Determining the nature and impact of fatigue after liver transplantation

For the past 20 years, a number of publications have described the success of liver transplantation (LT) in terms of patient and graft survival. In turn, a sizable body of literature has demonstrated that significant improvements in health-related quality of life (HRQL) result from LT when compared to preoperative states affected by end-stage liver disease. In the majority of reports, however, the average HRQL for a group of LT recipients (both shortand long-term) is still reduced when compared to ageand sex-matched general population data. While symptoms including pruritus and hepatic encephalopathy often contribute to poor HRQL and subsequently resolve with LT, a similar explanation for the symptom of fatigue is not as easily proposed. Natural history and controlled trial investigations described the presence of fatigue in a majority of patients with various chronic liver diseases. Primary biliary cirrhosis and chronic hepatitis C have been the most common etiologies studied. Further investigation reveals that fatigue is often independent of hepatic disease severity but usually intensifies with progressive liver failure. Alterations in central neurotransmission, impaired corticotrophin-releasing hormone response, and systemic cytokine release have been hypothesized yet remain unproven as putative mechanisms. Fatigue after LT has also been described in a number of investigations to date. The natural history of this symptom, however, remains uncertain. Among patients undergoing LT for cholestatic liver disease, the presence of significant fatigue was commonly observed among recipients for up to 1 year after LT. Similar findings were noted from a multicenter database report of 346 patients undergoing LT for various etiologies of chronic liver disease. Determining the frequency and severity of fatigue in this population, however, has not been performed to date. In this month’s edition of Liver Transplantation, van den Berg-Emons and colleagues present a cross-sectional investigation examining the frequency and risk factors associated with fatigue after LT. A total of 96 recipients (45 men and 51 women) comprised the study cohort. The major hepatic disease etiologies for which LT was performed included viral (25%) and cholestatic (24%) etiologies. Only 6% of patients were transplanted for alcoholic liver disease. Exclusion criteria were noted for severe concomitant medical conditions (specific details unknown) or LT within 3 weeks of study enrollment. The nature and severity of fatigue was assessed using the Fatigue Severity Score (FSS) and Multidimensional Fatigue Inventory-20 instruments, which are known for excellent reliability and validity. Level of perceived disability was characterized by the Sickness Impact Profile, which has been previously used in patients with liver disease undergoing transplantation. Finally, the Dutch version of the Short-Form 36 health survey was administered to assess the level of association between fatigue severity and health-related quality of life. In this study, the prevalence rate of fatigue was 66% (defined by FSS scores 1 standard deviation above the mean score in healthy individuals). An estimated 44% of LT recipients had severe involvement with fatigue (defined by an FSS score 2 standard deviations beyond the mean). In this cohort, the presence of reduced physical function and low activity level were strongly associated with self-reported fatigue. Risk factors in-