Management of primary sclerosing cholangitis and its complications: an algorithmic approach

Abstract

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterized by multiple strictures and dilatations of the intra- and extrahepatic bile ducts, leading to progressive liver fibrosis, in 10-15% cholangiocarcinoma, and ultimately end-stage liver disease. The pathogenesis is poorly understood, but (epi-)genetic factors, mechanisms of innate and adaptive immunity, toxic effects of hydrophobic bile acids, and possibly intestinal dysbiosis appear to be involved. The strong link with inflammatory bowel disease (IBD) is associated with a markedly enhanced risk of colorectal cancer which next to cholangiocarcinoma represents the most serious diagnostic challenge in long-term PSC management. Despite extensive research, no medical treatment has been proven so far to prolong the time to liver transplantation (LTx), which remains the effective treatment in late-stage disease. Recurrence of PSC after LTx is observed in up to 20% of patients. Here, we briefly summarize actual views on PSC pathogenesis and provide an algorithmic approach to diagnostic procedures and recommendations for the management of PSC and its complications. We describe promising treatment options subject to current clinical trials.

Keywords: Bezafibrate; Bile acids; Cholangiocarcinoma; Cholestasis; FXR; Liver transplantation; Obeticholic acid; Primary sclerosing cholangitis; Pruritus; Ursodeoxycholic acid.

Fig. 1

The algorithmic approach to the patient with cholestasis [2, 60]. AMA anti-mitochondrial antibodies, ANA antinuclear antibodies, sp100 sp100 nuclear antigen, gp210 glycoprotein 210, ALP alkaline phosphatase, GGT gamma-glutamyl transferase, ERCP endoscopic retrograde cholangiopancreatography, MRCP magnetic resonance cholangiopancreatography, PBC primary biliary cholangitis, PSC primary sclerosing cholangitis

Fig. 2

Typical cholangiogram in PSC. Multiple short strictures (indicated by arrows) and dilatations of intra- and extrahepatic bile ducts forming a “beaded pattern” are visible representing the characteristic ERCP finding in a PSC patient

Fig. 3

Histological findings in PSC. Concentric periductal fibrosis (“onion-skin”, indicated by arrows) with oedema and inflammatory portal cell infiltrate (Giemsa stain). The biopsy was performed on a 19-year-old man with newly diagnosed ulcerative colitis, markedly elevated cholestatic serum markers, and no cholangiographic changes. Five years later cholangiography showed typical findings of PSC

Fig. 4

Algorithmic approach to the patient with sclerosing cholangitis. Causes of secondary sclerosing cholangitis have to be excluded before a diagnosis of PSC can be made

Fig. 5

Major mechanisms and sites of action of UDCA in cholestatic diseases [60]. Reprinted with permission from the author and Elsevier

Fig. 6

Algorithmic approach to (1) diagnosis and (2) management of PSC and its complications, and (3) recommended screening for patients with PSC