Elevated indoleamine 2,3-dioxygenase activity is associated with endothelial dysfunction in people living with HIV and ROS production in human aortic endothelial cells in vitro.

The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.

Heparin-binding protein and procalcitonin in the diagnosis of pathogens causing community-acquired pneumonia in adult patients: a retrospective study.

The performance of inflammatory markers in community-acquired pneumonia (CAP) caused by different pathogens has not been fully studied. We sought to find the differences in the concentrations of procalcitonin (PCT) and heparin-binding protein (HBP) between patients with CAP caused by different pathogens. We enrolled 162 patients with CAP, divided into three groups on the basis of bacterial (n = 108), fungal (n = 21) and viral (n = 33) infection. Complete leukocyte counts and the concentration of HBP and PCT were measured, and the differences were compared with nonparametric tests. The receiver operating characteristic (ROC) curve was used to evaluate the significant differences in the sensitivity and specificity of the indicators. The leukocyte and neutrophils counts and the concentrations of HBP and PCT in the viral group were significantly lower than those in the other two groups (p < 0.001). The area under the ROC curve (AUC) of the concentration of HBP and PCT as well as leukocyte and neutrophils counts were 0.927, 0.892, 0.832 and 0.806 for distinguishing bacterial from viral infection, respectively. The best cut-off value was 20.05 ng/mL for HBP, with a sensitivity of 0.861 and specificity of 0.939. The best cut-off value was 0.195 ng/mL for PCT, with a sensitivity of 0.991 and specificity of 0.636. The best cut-off value was 5.195 × 109/L and 4.000 × 109/L for leukocyte and neutrophils counts, with sensitivity of 0.694 and 0.880 and specificity of 0.667 and 0.636, respectively. The AUC of HBP, PCT and leukocyte and neutrophil counts for distinguishing fungal from viral infection were 0.851, 0.883, 0.835 and 0.830, respectively. The best cut-off values were 29.950 ng/mL, 0.560 ng/mL, 5.265 × 109/L and 3.850 × 109/L, with sensitivity of 0.667, 0.714, 0.905 and 0.952 and specificity of 0.970, 0.879 0.667 and 0.606, respectively. There were no significant differences in the three indicators between the bacterial and fungal infection groups. The concentration of CRP showed no significant differences among the three groups. Consequently, the stronger immune response characterized by higher inflammation markers including HBP and PCT can help distinguish bacterial and fungal CAP from viral CAP.

Increased expression of caspase 1 during active phase of connective tissue disease.

Key factors of pyroptosis play an important role in the inflammatory response to connective tissue disease (CTD). However, information on active and stable stages of CTD is scarce. To distinguish the differences of concentrations of C-reactive protein (CRP), caspase 1, caspase 4, caspase 5 and sCD14 in plasma between the patients with active and stable stages of CTD. A cohort study was conducted to recruit patients diagnosed with CTD of active phase and stable phase as well as health control. These data included the analysis of the concentration of sCD14, caspase 1, caspase 4 and caspase 5 in peripheral plasma by ELISA. The Wilcoxon rank-sum test was used to compare the two groups. The sex ratio and ages of the three groups were not different statistically. The concentrations of sCD14, caspase4 and caspase5 of plasma in the CTD of active phase and the stable phase as well as the health control. The concentration of caspase 1 in active phase of CTD (470.19 [422.33-513.14] pmol/L) was significantly higher than that in stable group (203.95 [160.94-236.12] pmol/L) and healthy control (201.65 [191.11-240.35] pmol/L] pmol/L) (p < 0.001, both), but there was no significant difference between stable group and healthy control (p = 0.2312). Similarly, the concentration of CRP in the active phase of CTD (8.96 [3.06-20.28] mg/L) was significantly higher than that in the stable group (3.00 [1.30-11.40] mg/L) and the healthy control (3.70 [2.30-4.73] mg/L) (p = 0.0013, p = 0.0006, respectively), but there was no significant difference between the stable group and the healthy control (p = 0.3205). However, there were no significant differences in the concentration of sCD14, caspase 4 and caspase 5 in the active phase of CTD and the stable group as well as the health group. Consequently, the patients of the active phase of CTD showed increased expression of caspase 1.

Involvement of multiple transcription factors in regulation of IL-ß-induced MCP-1 expression in alveolar type II epithelial cells.

During acute lung injury, a large number of monocytes are recruited into the pulmonary tissue, which is mainly mediated by local production of monocyte chemotactic protein 1 (MCP-1). As an essential component of the lung tissues, alveolar type II epithelial cells are one of the major sources of MCP-1. Therefore, uncovering the mechanism whereby MCP-1 production is regulated in the alveolar type II cells will provide a pivotal theoretical basis for clinical intervention in acute lung injury. In the current study, we find that there is a κB binding site in the MCP-1 promoter region, and mutation of the site leads to reduced production of MCP-1 in alveolar type II epithelial cells. In contrast, overexpression of NF-κB p65 significantly increases MCP-1 expression. Furthermore, we elucidate that IKKα/ß-NF-κB p65 signaling pathway and phosphorylation of serine 534 in NF-κB p65 are required for the maximal expression of MCP-1. Also, Activator protein 1 (AP-1) site in the promoter region and JNK1/2-c-Jun signaling are required for MCP-1 generation in alveolar type II epithelial cells. Moreover, a CCAAT/enhancer-binding protein (C/EBP) element is identified in the MCP-1 promoter region through the point mutation technique, and further experiments demonstrate that both C/EBPß and C/EBPδ are involved in basic and IL-1ß-mediated MCP-1 expression. Of note, specificity protein 1-Sp1 expression is not changed in alveolar type II epithelial cells incubated with IL-1ß, but it still control MCP-1 production by binding to the consensus sequence in the promoter region. More importantly, we find that the results derived from the cell line-MLE-12 cells and primary cells are consistent. Taken together, our data provide insights into the molecular mechanism how MCP-1 expression in inflammatory alveolar type II epithelial cells is regulated at transcription level.

TNF-α induction of IL-6 in alveolar type II epithelial cells: Contributions of JNK/c-Jun/AP-1 element, C/EBPδ/C/EBP binding site and IKK/NF-κB p65/κB site.

Although participation of IL-6 in lung inflammation has been widely elucidated, the transcriptional regulation of its generation in alveolar type II cells stimulated by TNF-α remain unclear. Here, we find that TNF-α significantly induces IL-6 production, and TNF-α induction of IL-6 is mainly regulated at transcriptional level. Upon stimulated by TNF-α, Activator Protein-1 (AP-1)-mediated transcriptional activity is apparently increased in alveolar type II epithelial cells, which might be derived from elevated phosphorylation of JNK and subsequent activation of c-Jun. Either down-regulation of c-Jun or the AP-1 site mutation leads to significant reduction of IL-6 expression. In contrast, ectopic expression of c-Jun notably increases IL-6 generation. So, c-Jun, one of the AP-1 family members, plays a pivotal role in TNF-α-induced IL-6 generation. CCAAT/enhancer binding protein δ (C/EBPδ) expression is significantly amplified by TNF-α, which may contribute to the rise of C/EBP activity in alveolar type II cells. C/EBPδ shRNA treatment results in attenuation of IL-6 expression in the cells, which is consistent with data by introduction of mutations into the C/EBP site in the promoter. However, overexpression of C/EBPδ greatly increases the IL-6 promoter activity. In addition, data regarding another transactivator in the family-C/EBPß show that it does not affect IL-6 production. We also find that the IKK/NF-κB p65 pathway is activated in TNF-α-treated alveolar type II epithelial cells, and plays an essential role in positive regulation of IL-6 expression in TNF-α-treated alveolar type II epithelial cells via knockdown or forced expression of NF-κB p65, or elimination of κB sites in the IL-6 promoter. Notably, IL-6 promoter-driven luciferase production in primary alveolar type II epithelial cells can also be increased by the ectopic expression of c-Jun, C/EBPδ, and NF-κB p65, respectively. Collectively, our data provide insights into molecular mechanism involved in IL-6 expression in alveolar type II epithelial cells on TNF-α treatment, which provides a theoretical basis for specific inhibition of IL-6 production at the transcriptional level.

Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

BACKGROUND: It is difficult to quickly distinguish non-tuberculous mycobacterial (NTM) infection from tuberculosis (TB) infection in human immunodeficiency virus (HIV)-infected patients because of many similarities between these diseases. A simple and effective way to determine the differences using routine blood tests is necessary in developing countries. METHODS: A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016. These data included the analysis of blood cells, liver function, renal function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and were compared between the HIV/TB and HIV/NTM groups. RESULTS: A total of 240 patients were enrolled. The number of HIV/TB and HIV/NTM patients was 113 and 127, respectively. There were no significant differences in the CD4 T-cell count, age, sex, percentage of patients initiating antiretroviral therapy (ART) before the explicit diagnosis of TB or NTM infection. NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites. Both the leukocyte count(5.60 × 109/L) and the proportion of neutrophils in the leukocyte count (76.70%) in the HIV/TB group were significantly higher than those in the HIV/NTM group (4.40 × 109/L [P = 0.0014] and 69.30% [P < 0.001]. The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group (P < 0.001). The creatinine and urea levels were not significantly different between the two groups. The ESR (84.00 mm/h) and the concentration of CRP (59.60 mg/L) were significantly higher in the HIV/TB group than in the HIV/NTM group (52.00 mm/h and 19.60 mg/L, respectively) (P < 0.001). To distinguish TB infection from NTM infection, the best cut-off value was 69.5 mm/h for ESR, with a positive predictive value (PPV) of 0.740 and negative predictive value (NPV) of 0.721, and 48.8 mg/L for CRP, with a PPV of 0.676 and NPV of 0.697. CONCLUSION: The dissemination character as well as stronger immune response characterized by higher inflammation markers (e.g. WBC, ESR, CRP) can help distinguish TB from NTM infection in HIV-infected patients who need empirical therapy or diagnostic therapy immediately in low-income areas.

Correction to: Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

CORRECTION: After publication of this article [1] it came to our attention that the affiliation of Jun Chen and Hong-zhou Lu were incorrectly shown.Jun Chen's affiliation should have been given as Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.Hong-zhou Lu should have been given as Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Huashan Hospital affiliated to Fudan University, Shanghai, China. Medical College of Fudan University, Shanghai, China.The original article has been updated to reflect this change.

Caspase-1 Activity in CD4 T Cells Is Downregulated Following Antiretroviral Therapy for HIV-1 Infection.

Both Caspase 1-induced cell death and Caspase 3-induced cell death were reported to be the causes of CD4+ T cell depletion in HIV infection. We measured by flow cytometry the expression of key proteins associated with pyroptosis (Caspase 1), apoptosis (Caspase 3, Caspase 8, Caspase 9), and immune activation in peripheral T cells. The percentages of CD4+ T cells that expressed Caspase 1 and Caspase 3 were significantly higher in untreated human immunodeficiency virus 1 (HIV-1) patients compared with healthy control (Caspase 1: 19.40% vs. 4.65%, p = .006; Caspase 3: 12.75% vs. 4.18%, p < .001). However, the percentages of Caspase 3 in CD8+ T cells increased significantly, while the percentages of Caspase 1 in CD8+ T cells did not change significantly (Caspase 1: 3.33% vs. 1.99%, p = .821; Caspase 3: 20.35% vs 4.74%, p < .001). The percentages of HLA-DR+ CD38+ CD8+ T cells were positively correlated with those of Caspase 1+ CD4+ T cells, but not with those of Caspase 3+ CD4+ T cells. After highly active antiretroviral therapy, the percentages of Caspase 1, but not of Caspase 3, -expressing CD4+ T cells decreased to a level comparable with those of healthy controls (Caspase 1: 6.05% vs. 4.65%, p = .514; Caspase 3: 9.67% vs. 4.18%, p < .001). Our study indicated that CD4+ T cells experience both pyroptosis and apoptosis, while CD8+ T cells undergo only apoptosis in HIV-1 infection. Pyroptosis, but not apoptosis, in CD4+ T cells may be inhibited by effective antiretroviral therapy.

Spectrum of Opportunistic Infections and Risk Factors for In-Hospital Mortality of Admitted AIDS Patients in Shanghai.

To investigate the frequency and the spectrum of major opportunistic infections (OIs), evaluate the major clinical factors associated with each specific OI, and identify the risk factors for in-hospital death among HIV patients in East China.A retrospective cohort study was made including all the HIV-infected patients who were admitted for the first time to the Shanghai Public Health Clinical Center during June 1, 2013 to June 1, 2015. The demographic and clinical data were collected. Comparison of continuous variables was analyzed by one-way ANOVA and rank sum test. Person χ test and Fisher exact test were applied to analyze the categorical variables. A Cox proportional hazards regression model was used to determine the risk for the occurrence of in-hospital death.In total, 920 patients were enrolled with age of 41.59 ± 13.36 years and 91% male. Median CD4 was 34 (IQR, 13-94) cells/µL. Among these patients, 94.7% acquired OIs while the rest developed malignancies. Pneumocystis pneumonia and bacterial coinfection (42.1%) was found to be the most common OIs, followed by tuberculosis (31.4%), CMV (20.9%), Cryptococcosis (9.0%), and MAC infection (5.2%). Of the above 5 major OIs, CMV-infected patients had the lowest median CD4 cell count 22.50 (IQR, 7.50-82.00) while the patients with tuberculosis infection had the highest count 61.00 (IQR, 27.00-176.00). In-hospital death rate was 4.2 per 100 person-years among these patients. Of note, admitted patients with 2 types of OIs (2.20, 95% CI 1.39-3.48) and those patients who were 40-year old or older (1.75, 95% CI 1.10-2.78) had a higher risk of such death.Pneumocystis pneumonia and tuberculosis were still the leading causes for the admission of HIV-infected patients in East China, and these patients tended to have very low CD4 cell counts. It is believed that expanding the HIV screening test and pushing the infected ones get ART earlier is required for generating a more successful HIV management strategy.

Fecal bacterial microbiome diversity in chronic HIV-infected patients in China.

The purpose of this study was to identify fecal bacterial microbiome changes in patients with chronic human immunodeficiency virus (HIV) infection in China. Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and clustered into operational taxonomic units using the QIIME software. Relative abundance at the phylum and genus levels were calculated. Alpha diversity was determined by Chao 1 and observed-species indices, and beta diversity was determined by double principal component analysis using the estimated phylogeny-based unweighted Unifrac distance matrices. Fecal samples of the patients with chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes (47.20% ± 0.43 relative abundance) and Proteobacteria (37.21% ± 0.36) compared with those of the non-HIV infected controls (17.95% ± 0.06 and 3.81% ± 0.02, respectively). Members of the genus Bilophila were exclusively detected in samples of the non-HIV infected controls. Bacteroides and arabacteroides were more abundant in the chronic HIV-infected patients. Our study indicated that chronic HIV-infected patients in China have a fecal bacterial microbiome composition that is largely different from that found in non-HIV infected controls, and further study is needed to evaluate whether microbiome changes play a role in disease complications in the distal gut, including opportunistic infections.

Relationship between T-SPOT.TB responses and numbers of circulating CD4+ T-cells in HIV infected patients with active tuberculosis.

This study sought to evaluate the performance of the T-SPOT.TB assay for the diagnosis of active tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients. One hundred confirmed HIV-infected patients with active TB and known T-SPOT.TB and CD4+ T-cell counts were enrolled in this clinical retrospective study. We found that patients with lower CD4+ T-cell counts (11-50 cells/µL) had the lowest T-SPOT.TB positive rates (50%), and patients with higher CD4+ T-cell counts (50-100 cells/µL) had the highest T-SPOT.TB positive rates (75%). However, there were no significant differences between the T-SPOT.TB positive rates of patients with different CD4+ T-cell counts (< 10, 11-50, 51-100 and > 100 cells/µL) (χ(2) = 3.7747, p = 0.287). The patients with positive TB culture results had significantly higher T-SPOT.TB positive rates (78.9%) than patients that were culture-negative (44.3%) (χ(2) = 12.8303, p < 0.001). Other variables, including gender, age, TB disease classification, HIV RNA level, and highly reactive antiretroviral therapy (HAART), had no significant effects on T-SPOT.TB positive rates. The number of spot-forming cells (SFCs) reactive with ESAT-6, CFP-10 and ESAT-6/CFP-10-specific T cells detected by T-SPOT.TB were positively is strongly related to the degree of immunodeficiency, while the T-SPOT.TB positive rates are less dependent on the level of CD4+ T-cell depletion in HIV infection and active TB.

Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established. METHODS: We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14). RESULTS: Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity. CONCLUSIONS: IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.

Central nervous system infection with non-tuberculous mycobacteria: a report of that infection in two patients with AIDS.

Meningitis caused by non-tuberculous mycobacteria (NTM) has a low incidence and is a rare form of NTM infection. In an increasing number of cases, however, disseminated mycobacterial infection is noted in acquired immune deficiency syndrome (AIDS). Described here are two patients with AIDS who were infected with NTM. Both patients eventually died, but one did receive anti-NTM treatment. Non-tuberculous mycobacterial meningitis must be suspected in patients with AIDS who present with prolonged fever and brain symptoms, and anti-NTM drugs should be promptly administered if necessary.

[Effect of antiviral treatment on expression of programmed death 1 and programmed death ligand 1 on peripheral T lymphocytes in patients with chronic hepatitis C].

OBJECTIVE: To evaluate the changes in programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) expression on peripheral blood T lymphocytes of patients with chronic hepatitis C (CHC) over the 24 weeks course of antiviral therapy. METHODS: Twenty-four CHC patients administered 24 weeks of combination antiviral therapy with pegylated-interferon-alpha-2a (Peg-IFNa-2a) and ribavirin (RBV) were enrolled for study from the Nanjing Second Hospital between October 2008 and October 2011. Peripheral blood was collected before treatment initiation, at treatment weeks 4, 12 and 24, and post-treatment week 24 (to investigate sustained virologic response (SVR), and used to measure expression of PD-1 and PD-L1 on CD4+ and CD8+ T lymphocytes by flow cytometry, load of serum hepatitis C virus (HCV) RNA by real-time polymerase chain reaction, and level of serum alanine aminotransferase (ALT) by auto-biochemical analyzer. Intergroup differences were analyzed by the two-sample t-test, and the significance of differences between pre- and post-treatment measurements was determined by one-way or two-way repeated measurements analysis of variance tests. RESULTS: At treatment week 4, 19 of the CHC patients were HCV RNA-negative. Among those patients the PD-1 expression on both T lymphocyte subsets showed a significant decrease from pre-treatment to post-treatment week 24 (CD4+: 18.6 +/- 6.1% vs. 10.3 +/- 7.7%, F = 12.406, P = 0.002; CD8+: 16.6 +/- 13.8% vs. 9.4 +/- 4.6%, F = 4.955, P = 0.039). However, the CD8+ lymphocyte subset showed significant increase in PD-L1 expression during treatment (pre-treatment: 17.5 +/- 13.7% vs. treatment week 4: 25.9 +/- 11.1%, F = 9.063, P less than 0.01; 12: 29.6 +/- 15.1%, F = 8.365, P less than 0.01; 24: 32.0 +/- 15.7%, F = 9.736, P less than 0.01). Among the five CHC patients showing HCV RNA-positivity at treatment week 4 there was only a significant difference observed in the increased expression of PD-L1 on CD8+ lymphocyte subset from pre-treatment to treatment week 24 (17.4 +/- 16.7% vs. 39.2 +/- 15.6%, F = 10.292, P = 0.033). Twenty of the CHC patients achieved SVR. among whom the PD-1 expression was significantly decreased during treatment on the CD4+ lymphocyte subset (pre-treatment: 20.2 +/- 7.5% vs. treatment week 4: 14.4 +/- 7.5%, F = 6.133, P less than 0.05; 12: 14.0 +/- 6.9%, F = 5.541, P less than 0.05; 24: 10.7 +/- 7.6%, F = 14.780, P less than 0.05) and on the CD8+ lymphocyte subset (pre-treatment: 16.8 +/- 13.4% vs. treatment week 12: 10.2 +/- 4.6%, F = 4.964, P less than 0.05; 24: 10.1 +/- 4.9%, F = 4.613, P less than 0.05). Additionally, the PD-L1 expression was significantly increased during treatment on the CD8+ lymphocyte subset (pre-treatment: 19.0 +/- 14.5% vs. treatment week 12: 30.8 +/- 16.6%, F = 6.442, P = 0.020; 24: 35.2 +/- 16.5%, F = 12.349, P = 0.002). Among the four CHC patients who relapsed there were no significant differences observed in the expressions of PD-1 or PD-L1 on the CD4+ or CD8+ T lymphocytes. CONCLUSION: The standard Peg-IFNa-2a + RBV combination antiviral therapy reduces PD-1 expression on CD4+ and CD8+ T lymphocytes and increases PD-L1 expression on CD8+ T lymphocytes in peripheral blood. The clinical outcome of CHC patients may be related to the antiviral therapy-induced changes in expressions of PD-1 and PD-L1 on T lymphocytes.

Application of interferon response-related gene array to the antiviral treatment outcome in chronic hepatitis C.

BACKGROUND/AIMS: It has been known that viral factors such as genotype and viral load have a major influence on the outcome of antiviral treatment. Nevertheless, researchers have become increasingly aware that host genetic factors can modulate the response to antiviral treatment. The underlying mechanisms for the varying virologic response rates to IFNalpha-based antiviral therapy are unknown. METHODOLOGY: RNA was isolated from peripheral blood monocytes from treatment-naïve patients with chronic hepatitis C before and at the end of treatment. Gene expression was measured using SuperArray microarrays and compared to that of healthy controls. RESULTS: Ten patients were classified as rapid responders (RRs) and seven patients as non-RRs according to the serum HCV RNA level after 4 weeks of treatment in 17 patients with CHC. Compared with healthy controls, nine and eighteen different expression genes were found significantly in patients with RR and N-RR, respectively. Five different expression genes were found between the patients with RR and N-RR. Two genes that were down-regulated were found between HCV genotype 1b and genotype 2a. Seven different expression genes that were all down-regulated were found between the patients with ETVR and N-ETVR. CONCLUSIONS: (1) The down-regulation of some IFN response-related genes are associated with null response to treat with interferon. (2) It should be HCV genotype 1b is more successful in inducing the down-regulation of IFN response-related genes than HCV genotype 2a, thus contribute to the resistance to IFN.