S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood–Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder

Jennifer Loftis, Juno Valerio, Jonathan Taylor, Elaine Huang, Rebekah Hudson, Patricia Taylor-Young, Michael Chang, Samuel B. Ho, Eric Dieperink, Juan Luis Miranda, Peter Hauser

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. Methods: Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood–brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. Results: Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. Conclusions: These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.

Original languageEnglish (US)
Pages (from-to)1466-1475
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume42
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Virus Diseases
Hepatitis C
Psychiatry
Blood
Alcohols
Cytokines
Hepacivirus
Viruses
Viral Load
Interleukin-8
Alcohol Drinking
Interleukin-10
Liver
Calcium-Binding Proteins
Aptitude
Cell signaling
Immunologic Factors
Veterans
Chronic Hepatitis C
Immunoassay

Keywords

  • Alcohol Use Disorders
  • Blood–Brain Barrier
  • Cytokines
  • Depression
  • Hepatitis C

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood–Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder. / Loftis, Jennifer; Valerio, Juno; Taylor, Jonathan; Huang, Elaine; Hudson, Rebekah; Taylor-Young, Patricia; Chang, Michael; Ho, Samuel B.; Dieperink, Eric; Miranda, Juan Luis; Hauser, Peter.

In: Alcoholism: Clinical and Experimental Research, Vol. 42, No. 8, 01.08.2018, p. 1466-1475.

Research output: Contribution to journalArticle

Loftis, Jennifer ; Valerio, Juno ; Taylor, Jonathan ; Huang, Elaine ; Hudson, Rebekah ; Taylor-Young, Patricia ; Chang, Michael ; Ho, Samuel B. ; Dieperink, Eric ; Miranda, Juan Luis ; Hauser, Peter. / S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood–Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder. In: Alcoholism: Clinical and Experimental Research. 2018 ; Vol. 42, No. 8. pp. 1466-1475.
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abstract = "Background: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. Methods: Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood–brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. Results: Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. Conclusions: These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.",
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T1 - S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood–Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder

AU - Loftis, Jennifer

AU - Valerio, Juno

AU - Taylor, Jonathan

AU - Huang, Elaine

AU - Hudson, Rebekah

AU - Taylor-Young, Patricia

AU - Chang, Michael

AU - Ho, Samuel B.

AU - Dieperink, Eric

AU - Miranda, Juan Luis

AU - Hauser, Peter

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Background: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. Methods: Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood–brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. Results: Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. Conclusions: These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.

AB - Background: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. Methods: Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood–brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. Results: Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. Conclusions: These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.

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KW - Blood–Brain Barrier

KW - Cytokines

KW - Depression

KW - Hepatitis C

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