The Number and Function of Dendritic Cells in Patients with Hepatitis C Virus Genotype 1 Infection Treated with Pegylated Interferon plus Ribavirin
Date Issued
2009
Date
2009
Author(s)
Liang, Cheng-Chao
Abstract
Backgound The rate of sustained virologic response (SVR) achieved by the combination therapy with pegylated interferon (PEG-IFN) plus ribavirin for patients with hepatitis C virus (HCV) infection has been up to 50-60%. The impact of host immunity on treatment effect remains unclear. Reduced number of dendritic cells (DC) in the peripheral blood with decreased capacity to drive T cell proliferation and cytokines (IL-12, IFN-α and IFN-γ) production has been reported in chronic hepatitis C patients. In addition, the number and capacity of DC to induce T-cell proliferation in self-limited patients and sustained virologic responders are comparable to those in healthy controls. However, little is known about the relationship between changes of number and function of DC before and after anti-viral treatment as well as treatment outcomes. im of this study The aim of this study is to evaluate the association of number and function of DC with treatment outcomes in patients with HCV genotype 1 infection treated with PEG-IFN plus ribavirin. ethods In this prospective study, we enrolled patients with HCV genotype 1 infection treated with PEG-IFN plus ribavirin for 24 weeks. Serum HCV RNA level was determined quantitatively by RT-PCR analysis at baseline, week 4, week 12, end of treatment, and 24 weeks post-treatment. The number and function of DC were assayed at baseline and 24 weeks post-treatment. The functional assays of DC included expression of co-stimulatory molecules (CD80, CD83, CD86, HLA-DR), allogeneic mixed lymphocyte reaction, and cytokines production (IL-5, IL-10, IL-12, IFN-γ). Age and sex-matched healthy adults were served as controls. The treatment outcomes were divided into SVR, relapse, and non-response. esults Twenty patients were enrolled in this study, and fifteen were males. The age ranged from 26 to 62 years old. Ten healthy volunteers were enrolled as controls. Nineteen patients completed the 24 weeks of combination therapy. One patient dropped out at week 16 due to poor virologic response. Fifteen patients achieved rapid virologic response (undetectable HCV RNA at week 4). Of 5 patients without RVR, three achieved complete early virologic response (undetectable HCV RNA at week 12). One patient had non-response (detectable HCV RNA at week 24). At the time of this writing, eight patients completed the follow-up and five achieved SVR. The other three patients had relapse.he numbers of myeloid DC (mDC) and plasmacytoid DC (pDC) in the peripheral blood were significantly lower in patients with chronic hepatitis C than in healthy donors (mDC 0.2% vs 0.28%, p=0.009; pDC 0.05% vs 0.09%, p=0.004) at baseline. The number of DC was not correlated with viral load and RVR. The expression of co-stimulatory molecules was comparable between chronic hepatitis C patients and healthy controls. However, CD83 expression in patients with baseline serum HCV RNA levels > 800,000 IU/ml was lower than those with HCV RNA levels < 800,000 IU/ml. Of 5 patients without RVR, lower expression of co-stimulatory molecules was observed in 3. Although the ability to drive T cell proliferation was not significantly different between chronic hepatitis C patients and healthy controls, 2 patients with non response seemed to have lower ability. In addition, cytokine production of DC in chronic hepatitis C patients was similar to healthy controls. However, IL-10 production was significantly higher in patients without RVR than those with RVR (p<0.001). onclusions The numbers of mDC and pDC in the peripheral blood are significantly lower in chronic hepatitis C patients than healthy controls. However, the number of DC is not correlated with viral load and achievement of RVR in patients treated with PEG-IFN plus ribavirin. The expression of co-stimulatory molecules, ability to drive T cell proliferation, and cytokines production of DC are comparable between chronic hepatitis C patients and healthy controls. Lower expression of co-stimulatory molecules and impaired ability to drive T cell proliferation as well as higher production of IL-10 of DC may imply a poor treatment response in patients with HCV genotype 1 infection treated with PEG-IFN plus ribavirn.
Subjects
Chronic hepatitis C
Dendritic cells
SDGs
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