Primary Sclerosing Cholangitis: Diagnosis, Management, and Clinical Challenges
Abstract
Primary sclerosing cholangitis is a rare, chronic, inflammatory disease of the biliary tree that leads to progressive ductal obliteration, hepatic dysfunction, and ultimately liver cirrhosis. Most patients eventually require liver transplantation or develop serious complications, the most severe being end-stage liver disease and cholangiocarcinoma. The global prevalence of PSC is rising and has been reported to reach up to 31.7 cases per 100,000 individuals, representing a significant challenge in both diagnosis and management. In this review, we aim to provide a clinically oriented overview of the diagnosis and management of PSC. Furthermore, we seek to highlight key challenges and areas of uncertainty that clinicians encounter in the diagnosis and treatment of patients with this complex disease.
Keywords:
sclerosing cholangitis; PSC; cholangiocarcinoma; diagnosis; clinical challenges
1. Introduction
Primary sclerosing cholangitis (PSC) is a rare, chronic, inflammatory disease that affects the biliary tract, leading to progressive destruction of extrahepatic and intrahepatic bile ducts. This translates into liver dysfunction, cholestasis, and eventually cirrhosis [1]. Most patients develop end-stage liver disease and require liver transplantation [2]. The global prevalence of PSC can be as high as 31.7 per 100,000 individuals, although prevalence varies significantly worldwide, with the highest rates reported in northern Europe (particularly in the Scandinavian region) and a lower incidence in southern Europe and the Middle East [3,4,5].
In addition, other autoinflammatory conditions may co-occur in patients with PSC [6,7], including inflammatory bowel disease (IBD), in up to 80% of cases [7]. The coexistence of IBD and PSC is higher in Scandinavian countries compared to southern Europe. Nevertheless, this difference may reflect selection bias, as Scandinavian countries have easier access to colonoscopy and therefore a lower rate of undiagnosed IBD. In general, the prevalence of PSC in patients with IBD is around 2%, and it correlates with the extent of colitis, being higher in cases of pancolitis [8].
Although symptoms may significantly impact patients’ quality of life, the role of PSC in the development of subsequent cancer warrants particular attention. Indeed, PSC is considered to be the major risk factor for hepato-pancreato-biliary cancers (HPB-cancers), and the risk of cholangiocarcinoma is approximately 400-fold higher that observed in the general population [9,10,11]. Up to 50% of patients with cholangiocarcinoma were diagnosed within the first year after the PSC diagnosis, while the lifetime cumulative incidence is as high as 20% [9,12,13,14,15,16]. In addition to cholangiocarcinoma, PSC harbors an increased lifetime risk for the occurrence of hepatocellular carcinoma (HCC), gallbladder carcinoma, pancreatic cancer, and colorectal carcinoma [17,18,19]. Although follow-up cross-sectional abdominal imaging with magnetic resonance imaging (MRI) has been shown to reduce mortality by approximately 71%, this effect appears to be more related to the earlier identification of conditions amenable to endoscopic treatment, rather than a direct impact on mortality after the diagnosis of cholangiocarcinoma [20].
Table 1. Non-invasive prognostic models/scores. Figure legend: Bil = bilirubin, AST = aspartate aminotransferase, ALP = alkaline phosphatase, PLT = platelets, Hb = hemoglobin, Liver Tx = Liver Transplant.
| Model | Main Endpoint | Variables |
|---|---|---|
| Mayo risk score | 4-year mortality | Age, Bil., AST, albumin and prior variceal bleeding |
| PSC risk estimate tool (PREsTo) | Hepatic decompensation | Bil., albumin, ALP, PLT, AST, Hb, Na, Age, the number of years since PSC was diagnosed |
| UK-PSC scores | Liver Tx or death at 2 and 10 years | Age, Bil., ALP, albumin, PLT, extrahepatic biliary disease and variceal hemorrhage |
| Amsterdam-Oxford model | Death and/or Liver Tx |
PSC subtype, Age, albumin, PLT, AST, ALP, and Bil. |
| Enhanced liver fibrosis (ELF) score | Tx-free survival, liver-related outcomes | Hyaluronic acid, tissue inhibitor of metalloproteinases-1, and pro-peptide of type III procollagen, |
