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

Abstract

INTRODUCTION 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 (DHEAS) in the liver, has been linked with healthrelated quality of life (HRQoL) in various conditions. OBJECTIVES We aimed to assess the sulfation capacity of the liver in PSC using DHEAS as a surrogate marker. PATIENTS AND METHODS We assessed serum levels of DHEAS 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 DHEAS on the course of PSC and HRQoL assessed using the 36Item Short Form Health Survey (SF36) and the PBC40. RESULTS The proportion of patients with low DHEAS in the PSC group was 7fold higher than in the control group (21% vs 3%; P <0.001). Patients with decreased levels of DHEAS 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 SF36. Patients with low DHEAS also complained of more severe fatigue (31 vs 23; P = 0.006) assessed with the PBC40. CONCLUSIONS Our findings support the role of impaired liver sulfation capacity in the development of PSC. Low levels of DHEAS 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.