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- [Efficacy of 48-week tenofovir disoproxil fumarate therapy in patients who were unresponsive to nucleoside-analogue treatments.] [JOURNAL ARTICLE]
- Zhonghua Gan Zang Bing Za Zhi 2014 Apr; 22(4):266-271.
To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated.Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline),4,12,24,36 and 48 were collected for evaluation.The lower limit of HBV DNA detection was 100 IU/ml.The serum alanine aminotransferase (ALT) normalization rate,hepatitis B e antigen (HBeAg) seroconversion rate,viral breakthrough (VBT) rate,viral response (VR) rate,and adverse events were determined upon treatment completion.Statistical analyses were carried out using the Student's t-test,the x2 test or the Kaplan-Meier method.Over the 48-week treatment period,HBV DNA levels declined significantly from baseline (week 4:(2.11 +/- 0.38) log10 IU/ml,t =5.582; week 12:(0.93 +/- 0.31) log10 IU/ ml,t =9.303; week 24:(0.75 +/- 0.20) log10 IU/ml,t =3.123; week 36:(0.16 +/- 0.19) log10 IU/ml,t =10.759; week 48:(0.14 +/- 0.25) log10 IU/ml,t =12.202) (all P less than 0.01).However,the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24,36 and 48 (all P more than 0.05).The most robust decline in HBV DNA levels was observed at week 4 ((2.11 +/- 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 +/- 0.37) log10 IU/ml).The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%,P less than 0.01),36 (80.0%,P=0.007),and 48 (88.9%, P=0.001).The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks).At week 48,the rates ofVR,HBeAg seroconversion,and VBT were 88.9%,6.7%,and 0% respectively.During treatment,the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients,and were comparable at each time point examined (all P more than 0.05).All patients showed a normal level of serum creatinine throughout the treatment period.For CHB patients with non-response to NAs,TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.
- [Short-term curative effect of ribavirin combination therapy with pegylated interferon alfa-2a vs.interferon alfa-2a in patients with chronic hepatitis C.] [JOURNAL ARTICLE]
- Zhonghua Gan Zang Bing Za Zhi 2014 Apr; 22(4):255-259.
To perform a retrospective cohort study in order to determine the differences in short-term curative effect of ribavirin in combination with interferon alfa (IFNa)-2a vs.pegylated (Peg)-IFNa-2a in patients with chronic hepatitis C (CHC).One-hundred-and-eighty-eight treatmentna(i)ve CHC patients who were administered combination therapy of ribavirin with IFNa from 2010 to 2012.One-hundred-and-thirty-three of the patients received the therapy with IFNa-2a and the remaining 55 received Peg-IFNa-2a.Hepatitis C virus (HCV) load and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at treatment weeks 4,12,24,and 48.Adverse reactions were recorded.Differences between the groups were assessed by statistical analysis.The patients in the Peg-IFNa-2a group and the IFNa-2a group showed no significant difference in sex distribution,age,smoking habits,or drinking habits at baseline (all P more than 0.05).Both antiviral therapies significantly reduced the HCV load and levels of ALT and AST (baseline levels vs.all treatment weeks examined,P less than 0.05); however,the reduction in the HCV load at week 4 was significantly more robust with the Peg-IFNa-2a therapy (2.96 +/- 0.66) log10 IU/ ml vs.(3.47 +/- 1.42)1og10 IU/ml; F =4.14,P=0.04).The Peg-IFNa-2a group also showed a significant higher rate of rapid virological response (RVR) than the IFNa-2a group (72.72% vs.57.14%;x2=4.37,P=0.04),but there were no statistically significant differences found between the two groups for early virological response rate (EVR),endpoint antiviral treatment virologic response rate (ETR),biochemical response rate,or rate of adverse reactions (all P more than 0.05).Ribavirin in combination with Peg-IFNa-2a produces a better RVR than in combination with IFNa-2a.Yet,the EVR,ETR,biochemical response rate,and rate of adverse reactions is similar for the two forms of IFNa-2a,Further studies are required to determine the potential superiority of Peg-IFNa-2a for a long-term curative effect.
- [A preliminary assessment of the clinical utility of measuring hepatitis C virus antibody to evaluate infection status.] [JOURNAL ARTICLE]
- Zhonghua Gan Zang Bing Za Zhi 2014 Apr; 22(4):244-250.
To investigate the potential of hepatitis C virus (HCV) antibody measurement as a clinical approach to determine the infection status and potential for spontaneous-resolution among patients with HCV mono-infection and HCV/human immunodeficiency virus (HIV) co-infection.A total of 340 individuals who tested positive for serum anti-HCV antibodies and/or serum anti-HW antibodies were enrolled for study in 2009 from a single village in central China. Markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and infection (anti-HCV antibodies, CD4+ T cell counts, HCV genotype, and HCV viral load) were measured at baseline and follow-up (in July 2012). At follow-up,the subjects were grouped according to ongoing HCV mono-infection (n=129), ongoing HCV/HIV co-infection (n=98), spontaneously resolved (SR)-HCV in mono-infection (n=65),and SR-HCV in HCV/HIV co-infection (n=48) for statistical analysis.Almost all of the subjects in the ongoing HCV mono-infection group showed high levels of HCV antibodies (S/CO more than or equal to 10), but the majority of the subjects in the SR-HCV in mono-infection group and in the ongoing HCV/HIV co-infection group.The SR-HCV mono-infection group showed a remarkable decrease in HCV antibodies from 2009 (HIV:7.75 +/- 3.8; HIV+:7.61 +/- 3.47) to 2012 (HIV:5.51 +/- 3.67; HIW:4.93 +/- 3.35) (HIV:t =10.67, P less than 0.01; HIV+:t =9.52, P less than 0.01). The ongoing HCV/HIV co-infection group showed a positive correlation between HCV antibodies S/CO ratio and CD4+ T cell count (r=028, P=0.008). In the ongoing HCV mono-infection group,the levels of HCV antibodies were significantly higher in individuals infected with HCV-1b than in those with HCV-2a (14.74 +/- 1.68 vs.14.08 +/- 1.44, t=2.20, P=0.03). In the ongoing HCV/HIV co-infection group, the numbers of subjects with elevated (more than 40 U/L) liver function markers were significantly different according to the HCV genotype infection:HCV-1b:ALT, 25/42 vs.16/56 (x2=9.45, P=0.002); HCV2a:AST, 28/42 vs.18/56 (x2=11.49, P=0.001). The HCV RNA positive rate was significantly higher in subjects with high HCV antibody cutoff values (S/CO more than or equal to 10) than in those with low HCV antibody (S/CO less than 10) (HIV:128/151 vs.1/43, x2=102.11, P less than 0.01; HIV+:88/98 vs.10/48, x2=69.44, P less than 0.01), regardless of HIV co-infection. Significantly more subjects in the ongoing HCV mono-infection group had elevated (more than 40 U/L) ALT or AST than the subjects in the SR-HCV mono-infection group with high levels of HCV antibody (S/CO more than or equal to 10) (ALT:57/128 vs.2/23, x2=10.52, P=0.001; AST:57/128 vs.0/23, x2=16.45, P less than 0.01).Serum HCV antibody levels, in combination with other clinical information such as liver function and HIV infection status, may aid in the preliminarily evaluation of an individual's HCV infection status and likelihood for spontaneous resolution. Low levels of HCV antibody (S/CO less than 10) may indicate a better chance of SR-HCV, after ruling out the possibility of suffering from immunosuppressive diseases such as HIV infection.
- Persistent organic pollutants and liver dysfunction biomarkers in a population-based human sample of men and women. [JOURNAL ARTICLE]
- Environ Res 2014 Aug 27.:251-256.
Persistent organic pollutants (POPs) are stable organic compounds generated through different industrial activities. Liver is involved in the metabolism of POPs, and hence exposure to POPs may interfere with liver function. Although a few studies have shown adverse effects of POPs on liver function, large-scale studies involving humans are lacking. We performed this large population-based cross-sectional study to assess the associations between different POPs and liver dysfunction biomarkers.A total of 992 individuals (all aged 70 years, 50% males) were recruited as part of Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The total toxic equivalency (TEQ) value was calculated for seven mono-ortho and two non-ortho substituted polychlorinated biphenyls (PCBs) and octachloro-p-dibenzodioxin (OCDD) to assess their toxicological effects. The association of TEQ values, summary measures of 16 PCBs (sum of PCBs) and three organochlorine pesticides (sum of OC pesticides) with liver dysfunction biomarkers (bilirubin; alkaline phosphatase, ALP; alanine aminotransferase, ALT; and gamma-glutamyltransferase, GGT) was analyzed utilizing linear regression analysis.The mono-ortho PCB TEQ values were found to be significantly positively associated with bilirubin (β=0.71, P=0.008), while sum of OC pesticide concentrations was negatively associated with ALP (β=-0.02, P=0.002) after adjusting for various potential confounders. When analyzed individually, a number of different POPs were associated with ALP, ALT and bilirubin. No such association with GGT was observed.Various POPs including PCBs, OCDD and pesticides were associated with the liver dysfunction biomarkers bilirubin, ALT and ALP, suggesting adverse effects on liver function from these environmental pollutants.
- Amino acid, mineral, and polyphenolic profiles of black vinegar, and its lipid lowering and antioxidant effects in vivo. [JOURNAL ARTICLE]
- Food Chem 2015 Feb 1.:63-69.
Black vinegar (BV) contains abundant essential and hydrophobic amino acids, and polyphenolic contents, especially catechin and chlorogenic acid via chemical analyses. K and Mg are the major minerals in BV, and Ca, Fe, Mn, and Se are also measured. After a 9-week experiment, high-fat/cholesterol-diet (HFCD) fed hamsters had higher (p<0.05) weight gains, relative visceral-fat sizes, serum/liver lipids, and serum cardiac indices than low-fat/cholesterol diet (LFCD) fed ones, but BV supplementation decreased (p<0.05) them which may resulted from the higher (p<0.05) faecal TAG and TC contents. Serum ALT value, and hepatic thiobarbituric acid reactive substances (TBARS), and hepatic TNF-α and IL-1β contents in HFCD-fed hamsters were reduced (p<0.05) by supplementing BV due to increased (p<0.05) hepatic glutathione (GSH) and trolox equivalent antioxidant capacity (TEAC) levels, and catalase (CAT) and glutathione peroxidase (GPx) activities. Taken together, the component profiles of BV contributed the lipid lowering and antioxidant effects on HFCD fed hamsters.
- Assembly of telomeric chromatin to create ALTernative endings. [REVIEW]
- Trends Cell Biol 2014 Aug 26.
Circumvention of the telomere length-dependent mechanisms that control the upper boundaries of cellular proliferation is necessary for the unlimited growth of cancer. Most cancer cells achieve cellular immortality by up-regulating the expression of telomerase to extend and maintain their telomere length. However, a small but significant number of cancers do so via the exchange of telomeric DNA between chromosomes in a pathway termed alternative lengthening of telomeres, or ALT. Although it remains to be clarified why a cell chooses the ALT pathway and how ALT is initiated, recently identified mutations in factors that shape the chromatin and epigenetic landscape of ALT telomeres are shedding light on these mechanisms. In this review, we examine these recent findings and integrate them into the current models of the ALT mechanism.
- Evaluation of Serum Perforin, Caspase-3, sFasL, and M-30 Levels as Apoptotic Markers in Children with Crimean-Congo Hemorrhagic Fever. [JOURNAL ARTICLE]
- Pediatr Infect Dis J 2014 Aug 28.
Apoptosis is a main regulator in responses of cellular immunity throughout systemic viral infections. Perforin, soluble Fas ligand (sFasL), caspase-3, and caspase-cleaved cytokeratin-18 (M-30) are mediators of apoptosis. The aim of this study is the evaluation of Crimean-Congo hemorrhagic fever (CCHF) disease changes in the levels of these apoptotic markers and the relation of these changes with disease severity.Forty-nine hospitalized children with CCHF and 36 healthy controls (HC) were enrolled in this prospective study. The CCHF patients were classified into two groups based on disease severity (severe group and non-severe group). Demographic characteristics, and clinical and laboratory findings of all patients were recorded on admission.Serum perforin, caspase-3, and sFasL levels were found to be significantly higher both in the severe and non-severe CCHF groups than the HC group (p<0.05), but there was no significant difference in these apoptotic markers between severe and non-severe CCHF groups (p>0.05). In addition, serum M-30 levels did not differ significantly among all groups (p>0.05). There was a positive correlation between serum values for perforin, caspase-3, and M-30, and the disease's severity criteria such as AST and/or ALT. The serum levels of all these markers were negatively correlated with disease severity criteria such as the platelet count.In this study we concluded that the interactions of cytolytic granules containing perforin and caspase cascade and Fas-FasL may play an important role in the pathogenesis of CCHF in children.
- Entecavir Is Safe and Effective in Patients Previously Treated with Adefovir, including Those with Adefovir-Resistance. [JOURNAL ARTICLE]
- J Gastroenterol Hepatol 2014 Aug 28.
Suboptimal viral suppression with adefovir (ADV) poses a challenge in managing chronic hepatitis B (CHB). Few studies have evaluated the efficacy of entecavir (ETV) in ADV-experienced patients. Our aim is to assess treatment effectiveness of ETV in ADV-experienced patients.ADV-experienced patients switched to ETV were enrolled from six U.S. clinics. Patients completed a median of 24 months of ETV after switch. Patients were categorized into partial responders (detectable HBV DNA at switch) or complete responders (undetectable HBV DNA at switch) to ADV. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV DNA <60 IU/mL) and biochemical response (BR, ALT < 40 U/L), respectively.A total of 120 patients were included in the analysis (80 ADV partial responders; 40 ADV complete responders). In partial responders, CVS rate was 84% after 24 months of ETV. BR rate was 58% at switch to ETV and increased to 90% after 24 months. All complete responders continued to experience CVS after switch. On multivariate analysis inclusive of age, male gender, ALT level at switch, and history of lamivudine (LAM) exposure, we identified positive HBeAg status before ADV and higher HBV DNA level at time of switch as significant independent negative predictors of CVS. In eight patients with ADV-resistance, seven achieved CVS after 24 months of ETV and all achieved BR.In ADV-experienced patients, high rates of CVS and BR can be achieved/sustained after switching to ETV, including those with ADV resistance or with prior exposure to LAM.
- Ultrathin Ammonium Heptamolybdate Films as Efficient Room-temperature Hole Transport Layers for Organic Solar Cells. [JOURNAL ARTICLE]
- ACS Appl Mater Interfaces 2014 Aug 29.
Ammonium heptamolybdate (NH4)6Mo7O24•4H2O (AHM) and its peroxo derivatives are analyzed as solution-processed room temperature hole transport layer (HTL) in organic solar cells. Such AHM based HTLs are investigated in devices with three different types of active layers, i.e. solution-processed poly(3-hexylthiophene)/[6,6]-phenyl C61-butyric acid methyl ester (P3HT/PC60BM), poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'- benzothiadiazole)]/ [6,6]-phenyl C70-butyric acid methyl ester (PCDTBT/PC70BM) and evaporated small molecule chloro(subphthalocyaninato)boron (III) (SubPc)/C60. By virtue of their high work functions, AHM based HTLs outperform the commonly used poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) HTL for devices employing deep HOMO level active materials. Moreover, devices using AHM based HTLs can achieve higher short circuit current (Jsc) than the ones with evaporated molybdenum oxide (eMoO3), and thus better power conversion efficiency (PCE). In addition, P3HT/PC60BM devices with AHM based HTLs show air stability comparable to those with eMoO3, and much better than the ones with PEDOT:PSS.
- Changes in the Levels of Cytokines in Both Diabetic/Non-Diabetic Type I Children Living in a Moderate Altitude Area in Saudi Arabia. [JOURNAL ARTICLE]
- High Alt Med Biol 2014 Aug 28.
Abstract Allam, Gamal, Adnan A. Alsulaimani, Hamed Alghamdi, Hameed Alswat, Burhan M. Edrees, Iftikhar Ahmad, and Amre Nasr. Changes in the levels of cytokines in both diabetic/non-diabetic type I children living in a moderate altitude area in Saudi Arabia. High Alt Med Biol 15:000-000, 2014.-The aim of the present study was to investigate the possible effects of living in moderate altitude area on pro/anti-inflammatory cytokines profile (IFN-γ, TNF-α, IL-6, IL-1β, IL-10, and IL-4) among type I diabetic (T1D) and non- T1D children compared with those living at sea level area. A prospective clinical study was carried out at pediatric outpatient endocrine clinics in Taif City, which is a moderate altitude area in Saudi Arabia, that stands about 1800-2000 meters above sea-level; and in Mecca City, which is a sea level area, that lies in the middle west of Saudi Arabia. Hemoglobin A1c (HbA1c) percentage was estimated and cytokine measurements were performed in sera by flow cytometry using Cytometric Bead Array (CBA) technology. In this study we included 600 children who were consecutively enrolled (sex and age were matched). The HbA1c was statistically significantly higher in children living in moderate altitude compared to those living at sea level (overall p<0.001). Furthermore, T1D patients had higher values of serum cytokine levels (IFN-γ, TNF-α, IL-6, IL-1β, IL-4, and IL-10) in comparison to non-T1D control group (overall p<0.001). In conclusion, the data of the present study clearly showed that in both T1D and non-T1D children, moderate altitude-natives expressed high HbA1c and both pro-and anti-inflammatory cytokines. Type I diabetic children living in moderate altitude or at sea level showed elevated levels of IFN-γ, TNF-α, IL-6, IL-1β, IL-4, and IL-10 than control subjects. Glycemic control in non-diabetic children was affected by living in moderate altitude, however, HbA1c significantly increased in diabetic children living in moderate altitude.