Serum bilirubin concentrations and their association with clinical and radiological outcomes in multiple sclerosis: A large cohort study.

Introduction and objectives: Bilirubin is negatively associated with neurodegenerative diseases, including multiple sclerosis (MS). Since previous studies were small or did not evaluate all diagnostic aspects, the objective of the present study was to assess a large cohort of MS patients with multiple determinations of serum bilirubin.

Patients and methods: The study was carried out in 2,696 consecutive MS patients (median age=37.1 years, disease duration=6.8 years, follow-up duration=7.2 years, and Expanded Disability Status Scale (EDSS)=2.5) with 28,501 visits. Individuals from the Czech post-MONICA study representing the general Czech population (n=2,621) were used as controls. Serum bilirubin concentrations in study subjects were compared with multiple diagnostic and clinical parameters.

Results: Serum bilirubin concentrations in MS patients were significantly lower compared to the general population (8.3 vs. 9.6 μmol/L, P<0.001). Hyperbilirubinemia >17 µmol/L in MS patients was much less frequent compared to the general population (8.2 vs. 12.5 %, P<0.001). An increase in disease duration by 10 years was associated with an 8 % decrease in bilirubin concentration (p<0.0001). Ten percent higher serum bilirubin concentration was associated with a 9 % decrease in EDSS (p=0.001) and a 1.5 % decrease in normalized brain volume (p<0.0001). The frequencies of individual UGT1A1 (TA)n/n genotypes did not differ between MS patients and the control population.

Conclusions: MS patients have markedly lower serum bilirubin concentrations, most likely due to consumption during the increased oxidative stress since the frequencies of UGT1A1 were comparable in the MS and control populations. Higher serum bilirubin is associated with lower disability and lower brain atrophy.