Fatigue and Quality of Life in Patients with Primary Biliary Cholangitis

Prevalence and Pathogenesis of Fatigue in PBC Patients

Fatigue occurs in 40–80% of patients with PBC, and there is no correlation between its presence and the severity or duration of the disease. Up to 20% of patients with PBC experience a reduction in quality of life due to fatigue, with the impact being more pronounced in younger individuals. Fatigue has a devastating effect on social and mental health, family and sexual life, and work performance. 71% of PBC patients experiencing fatigue also suffer from depression, compared to 18% of PBC patients without fatigue.

The pathogenesis of fatigue in PBC is multifactorial and involves both central and peripheral mechanisms. Central mechanisms include depression, sleep disorders, autonomic dysfunction, and organic brain changes. Peripheral causes include excessive redirection from aerobic to anaerobic metabolism resulting in lactate accumulation, abnormal serum amino acid levels, and autoimmune manifestations.

Assessing Quality of Life with the PBC-40 Questionnaire

The PBC-40 questionnaire was developed and validated to measure the quality of life in PBC patients. It is available in English and has been validated in other languages. The questionnaire contains 40 questions across 6 domains: fatigue, general symptoms, itching, social, emotional, and cognitive functions. The PBC-40 has proven validity, reliability, accuracy, and acceptability for patients and has shown significantly higher validity in PBC patients compared to other health-related quality of life questionnaires.

Active Management of Accompanying Symptoms

There is currently no approved treatment for fatigue in PBC patients, making basic disease treatment crucial. It's essential to always exclude other possible causes of fatigue like hypothyroidism, depression, sleep disorders, anemia, or medication side effects in these patients.

Various drugs are being tested for treating fatigue in PBC: rituximab, modafinil, fluoxetine, antioxidants, ondansetron, methotrexate, corticosteroids, fluvoxamine, and plasmapheresis. Other potential treatments involve addressing accompanying symptoms and disorders such as treating depression, sicca syndrome, vitamin D deficiency, restless legs syndrome, or obstructive sleep apnea. Patients should also avoid unsuitable antihypertensive drugs and stay well-hydrated. Non-pharmacological supportive therapy can include energy-saving daily activity plans, graded exercise, physiotherapy, occupational therapy, psychological support, smoking cessation assistance, and patient groups.

Despite the lack of effective approved treatment for fatigue in PBC patients, basic disease treatment remains crucial and essential.

Part of Treatment Efficacy Assessment

The annual assessment of the efficacy of PBC treatment with ursodeoxycholic acid (UDCA) should also include quality of life evaluation. If UDCA is insufficiently effective and quality of life declines, referral to one of the 11 specialized centers can be considered (see www.prolekare.cz/tema/primarni-biliarni-cholangitida), where switching to second-line therapy, such as obeticholic acid, is possible.

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Sources:
1. Laschtowitz A., de Veer R. C., Van der Meer A. J., Schramm C. Diagnosis and treatment of primary biliary cholangitis. United European Gastroenterol J 2020 Jul; 8 (6): 667–674, doi: 10.1177/2050640620919585.
2. Galoosian A., Hanlon C., Zhang J. et al. Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches. J Clin Transl Hepatol 2020 Mar 28; 8 (1): 49–60, doi: 10.14218/JCTH.2019.00049. 
3. Jacoby A., Rannard A., Buck D. et al. Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut 2005; 54(11): 1622–1629, doi: 10.1136/gut.2005.065862. 
4. Khanna A., Hegade V. S., Jones D. E. Management of fatigue in primary biliary cholangitis. Curr Hepatol Rep 2019; 18: 127–133, 10.1007/s11901-019-00458-0.