EASL Clinical Practice Guidelines

PSC–AIH overlap syndrome

Diagnosis

PSC–AIH overlap syndrome is an ill-defined immune-mediated disorder which is predominantly found in children, adolescents and young adults [[98], [140], [141], [142], [143], [144], [145], [146], [147], [148]]. Its characteristics include clinical, biochemical, and histologic features of AIH as summarized in the modified AIH score defined by an international group of experts for study purposes [62] and cholangiographic features typical of PSC [60]. Retrospective diagnosis of an overlap syndrome by use of the modified AIH score was established in 8% of 113 PSC patients from The Netherlands [149], and in 1.4% of 211 PSC patients from the U.S. (with somewhat incomplete data available for retrospective analysis) [150]. Prospective analysis of 41 consecutive PSC patients from Italy for the presence of: (i) a revised AIH score >15; (ii) ANA or ASMA antibodies present in a titre of at least 1:40; and (iii) liver histology with piecemeal necrosis, lymphocyte rosetting, and moderate or severe periportal or periseptal inflammation revealed a PSC–AIH overlap syndrome as defined by these criteria in 17% [151]. These patients were treated with UDCA (15–20 mg/kg daily), prednisolone (0.5 mg/kg daily, tapered to 10–15 mg/d) and 50–75 mg azathioprine with good biochemical response.

The largest case series reported so far consisted of 27 children with PSC–AIH overlap syndromes from England [98] out of 55 children with clinical, biochemical, and histological signs of AIH, followed prospectively for 16 years. Children and adolescents with PSC–AIH overlap syndrome more commonly suffered from IBD and more often were positive for atypical pANCA in serum than those with AIH only. Otherwise, they presented with similar signs and symptoms. Serum transaminases tend to be higher in AIH, but serum AP although mostly elevated in PSC, may be normal both in PSC–AIH overlap syndrome and AIH. Increasing awareness for the PSC–AIH overlap syndrome has led to the observation that AIH and PSC may be sequential in their occurrence, and this has been described in children [98] and adults [152]. Thus, in patients with AIH who become cholestatic and/or resistant to immunosuppression, PSC should be ruled out.

Therapy

UDCA is widely used in the treatment of PSC although long-term efficacy remains unproven so far [[112], [113], [114], [115], [116], [117]]. UDCA has been used in combination with immunosuppressive regimens in PSC–AIH overlap syndrome [[98], [151]]. A response to immunosuppressive therapy has been documented in children [98]. UDCA in combination with an immunosuppressive regimen might, therefore, be an adequate medical treatment for most patients with PSC–AIH overlap syndrome [151], although no data of controlled trials exist. Prognosis of PSC–AIH overlap syndrome was reported to be better than that of PSC [151], but worse than that of AIH [148]. Liver transplantation is indicated in end-stage disease.

Recommendations

  1. PSC–AIH overlap syndrome is an ill-defined immune-mediated disorder characterized by histological features of AIH and cholangiographic findings typical of PSC (III/C2).
  2. Medical treatment of AIH–PSC overlap syndrome with UDCA and immunosuppressive therapy is recommended, but is not evidence-based due to lack of adequate studies (III/C2). Liver transplantation is the treatment of choice for end-stage disease (III/A1).