title: Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid.
abstract: BACKGROUND, & AIMS: Studies of primary biliary cirrhosis (PBC) phenotypes largely have been performed using small and selected populations. Study size has precluded investigation of important disease subgroups, 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 rate; P < .05); male sex was an independent predictor of nonresponse on multivariate analysis. Age at diagnosis was associated strongly and independently with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than age 70, to less than 50% for those younger than age 30 (P < .0001). Patients who presented at younger ages also were significantly more likely not to 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 related strongly (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 younger than age 50. Increased severity of fatigue in women is related to increased autonomic symptoms, making dysautonomia a plausible therapeutic target.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Carbone
authors.forename: George F
authors.initials: GF
authors.lastname: Mells
authors.forename: Greta
authors.initials: G
authors.lastname: Pells
authors.forename: Muhammad F
authors.initials: MF
authors.lastname: Dawwas
authors.forename: Julia L
authors.initials: JL
authors.lastname: Newton
authors.forename: Michael A
authors.initials: MA
authors.lastname: Heneghan
authors.forename: James M
authors.initials: JM
authors.lastname: Neuberger
authors.forename: Darren B
authors.initials: DB
authors.lastname: Day
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Ducker
authors.forename: Richard N
authors.initials: RN
authors.lastname: Sandford
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Alexander
authors.forename: David E J
authors.initials: DE
authors.lastname: Jones
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D016896:Treatment Outcome; D006113:United Kingdom; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014580:Ursodeoxycholic Acid