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Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency

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Abstract

Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants (n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 %) had HADS-A score ≥8 and 13/60 (22 %) had HADS-D scores ≥8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2–4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression.

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Abbreviations

HCV:

Hepatitis C virus

CHC:

Chronic hepatitis C

apo:

Apolipoprotein

HRQOL:

Health-related quality of life

PUFAs:

Polyunsaturated fatty acids

SOC:

Standard of care

HADS:

Hospital Anxiety and Depression Scale

PegIFNα:

Pegylated interferon alpha

NAFLD:

Non-alcoholic fatty liver disease

BMI:

Body mass index

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Acknowledgments

This study was funded by the Medical Research Council (UK) (G0502028). The UK NIHR Biomedical Research Facility at Imperial College London provided infrastructure support to HCT, MMEC and STR.

Disclosures

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, and the authors have no financial disclosures.

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Authors and Affiliations

  1. Institute of Cellular Medicine (Hepatology), Newcastle University, William Leech Building, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK

    David A. Sheridan, S. H. Bridge, D. J. Felmlee & M. F. Bassendine

  2. Department of Biomedical Sciences, School of Life Sciences, Northumbria University, Newcastle Upon Tyne, UK

    S. H. Bridge

  3. Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, St Mary’s Hospital Campus, London, UK

    M. M. E. Crossey, H. C. Thomas & S. D. Taylor-Robinson

  4. Inserm U1110, Institute of Virology, Strasbourg, 67000, France

    D. J. Felmlee

  5. Department of Clinical Biochemistry, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle Upon Tyne, UK

    R. D. G. Neely

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  1. David A. Sheridan
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  2. S. H. Bridge
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  3. M. M. E. Crossey
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  4. D. J. Felmlee
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  5. H. C. Thomas
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  6. R. D. G. Neely
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  7. S. D. Taylor-Robinson
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  8. M. F. Bassendine
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Correspondence to David A. Sheridan.

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Sheridan, D.A., Bridge, S.H., Crossey, M.M.E. et al. Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency. Metab Brain Dis 29, 625–634 (2014). https://doi.org/10.1007/s11011-014-9520-9

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  • DOI: https://doi.org/10.1007/s11011-014-9520-9

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