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HCV protein‐induced cytokine predicts treatment outcomes in chronic hepatitis C virus infection
Author(s) -
Krueger Carla,
Collister Mark,
Minuk Gerald Y.,
Janke Alyssa,
Lerner Jordyn,
Wong Stephen G. M.,
Rempel Julia D.
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12418
Subject(s) - medicine , peripheral blood mononuclear cell , cytokine , immunology , ribavirin , immune system , tumor necrosis factor alpha , hepatitis c virus , adiponectin , leptin , pegylated interferon , hepatitis c , liver injury , virus , biology , obesity , biochemistry , insulin resistance , in vitro
Background & Aims Immune‐mediated processes are thought to influence the efficacy of treatment in chronic hepatitis C virus ( HCV ) infection. This study evaluated the association of baseline immune responses with the achievement of a sustained viral response ( SVR ) upon pegylated interferon and ribavirin treatment. Methods Baseline serum and peripheral blood mononuclear cells (PBMC) cytokine activity was assessed. Metabolic and liver injury parameters were evaluated as underlying factors. Results Baseline demographics and disease parameters did not differ between the SVR − ( n = 14) and SVR + ( n = 25) cohorts except for body mass index ( BMI ) values and liver injury scores. Baseline circulating TNF ‐α levels were three‐fold higher with subsequent treatment failure vs. success ( P = 0.124). Baseline peripheral blood mononuclear cells ( PBMC , n = 25) were cultured with HCV core and non‐structural ( NS )3 proteins. Core ( P = 0.0003) and NS 3 ( P = 0.018) induced greater TNF ‐α production within the SVR −, compared with the SVR +, cohorts. Similar findings were noted for interleukin ( IL )‐1β and IL ‐10 synthesis. Furthermore, HCV core‐induced TNF ‐α synthesis correlated with patient BMI values ( r = 0.489, P = 0.015). Core ( r = 0.432, P = 0.065) and NS 3 ( r = 0.530, P = 0.020)‐induced TNF ‐α displayed a positive relationship with serum adiponectin concentrations. In addition, lipopolysaccharide stimulated cytokine synthesis associated with BMI and adiponectin levels. Although unable to predict treatment outcomes, NS 3‐induced IL ‐6 synthesis and serum leptin concentrations corresponded to liver injury scores. Conclusion An enhanced PBMC susceptibility to core and NS 3‐induced TNF ‐α synthesis at baseline was associated with treatment failure. This phenomenon appeared to involve the interaction of virally generated TNF ‐α activity and metabolic disease. In contrast, IL ‐6 activity and leptin levels may indicate liver damage.