Primary Sclerosing Cholangitis: Multiple Phenotypes, Multiple Approaches

Abstract

Primary sclerosing cholangitis (PSC) is a heterogeneous, idiopathic, inflammatory disorder frequently associated with inflammatory bowel diseases. PSC patients may be classified into several subphenotypes. Investigations of pediatric, nonwhite, and female PSC patients have revealed distinguishing features. The natural history of PSC is variable in progression with numerous possible clinical outcomes. PSC patients may suffer bacterial cholangitis, cholangiocarcinoma, or colorectal adenocarcinoma. Treatments focusing on bile acid therapy and immunosuppression have not proven beneficial. Interest in PSC and international collaboration has led to improved understanding of the heterogeneity and the genetic structure and introduced possible effective therapeutics.

Keywords: Autoimmune hepatitis; Diagnosis; IgG4-related sclerosing cholangitis; Primary sclerosing cholangitis; Treatment.

Figure 1

Multiple clinical features have been identified which can be used to describe a variety of PSC phenotypes. In isolation, each has been shown to segregate groups of PSC patients with differences in outcomes or response to treatment.

Figure 2

A proposed management algorithm for PSC patients presenting with sclerosing cholangitis. Data is limited to case series for PSC patient with elevated IgG4 levels or PSC-AIH Overlap and response-guided treatment with ursodeoxycholic acid (UDCA) has not been prospectively validated. ^{, ,} A biochemical response is defined by a reduction in alkaline phosphatase to lower than 1.5 X ULN. In addition to treatment, monitoring and surveillance studies should include those to investigate liver disease progression (laboratories, transient elastography or MR elastography); malignancy (annual colonoscopy if inflammatory bowel disease is present; annual abdominal imaging and serum CA19-9); and co-morbid conditions (bone density scan; fat soluble vitamins; celiac disease serologies).

Figure 3

Graphical representation of the possible combinations of clinical features associated with PSC phenotypes. Not included is sex/gender.