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1.
Stella De Nicola Paola Dongiovanni Alessio Aghemo Cristina Cheroni Roberta D'Ambrosio Michele Pedrazzini Francesco Marabita Lorena Donnici Marco Maggioni Silvia Fargion Massimo Colombo Raffaele De Francesco Luca Valenti 《PloS one》2014,9(8)
Background and Aims
The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M) on the fibrosis progression rate (FPR) and the interaction with age at infection in chronic hepatitis C (CHC).Methods
FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score.Results
Older age at infection was the strongest determinant of FPR (p<0.0001). PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; −0.64±0.2, n = 8 vs. −0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05), but not in those infected at younger age (p = ns). The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2–3 steatosis, genotype 3, and overweight; p<0.05). At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022), independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025). The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032).Conclusions
We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients. 相似文献2.
El?bieta Jab?onowska Kamila Wójcik Bo?ena Szymańska Aleksandra Omulecka Hanna ?wiklińska Anna Piekarska 《PloS one》2014,9(4)
Aim
To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1.Materials and Methods
The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed.Results
HCV mono-infected patients, with lower grading score (G<2) and higher HCV viral load (>600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman’s ρ = 0.586, p = 0.000001) and miR-122 (Spearman’s ρ = 0.270, p = 0.014059).Conclusions
HMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C. 相似文献3.
Rembeck K Alsiö A Christensen PB Färkkilä M Langeland N Buhl MR Pedersen C Mørch K Westin J Lindh M Hellstrand K Norkrans G Lagging M 《PloS one》2012,7(1):e29370
Background and Aims
Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver histology in the context of a phase III treatment trial (NORDynamIC) for treatment-naïve patients with chronic HCV genotype 2 or 3 infection, where pretreatment liver biopsies were mandatory.Methods
Three hundred and thirty-nine Caucasian patients had samples available for IL28B genotyping (rs12979860) of whom 314 had pretreatment liver biopsies that were evaluated using the Ishak protocol, allowing for detailed grading and staging of liver histopathology.Results
IL28B CCrs12979860 genotype in HCV genotype 3 infected patients was associated with higher ALT levels (p<0.0001), higher AST to platelet ratio index (APRI; p = 0.001), and higher baseline viral load (p<0.0001) as compared to patients with the CT or TT genotypes. Additionally the CCrs12979860 genotype entailed more pronounced portal inflammation (p = 0.02) and steatosis (p = 0.03). None of these associations were noted among HCV genotype 2 infected patients.Conclusion
This study shows that the CCrs12979860 SNP is associated with more pronounced liver histopathology in patients chronically infected with HCV genotype 3, which may be secondary to higher viral load. The finding that IL28B variability did not impact on liver pathology or viral load among genotype 2 infected patients implies that IL28B may differentially regulate the course of genotype 2 and 3 infection. 相似文献4.
Iva Subhanova Lucie Muchova Martin Lenicek Hendrik J. Vreman Ondrej Luksan Kristyna Kubickova Miluse Kreidlova Tomas Zima Libor Vitek Petr Urbanek 《PloS one》2013,8(3)
Background and Aims
Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV.Methods
Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naïve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy.Results
Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naïve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05–214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome.Conclusion
Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential. 相似文献5.
Antonio Rivero-Juarez Rafael Gonzalez Angela Camacho Barbara Manzanares-Martin Antonio Caruz Antonio Martinez-Peinado Julian Torre-Cisneros Juan A. Pineda José Pe?a Antonio Rivero 《PloS one》2013,8(4)
Aim
To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patientsMethods
HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed.Results
Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week1: p = 0.01; week2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week1: p<0.001; week2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1.Conclusion
Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates. 相似文献6.
Lene Fogt Lundbo Louise Nygaard Clausen Nina Weis Kristian Sch?nning Lene Rosen?rn Thomas Benfield Peer Brehm Christensen 《PloS one》2014,9(12)
Objective
Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.Patients and Methods
This cross-sectional study consists of 369 patients with chronic hepatitis C (CHC). Liver stiffness was evaluated using transient elastograhy (TE). Factors associated with development of liver fibrosis were identified by logistic regression analysis.Results
We identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR) 5.7–12.1). HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log10 IU/mL, p = 0.03). Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9–14.5) compared to genotype 1 (6.9 kPa; IQR, 5.4–10.9) and 2 (6.7 kPa; IQR, 4.9–8.8) (p = 0.02). Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04). However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR) 1.09 (95% confidence interval (CI), 1.05–1.14 per year increment)), ALT (OR 1.01 (95% CI, 1.002–1.011), per unit increment) and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19–4.81), were consistently associated with cirrhosis (TE>17.1 kPa).Conclusions
Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study. 相似文献7.
Gloria Taliani Martina Spaziante Elisa Biliotti Marina Borro Donatella Palazzo Stefania Grieco Cristiana Franchi Giancarlo Iaiani Caterina Furlan Valentina Gallinaro Maurizio Simmaco 《PloS one》2013,8(8)
Background
Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients.Aims
The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects.Methods and patients
We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects.Results
CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03).Conclusions
Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile. 相似文献8.
Xia Rong Ling Lu Junzhi Wang Huaping Xiong Jieting Huang Jinyan Chen Ke Huang Ru Xu Min Wang Xuemei Zhang Tai Guo Yueyue Liu Guoquan Gao Yongshui Fu Kenrad E. Nelson 《PloS one》2012,7(12)
Background
Both HCV genotypes and viral loads are predictors of therapeutic outcomes among patients treated with α-interferon plus ribavirin; however, such correlation has only been studied for genotypes 1, 2, and 3 but not for genotype 6.Methodology/Findings
299 voluntary blood donors were recruited who were HCV viremic. Their mean age was 31.8; the male/female ratio was 3.82 (225/59). The viral loads of HCV were measured using the COBAS AmpliPrep/COBAS TaqMan test (CAP/CTM) while HCV genotypes were determined by direct sequencing the partial NS5B region. HCV genotypes 1, 2, 3, and 6 were determined in 48.9%, 8.7%, 12.3%, and 30.1% of the donors, respectively, and the levels of mean viral loads in genotype 1 and 6 significantly higher than that of 2 and 3 (P<0.001). As a whole, the viral loads in male donors were higher than in female (P = 0.006). Moreover, the donors'' gender and HCV genotypes are independently correlated with the measured viral loads.Conclusion
HCV genotype 1 and 6 had significantly higher viral loads than genotype 2 and 3. 相似文献9.
Background
Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several carcinogens and may play an important role in carcinogenesis of cancer. Previous studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk reported inconclusive results. To clarify the possible association, we conducted a meta-analysis of eligible studies.Methods
We searched in the Pubmed, Embase, and Wangfang Medicine databases for studies assessing the association between GSTT1 null genotype and gastric cancer risk. The pooled odds ratio (OR) and its 95% confidence interval (95%CI) was calculated to assess the strength of the association. A total of 48 studies with a total of 24,440 individuals were ultimately eligible for meta-analysis.Results
Overall, GSTT1 null genotype was significantly associated with increased risk of gastric cancer (Random-effect OR = 1.23, 95%CI 1.13–1.35, P OR <0.001, I2 = 45.5%). Significant association was also found in Caucasians, East Asians, and Indians (P Caucasians = 0.010; P East Asians = 0.003; P Indians = 0.017). After adjusting for other confounding variables, GSTT1 null genotype was also significantly associated with increased risk of gastric cancer (Random-effect OR = 1.43, 95%CI 1.20–1.71, P OR <0.001, I2 = 48.1%).Conclusion
The meta-analysis provides strong evidence for the significant association between GSTT1 null genotype and increased risk of gastric cancer. 相似文献10.
Yuan Kong Xiaoping Wang Yushu Shang Paul M. Schroder Wenhua Liang Xiaoting Ling Zhiyong Guo Xiaoshun He 《PloS one》2012,7(12)
Background
Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatic cirrhosis and hepatocellular carcinoma, and HCV genotype 1 is the most prevalent genotype and is resistant to current standard therapy. We performed this meta-analysis to evaluate the efficacy and safety of telaprevir-based therapy for chronic HCV genotype 1 infection.Methods
We included randomized controlled trials with no year or language restriction. All data were analyzed using a random-effects model by Review Manager v5.0. The primary outcome was the proportion of patients achieving sustained virologic response (SVR), and the secondary outcomes were HCV relapse rate, incidence of severe adverse events (SAEs), and discontinuation due to adverse events.Results
The proportion of achieving SVR was significantly higher in the telaprevir group (odds ratio [OR] = 3.40 [1.92, 6.00], P<0.0001; I2 = 87%) regardless of a patients’ previous treatment status. It was also significantly higher in the 24-week and 48-week treatment groups (OR = 4.52 [2.08, 9.81], P<0.001; I2 = 85%, and OR = 4.05 [1.56, 10.56], P = 0.004; I2 = 92%, respectively), while it was comparable in the 12-week treatment group (OR = 1.32 [0.63, 2.75], P = 0.46; I2 = 35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR = 0.28 [0.16, 0.49], P<0.001; I2 = 76%). However, the incidence of SAE (OR = 1.56 [1.15, 2.10], P = 0.004; I2 = 0%) and study discontinuation due to adverse events (OR = 2.24 [1.43, 3.50], P<0.001; I2 = 37%) were significantly higher in the telaprevir group.Conclusion
Despite its higher incidence of SAEs and discontinuation due to adverse events, telaprevir-based therapy can increase the proportion of achieving SVR in both previously treated and untreated chronic HCV-1 infected patients. 相似文献11.
Antonio Rivero-Juárez Luis F. Lopez-Cortes Angela Camacho Almudena Torres-Cornejo Juan A. Pineda Manuel Marquez-Solero Antonio Caruz Rosa Ruiz-Valderas Julian Torre-Cisneros Alicia Gutierrez-Valencia Antonio Rivero 《PloS one》2012,7(11)
Background
The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment.Methods
Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG) included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG) patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model.Results
One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1∶1.72±0.74 log10 IU/mL versus 1.78±0.67 log10 IU/mL, p = 0.827; week 2∶2.3±0.89 log10 IU/mL versus 3.01±1.02 log10 IU/mL, p = 0.013; week 4∶3.52±1.2 log10 IU/mL versus 4.09±1.1 log10 IU/mL, p = 0.005). The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4.Conclusions
Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients. 相似文献12.
Luciana G. S. Orsini Marcelo M. Pinheiro Charlles H. M. Castro Ant?nio E. B. Silva Vera L. Szejnfeld 《PloS one》2013,8(11)
Introduction
The high prevalence of chronic hepatitis C (CHC) and its consequent cirrhosis has been associated with bone fragility. Whether CHC may cause bone and mineral abnormalities in the absence of hepatocellular dysfunction is still unknown. In this study we aimed to determine the prevalence of osteoporotic vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk factors for low BMD and fractures were also investigated.Methods
Morphometric vertebral fractures and BMD measurements were performed in 60 non-cirrhotic untreated men with CHC and 59 healthy controls, matched for age and gender, weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline phosphatase and vitamin D (25OHD) concentrations were measured in all participants. Clinical risk factors for low BMD and fractures were evaluated by a structured questionnaire as well as details regarding HCV infection.Results
Trochanter and total femur BMD were significantly lower in CHC patients as compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels of physical activities and more often report of prolonged immobilization were observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load and genotype did not correlate with BMD measurements. Bone markers and 25OHD concentrations were similar in both groups. Only a few vertebral fractures were observed.Conclusions
Our results demonstrate that non-cirrhotic untreated CHC patients have lower BMD at the femur as compared to healthy men in spite of the absence of significant bone and mineral abnormalities. 相似文献13.
Mark H. Kuniholm Christina M. Parrinello Kathryn Anastos Michael Augenbraun Michael Plankey Marek Nowicki Marion Peters Elizabeth T. Golub Nell Lurain Alan L. Landay Howard D. Strickler Robert C. Kaplan 《PloS one》2013,8(4)
Background
Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.Methods
Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.Results
In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (P interaction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.Conclusions
CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients. 相似文献14.
Purpose
Xeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population.Methods
This two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI).Results
Our case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34–0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46–0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: Pinteraction = 0.002; Gene-sex: Pinteraction = 0.002; Gene-smoking: Pinteraction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls.Conclusion
These findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC. 相似文献15.
Carolin Lechtermann Berthold P. Hauffa Ralf Herrmann Michael M. Schündeln Alexandra Gellhaus Markus Schmidt Corinna Grasemann 《PloS one》2014,9(8)
Preeclampsia, a hypertensive disorder in pregnancy develops in 2–8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.
Objective
To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.Methods
25-OH vitamin D and 1,25-(OH)2 vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.Results
In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)2 vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = −0.81, P<0.0001).Summary
Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia. 相似文献16.
Paolo Zanotti-Fregonara Jussi Hirvonen Chul Hyoung Lyoo Sami S. Zoghbi Denise Rallis-Frutos Marilyn A. Huestis Cheryl Morse Victor W. Pike Robert B. Innis 《PloS one》2013,8(4)
Background
Population-based input function (PBIF) may be a valid alternative to full blood sampling for quantitative PET imaging. PBIF is typically validated by comparing its quantification results with those obtained via arterial sampling. However, for PBIF to be employed in actual clinical research studies, its ability to faithfully capture the whole spectrum of results must be assessed. The present study validated a PBIF for [18F]FMPEP-d 2, a cannabinoid CB1 receptor radioligand, in healthy volunteers, and also attempted to utilize PBIF to replicate three previously published clinical studies in which the input function was acquired with arterial sampling.Methods
The PBIF was first created and validated with data from 42 healthy volunteers. This PBIF was used to assess the retest variability of [18F]FMPEP-d 2, and then to quantify CB1 receptors in alcoholic patients (n = 18) and chronic daily cannabis smokers (n = 29). Both groups were scanned at baseline and after 2–4 weeks of monitored drug abstinence.Results
PBIF yielded accurate results in the 42 healthy subjects (average Logan-distribution volume (V T) was 13.3±3.8 mL/cm3 for full sampling and 13.2±3.8 mL/cm3 for PBIF; R2 = 0.8765, p<0.0001) and test-retest results were comparable to those obtained with full sampling (variability: 16%; intraclass correlation coefficient: 0.89). PBIF accurately replicated the alcoholism study, showing a widespread ∼20% reduction of CB1 receptors in alcoholic subjects, without significant change after abstinence. However, a small PBIF-V T bias of −9% was unexpectedly observed in cannabis smokers. This bias led to substantial errors, including a V T decrease in regions that had shown no downregulation in the full input function. Simulated data showed that the original findings could only have been replicated with a PBIF bias between −6% and +4%.Conclusions
Despite being initially well validated in healthy subjects, PBIF may misrepresent clinical protocol results and be a source of variability between different studies and institutions. 相似文献17.
Ming-Ling Chang Yung-Kuan Tsou Tsung-Hui Hu Cheng-Hui Lin Wey-Ran Lin Chang-Mu Sung Tsung-Hsing Chen Mei-Ling Cheng Kuo-Chin Chang Cheng-Tang Chiu Chau-Ting Yeh Jong-Hwei Su Pang Ming-Shi Shiao 《PloS one》2014,9(8)
Background
The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive.Methods
A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) ≥2.5). Paired t-tests were used to compare the pre- and post-treatment variables.Results
Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p = 0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01) ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019) and apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p = 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002) was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041) and triglyceride (p = 0.044) levels than G2 patients.Conclusions
G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR. 相似文献18.
Xiang Zhou Wenhui Xie Qian Li Yifan Zhang Jie Zhang Xiaoping Zhao Jianjun Liu Gang Huang 《PloS one》2013,8(12)
Objective
Evaluation of 18F-FDG uptake value via PET is central to current methods of diagnosis and staging of non-small cell lung cancer (NSCLC) due to its ability to evaluate expression levels of key regulators associated with glucose metabolism in tumor cells. Tp53-induced glycolysis and apoptosis regulator (TIGAR) is an important P53-induced protein that can inhibit glycolysis; however, there have been few clinical studies on its mechanism. Here we have investigated the relationship between TIGAR expression and 18F-FDG PET in tumors, along with its relationship with the clinical characteristics of NSCLC.Methods
We analyzed SUVmax in 79 patients with NSCLC through immunohistochemical staining of TIGAR and five other biological markers associated with tumor cell glycolysis, in order to evaluate the correlation between their expression and SUVmax. We also plotted Kaplan-Meier survival curves to assess TIGAR expression with the prognosis and survival of patients with NSCLC.Results
The key findings were as follows: SUVmax was negatively correlated with the expression of TIGAR (r = −0.31, p<0.01); TIGAR expression was correlated with tumor size (p = 0.01), histological type (p<0.01), differentiation degree (p<0.01) and lymph node metastasis(p<0.01) in patients with NSCLC; and the survival time of patients whose TIGAR was negatively expressed was significantly shorter than for those whose TIGAR was positively expressed (P = 0.023).Conclusions
The expression of TIGAR in primary tumors is significantly correlated with SUVmax, and low expression of TIGAR may predict a worse clinical outcome in patients with NSCLC. 相似文献19.
Eliford Ngaimisi Abiy Habtewold Omary Minzi Eyasu Makonnen Sabina Mugusi Wondwossen Amogne Getnet Yimer Klaus-Dieter Riedel Mohammed Janabi Getachew Aderaye Ferdinand Mugusi Leif Bertilsson Eleni Aklillu Juergen Burhenne 《PloS one》2013,8(7)
Objectives
We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations.Methods
ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done.Result
Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART.Conclusion
We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations. 相似文献20.
Meng-Rui Lee Ching-Yao Yang Kai-Ping Chang Li-Ta Keng David Hung-Tsang Yen Jann-Yuan Wang Huey-Dong Wu Li-Na Lee Chong-Jen Yu 《PloS one》2013,8(3)