Liver and Bile
J Hepatol. 2023;79(4):955–66
Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation
Background and aims: The authors 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, they define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT).
Methods: They used targeted liquid chromatography-tandem mass spectrometry 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 their earlier findings. Furthermore, they included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. Cox regression was used to measure the added value of PLP to predict outcomes before and after LT.
Results: In 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 was 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.
Conclusions: Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of primary sclerosing cholangitis (PSC). Pyridoxal 5’-phosphate (PLP) was a strong prognostic biomarker for liver transplant-free survival both in PSC and recurrent disease. These findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation.