Vitamin B6 predicts poor outcomes in geographically distinct populations with primary sclerosing cholangitis

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BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) has a variable disease course, complicating patient counseling and the timing of liver transplantation. Vitamin B6 deficiency predicts reduced liver transplantation-free survival in Scandinavian PSC cohorts. Here, we aimed to validate this observation in US and German PSC cohorts and to expand our analyses to include hepatic decompensation as a clinical outcome. METHODS: Serum active vitamin B6 (pyridoxal 5'-phosphate [PLP]) was analyzed using liquid chromatography-tandem mass spectrometry in retrospective cohorts of people with PSC from Norway (n = 315), the USA (n = 756), and Germany (n = 149). Cox proportional hazards and Fine and Gray competing risk models were fitted to estimate the ability of PLP to predict liver transplantation-free survival and the cumulative incidence of hepatic decompensation, respectively. RESULTS: The prevalence of vitamin B6 deficiency (PLP <20 nmol/L) in pre-transplant PSC was 50% in the Norway cohort and 25% in the USA cohort. The prevalence was higher among those with previous hepatic decompensation. The cumulative incidence of hepatic decompensation was higher in the USA cohort, while individuals in the Norway cohort were more commonly transplanted for indications other than hepatic decompensation. Despite differences in clinical practice, low PLP was consistently associated with shorter liver transplantation-free survival, and PLP added predictive value for liver transplantation or death from PSC over and above contemporary prediction models. Low PLP was also associated with a higher incidence of hepatic decompensation, which was mainly evident in the USA cohort, where decompensation was more common. The risk of both outcomes increased sharply within the deficient and marginal ranges and plateaued at sufficient PLP levels. CONCLUSIONS: Vitamin B6 deficiency is common in PSC outside Scandinavia and is consistently associated with poor outcomes across geographically distinct PSC populations. IMPACT AND IMPLICATIONS: We previously showed that vitamin B6 deficiency is prevalent and associated with reduced liver transplantation-free survival in Scandinavian PSC cohorts. The current work shows that these observations generalize to a US population and that low vitamin B6 is also associated with the development of hepatic decompensation. Our results indicate that vitamin B6 provides incremental value for predicting outcomes in PSC across geographically distinct populations and that efforts to restore B6 sufficiency should be focused on the many individuals who present with vitamin B6 levels within the marginal-to-definitive deficiency range.

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