Original article
High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis

https://doi.org/10.1016/j.ejim.2008.06.004Get rights and content

Abstract

Background

Overlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.

Methods

We sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis autoimmune hepatitis. Endoscopic retrograde cholangiography and/or magnetic resonance cholangiography were used to separate the primary sclerosing cholangitis cases diagnosed through liver biopsy into small and large primary sclerosing cholangitis. A histologocial diagnosis compatible with both autoimmune hepatitis and primary sclerosing cholangitis was required for inclusion.

Results

26 patients fulfilled our criteria for histological overlap of autoimmune hepatitis and primary sclerosing cholangitis, 7 (27%) of which had small duct primary sclerosing cholangitis. The reliability of the diagnosis small duct primary sclerosing cholangitis was supported by a very close similarity between small and large duct primary sclerosing cholangitis patients in clinical and laboratory data, and by a poor response to immunosuppressive therapy in the small duct primary sclerosing cholangitis patients. Patients with large duct overlap syndrome had a good response to immunosuppressive therapy. In both groups, our limited experience from ursodeoxycholic acid was largely poor.

Conclusions

Small duct primary sclerosing cholangitis is prevalent in the overlap syndrome between 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

  • Patients with autoimmune hepatitis, who have biochemical features of cholestatic liver disease, may have an overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.

  • If the cholangiogram is normal, the patient may have a small duct primary sclerosing cholangitis, a diagnosis that requires a liver biopsy.

  • 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.

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