Factors Related to Fatigue in Patients With Cirrhosis Before and After Liver Transplantation

Evangelos Kalaitzakis; Axel Josefsson; Maria Castedal; Pia Henfridsson; Maria Bengtsson; Irene Hugosson; Bengt Andersson; Einar Björnsson


Clin Gastroenterol Hepatol. 2012;10(2):174-181. 

In This Article

Abstract and Introduction


Background & Aims: We performed a prospective study to evaluate fatigue and identify potential determinants among patients with cirrhosis. We also studied the effects of liver transplantation on fatigue in these patients.
Methods: A total of 108 patients with cirrhosis being evaluated before liver transplantation completed the fatigue impact scale (FIS), the hospital anxiety and depression (HAD) scale, and the short-form 36 (SF-36). Results were compared with controls from the general population. Fasting serum levels of insulin and glucose were measured in all patients. Levels of serum thyrotropin, free T3 and T4, cortisol, free testosterone, dehydroepiandrosterone sulfate, estradiol, interleukin-6, and tumor necrosis factor-α were measured in a subgroup of 80 patients. Transplant recipients were followed for 1 year.
Results: Compared with controls, patients with cirrhosis had more pronounced fatigue, on the basis of higher FIS domain and total scores (P < .05), which were related to all SF-36 domains (r = −0.44 to −0.77, P < .001). All FIS scores improved significantly after liver transplantation, although physical fatigue levels remained higher than in controls (P < .05). In multivariate analysis, pretransplant FIS scores were only related to depression, anxiety, cirrhosis severity, and low serum levels of cortisol (P < .05 for all). Impaired renal function and anemia were independent predictors of physical fatigue (P < .05).
Conclusions: Fatigue is common among patients with cirrhosis and associated with impaired quality of life. Psychological distress, severity of cirrhosis, and low levels of cortisol determine general fatigue, whereas anemia and impaired renal function also contribute to physical fatigue. Physical fatigue remains of concern for patients who have received liver transplants for cirrhosis.


Fatigue is considered to be common in chronic liver disease. Although there are reports on fatigue in patients with cholestatic liver disease,[1–3] chronic hepatitis C,[4,5] and nonalcoholic fatty liver disease,[6] few of the patients in these studies had overt cirrhosis. Thus, published data on fatigue and its possible association with health-related quality of life (HRQL) in cirrhosis are scarce. Furthermore, fatigue is a troublesome and persistent symptom after liver transplantation.[7–11] However, to our knowledge, there are no longitudinal studies specifically addressing the effect of transplantation on fatigue in cirrhosis.

The pathogenesis of fatigue in chronic diseases is usually multifactorial.[12,13] Patients with cirrhosis often experience psychological distress[14,15] and potentially debilitating complications such as hepatic encephalopathy, malnutrition, or hepatocellular carcinoma (HCC)[16–19] that could lead to cognitive and physical weakness. However, it is unknown the extent to which these factors contribute to fatigue in cirrhosis.

Hormonal abnormalities and systemic inflammation are common in cirrhosis. In particular, diabetes,[17] thyroid dysfunction,[20] dysfunction of the hypothalamic-pituitary-adrenal axis,[21] reduced dehydroepiandrosterone sulfate (DHEA-S),[22] and reduced serum testosterone[23] as well as increased interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)[24] have been reported. These abnormalities are thought to be involved in the pathogenesis of fatigue in noncirrhotic patients,[12,13,25–28] but it is unclear whether they contribute to fatigue in cirrhosis.

Our primary aim was to evaluate the severity of fatigue in patients with cirrhosis undergoing assessment for transplantation in comparison with the general population. We also aimed to identify determinants of fatigue in these patients and to study its potential relation to HRQL as well as to assess the effect of liver transplantation on fatigue.


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