Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation

Background & aimsWe previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5’-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation.MethodsWe used targeted LC-MS/MS to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n=158) sampled prior to and serially after liver transplantation (LT), and cohorts of people with inflammatory bowel disease (IBD) without PSC (n=51) and primary biliary cholangitis (PBC) (n=100) as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT.ResultsIn different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant-recipients with recurrent disease.ConclusionsLow vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings may suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation.Lay summaryWe have discovered that people with primary sclerosing cholangitis often lack enough vitamin B6, and even after a liver transplant, this deficiency remains common. People with PSC with low level of vitamin B6 had low activity of cellular functions important for human health, and low vitamin B6 resulted in poor outcomes for both transplanted and non-transplanted individuals. Our research provides a good reason to measure vitamin B6 investigate whether taking vitamin B6 supplements can help improve outcomes for people with primary sclerosing cholangitis.