AIM: The aim of this systematic review was to determine if the human colon, through the lower gut-liver axis, drives PSC activity by assessing the progression of the disease in patients with and without colectomy for colonic disease. BACKGROUND: The gut-liver axis is involved in the pathogenesis of liver disease. Abnormal immune-mediated responses to intestinal microbiome are implicated in primary sclerosing cholangitis (PSC) however the mechanisms remain poorly understood. Currently, no single animal model recapitulates all attributes of PSC in humans and this limits further studies of gut-liver interactions. METHODS: A systematic search of PubMed, Medline, and Scopus was performed for articles that contained the terms "colectomy" or "bowel resection" AND "primary sclerosing cholangitis" up to 15th April 2018. Articles were reviewed by 2 reviewers and raw data collated. A Forest plot was used to illustrate the effect of colectomy on subsequent liver transplantation for PSC. Linear regression was used to estimate mortality risk. RESULTS: Colectomy appeared to have no effect on PSC progression, although high-quality studies were lacking. Rates of liver transplantation or transjugular intrahepatic portosystemic shunt for PSC were not affected by colectomy (OR 0.59, 95% CI 0.14 - 2.53, p=0.48). Mortality risk following colectomy in patients with PSC is 2.11% per year (95% CI 0.03% - 4.18%, p=0.032, R2 = 0.722). CONCLUSION: Current evidence is limited but suggests colectomy does not affect the progression of PSC in patients with colonic disease. Pathogenic micro-organisms or antigens that drive PSC may not be limited to the lower gut.