Discrepancy in virological and biochemistry response of patients with chronic hepatitis HCV positive on treatment with PEG-IFN plus ribavirin

Combination therapy of PEG-IFN alpha-2a o alpha-2b plus ribavirin represents a further improvement in treatment of chronic hepatitis HCV+ with a sustained virological response (SVR) either in monotherapy (25-39%) either in association with ribavirin (59-56%). SVR is highly predictable: 75% of all patients who achieve viral clearance at week 12 (EVR), if they had an adherence > 80% of planned therapy, they become sustained viral responders. In spite of virological response, 16-34% of patients on PEG-IFN monotherapy have high value of ALT, and this make them to reduce adherence. 62 patients whith chronic hepatitis HCV+ and no corrhosis, have been treated for 48 weeks with PEG-IFN and ribavirin to evaluate discrepancy incidence between virological (HCVRNA < 200UI) and biochemical (normal value of ALT) response of patients treated with PEG-IFN plus ribavirin and to verify the impact that stuch discrepancy can produce on SVR of treated patients. Our preliminary data confirm that PEG-IFN bring a superior virological response than biochemical one, either on naive patients either on experienced ones even with ribavirin in association. It will be useful to verify if this discepancy cause a superior SVR as already reported by several studies. Even the follow-up of our 5 discordant patients confirm this trend.     

High plasma fractalkine (CX3CL1) levels are associated with severe liver disease in HIV/HCV co-infected patients with HCV genotype 1

BackgroundInappropriate persistence of chemokines expression in hepatitis C virus (HCV) infection can drive tissue damage, intrahepatic inflammation, and liver cell injury. The aim of study was to study the association of plasma fractalkine (CX3CL1) levels with fibrosis stage and necroinflammatory activity grade of liver biopsies in human immunodeficiency virus (HIV)/HCV co-infected patients with HCV genotype 1.MethodsWe carried out a cross-sectional study on 125 patients. Grading and staging of liver biopsies were carried out by METAVIR score. Plasma CX3CL1 was measured using an immunoassay kit.ResultsPatients with advanced fibrosis had higher CX3CL1 levels than those with mild or no fibrosis (p = 0.010); and patients with severe activity grade had higher CX3CL1 levels than those with low activity grade (p = 0.040). Plasma CX3CL1 levels were significantly associated with increased odds of significant fibrosis (odds ratio (OR): 3.47 (95% of confidence interval (95%CI): 1.04; 11.58)), advanced fibrosis (OR: 6.78 (95%CI: 1.70; 26.93)), and moderate necroinflammatory activity grade (OR: 4.09 (95%CI: 1.21; 13.87)). When we analyzed fibrosis stages and activity grades of METAVIR score together, we found a positive significant association of CX3CL1 levels with moderate activity grade/significant fibrosis (OR: 5.49 (95%CI: 1.46; 20.58)) and moderate activity grade/advanced fibrosis (OR: 8.99 (95%CI: 2.06; 39.23)).ConclusionPlasma CX3CL1 levels were independently associated with several characteristics of severe liver disease in HIV/HCV coinfected patients with HCV-genotype 1, suggesting a role of CX3CL1 in the pathogenesis of HCV infection.     

Predictive value of early virological response to treatment with different interferon-based regimens plus ribavirin in patients with chronic hepatitis C

Early virological response (EVR) to different interferon-based regimens plus ribavirin and its ability to predict the outcome of therapy in patients with chronic hepatitis C were investigated. The study design was as follows: 64 naive patients were considered, 32/64 received pegylated interferon alpha-2b (Peg-IFN-alpha2b) plus ribavirin and the remaining 32 received leucocyte interferon alpha (IFN-alpha) plus ribavirin. At week 4 of treatment, EVR was present in 68.7% and 37.5% of patients treated with Peg-IFN-alpha2b plus ribavirin, and with leucocyte interferon alpha (IFN-alpha) plus ribavirin, respectively (p = 0.024). At week 12, the cumulative EVR rates did not differ between the two groups (71.9% vs 56.2%, p >0.05) because a higher proportion of patients achieved EVR for the first time after more than 4 weeks of therapy in the standard IFN-alpha group. Sustained virological response (SVR) rates, however, resulted significantly higher in the Peg-IFN-alpha2b group (65.6% vs 37.5%; p = 0.045) since a higher proportion of patients who received standard IFN-alpha relapsed during the follow-up. In the standard IFN-alpha group, HCV genotype 1 (p = 0.035), high baseline viral load (p = 0.035) and the presence of bridging fibrosis/cirrhosis (p = 0.011) were closely associated with significantly lower SVR rates. In the Peg-IFN-alpha2b group, only bridging fibrosis/cirrhosis (p = 0.02) negatively influenced the outcome of treatment. Overall, 33/41 (80.5%) patients with EVR at week 12 were sustained responders, yielding a positive predictive value (PPV) of 0.80. However, when SVR was related to the time taken to reach EVR, 32/34 (94.1%) patients with EVR at week 4 of therapy (PPV = 0.94) versus 1/7 (14.3%) patients who had EVR after more than 4 weeks of therapy (PPV = 0.14) resulted sustained responders (p = 0.000057). In conclusion, EVR at week 4 of treatment is strongly associated with the likelihood of achieving SVR, regardless of the therapeutic regimen. However, when compared with standard IFN-alpha plus ribavirin, treatment with Peg-IFN-alpha2b plus ribavirin significantly increases the probability of viral clearance within the first 4 weeks of treatment. Finally, patients who do not clear the virus within the first 12 weeks of treatment have no chance of achieving SVR, justifying discontinuation of therapy in these patients.     

Rate of cirrhosis progression reduced in HIV/HCV co-infected non-responders to anti-HCV therapy

This is a retrospective longitudinal follow-up study of 25 HIV/HCV positive cirrhotic patients not responding to peg-IFN plus ribavirin, and 25 untreated controls matched for age (+/-5 years), gender and Child-Pugh score. The primary endpoint of the study was the incidence of cirrhosis progression (CP) defined as the occurrence of at least one of the following events: death, ascites, jaundice, encephalopathy, gastrointestinal bleeding and hepatocellular carcinoma (HCC). During the median follow-up of 54 months (34-89), four treated (16%) and 13 untreated patients (52%) experienced CP (p = 0.02). Poisson's regression model showed that the independent predictors of CP were Peg-IFN therapy (p = 0.016), positive HIV-RNA (p = 0.024), and altered ALP values (p = 0.012). Peg-IFN therapy seems to slow down the rate of cirrhosis progression also in HIV/HCV co-infected patients nonresponders to anti-HCV therapy, in comparison with untreated patients.     

Ability of peripheral blood mononuclear cells to activate interferon response in vitro is predictive of virological response in HCV patients

The most reliable predictor of treatment efficacy in hepatitis C is HCV viremia decay at week 12 [early virological response (EVR)]. We investigated whether the ability of peripheral blood mononuclear cells (PBMC) to mount an interferon (IFN) response in vitro could be predictive of EVR. Fifteen patients treated with PEG IFNalpha + RBV, with pre-therapy frozen PBMC, were retrospectively selected. After a 3 hr PBMC exposure to IFNalpha in vitro, up-regulation of mRNA for IFN-stimulated genes (ISG) was measured by membrane super-array. ISG mRNA levels in unstimulated PBMC were low, but beta2M and CASP1 were significantly higher in EVR vs non-EVR. ISG mRNA up-regulation by IFN was more pronounced in EVR vs non-EVR. For 7 genes (IP-10, IFIT1, IFIT2, IFIT3, TRAIL, KIAA1628 and OAS2) cut-off levels were established, by ROC analysis, able to correctly classify all EVR and non-EVR. Early virological response to PEG IFNalpha +RBV is correlated with the pre-therapy ability of PBMC to activate an IFN response in vitro. If validated in a wider cohort of patients, the ability of this set of ISG to discriminate between EVR and non-EVR may be useful for pre-therapy evaluation, particularly in patients with unfavourable combinations of conventional response predictors.     

Liver function parameters in HIV/HCV co-infected patients treated with amprenavir and ritonavir and correlation with plasma levels

Acute liver toxicity is a frequent adverse event that occurs during antiretroviral therapy and was observed in 6-30% of the patients on treatment, especially in presence of HCV coinfection (Cooper et al., 2002, Maida et al., 2006, Sulkowski et al., 2000). A correlation between HCV-associated liver-fibrosis severity and the risk of HAART associated hepatoxicity has been demonstrated (Aranzabal et al., 2005, Sulkowski et al., 2004). This high liver toxicity rate might be due to increased drug exposure in patients with liver disease (Veronese et al., 2000). It has been reported that patients with chronic hepatitis C show significantly reduced CPY3A4 and CYP2D6 activity in comparison with healthy volunteers (Becquemont et al., 2002). The aim of this study was to evaluate the liver function tests in HCV-co-infected patients treated with fos-amprenavir and ritonavir.     

Cumulative insults to mitochondrial function may promote the emergence of 'syndrome X' and diabetes mellitus in HIV/HCV co-infected patients

The 'metabolic syndrome' or 'syndrome X' affects approximately a quarter of the general population of the United States. A significant number of patients, therefore, may have predisposing risk factors for developing 'syndrome X' and/or diabetes mellitus (DM) prior to HIV infection, hepatitis C (HCV) infection, and/or institution of highly active antiretroviral therapy (HAART). Metabolic perturbations identical to 'syndrome X' develop in many HIV-infected patients who are undergoing HAART. A series of cumulative and possibly synergistic insults to mitochondrial function which occur in HIV/HCV co-infected patients who are receiving HAART may promote the emergence of 'syndrome X' and DM. HIV-infected patients, especially those who are co-infected with HCV and who are undergoing HAART, may, therefore, be at increased risk of developing the cardiovascular complications that are associated with 'syndrome X' and DM.     

Factors associated with elevated ALT in an international HIV/HBV co-infected cohort on long-term HAART

Background

Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group.

Methods/Principal findings

To identify factors associated with ALT elevations in an HIV-HBV co-infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (≥2.5×ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4–13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA ≥2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04–4.11, p = 0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03–4.79, p = 0.04) were independently associated with ALT elevation.

Conclusions

In this HIV-HBV co-infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations.     

Differences in hepatitis C virus (HCV)-specific CD8 T-cell phenotype during pegylated alpha interferon and ribavirin treatment are related to response to antiviral therapy in patients chronically infected with HCV

CD8 T cells play a major role in antiviral immune responses. Their importance for progression to chronic hepatitis C and response to treatment are still unclear. To address these issues, hepatitis C virus (HCV)-specific CD8 T-cell responses were monitored, at the single-cell level, using HLA class I pentamers specific for HCV core and HCV NS3 epitopes, in 23 chronically infected patients during treatment with pegylated alpha interferon and ribavirin. Patients who presented a sustained-response to therapy had stronger HCV-specific CD8 T-cell responses at all time points studied. Moreover, there were clear differences in the phenotypes of these cells during therapy: in responder patients, terminally differentiated effector cells increased more rapidly, and their frequency was always higher than in nonresponder patients. Sustained-responder patients also showed a higher frequency of HCV-specific CD8 T cells producing cytotoxic factors. Overall, a late and inefficient differentiation process of HCV-specific CD8 T cells might be associated with lack of response to treatment. A better knowledge of the mechanisms underlying this impairment may be important for the development of new therapeutic strategies to maintain, restore, or increase CD8 T-cell effectiveness in chronic HCV infection.     

Circulating MiRNA-122 Levels Are Associated with Hepatic Necroinflammation and Portal Hypertension in HIV/HCV Coinfection

BackgroundIntroduction of combined antiretroviral therapy (cART) has improved survival of HIV infected individuals, while the relative contribution of liver-related mortality increased. Especially in HIV/HCV-coinfected patients hepatic fibrosis and portal hypertension represent the main causes of liver-related morbidity and mortality. Circulating miRNA-122 levels are elevated in HIV patients and have been shown to correlate with severity of liver injury. However, the association of miRNA-122 levels and hepatic fibrosis and portal hypertension remains to be explored in HIV/HCV coinfection.MethodsFrom a total of 74 (31% female) patients with HIV/HCV coinfection were included. Serum levels of miRNA-122 were analyzed by quantitative polymerase chain reaction (PCR) and normalized to SV-40 spike-in RNA. Hepatic venous pressure gradient (HVPG) was measured in 52 (70%) patients and the fibrosis stage was determined in 63 (85%) patients using transient elastography.ResultsThe levels of circulating miRNA-122 were increased in HIV/HCV coinfected patients and significantly correlated with the alanine aminotransferase (ALT) (r_s = 0.438; p<0.001) and aspartate transaminase AST values (r_s = 0.336; p = 0.003), but not with fibrosis stage (p = n.s.). Interestingly, miRNA-122 levels showed an inverse correlation with hepatic venous pressure gradient (HVPG) (r_s = −0.302; p = 0.03).ConclusionElevated miRNA-122 levels are associated with liver injury, and with low HVPG. Though, miRNA-122 levels are not suitable to predict the degree of fibrosis, they might function as indicators for portal hypertension in HIV/HCV coinfected patients.     

Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV

Background

Toxoplasma encephalitis is caused by the opportunistic protozoan parasite Toxoplasma gondii. Primary infection with T. gondii in immunocompetent individuals remains largely asymptomatic. In contrast, in immunocompromised individuals, reactivation of the parasite results in severe complications and mortality. Molecular changes at the protein level in the host central nervous system and proteins associated with pathogenesis of toxoplasma encephalitis are largely unexplored. We used a global quantitative proteomic strategy to identify differentially regulated proteins and affected molecular networks in the human host during T. gondii infection with HIV co-infection.

Results

We identified 3,496 proteins out of which 607 proteins were differentially expressed (≥1.5-fold) when frontal lobe of the brain from patients diagnosed with toxoplasma encephalitis was compared to control brain tissues. We validated differential expression of 3 proteins through immunohistochemistry, which was confirmed to be consistent with mass spectrometry analysis. Pathway analysis of differentially expressed proteins indicated deregulation of several pathways involved in antigen processing, immune response, neuronal growth, neurotransmitter transport and energy metabolism.

Conclusions

Global quantitative proteomic approach adopted in this study generated a comparative proteome profile of brain tissues from toxoplasma encephalitis patients co-infected with HIV. Differentially expressed proteins include previously reported and several new proteins in the context of T. gondii and HIV infection, which can be further investigated. Molecular pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis.

Electronic supplementary material

The online version of this article (doi:10.1186/1559-0275-11-39) contains supplementary material, which is available to authorized users.     

Adverse events among HIV/MDR-TB co-infected patients receiving antiretroviral and second line anti-TB treatment in Mumbai, India

Background

Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.

Methods

Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE.

Results

Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen.

Conclusions

AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.     

Analysis of the virus dynamics model reveals that early treatment of HCV infection may lead to the sustained virological response

Considerable progress has been made towards understanding hepatitis C virus, its pathogenesis and the effect of the drug therapy on the viral load, yet around 50% of patients do not achieve the sustained virological response (SVR) by the standard treatment. Although several personalized factors such as patients' age and weight may be important, by mathematical modeling we show that the time of the start of the therapy is a significant factor in determining the outcome. Toward this end, we first performed sensitivity analysis on the standard virus dynamics model. The analysis revealed four phases when the sensitivity of the infection to drug treatment differs. Further, we added a perturbation term in the model to simulate the drug treatment period and predict the outcome when the therapy is carried out during each of the four phases. The study shows that while the infection may be difficult to treat in the late phases, the therapy is likely to result in SVR if it is carried out in the first or second phase. Thus, development of newer and more sensitive screening methods is needed for the early detection of the infection. Moreover, the analysis predicts that the drug that blocks new infections is more effective than the drug that blocks the virus production.     

Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment

Introduction  

Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response.     

Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation

Background

Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.

Methods

A case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy (¹H-MRS) and positron emission tomography (PET) using a ¹¹C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling.

Results

Twenty-four aHCV cases completed NCT and ¹H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent ¹H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on ¹H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in ¹¹C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations.

Discussion

Poorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher ¹¹C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.     

Complexity and catalytic efficiency of hepatitis C virus (HCV) NS3 and NS4A protease quasispecies influence responsiveness to treatment with pegylated interferon plus ribavirin in HCV/HIV-coinfected patients

The role of the hepatitis C virus (HCV) NS3/4A protease in ablating the signaling pathway involved in the production of alpha/beta interferon (IFN-α/β) suggests a relationship between NS3/4A proteolytic activity and a patient's response to IFN-based therapy. To identify viral factors associated with the HCV treatment response, we analyzed the pretreatment NS3/4A protease gene quasispecies composition of 56 HCV genotype 1-HIV-1-coinfected patients treated in our clinic with pegylated IFN (pegIFN) plus ribavirin (RBV). The catalytic efficiency of the dominant (i.e., the most abundant) quasispecies was also assayed for Cardif cleavage and correlated with treatment outcome. A total of 1,745 clones were isolated and sequenced. Significantly less nucleotide quasispecies heterogeneity and lower Shannon entropy values were detected within the responder group (P < 0.05). A correlation was also found between the efficiency of NS3/4A protease Cardif cleavage and therapy outcome. Proteases from sustained responder patients were more efficient at processing Cardif (mean ± standard error of the mean [SEM], 0.8960 ± 0.05568; n = 19) than proteases from nonresponders (mean ± SEM, 0.7269 ± 0.05306; n = 37; P < 0.05). Finally, the amino acid p distance (the proportion [p] of nucleotide sites at which two sequences being compared are different) was significantly shorter in patients with an interleukin-28B (IL-28B) risk allele (P < 0.01), suggesting that IL-28B risk allele carriers exert a lower positive selection pressure on the NS3/4A protease. NS3/4A protease efficiency in cleaving Cardif may be associated with the pegIFN-RBV treatment response, as shown in our cohort of HIV-HCV-coinfected patients. Greater NS3/4A nucleotide heterogeneity and higher Shannon entropy values in nonresponders suggest that less HCV quasispecies complexity may favor a better response to pegIFN-RBV.     

狼疮性肾炎患者血清和尿液sCD14、sCD163水平的表达及其临床意义

摘要 目的：探讨狼疮性肾炎（LN）患者血清和尿液可溶性白细胞分化抗原14（sCD14）、可溶性白细胞分化抗原163（sCD163）水平的表达及其临床意义。方法：选取2019年12月至2022年6月我院肾内科收治的90例LN患者,根据系统性红斑狼疮疾病活动指数2000（SLEDAI-2000）评分将LN患者分为活动期LN组（＞4分,53例）和非活动期LN组（≤4分,37例）,另选取45例于我院门诊体检的健康志愿者为对照组。检测各组血清和尿液中sCD14、sCD163水平,分析其与SLEDAI-2000评分及常规实验室指标的相关性。多因素Logistic回归分析LN患者处于疾病活动期的危险因素。结果：活动期LN组血清和尿sCD14、血清和尿sCD163水平均高于非活动期LN组、对照组（P＜0.05）,且非活动期LN组血清和尿sCD14、血清和尿sCD163水平均高于对照组（P＜0.05）。LN患者血清和尿sCD14、血清和尿sCD163水平与SLEDAI-2000评分、尿蛋白、尿素氮、肌酐水平呈正相关（P＜0.05）。多因素Logistic回归分析显示,血清和尿sCD14、血清和尿sCD163及尿蛋白水平升高是LN患者处于疾病活动期的危险因素（P＜0.05）。结论：LN活动期患者血清和尿液sCD14、sCD163水平显著增高,高水平sCD14、sCD163与LN患者肾功能损伤以及LN疾病活动度增加有关。     

Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients

Background

Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.

Methods

We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO₂Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.

Results

Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV₁/VC, FEF₅₀/FIF₅₀ ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO₂Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO₂Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.

Conclusion

The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.     

上海地区人类免疫缺陷病毒/艾滋病合并乙型、丙型肝炎病毒感染的临床流行病学研究

目的 研究人类免疫缺陷病毒1型(HIV-1)感染者中乙型肝炎病毒(HBV)和(或)丙型肝炎病毒(HCV)感染的流行现状及其特点。方法 对上海市(复旦大学附属)公共卫生中心就诊的170例HIV-1感染者采集血标本,使用微粒子酶联免疫法(MEIA)检测HIV-1感染者血清的乙型肝炎二对半(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc),应用酶联免疫吸附试验(ELISA)检测HCV抗体。结果 170名HIV-1感染者中,男性146人,女性24人,最小年龄16岁,最大年龄74岁,平均年龄41±13岁;HBsAg阳性患者19人(11．2％),抗-HBs阳性者87人(51．2％),HBeAg阳性者7人(4．1％)．抗-HBe阳性者49人(28．8％),抗-HBc阳性者111人(65．2％);抗-HCV阳性者77人(45．3％)。HIV-1、HBV和HCV三重感染者9人,约占5．3％。结论 HIV-1感染者HBsAg阳性率与普通人群相近,但HIV-1与HCV混合感染的比例显著高于普通人群。     

CD8<Superscript>+</Superscript> T cell expansion in HIV/HCV coinfection is associated with systemic inflammation

High prevalence of non-AIDS-defining illnesses in treated HIV-infected patients is associated with increased peripheral CD8⁺ T cell counts. Hepatitis C virus (HCV) coinfection is an additional risk factor for the development of non-AIDS events. We found that, in HIV/HCV coinfection, the increased proportion of CD8⁺ T lymphocytes is due to the effector memory and terminal effector T cells gain. Moreover, in these patients, the accumulation of highly differentiated forms of CD8⁺ T lymphocytes was associated with increased concentrations of inflammatory indices.