Chronic Fatigue Persists in a Significant Proportion of Female Patients After Transplantation for Primary Sclerosing Cholangitis

Abstract

Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the wellbeing of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.

AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma

“…Patient and graft survival in PSC are comparable with those transplanted for other liver diseases 374. In addition, transplantation results in substantial improvement in all aspects of quality of life,375–377 although fatigue persists in a significant proportion of female patients 378…”

“…[374] In addition, transplantation results in substantial improvement in all aspects of quality of life, [375][376][377] although fatigue persists in a significant proportion of female patients. [378] Given the potential risk of biliary strictures and CCA in the remnant duct, Roux-en-Y choledochojejunostomy has been the preferred method for biliary reconstruction. [379] Still, due to difficulties in managing biliary strictures in rPSC, there is a trend by some centers to perform duct-toduct anastomosis if the bile duct appears normal or in the absence of HGD at the time of transplantation.…”

Current Therapeutics in Primary Sclerosing Cholangitis

“… 8 A prospective case-control study found that female patients were less likely to have improvement in fatigue after LT compared with male patients. 158 Further large-scale studies are required to further corroborate these findings and allow us to explore the potential of treating autonomic dysregulation and LT as a management of fatigue in PSC.…”

“…Focusing on lifestyle measures such as optimizing sleep hygiene and having a regular exercise regimen may assist in improving troublesome fatigue. 9 Although there is some data to suggest that LT significantly decreases chronic fatigue, 157 , 158 it is not currently an indication for LT as an isolated symptom. 8 A prospective case-control study found that female patients were less likely to have improvement in fatigue after LT compared with male patients.…”

Management of Autoimmune Liver Diseases after Liver Transplantation

“…Symptomatic patients present most commonly with fatigue, upper quadrant abdominal pain, and pruritus [85]. Recent studies showed that fatigue might persist after LT in female recipients [87]. A more aggressive presentation of the disease is characterized by recurrent episodes of biliary tract obstruction and subsequent cholangitis that may progress to cirrhosis, liver failure, or develop hepatobiliary malignancies [77,80].…”