Sex and Age Are Determinants of the Clinical Phenotype of Primary Biliary Cirrhosis and Response to Ursodeoxycholic Acid
Gastroenterology | 19 Dec 2012
M Carbone, G Mells, G Pells, MF Dawas, JL Newton, M Heneghan, J Neuberger, D Day, SJ Ducker, R Sandford, G Alexander and DE Jones
BACKGROUND & AIMS:: Studies of primary biliary cirrhosis (PBC) phenotypes have largely been performed using small and used selected populations. Study size has precluded investigation of important disease sub-groups, such as men and young patients. We used a national patient cohort to obtain a better picture of PBC phenotypes. METHODS:: We performed a cross-sectional study using the United Kingdom-PBC patient cohort. Comprehensive data were collected for 2353 patients on diagnosis reports, response to therapy with ursodeoxycholic acid (UDCA), laboratory results, and symptom impact (assessed using the PBC-40 and other related measures). RESULTS:: Seventy-nine percent of the patients reported current UDCA therapy, with 80% meeting Paris response criteria. Men were significantly less likely to have responded to UDCA than women (72% vs 80% response, P <.05); male sex was an independent predictor of non-response on multivariate analysis. Age at diagnosis was strongly and independently associated with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than 70 y, to less than 50% for those younger than 30 y ( P <.0001). Patients who presented at younger ages were also significantly more likely not respond to UDCA therapy, based on alanine aminotransferase and aspartate aminotransferase response criteria, and more likely to report fatigue and pruritus. Women had mean fatigue scores 32% higher than men's ( P <.0001). The increase in fatigue severity in women was strongly related (r=0.58, P <.0001) to higher levels of autonomic symptoms ( P <.0001). CONCLUSIONS:: Among patients with PBC, response to UDCA treatment and symptoms are related to sex and age at presentation, with the lowest response rates and highest levels of symptoms in women presenting at <50 years of age. Increased severity of fatigue in women is related to increased autonomic symptoms, making dysautonomia a plausible therapeutic target.
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