Impaired natural killer cell cytotoxic activity in chronic hepatitis C viral infection: A single-center, controlled study

Abstract

Background: The role of the innate immune response in hepatitis C virus (HCV)-related chronic liver disease is controversial and poorly understood. Objective: We studied peripheral natural killer (NK) cell cytotoxic activity in relation to liver function and structure, HCV genotype, and viremia and investigated whether NK cell cytotoxic activity detected before 1-year interferon (IFN)-alfa therapy could predict treatment outcome. Methods: Patients with biopsy-proven HCV-related chronic liver disease and age- and sex-matched healthy volunteers were enrolled. Patients were investigated using conventional liver function tests, histology, quantitative HCV-RNA, and genotype. NK cell cytotoxic activity was assessed with a newly developed enzyme-linked immunosorbent assay based on the assessment of NK cell-induced apoptosis of target cells (K562). Results: A total of 38 people (26 men, 12 women; mean [SD] age, 45.5 [1.9] years) were enrolled (15 patients, 23 healthy volunteers). NK cell cytotoxic activity was ∼50% in HCV-positive patients compared with controls ( P = 0.003) and was inversely related to age in patients ( r 2 = −0.33; P = 0.017) and controls ( r 2 = −0.58; P = 0.004). However, it did not correlate with fibrosis, sex, alanine aminotransferase levels, necroinflammatory lesions, viremia levels, HCV genotype, or response to treatment. Conclusions: NK cell cytotoxic activity is markedly reduced in chronic HCV infection. Such impairment is independent of viral and host characteristics, except age, and does not seem to help predict the outcome of IFN therapy.