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Depression, fatigue and neurocognitive deficits in chronic hepatitis C

Abstract

Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood–brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.

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Abbreviations

HCV:

Hepatitis C virus

HRQOL:

Health-related quality of life

PBC:

Primary biliary cholangitis

BBB:

Blood–brain barrier

IL:

Interleukin

HPA:

Hypothalamic–pituitary–adrenal

RNA:

Ribonucleic acid

MRS:

Magnetic resonance spectroscopy

HIV:

Human immunodeficiency virus

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Correspondence to Sern Wei Yeoh.

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Sern Wei Yeoh, Alex C. N. Holmes, Michael M. Saling, Ian P. Everall and Amanda J. Nicoll declare that they have no conflict of interests, funding sources or financial support relevant to this work.

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Yeoh, S.W., Holmes, A.C.N., Saling, M.M. et al. Depression, fatigue and neurocognitive deficits in chronic hepatitis C. Hepatol Int 12, 294–304 (2018). https://doi.org/10.1007/s12072-018-9879-5

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  • DOI: https://doi.org/10.1007/s12072-018-9879-5

Keywords

  • Hepatitis C
  • Depression
  • Fatigue
  • Cognition
  • Quality of life