Patients with Primary sclerosing cholangitis show signs of intestinal inflammation even in the absence of clinically manifest IBD
Primary Sclerosing Cholangitis (PSC) is a progressive liver disease frequently associated with Inflammatory Bowel Disease (IBD). The percentage of PSC patients diagnosed with concomitant IBD varies considerably between studies, with the highest incidence of IBD reported in studies that use both endoscopy and histology to screen for intestinal inflammation. This raises the question whether all PSC patients show intestinal inflammation if screened thoroughly, but it only becomes clinically manifest in a subset of patients.   To address this question, we collected intestinal biopsies of healthy controls, PSC, PSC-IBD and IBD patients. Using cytokine expression profiling, 16S sequencing, and in-depth histology and endoscopy scoring, we found that the vast majority of PSC patients even without clinically manifest IBD showed infiltration of immune cells and increased expression of IL17A and IFN? in intestinal biopsies, suggesting that PSC patients have intestinal inflammation on a molecular level. This subclinical inflammation in PSC patients was focused in the distal colon, while PSC-IBD patients presented with inflammation either at the distal colon or on the right side of the colon and the terminal ileum. Furthermore, we also observed that PSC patients without IBD symptoms show signs of dysbiosis and exhibit a distinct microbial profile compared to healthy controls. In summary, we found multiple signs of intestinal inflammation in the majority of PSC patients even in the absence of clinically manifest IBD. Of note, the presence of IBD increases the risk for colorectal cancer. Thus, further studies evaluating the effect of anti-inflammatory therapies and shortened endoscopic screening intervals for colorectal cancer in PSC patients are needed.