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

Background and aims We 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 (LT). Methods We 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 our earlier findings. Furthermore, we 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. We used Cox regression 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 PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. Impact and implications We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.publishedVersio

“Inclusive Working Life” in Norway – Experience from “Models of Good Practice” Enterprises

Aim To determine whether enterprises belonging to the Bank of Models of Good Practice were more successful than average Norwegian enterprises in the reduction of sickness absence, promotion of early return to work, and prevention of early retirement. Methods In 2004 we selected 86 enterprises with a total of approximately 90 000 employees from the Inclusive Working Life (IWL) Bank of Models of Good Practice. One representative of workers and one of management from each enterprise received a questionnaire on the aims, organization, and the results of the IWL program by mail. Data on sickness absence, use of early retirement, and disability retirement in the 2000-2004 period were collected from the National Insurance Registry. Data on comparable enterprises were obtained from the National Bureau of Statistics. Results The response rate was 65%. Although the IWL campaign was directed at reducing sickness absence, preventing early retirement, and promoting employment of the functionally impaired, most attention was paid to reducing sickness absence. Sickness absence rate in Models of Good Practice enterprises (8.2%) was higher than in comparable enterprises that were not part of the Models of Good Practice (6.9%). Implementation of many IWL activities, empowerment and involvement of employees, and good cooperation with the occupational health service were associated with a lower rate of sickness absence. On average, 0.7% new employees per year received disability pension, which is a significantly lower percentage than expected on the basis of the rate of 1.3% per year in comparable enterprises. Frequent use of disability pensioning was associated with high rate of sickness absence and having many employees older than 50 years. On average, 0.4% employees per year received early retirement compensation, which was expected on the basis of national estimates. Frequent use of early retirement was associated with having many employees older than 50 years. Conclusion Models of Good Practice enterprises had a higher than expected sickness absence rate. This indicates that it is difficult to identify Models of Good Practice enterprises and that they cannot be treated as role model enterprises. Good cooperation with the occupational health service and the empowerment and involvement of the employees is associated with a low sickness absence rate