Changes in Serum Interferon Gamma and Interleukin-10 in Relation to Direct-Acting Antiviral Therapy of Chronic Hepatitis C Genotype 4: A Pilot Study

Abstract

Introduction: This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers.

Methods: This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay.

Results: All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers.

Conclusion: Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.

Keywords: ALT, alanine transaminase; AST, aspartate transaminase; CHC, chronic hepatitis c; DAA, Direct-acting antivirals; DAC, daclatasvir; DM, diabetes melliteus; EDTA, ethylenediaminetetraacetic acid; HCV, Hepatitis C virus; HTN, systemic hypertension; IFN-γ, interferon gamma; IL-10, interleukin 10; INR, international normalized ratio; NCCVH, National Committee for Control of Viral Hepatitis; SOF, sofosbuvir; STROBE, strengthening the reporting of observational studies in epidemiology; SVR, sustained virological response rates; Th, T-helper; cytokines; direct-acting antivirals; hepatitis C virus; interferon gamma; interleukin-10.

Figure 1

IL-10 and IFN-γ throughout the study in both groups. Left pane showing IL-10 levels; ∗Significant decline (P < 0.05) between baseline and Week 4 PT in both groups. There is also significant decline between Week 4 and Week 12 PT in Group 2. Thus, the significant difference between Groups 1 and 2 in Week 12 PT values. Right pane showing IFN g levels. ∗Significant rise in IFN-γ level after Week 4 PT. It also shows the significant difference between Groups 1 and 2 in 12 weeks PT levels.

Figure 2

(A) Patient distribution according to serum changes of IL-10 during DAAs therapy. (B) Patient distribution according to serum changes of IFN-gamma during DAAs therapy.