目的纵向研究高效抗逆转录病毒治疗(HAART)对HIV单一感染者和HIV/HCV合并感染者外周血单个核细胞(PBMCs)中粘病毒抵抗蛋白Mx A mRNA表达水平的影响,分析HAART后HIV/HCV合并感染者抗HCV前基线Mx A mRNA水平是否与后续干扰素抗HCV疗效有...目的纵向研究高效抗逆转录病毒治疗(HAART)对HIV单一感染者和HIV/HCV合并感染者外周血单个核细胞(PBMCs)中粘病毒抵抗蛋白Mx A mRNA表达水平的影响,分析HAART后HIV/HCV合并感染者抗HCV前基线Mx A mRNA水平是否与后续干扰素抗HCV疗效有关。方法以广州市第八人民医院收治的艾滋病患者(HIV单一感染组,HAART前CD4+T淋巴细胞<200个/mm3,42例)和HIV/HCV合并感染患者(HIV/HCV合并感染组,HAART前CD4+T淋巴细胞<200个/mm3,33例)为研究对象,并以22名健康自愿者作为对照;观察患者在抗HCV治疗前的HAART的不同时间点(0 W、4 W、12 W、24 W、48 W、72 W、96 W)PBMCs中Mx A mRNA表达水平;对比分析后继抗HCV治疗效果(有早期病毒学应答EVR,无早期病毒学应答NEVR)与Mx A mRNA表达水平的关系。结果 HIV单一感染组PBMCs中Mx A mRNA水平在HAART 4 W后下降(P<0.05),其他各时间点及与健康对照组之间差异均无统计学意义(P>0.05);HIV/HCV合并感染组PBMCs中HAART各时间点及与健康对照组之间差异均无统计学意义(P>0.05);HAART 96 W后进行抗HCV治疗,EVR组抗HCV治疗前Mx A mRNA水平较NEVR组高(P<0.05)。结论长期HAART对HIV/HCV合并感染者PBMCs中Mx A mRNA表达水平无显著影响;但HAART后抗HCV治疗前PBMCs中Mx A mRNA水平可作为HIV/HCV合并感染者抗HCV疗效的预测指标之一。展开更多
AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examina...AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P < 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P < 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P < 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P < 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P < 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P < 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P < 0.001),waist circumference(r =0.356,P < 0.001),percent body fat(r = 0.296,P < 0.001),systolic blood pressure(r = 0.202,P < 0.001),total cholesterol(r = 0.134,P < 0.001),triglycerides(r = 0.292,P < 0.001),cystatin C(r = 0.069,P < 0.001) and uric acid(r = 0.142,P < 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P < 0.001),waist circumference(r = 0-0.243,P < 0.001),percent body fat(r =-0.217,P < 0.001),systolic blood pressure(r =-0.132,P < 0.001),total cholesterol(r =-0.106,P < 0.001),triglycerides(r =-0.205,P < 0.001),cystatin C(r =-0.044,P < 0.001) and uric acid(r =-0.096,P < 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.展开更多
To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug naive AIDS patients, 118 AIDS patients who rec...To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug naive AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview. Meanwhile, 14ml EDTA anticoagulant blood was drawn. CD4/CD8 T cell count, viral load and genotypic drug resistance were tested. The rates of clinical improvement were 55.1% and 50.8% respectively three months and six months after antiretroviral therapy. The mean CD4 cell count after antiretroviral therapy was significantly higher than in drug naive patients. The prevalence rate of drug resistant HIV strains were 13.9%, 45.4% and 62.7% in drug naive patients, three month treatment patients and six month treatment patients, respectively. The number of resistance mutation codons and the frequency of mutations increased significantly with continued antiretroviral therapy. The mutation sites were primarily at the 103, 106 and 215 codons in the three-month treatment group and they increased to 15 codon mutations in the six-month treatment group. From this result, the evolution of drug resistant strains was inferred to begin with the high level NNRTI resistant strain, and then develop low level resistant strains to NRTIs. The HIV strains with high level resistance to NVP and low level resistance to AZT and DDI were highly prevalent because of the AZT＋DDI＋NVP combination therapy. These HIV strains were also cross resistant to DLV, EFV, DDC and D4T. Poor adherence to therapy was believed to be the main reason for the emergence and prevalence of drug resistant HIV strains. The prevalence of drug resistant HIV strains was increased with the continuation of antiretroviral therapy in the southern part of Henan province. Measures, that could promote high level adherence, provide new drugs and change ART regimens in failing patients, should be implemented as soon as possible.展开更多
The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, wherea...The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.展开更多
Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular ca...Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.展开更多
文摘目的纵向研究高效抗逆转录病毒治疗(HAART)对HIV单一感染者和HIV/HCV合并感染者外周血单个核细胞(PBMCs)中粘病毒抵抗蛋白Mx A mRNA表达水平的影响,分析HAART后HIV/HCV合并感染者抗HCV前基线Mx A mRNA水平是否与后续干扰素抗HCV疗效有关。方法以广州市第八人民医院收治的艾滋病患者(HIV单一感染组,HAART前CD4+T淋巴细胞<200个/mm3,42例)和HIV/HCV合并感染患者(HIV/HCV合并感染组,HAART前CD4+T淋巴细胞<200个/mm3,33例)为研究对象,并以22名健康自愿者作为对照;观察患者在抗HCV治疗前的HAART的不同时间点(0 W、4 W、12 W、24 W、48 W、72 W、96 W)PBMCs中Mx A mRNA表达水平;对比分析后继抗HCV治疗效果(有早期病毒学应答EVR,无早期病毒学应答NEVR)与Mx A mRNA表达水平的关系。结果 HIV单一感染组PBMCs中Mx A mRNA水平在HAART 4 W后下降(P<0.05),其他各时间点及与健康对照组之间差异均无统计学意义(P>0.05);HIV/HCV合并感染组PBMCs中HAART各时间点及与健康对照组之间差异均无统计学意义(P>0.05);HAART 96 W后进行抗HCV治疗,EVR组抗HCV治疗前Mx A mRNA水平较NEVR组高(P<0.05)。结论长期HAART对HIV/HCV合并感染者PBMCs中Mx A mRNA表达水平无显著影响;但HAART后抗HCV治疗前PBMCs中Mx A mRNA水平可作为HIV/HCV合并感染者抗HCV疗效的预测指标之一。
文摘AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P < 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P < 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P < 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P < 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P < 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P < 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P < 0.001),waist circumference(r =0.356,P < 0.001),percent body fat(r = 0.296,P < 0.001),systolic blood pressure(r = 0.202,P < 0.001),total cholesterol(r = 0.134,P < 0.001),triglycerides(r = 0.292,P < 0.001),cystatin C(r = 0.069,P < 0.001) and uric acid(r = 0.142,P < 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P < 0.001),waist circumference(r = 0-0.243,P < 0.001),percent body fat(r =-0.217,P < 0.001),systolic blood pressure(r =-0.132,P < 0.001),total cholesterol(r =-0.106,P < 0.001),triglycerides(r =-0.205,P < 0.001),cystatin C(r =-0.044,P < 0.001) and uric acid(r =-0.096,P < 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.
文摘To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug naive AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview. Meanwhile, 14ml EDTA anticoagulant blood was drawn. CD4/CD8 T cell count, viral load and genotypic drug resistance were tested. The rates of clinical improvement were 55.1% and 50.8% respectively three months and six months after antiretroviral therapy. The mean CD4 cell count after antiretroviral therapy was significantly higher than in drug naive patients. The prevalence rate of drug resistant HIV strains were 13.9%, 45.4% and 62.7% in drug naive patients, three month treatment patients and six month treatment patients, respectively. The number of resistance mutation codons and the frequency of mutations increased significantly with continued antiretroviral therapy. The mutation sites were primarily at the 103, 106 and 215 codons in the three-month treatment group and they increased to 15 codon mutations in the six-month treatment group. From this result, the evolution of drug resistant strains was inferred to begin with the high level NNRTI resistant strain, and then develop low level resistant strains to NRTIs. The HIV strains with high level resistance to NVP and low level resistance to AZT and DDI were highly prevalent because of the AZT＋DDI＋NVP combination therapy. These HIV strains were also cross resistant to DLV, EFV, DDC and D4T. Poor adherence to therapy was believed to be the main reason for the emergence and prevalence of drug resistant HIV strains. The prevalence of drug resistant HIV strains was increased with the continuation of antiretroviral therapy in the southern part of Henan province. Measures, that could promote high level adherence, provide new drugs and change ART regimens in failing patients, should be implemented as soon as possible.
基金Supported by A Grant, PAI-CTS-532, from Junta de Andalucía, Andalucía, Spain. CIBEREHD was Funded by Instituto de Salud Carlos Ⅲ
文摘The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.
文摘Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.
