neoplasmin liver biopsy specimens; ④Imageology-scopy found small bile duct associated big bile duct abnormality and/or inflammatory bowel disease signs. However, the criteria needed to be modified further more. First, the diagnosed age had to be debated. Some scholars proposed whether to include adolescence. Second, some documents indicated when most of the intrahepatic biliary ducts injured, having inflammation, and the rest of small biliary ducts disappeared absolutely, appearing destructive biliary ducts injuring, though disappearance of interlobular bile ducts was not up to the index (≥50%), it could also diagnose IAD; Besides，disappearance of interlobular bile ducts less than 50% was definite mild IAD in some documents[16-21]. The third, the author presumed, although serum positive AMA was the exclusive criteria of IAD, for it is conceivable that IAD could be considered a form of isolated, atypical, or limited variant of primary sclerosing cholangitis, positive AMA could not exclude IAD. Our documents showed, though AMA was slight positive, liver biopsy specimens before and after operation all confirmed IAD.
Pathematology diagnostic criteria: Absence of interlobular bile ducts in at least 50% of small portal tracts on an adequatesized liver biopsy specimen. Microscope-scopy found destructive cholangeitis, biliary tract piecemeal necrosis, cholestasis, canals of Hering accrementition, portal areas inflammation and secondary primary biliary fibrosis, cirrhosis[1-5].

Treatment and prognosis of IAD
So far no medicine can be used to treat IAD. Since the etiological factors of IAD were not definite yet, patients can be only given palliative treatments. Many groups[9, 12] proposed that adrenal cortex steroid, ursodeoxycholic acid could obtain satisfying effects (mainly for inchoate longitudinalcholestasis), such as improvement of liver function and decrease of the clinical symptoms. However, large-sample random investigation is lacking. The effects of ursodeoxycholic acid to the progression of disease are unclear. The patients in our team had already used adrenal cortex steroid, ursodeoxycholic acid, and the effect was not significant.
Asymptomatic IAD progressed slowly, and the prognosis was better. Whether liver transplantation is needed for treatment needs further investigation. Some documents represented giving supportive treatment and monitoring biochemical indicator carefully[5], others claimed liver transplantation in nonage was more effective[17]. When patients with IAD appeared to liver failure, or severe intractable cholestatic symptoms such as refractory severe pruritus, OLT is an only effective therapeutics approach[16]. The symptoms and biochemical indexes were improved in short time. Summarizing the documents, there were 8 patients of IAD accepting liver transplantation so far, in which 4 cases survived more than 1 year. Sherlock[11] and Burak[10] respectively reported 1 patient survived for 7 years and the other survived for 12 years after liver transplantation. Both of them were fine. The patient in our group, at follow-up 51 months after transplantation, was doing well with normal results of liver function studies and no evidence of recurrence.
For patients of IAD after liver transplantation，there was no standard immunodepressive treatment. Numerical documents manifested that the patients often needed combination with low dose steroid for immunodepressive treatment in long term. Sherlock[11] reported 1 case, who took ciclosporin azathiopurine and radiosone, emerged rapid rejection on day 5 after liver transplantation. When steroid impulsing treatment was carried, liver function reversed in short time. Then low doses steroid was used continuously until 5 years after liver transplantation. During follow-up 7 years after transplantation, she was doing well with normal liver function and no evidence of recurrence. The patient from our report, who used tacrolimus, MMF and methylprednisolone for immunodepressive treatment, had one episode of acute cellular rejection 21 months after liver transplantation because of lower steroid doses. But when she got higher sterol doses, liver function recovered quickly. Up to now, During follow-up, 51 months after transplantation, she had been doing well with low doses steroid therapy. The effect of sterol is still unknown, but many groups showed that combination with low doses sterol for immunodepressive treatment could reduce the danger of rejection.