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CD3(bright)CD56(+) T cells associate with pegylated interferon-alpha treatment nonresponse in chronic hepatitis B patients.

ABSTRACT: Chronic hepatitis B (CHB) infection is a serious and prevalent health concern worldwide, and the development of effective drugs and strategies to combat this disease is urgently needed. Currently, pegylated interferon-alpha (peg-IFNα) and nucleoside/nucleotide analogues (NA) are the most commonly prescribed treatments. However, sustained response rates in patients remain low, and the reasons are not well understood. Here, we observed that CHB patients preferentially harbored CD3(bright)CD56(+) T cells, a newly identified CD56(+) T cell population. Patients with this unique T cell population exhibited relatively poor responses to peg-IFNα treatment. CD3(bright)CD56(+) T cells expressed remarkably high levels of the inhibitory molecule NKG2A as well as low levels of CD8. Even if patients were systematically treated with peg-IFNα, CD3(bright)CD56(+) T cells remained in an inhibitory state throughout treatment and exhibited suppressed antiviral function. Furthermore, peg-IFNα treatment rapidly increased inhibitory TIM-3 expression on CD3(bright)CD56(+) T cells, which negatively correlated with IFNγ production and might have led to their dysfunction. This study identified a novel CD3(bright)CD56(+) T cell population preferentially shown in CHB patients, and indicated that the presence of CD3(bright)CD56(+) T cells in CHB patients may be useful as a new indicator associated with poor therapeutic responses to peg-IFNα treatment.

SUBMITTER: Guo C

PROVIDER: S-EPMC4865958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.

Project description:Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3- NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed.　Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.

| S-EPMC4428701 | biostudies-literature

Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C.

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| S-EPMC4385537 | biostudies-literature

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| S-EPMC3636226 | biostudies-literature

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| S-EPMC9817056 | biostudies-literature

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| S-EPMC5405394 | biostudies-literature

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| S-EPMC9230558 | biostudies-literature

Individualized treatment of chronic hepatitis C with pegylated interferon and ribavirin.

Project description:Chronic infection with hepatitis C virus (HCV) is a major public health problem, with perhaps 180 million people infected worldwide. A significant proportion of these will eventually develop clinical complications, such as cirrhosis, liver decompensation and hepatocellular carcinoma. Sustained virological response (SVR) to antiviral therapy is associated with improvement in liver histology and survival free of liver-related complications. Great effort has been made to improve SVR rate by adapting the duration of therapy according to HCV genotype and to on-treatment response. Rapid virological response (RVR, undetectable HCV RNA at week 4) usually has a high positive predictive value for achieving SVR and early virological response (EVR, ? 2 log reduction or undetectable HCV RNA at week 12) exhibits a high negative predictive value for non-response. Individualized approach can improve cost-effectiveness of HCV antiviral therapy by reducing side effects and the costs of therapy associated with unnecessary exposure to treatment and through extending therapy for those with unfavorable features. This article summarizes recent data on strategies of individualized treatment in naïve patients with mono-infection by the different HCV genotypes. The management of common side effects, the impact of HCV infection on health-related quality of life and the potential applications of host genomics in HCV therapy are also briefly discussed.

| S-EPMC3513206 | biostudies-other

The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C.

Project description:BACKGROUND:A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-?) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC). MATERIALS AND METHODS:In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-?/RBV were investigated. Single-nucleotide polymorphisms (SNPs) in IFNL genomic region including rs368234815, rs12979860, and rs8099917 were analyzed by DNA sequencing. RESULTS:Of the 92 patients, 63 (68.5%) achieved sustained virological response (SVR). Of the 43 patients with rs368234815 TT/TT genotype, 36 (83.7%) achieved SVR, while in 49 patients with non-TT/TT genotypes, 27 (55.1%) achieved SVR. Other pretreatment parameters predicted SVR were patients' body mass index, HCV genotype, rs12979860, and rs8099917 SNPs. In multivariate analysis, all above-mentioned parameters except rs8099917 remained as predictors of SVR. IFNL4 rs368234815 was a strong predictor of SVR; however, the prediction power of this SNP was the same as that of rs12979860 SNP in the patients of the current study. CONCLUSION:IFNL4 rs368234815 SNP can be considered for decision-making in the treatment of HCV-infected patients.

| S-EPMC5122234 | biostudies-literature

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B.

Project description:Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.

| S-EPMC7946504 | biostudies-literature

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