Peripheral TNFα elevations in abstinent alcoholics are associated with hepatitis C infection

Abstract

Substantial evidence supports the view that inflammatory processes contribute to brain alterations in HIV infection. Mechanisms recently proposed to underlie neuropathology in Alcohol Use Disorder (AUD) include elevations in peripheral cytokines that sensitize the brain to the damaging effects of alcohol. This study included 4 groups: healthy controls, individuals with AUD (abstinent from alcohol at examination), those infected with HIV, and those comorbid for HIV and AUD. The aim was to determine whether inflammatory cytokines are elevated in AUD as they are in HIV infection. Cytokines showing group differences included interferon gamma-induced protein 10 (IP-10) and tumor necrosis factor α (TNFα). Follow-up t-tests revealed that TNFα and IP-10 were higher in AUD than controls but only in AUD patients who were seropositive for Hepatitis C virus (HCV). Specificity of TNFα and IP-10 elevations to HCV infection status was provided by correlations between cytokine levels and HCV viral load and indices of liver integrity including albumin/globulin ratio, fibrosis scores, and AST/platelet count ratio. Because TNFα levels were mediated by HCV infection, this study provides no evidence for elevations in peripheral cytokines in "uncomplicated", abstinent alcoholics, independent of liver disease or HCV infection. Nonetheless, these results corroborate evidence for elevations in IP-10 and TNFα in HIV and for IP-10 levels in HIV+HCV co-infection.

Fig 1

Scatter plots of the a) the chemokine Interferon γ-induced Protein 10 (IP-10) and the b) cytokine Tumor Necrosis Factor α (TNFα) in the 4 groups (Control: black closed circles; AUD: black open circles; HIV: gray closed circles; HIV+AUD: gray open circles). * indicates significance at p = .001.

Fig 2

Scatter plots of Interferon γ-induced Protein 10 (IP-10) and Tumor Necrosis Factor α (TNFα) in a) the AUD group by HCV status (i.e., AUD without HCV: open black circles; AUD+HCV: blue squares) and b) all 4 study groups by HCV status (Control: black closed circles; AUD (-): AUD without HCV, black open circles; AUD (+): AUD +HCV, blue squares; HIV (-): HIV without HCV, gray closed circles; HIV (+): HIV+HCV: dark blue squares; HIV+AUD (-): HIV+AUD without HCV, gray open circles; HIV+AUD (+): HIV+AUD+HCV, midnight squares).

Fig 3

Scatter plots of a) HCV viral load, b) albumin/globulin ratio (AGR), c) fibrosis score (FIB-4), and d) AST/platelet count ratio index (APRI) in the 4 study groups by HCV status (see legend to Fig 2 for details).

Fig 4

Correlations in the HCV-seropositive patient subgroups between TNFα levels and a) HCV viral load, b) albumin/globulin ratio (AGR), c) fibrosis score (FIB-4), and d) AST/platelet count ratio index (APRI).