title: The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study.
abstract: OBJECTIVE
  The role of liver transplantation (LT) for the relief of fatigue in patients with primary biliary cirrhosis (PBC) is unclear, and while many centers exclude fatigue as an indication for transplantation, there have been no studies to prospectively evaluate the impact of LT on fatigue. We aimed at assessing the severity of fatigue in LT candidates with PBC and the impact of LT on fatigue.
  
  
  METHODS
  In a prospective, longitudinal study, we used the PBC-40 questionnaire in 49 adult patients with PBC at listing and at 6, 12, and 24 months after LT and in two sex- and age-matched cohorts of community controls and non-transplanted PBC patients. Correlation analysis was used to assess the relationship between liver function and fatigue. ANOVA was used to compare the variation of fatigue score before and after LT.
  
  
  RESULTS
  There was no correlation between MELD and fatigue before LT (r(2)=0.01). Overall, the fatigue score after LT was substantially lower than before LT, falling from 40.7 ± 11.4 pre-transplant to 27.7 ± 9.5, 28.7 ± 10.1, 26.2 ± 10.1 (p<0.0001) at 6, 12, and 24 months after LT, respectively. The same improvement of fatigue was observed in both low-MELD (<17) and high-MELD (≥ 17) patients. Improvement in fatigue was also evident in the comparison with a "non-transplant PBC" control group (31.1 ± 11.6, p=0.03). However, 44% of the total cohort, and 47% of those with low-MELD, for whom the probability of dying of LT may be higher than that of dying without LT, had moderate to severe fatigue (defined as a fatigue score ≥ 29) at two years after LT. Moreover, fatigue scores at two years were higher in the transplant PBC cohort compared to a cohort of community controls (17.8 ± 5.9, p<0.0001).
  
  
  CONCLUSIONS
  Liver transplantation is associated with improvement in fatigue in patients with PBC. However, a substantial proportion of patients continue to suffer from significant fatigue after two years. Whether the improvement is enough to justify organ allocation in patients with fatigue alone, without liver failure, is still an open issue. Certainly, in the era of organ shortage, with many patients dying waiting for a graft, this may not represent the optimal use of donated deceased organs.
authors.affiliation: Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Carbone
authors.forename: Sally
authors.initials: S
authors.lastname: Bufton
authors.forename: Andrea
authors.initials: A
authors.lastname: Monaco
authors.forename: Laura
authors.initials: L
authors.lastname: Griffiths
authors.forename: David E
authors.initials: DE
authors.lastname: Jones
authors.forename: James M
authors.initials: JM
authors.lastname: Neuberger
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005221:Fatigue / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000503:physiopathology* / Q000601:surgery*; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D018434:Sickness Impact Profile; D011795:Surveys and Questionnaires; D013997:Time Factors
keywords: AMA; AZA; CMV; CNS; Fatigue; HRQoL; LT; Liver transplantation; MELD; MMF; Model for End-Stage Liver Disease; PBC; PBC-40; PRED; Primary biliary cirrhosis; QOL; Quality of life; SD; TAC; UKELD; United Kingdom Model for End-Stage Liver Disease; antimitochondrial antibodies; azathioprine; central nervous system; cytomegalovirus; health-related quality of life; liver transplantation; mofetil mycophenolate; prednisone; primary biliary cirrhosis; quality of life; standard deviation; tacrolimus