Dehydroepiandrosterone sulfate indicates decreased sulfation capacity and impaired quality of life in patients with primary sclerosing cholangitis.

Abstract

Impaired elimination of toxic compounds via inadequate sulfation may contribute to the pathogenesis of primary sclerosing cholangitis (PSC). Dehydroepiandrosterone (DHEA), which is metabolized into its sulfated form (DHEA-S) in the liver, has been linked with health-related quality of life (HRQoL) in various conditions. We aimed to assess the sulfation capacity of the liver in PSC using DHEA-S as a surrogate marker. We assessed serum levels of DHEA-S in 233 patients with PSC and in 201 patients with other liver conditions serving as controls. We also evaluated the effect of low levels of DHEA-S on the course of PSC and HRQoL assessed using the 36-Item Short Form Health Survey (SF-36) and the PBC-40. The proportion of patients with low DHEA-S in the PSC group was 7-fold higher than in the control group (21% vs 3%; P <⁠0.001). Patients with decreased levels of DHEA-S were younger at the time of PSC diagnosis (median age, 23 vs 29 years; P = 0.007) and presented with lower HRQoL scores, particularly regarding the physical domains of the SF-36. Patients with low DHEA-S also complained of more severe fatigue (31 vs 23; P = 0.006) assessed with the PBC-40. Our findings support the role of impaired liver sulfation capacity in the development of PSC. Low levels of DHEA-S are associated with increased fatigue, a devastating symptom significantly affecting HRQoL. Thus, the effects of DHEA administration on chronic fatigue and other measures of HRQoL in patients with PSC warrant further attention.