Original articleHigh prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis☆
Introduction
The term Overlap Syndrome has been used since two decades to describe the concurrence of clinical, biochemical, serological and/or histological features reminiscent of AIH and PSC (or primary biliary cirrhosis), extensively reviewed by Czaja [24], [25]. However, the distinction between the disease entities is not clear-cut. Thus, Primary sclerosing cholangitis (PSC) has many histological and clinical features in common with autoimmune hepatitis (AIH). Interface hepatitis, formerly called piecemeal necrosis, a hallmark of AIH, may be seen also in PSC [1], [2], [3]. Increased serum immunoglobulin levels and circulating autoantibodies [1], [4], [5], [6], [7], [8], as well as an increased prevalence of extrahepatic autoimmune diseases [8] are established features of PSC, even though abnormalities in this respect are usually more pronounced in AIH than in PSC. Concurrence of PSC and ulcerative colitis is very common [9], [10]. Concurrence of AIH and ulcerative colitis has also been reported [11], [12], [13], [14], but an increased frequency of AIH in ulcerative colitis has not been observed. Up to 1996, altogether 6 cases of the simultaneous occurrence of AIH and PSC had been reported [15], [16], [17], [18], [19]. The same year two different groups published assessments of features of AIH in a large number of patients with a cholangiography based diagnosis of PSC, using the AIH scoring system proposed by the International Autoimmune Hepatitis Group in 1993 [20]. They observed that 2 to 3.4% of these patients obtained scores diagnostic for “definite” AIH, and 33 to 52% scores diagnostic for “probable” AIH [21], [22]. In 1999, the International Autoimmune Hepatitis Group published a revised version of the original AIH scoring system, aimed at improving the specificity and simplify its use [23]. Application of this modified scoring to one of the previously studied PSC cohorts reduced the percentage “probable” AIH from 33 to 8.8% [23]. Thus, even with the modified AIH scoring model, a considerable proportion of PSC patients have features consistent with AIH.
More recent studies that have applied the modified AIH scoring system have reported prevalences of “probable” or ”definite” AIH between 8 and 14% of PSC patients [26], [27]. Common to these publications was that the diagnosis of PSC was confirmed with cholangiography in all patients. The term small duct PSC was introduced to describe an entity with features in common with PSC but lacking the characteristic cholangiographic changes in extra- and/or intrahepatic bile ducts [15], [28]. Herein, we report a previously not described high prevalence of small duct PSC among patients with overlapping autoimmune hepatitis and PSC.
Section snippets
Methods
The authors, all members of the Swedish Internal Medicine Club (SILK) and working at six different regional university hospitals, decided to report for further histological and clinical evaluation all cases of a possible overlap syndrome between PSC and AIH, with the liver biopsy as diagnostic starting point, known to them. Altogether 31 patients were retrieved and reported. The study design was approved by the committees of human ethics in Gothenburg and by the local committees.
Results
The total cohort of 26 patients, that fulfilled our histological criteria for PSC and International Autoimmune Hepatitis Group criteria for AIH, corresponded to 5.1% of the PSC population and 4.2% of the AIH population in the participating centres. There were 9 women with a mean age of 37 (SD 18) years, and 17 men with a mean age of 30 (SD 15) years at first diagnosis of liver disease.
Discussion
The strength of the present study is that it highlights for the first time that patients with small duct PSC constitutes a considerable proportion of the cohort of patients with overlap syndrome between PSC and AIH. However, it should be pointed out this report is not based on a systematic reevaluation of biopsies from all AIH patients known by the authors, nor were cholangiograms performed in all patients with high alkaline phosphatase values. Also, cases with abnormal cholangiograms lacking
Learning points
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Patients with autoimmune hepatitis, who have biochemical features of cholestatic liver disease, may have an overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.
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If the cholangiogram is normal, the patient may have a small duct primary sclerosing cholangitis, a diagnosis that requires a liver biopsy.
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Therefore, even though a liver biopsy is nowadays not considered necessary in patients with primary sclerosing cholangitis, it should be performed in patients with
Acknowledgement
The authors gratefully acknowledge the financial support for the Swedish Internal Medicine Liver Club from Meda Ltd.
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The financial support from Media Ltd. is restricted to a 50% financial support for the SILK group meetings twice annually. The funding is independent of this and other SILK studies.