Faculty Bibliography

Primary sclerosing cholangitis (PSC) is a rare disease, autoimmune in nature, characterized by biliary strictures, chronic cholestasis, and progressive liver dysfunction. While its pathophysiology differs from primary biliary cholangitis (PBC), therapeutic targets still focus on bile acid regulation. PSC currently has no approved therapies, although several novel agents are under investigation. Cholestatic pruritus, a significant symptom in PSC and PBC, is now recognized as an approvable indication, with emerging therapies showing promise. This article highlights the investigational pipeline for PSC and cholestatic itch.

Primary biliary cholangitis (PBC) is a rare autoimmune liver disease that leads to chronic cholestasis and progressive liver dysfunction. It is often accompanied by extrahepatic symptoms such as pruritus and fatigue, which significantly impair the quality of life. Current treatment options include ursodeoxycholic acid, the standard first-line therapy, along with second-line agents like obeticholic acid, and recently approved seladelpar, and elafibranor. These treatments aim to alleviate symptoms, improve liver function, and slow disease progression. This article focuses on recently approved therapies for PBC, discusses the nuances in their use, and explores the investigational pipeline of novel therapies under development.

AIM/OBJECTIVE:Primary sclerosing cholangitis (PSC) increases the risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients; however, there is a paucity of literature to suggest PSC alone as an independent risk factor for CRC. We aimed to determine if PSC is an independent risk factor for CRC in a large tertiary care medical center. Optimizing screening intervals is of great importance, given the burden and risks associated with a lifetime of colonoscopy screening. METHODS:This retrospective cohort study consists of patients diagnosed with PSC preceding IBD (PSC-IBD) and PSC-only before January 6, 2023 from a large, tertiary, academic medical center. Patients diagnosed with IBD concurrently or before PSC were excluded to reduce IBD's impact on CRC risk. Demographic data and colonoscopy findings were collected and assessed. RESULTS:Overall, 140 patients from all NYU Langone Health clinical settings were included. Patients with PSC-IBD were more likely to be diagnosed with CRC (23.3% vs. 1.8%, p < 0.01) and either low-grade or uncharacterized dysplasia (16.7% vs. 0.0%, p < 0.01) compared with those with PSC-only. Among PSC-only patients, the estimated CRC risk was significantly elevated compared with that expected of the standard NYU Langone population (SIR 9.2, 95% CI 1.1, 33.2). CONCLUSIONS:Our study revealed a significantly heightened CRC risk in PSC-IBD patients compared with those with PSC-only. Importantly, individuals with PSC-only also face a greater CRC risk compared with the general population. Individuals with PSC-alone may require extended screening and surveillance colonoscopy intervals compared with those with PSC-IBD, yet still require more frequent monitoring than screening guidelines recommend for the general population.

The incidence of colorectal cancer (CRC) has declined over time, though it remains a significant cause of morbidity and mortality in the U.S. It has the third highest incidence in incidence among all cancers and is the second leading cause of cancer death in both men and women. Screening reduces the incidence and mortality from CRC. There are several modalities for CRC screening, but the most common ones are a choice between a non-invasive stool-based test, such as fecal immunochemical testing (FIT) or an invasive endoscopic modality, such as colonoscopy. In the U.S. colonoscopy is the predominant CRC screening modality, with observational studies reporting large reductions in CRC incidence and mortality. Recently, a large randomized controlled trial (RCT) on effectiveness of colonoscopy reported smaller than expected reduction in CRC incidence and no reduction in CRC mortality with colonoscopy screening. Explanations of the lower than expected benefit include low uptake of colonoscopy, short follow-up for mortality endpoints and quality indicators (QIs) for some of the endoscopists participating in the screening colonoscopies. The findings of the study need to be taken in context with other literature on effectiveness of colonoscopy, with the overall message of reassuring patients of the benefits of screening, and colonoscopy. Here, we discuss the latest evidence on colonoscopy screening and it in the context of other screening modalities and the landscape.