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TOPLINE:

Lower vitamin B6 levels were associated with a higher risk for liver transplantation or death and hepatic decompensation across geographically distinct populations with primary sclerosing cholangitis (PSC). Notably, the risk rose sharply at low vitamin B6 levels and plateaued once sufficient levels were reached.

METHODOLOGY:

• Patients with PSC commonly have reduced microbiome capacity to produce active vitamin B6 (pyridoxal 5’-phosphate [PLP]); low circulating PLP levels predict worse liver transplant-free survival and add prognostic value beyond established models, but this prognostic association has so far only been studied in Scandinavian cohorts.
• Researchers analyzed serum samples from 315 patients in Norway and 149 patients in Germany and 806 serum samples from 756 patients in the US to evaluate the prognostic impact of vitamin B6 on clinical outcomes in PSC; samples from the US and Norwegian cohorts were collected between 2004 and 2022 and 2008 and 2022, respectively.
• Serum levels of active vitamin B6 were measured using liquid chromatography-tandem mass spectrometry; patients were categorized as vitamin B6 deficient (PLP levels < 20 nmol/L), marginally deficient (PLP levels of 20 to < 40 nmol/L), and sufficient (PLP levels ≥ 40 nmol/L).
• The primary outcome was the composite endpoint of liver transplantation or PSC-related mortality within 5 years after blood sampling.
• The secondary outcome was hepatic decompensation within 5 years, defined as the composite endpoint of at least one complication (such as variceal bleeding, ascites, or encephalopathy).

TAKEAWAY:

• Vitamin B6 deficiency was prevalent in 50% of patients in the Norwegian cohort, 25% of those in the US cohort, and 62% of those in the German cohort; deficiency was more prevalent among those with hepatic decompensation.
• Over 5 years, elevated PLP levels were associated with improved liver transplantation-free survival across all cohorts: The hazard ratio (HR) was 0.47 (95% CI, 0.39-0.57) for the US cohort, 0.44 (95% CI, 0.35-0.55) for the Norwegian cohort, and 0.39 (95% CI, 0.31-0.51) for the German cohort; the associations remained significant after adjustments for sex and established risk scores in both the US and Norwegian cohorts.
• During the 5-year follow-up, increasing PLP levels were associated with a lower risk for hepatic decompensation in the US cohort (subdistribution HR, 0.49; 95% CI, 0.40-0.59), which remained significant after adjusting for sex and risk scores; however, in the Norwegian cohort, the association was significant in univariable analysis but not in multivariable models.
• Overall, the risk for liver transplantation or death and hepatic decompensation was higher among patients with low vitamin B6 levels, particularly within the marginal and deficient ranges; however, outcomes were similar among those with sufficient levels.

IN PRACTICE:

“Overall, we demonstrate that the prognostic value of PLP in [primary sclerosing cholangitis] translates to different countries with varying clinical practices. Hence, future efforts to develop risk prediction models for [primary sclerosing cholangitis] should consider PLP as a candidate prognostic factor,” the authors of the study wrote.

SOURCE:

The study was led by Peder R. Braadland, Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway, and Ahmad H. Ali, University of Missouri School of Medicine, Columbia, Missouri. It was published online in the Journal of Hepatology.

LIMITATIONS:

Patients in all three cohorts were referred to tertiary care centers for higher-level care, potentially limiting the generalizability of the findings to milder PSC phenotypes. In the US cohort, individuals without available biochemistry data were excluded from multivariable models. Additionally, analyses estimating the association of PLP with hepatic decompensation accounted for competing risks.

DISCLOSURES:

The study received funding from the South-Eastern Norway Regional Health Authority. Two authors reported receiving support from other sources. The authors declared having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.