This study showed that, of 24 patients who were identified from a cohort of 118 AIH patients by the development of cholestatic LFTs, one half (12/24) had features of PSC on MRC evaluation, indicating a diagnosis of AIH / PSC OLS. A retrospective comparison of this cholestatic group with a control population at the time of presentation, was performed in an attempt to identify important early predictive features for developing OLS. At time of original diagnosis of AIH, patients in the cholestatic group had lower transaminases, higher serum IgM levels and a greater incidence of ulcerative colitis. IAHG scores were lower than the control group. In our cohort, no other clinical or pathological differences between the two groups were statistically significant.
Many groups have studied patients with autoimmune liver disease. Abdamlian et al.11 prospectively studied 79 patients with a clinical diagnosis of AIH. They found that 10% had definite or probable PSC on MRC. Predictors of PSC were younger age at diagnosis, elevated alkaline phophatase at diagnosis, elevated bilirubin at time of MRC, and greater lobular activity on initial liver biopsy. Gheorghe et al.10 studied 82 patients with AIH. Only eight of this group underwent ERCP (based on a cholestatic biochemical or histological profile), of which seven were positive for features of PSC. Therefore at least 7% of their AIH cohort had features of AIH / PSC OLS. Our finding that at least 12 (10%) of 118 AIH patients developed AIH / PSC OLS is consistent with these studies. The most comprehensive descriptive epidemiology of autoimmune liver disease prevalence and categorisation comes from Czaja et al.15, who retrospectively reviewed 225 patients with any autoimmune liver disease. Of the 225 patients, 18% were reclassified as having OLS. 14 of 26 patients with PSC (54%) were found to have features of AIH and PSC.
Four large studies have reviewed patients with cholangiographically-proven PSC for features of AIH (assessed by IAHG criteria7). Kaya et al.12
(n=211) reported 1.4% of PSC cases had ‘definite’ AIH and 6% had ‘probable’ AIH. Floriani et al.14
(n=41) found 17% with AIH, van Burren et al.13
(n=113) found 8% with ‘definite’ AIH, and Boberg et al.4
(n=114) found 2% with ‘definite’ and 33% with ‘probable’ AIH.
The pathogenesis, time of disease onset, and sequence of progression of AIH / PSC OLS is poorly understood5,19,20
. Retrospective analysis of the initial diagnosis is usually impossible because most patients do not have both cholangiography and liver biopsy performed at time of diagnosis of AIH. McNair et al.21
presented five cases of AIH / PSC OLS. Two had ‘pure’ AIH at diagnosis, which transformed into AIH / PSC OLS subsequently. Three had concurrent features of AIH and PSC at presentation. Abdo et al.22
reviewed 91 patients with AIH. Six patients (7%) subsequently developed cholangiographically-proven PSC. This included three patients with a previously normal cholangiogram, performed after the initial diagnosis of AIH. Gregorio et al.23
prospectively studied children attending King's College Hospital liver clinic (London, UK) with a diagnosis of AIH (n=28) or PSC (n=27). All patients underwent biopsy and cholangiography at presentation. Of the 27 patients with PSC, 14 (52%) had ‘definite’ and 13 (48%) ‘probable’ AIH by IAHG scores. One patient with ‘pure’ AIH and normal cholangiography at presentation, subsequently developed cholangiographically-proven PSC. As discussed by these and other authors, it appears that some cases of ‘pure’ AIH, with no features to indicate AIH / PSC OLS at diagnosis originally, subsequently can transform into AIH / PSC OLS21,22
The main weaknesses of this study are the small number of patients and incomplete data. Clinical notes for baseline data at diagnosis were not always available due to the long duration of follow-up. Many cases did not have a liver biopsy performed and some liver biopsies were unavailable or uninterpretable. MRC scanning is clearly preferable to ERCP from a patient perspective, but may cause claustrophobia, which prevented MRC in one case. MRC has a sensitivity of 82 to 91% and specificity of 85 to 98%24,25
, when compared to the ‘gold standard’ ERCP for the diagnosis of PSC. The sensitivity of MRC has improved due to better availability and quality of MR scanning. ‘Small duct’ PSC (biochemical and histological features of PSC, but normal cholangiography) will not necessarily have been identified by our investigations. Angulo et al.26
identified 18 patients (5.8%) from their PSC cohort (n=309), with ‘small duct’ PSC. Only 25 AIH patients, out of our cohort of 118, underwent cholangiography. Therefore, the prevalence of AIH / PSC OLS may be even greater in our cohort.
This is the first study to examine whether an earlier diagnosis of AIH/PSC OLS could be made in patients with an initial clinical diagnosis of AIH. Our study reiterates the finding of other groups: a significant minority of patients diagnosed with AIH will eventually turn out to have AIH / PSC OLS. There are no clinical, biochemical, serological or histological findings which strongly predict this development. Therefore, we recommend that MRC should be performed in every case of AIH where there is an elevation of ALP and GGT, following a poor transaminase response to corticosteroids. In the event of a normal MRC, liver biopsy should be considered to look for small duct disease. The frequency with which MRC should be performed and whether MRC would reveal cases of AIH/PSC OLS in AIH patients with normal ALP and GGT remain to be determined.