AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response media...AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.展开更多
AIM： To evaluate pegylated interferon alpha2a （PegIFN-α2a） in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response r...AIM： To evaluate pegylated interferon alpha2a （PegIFN-α2a） in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS： A total of 73 nafve patients （61 with history of bilharziasis） with compensated chronic HCV genotype 4 were enrolled into： group A （38 patients） who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B （35 patients） received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS： Significant improvement in both end of treatment response （ETR） （P 〈 0.002） and sustained response （SR） （P 〈 0.05） was noted with pegylated interferon, where ETR was achieved in 29 （76.3%） and 14 patients （40%） in both groups respectively, and 25 patients in group A （65.8%） and 9 （25.7%） in group B could retain negative viraemia by the end of follow up period. Sustained virological response （SVR） showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR （P 〈 0.001）, but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis （grade 3 and 4） with PegIFN-α2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect, both drugs were comparable. CONCLUSION： PegIFN-~2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.展开更多
AIM:To assess sustained virological response(SVR) rates in a predominantly hepatitis C virus(HCV) genotype 4 infected population. METHODS:Between 2003-2007,240 patients who were treated for chronic hepatitis C infecti...AIM:To assess sustained virological response(SVR) rates in a predominantly hepatitis C virus(HCV) genotype 4 infected population. METHODS:Between 2003-2007,240 patients who were treated for chronic hepatitis C infection at our center were included.Epidemiological data,viral genotypes,and treatment outcomes were evaluated in all treated patients.Patients with chronic renal failure, previous non-responders,and those who relapsed after previous treatment were excluded from the study.Among all patients,57%were treated with PEG-interferon(IFN)α-2a and 43%patients were treated with PEG-IFNα-2b;both groups received a standard dose of ribavirin. RESULTS:89.6%of patients completed the treatment with an overall SVR rate of 58%.The SVR rate was 54%in genotype 1,44%in genotype 2,73%in genotype 3,and 59%in genotype 4 patients.There was no statistical difference in the SVR rate between patients treated with PEG-IFNα-2a and PEG-IFNα-2b (61.5%vs 53%).Patients younger than 40 years had higher SVR rates than older patients(75%vs 51%,P =0.001).SVR was also statistically significantly higher when the HCV RNA load(pretreatment)was below 800.000(64%vs 50%,P=0.023),in patients with a body mass index(BMI)less than 28(65%vs 49%,P =0.01),and in patients who completed the treatment duration(64%vs 8%,P≤0.00001).CONCLUSION:The SVR rate in our study is higher than in previous studies.Compliance with the standard duration of treatment,higher ribavirin dose,younger age,lower BMI,and low pretreatment RNA levels were associated with a higher virological response.展开更多
To analyze the genomic molecular structure and genotype of human astrovirus isolated from infant in Guangzhou of China, the primers were designed based on the genomic sequence of astrovirus from the C, enBank and the ...To analyze the genomic molecular structure and genotype of human astrovirus isolated from infant in Guangzhou of China, the primers were designed based on the genomic sequence of astrovirus from the C, enBank and the target sequence were amplified by RT-PCR. Then the PCR-products were cloned to T vector and sequenced. The genomic nucleotide sequences were analyzed by the programs CLUSTAL W and DNASTAR. It was found that the full genomic length of HASTVgz01 strain was 6721 bp and the ORFs were 6558 bp. The 5＇ and 3＇UTR were 82 and 81 nucleotides. The genome included 3 open reading frames （ORFs） ： ORFla, ORFlb and ORF2. The 5＇-terminal ORFla started at nueleotide 83 and extended to nucleotide 2845. ORFlb （nt 2785 to nt 4332） overlaped ORFla by 61 nueleotides. The 3＇-terminal ORF2 began at nucleotide 4325 and terminated at nucleotide 6640. ORF2 had 2316 nucleotides. Compared with other astrovirus sequences in GenBank, the homology of the amino acid sequence of ORF2 of HASTVgz01 strain with that of serotype 4 was 93%. Homology with other serotypes ranged from 61% to 70%. The complete nucleotide sequence of astrovirus HASTVgz01 strain isolated from Guangzhou in China was 6721 bp in length, GenBank accession NO. DQ344027. Comparing the ORF2 of astrovirus HASTVgz01 with the known sequences of types 1-8 the highest homology was serotype 4 （93%）. Comparative sequence analysis of the HASTVgz01 ORF2 with the reported human astrovirus sequences revealed that the isolated astrovirus belongs to genotype （serotype） 4.展开更多
AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 p...AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.展开更多
Introduction: Hepatitis C virus (HCV) genotype 4 is the most prevalent in Egypt. Vis-ceral adiposity index (VAI) and (TyG) index are newly developed indices for assess-ment of metabolic syndrome (MS) and insulin resis...Introduction: Hepatitis C virus (HCV) genotype 4 is the most prevalent in Egypt. Vis-ceral adiposity index (VAI) and (TyG) index are newly developed indices for assess-ment of metabolic syndrome (MS) and insulin resistance (IR). We aimed at comparing their levels in HCV-patients with healthy controls and validate their use for prediction of hepatic histopathological changes. Patient and Methods: 78 chronic HCV-infected patients proven by PCR, viral genotyping and hepatic histopathology, and 67 healthy controls were enrolled. Presence of MS, Homeostasis Model Assessment for IR esti-mation (HOMA-IR), TyG index, and VAI were assessed. Results: HOMA-IR, TyG and frequency of MS were significantly higher in patients’ group (p p p = 0.002). Conclusion: HCV genotype 4 is significantly associated with MS and increased values of HOMA IR and TyG index. TyG index and VAI are valuable simple indices that could predict the histopathological changes in Egyptian CHC pa-tients.展开更多
Objective: To assess the occurrence and pattern of Toll-like receptor 4(TLR4) cosegregated genotypes among children with Plasmodium falciparum malaria in Nigeria.Methods: In this case-control study, a total of 79 Plas...Objective: To assess the occurrence and pattern of Toll-like receptor 4(TLR4) cosegregated genotypes among children with Plasmodium falciparum malaria in Nigeria.Methods: In this case-control study, a total of 79 Plasmodium falciparum infected children aged 2–7 years and 105 age-matched uninfected controls of Yoruba descents in Lagos were studied. The extracted DNA samples were used for TLR4 genotyping at codons 299(Asp > Gly) and 399(Thr > Ile) by PCR-restriction fragment length polymorphism. Malaria infection was diagnosed by blood smear microscopy and infected children were stratified into asymptomatic, uncomplicated and severe malaria sub-groups.Malnutrition was determined by measuring the mid upper arm circumference and anemia was defined as hemoglobin < 11 g/dL.Results: The proportions of children with acute malnutrition and severe anemia were12.0% and 3.2%, respectively. Parasitemia and malnutrition were not correlated and four distinct patterns of TLR4 genotypes were found in the study population: Asp299Asp/Thr399Thr(90.2%), Asp299Gly/Thr399Thr(4.3%), Gly299Gly/Thr399Thr(3.8%) and Asp299Gly/Thr399Ile(1.6%). These genotypes did not differ significantly(P > 0.05) in frequency between infected and non-infected children. However, low and high occurrences of the TLR4 Asp299Asp/Thr399 Thr and Asp299Gly/Thr399 Thr genotypes were observed in the severe malaria subgroup.Conclusions: This study reveals a protective role for TLR4 Asp299Gly/Thr399 Ile and Asp299Asp/Thr399 Thr genotypes against severe malaria in Nigerian children.展开更多
AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze dif...AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.展开更多
AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS...AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.展开更多
文摘AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.
文摘AIM： To evaluate pegylated interferon alpha2a （PegIFN-α2a） in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS： A total of 73 nafve patients （61 with history of bilharziasis） with compensated chronic HCV genotype 4 were enrolled into： group A （38 patients） who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B （35 patients） received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS： Significant improvement in both end of treatment response （ETR） （P 〈 0.002） and sustained response （SR） （P 〈 0.05） was noted with pegylated interferon, where ETR was achieved in 29 （76.3%） and 14 patients （40%） in both groups respectively, and 25 patients in group A （65.8%） and 9 （25.7%） in group B could retain negative viraemia by the end of follow up period. Sustained virological response （SVR） showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR （P 〈 0.001）, but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis （grade 3 and 4） with PegIFN-α2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect, both drugs were comparable. CONCLUSION： PegIFN-~2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.
文摘AIM:To assess sustained virological response(SVR) rates in a predominantly hepatitis C virus(HCV) genotype 4 infected population. METHODS:Between 2003-2007,240 patients who were treated for chronic hepatitis C infection at our center were included.Epidemiological data,viral genotypes,and treatment outcomes were evaluated in all treated patients.Patients with chronic renal failure, previous non-responders,and those who relapsed after previous treatment were excluded from the study.Among all patients,57%were treated with PEG-interferon(IFN)α-2a and 43%patients were treated with PEG-IFNα-2b;both groups received a standard dose of ribavirin. RESULTS:89.6%of patients completed the treatment with an overall SVR rate of 58%.The SVR rate was 54%in genotype 1,44%in genotype 2,73%in genotype 3,and 59%in genotype 4 patients.There was no statistical difference in the SVR rate between patients treated with PEG-IFNα-2a and PEG-IFNα-2b (61.5%vs 53%).Patients younger than 40 years had higher SVR rates than older patients(75%vs 51%,P =0.001).SVR was also statistically significantly higher when the HCV RNA load(pretreatment)was below 800.000(64%vs 50%,P=0.023),in patients with a body mass index(BMI)less than 28(65%vs 49%,P =0.01),and in patients who completed the treatment duration(64%vs 8%,P≤0.00001).CONCLUSION:The SVR rate in our study is higher than in previous studies.Compliance with the standard duration of treatment,higher ribavirin dose,younger age,lower BMI,and low pretreatment RNA levels were associated with a higher virological response.
文摘To analyze the genomic molecular structure and genotype of human astrovirus isolated from infant in Guangzhou of China, the primers were designed based on the genomic sequence of astrovirus from the C, enBank and the target sequence were amplified by RT-PCR. Then the PCR-products were cloned to T vector and sequenced. The genomic nucleotide sequences were analyzed by the programs CLUSTAL W and DNASTAR. It was found that the full genomic length of HASTVgz01 strain was 6721 bp and the ORFs were 6558 bp. The 5＇ and 3＇UTR were 82 and 81 nucleotides. The genome included 3 open reading frames （ORFs） ： ORFla, ORFlb and ORF2. The 5＇-terminal ORFla started at nueleotide 83 and extended to nucleotide 2845. ORFlb （nt 2785 to nt 4332） overlaped ORFla by 61 nueleotides. The 3＇-terminal ORF2 began at nucleotide 4325 and terminated at nucleotide 6640. ORF2 had 2316 nucleotides. Compared with other astrovirus sequences in GenBank, the homology of the amino acid sequence of ORF2 of HASTVgz01 strain with that of serotype 4 was 93%. Homology with other serotypes ranged from 61% to 70%. The complete nucleotide sequence of astrovirus HASTVgz01 strain isolated from Guangzhou in China was 6721 bp in length, GenBank accession NO. DQ344027. Comparing the ORF2 of astrovirus HASTVgz01 with the known sequences of types 1-8 the highest homology was serotype 4 （93%）. Comparative sequence analysis of the HASTVgz01 ORF2 with the reported human astrovirus sequences revealed that the isolated astrovirus belongs to genotype （serotype） 4.
基金Supported by Hamad Hospital-HMC and Qatar UniversityHealth Sciences-Biomedical Labssponsored by HMC
文摘AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.
文摘Introduction: Hepatitis C virus (HCV) genotype 4 is the most prevalent in Egypt. Vis-ceral adiposity index (VAI) and (TyG) index are newly developed indices for assess-ment of metabolic syndrome (MS) and insulin resistance (IR). We aimed at comparing their levels in HCV-patients with healthy controls and validate their use for prediction of hepatic histopathological changes. Patient and Methods: 78 chronic HCV-infected patients proven by PCR, viral genotyping and hepatic histopathology, and 67 healthy controls were enrolled. Presence of MS, Homeostasis Model Assessment for IR esti-mation (HOMA-IR), TyG index, and VAI were assessed. Results: HOMA-IR, TyG and frequency of MS were significantly higher in patients’ group (p p p = 0.002). Conclusion: HCV genotype 4 is significantly associated with MS and increased values of HOMA IR and TyG index. TyG index and VAI are valuable simple indices that could predict the histopathological changes in Egyptian CHC pa-tients.
文摘Objective: To assess the occurrence and pattern of Toll-like receptor 4(TLR4) cosegregated genotypes among children with Plasmodium falciparum malaria in Nigeria.Methods: In this case-control study, a total of 79 Plasmodium falciparum infected children aged 2–7 years and 105 age-matched uninfected controls of Yoruba descents in Lagos were studied. The extracted DNA samples were used for TLR4 genotyping at codons 299(Asp > Gly) and 399(Thr > Ile) by PCR-restriction fragment length polymorphism. Malaria infection was diagnosed by blood smear microscopy and infected children were stratified into asymptomatic, uncomplicated and severe malaria sub-groups.Malnutrition was determined by measuring the mid upper arm circumference and anemia was defined as hemoglobin < 11 g/dL.Results: The proportions of children with acute malnutrition and severe anemia were12.0% and 3.2%, respectively. Parasitemia and malnutrition were not correlated and four distinct patterns of TLR4 genotypes were found in the study population: Asp299Asp/Thr399Thr(90.2%), Asp299Gly/Thr399Thr(4.3%), Gly299Gly/Thr399Thr(3.8%) and Asp299Gly/Thr399Ile(1.6%). These genotypes did not differ significantly(P > 0.05) in frequency between infected and non-infected children. However, low and high occurrences of the TLR4 Asp299Asp/Thr399 Thr and Asp299Gly/Thr399 Thr genotypes were observed in the severe malaria subgroup.Conclusions: This study reveals a protective role for TLR4 Asp299Gly/Thr399 Ile and Asp299Asp/Thr399 Thr genotypes against severe malaria in Nigerian children.
基金Supported by Fundación Burgos por la Investigación de la Salud and Gerencia Regional de Salud de Castilla y León,No.BUO/06/15
文摘AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.
基金Supported by A grant from National Research Center to M.Awady and grant from Yousef Jameel Science&Technology Research Center(YJ-STRC)at the American University in Cairo to H.Azzazy
文摘AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.
