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

Abstract

Primary sclerosing cholangitis (PSC) has a variable disease course, complicating patient counseling and 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 U.S. and German PSC cohorts and expanded our analyses to include hepatic decompensation as a clinical outcome. Serum active vitamin B6 (pyridoxal 5'-phosphate, PLP) was analyzed using LC-MS/MS in retrospective cohorts of people with PSC from Norway (NOR, N=315), the U.S. (USA, N=756), and Germany (GER, 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. The prevalences of vitamin B6 deficiency (PLP<20 nmol/L) in pre-transplant PSC from the NOR and USA cohorts were 50% and 25%. 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 NOR cohort were more commonly transplanted for indications other than hepatic decompensation. Despite differences in clinical practice, low PLP consistently associated with shorter liver transplant-free survival, and PLP added value to predict liver transplantation or death from PSC over and above contemporary prediction models. Low PLP also associated with higher incidence of hepatic decompensation, which was mainly evident in the USA cohort, where decompensation was more common. The risk of both outcomes rose sharply in the definitive and marginal deficiency ranges and plateaued beyond sufficiency levels. Vitamin B6 deficiency was common in PSC also outside Scandinavia and consistently associated with poor outcomes in geographically distinct PSC populations. We previously showed that vitamin B6 deficiency was prevalent and associated with reduced liver transplantation-free survival in Scandinavian PSC cohorts. The current work shows that these observations are translatable to a U.S population and that low vitamin B6 also associates with development of hepatic decompensation. Our findings show that vitamin B6 adds value to predict outcomes in PSC across geographically distinct PSC 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.