Low Hepatitis C Virus Viral Load Research Articles

Characteristics of CD8+ Stem Cell-Like Memory T Cell Subset in Chronic Hepatitis C Virus Infection.

The dysfunction of memory CD8+ T cell cannot be reverted by successful clearance of hepatitis C virus (HCV) after direct-acting antivirals (DAAs) therapy, increasing the risk of reinfection with HCV. Stem cell-like memory T cells (Tscm) with superior properties of long-lasting, self-renewing, and multipotency contribute to the maintenance of immune function. We investigated the impact of HCV infection on CD8+ Tscm, and their possible role in disease progression, by using DAA-naive HCV-infected and human immunodeficiency virus (HIV)/HCV-coinfected cohorts. The distribution of memory CD8+ T cell subsets and the level of T cell immune activation were determined by flow cytometry. Associations between CD8+ Tscm and other memory T cell subsets, HCV viral load, as well as the level of T cell immune activation were analyzed. We observed that the proportion of CD8+ Tscm increased in both HCV and HIV/HCV individuals. The proportion of CD8+ Tscm had positive and negative correlation with CD8+ Tcm (central memory T cells) and CD8+ Tem (effector memory T cell), respectively, representing the contribution of CD8+ Tscm in T cell homeostasis. In addition, higher frequency of CD8+ Tscm indicated lower HCV viral load and less T cell immune activation in HCV infection, which suggested that CD8+ Tscm is likely associated with effective control of HCV replication for protective immunity. Considering the characteristics of Tscm, our current findings provide implications for Tscm-based vaccine design and immunotherapy development to achieve HCV elimination.

Laboratory Evaluation of Hepatitis C Virus Infection in Patients Undergoing Hemodialysis from North East India

Subjects undergoing hemodialysis have enhanced vulnerability to hepatitis C virus (HCV) infection due to invasive procedures and poor infection control practices. Early detection and treatment are essential to prevent cross-infection and mortality/morbidity. However, common use anti-HCV antibody tests lack the necessary accuracy, and alternative tests (e.g. core antigen detection kits) which are available need to be examined as a viable alternative. A total of 270 continuous serum samples were collected from patients undergoing dialysis within 15 months of study period. Sequentially, multiple tests were performed - immunochromatography-based rapid test, third-generation ELISA i.e. (anti-HCV antibody detection), fourth-generation ELISA (HCV antigen-antibody combined detection assay), and HCV RNA quantitative real time polymerase chain reaction (qPCR) assay. Diagnostic parameters of serological kits were compared in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and so on. Statistical Package for the Social Sciences was used. HCV-combined core antigen-antibody assays performed better than other serological assays in reference to the gold standard HCV RNA. This fourth-generation assay yielded a Kappa value of 0.947 compared with the value of 0.747 and 0.619 for anti-HCV ELISAand rapid detection test. Other parameters such as sensitivity, specificity, PPV, NPV, and so on were also better for fourth-generation ELISA compared with third-generation ELISA and other serological assays. HCV RNA was negative in 7.3% of anti-HCV-positive patients and was detected in 11.4% of anti-HCV ELISA-negative patients. In about 1.6% of HCV RNA-positive cases, fourth-generation ELISA was negative and had low HCV viral load (650 IU/ml and below). Fourth generation ELISA detected additional 7.4% HCV positive cases (compared to third generation kits) and upon cost effective analyis, additional cost to be bear for the better detection (by fourth generation kit) was found to be only INR 27 per 1% increased case detection. In resource scant setup, screening and follow-up of patients undergoing hemodialysis can be performed by fourth-generation HCV ELISA (antigen-antibody combined assay) instead of the current practice of anti-HCV antibody ELISA. Better yield in detection rate will compensate for slight addition to costs.

First detection of human hepegivirus-1 (HHpgV-1) in Iranian patients with hemophilia

A novel blood-borne virus called the human hepegivirus 1 (HHpgV-1) was recently discovered in hemophilia patients. The present study aimed to investigate the presence of HHpgV-1 in hemophilia patients. A total of 436 serum samples were investigated for the presence of hepatitis C virus (HCV), human pegivirus-1 (HPgV-1), torque teno virus (TTV), and HHpgV-1. Out of the 436 patients, 163 (37.4%), 19 (4.4%), 76 (17.4%), and four (0.9%) patients were positive for HCV, HPgV-1, TTV, and HHpgV-1, respectively. HHpgV-1 patients had a mean viral load of 4.9 ± 0.3 log RNA copies/mL and were co-infected with HCV-1a, HPgV-1, and TTV. Moreover, three HHpgV-1-positive patients exhibited stage F0 liver fibrosis. HCV viral load in HHpgV-1-positive patients was lower than those of HHpgV-1-negative patients. Results also revealed that co-infection of HHpgV-1 with HPgV-1 and HCV may play a protective role in patients with chronic HCV. In conclusion, we detected a low frequency of HHpgV-1 infection in hemophilia patients, and results suggested that HHpgV-1 infection was correlated with the presence of other blood-borne viruses and is likely to also correlate with low HCV viral load and reduced severity of liver disease. Additional studies are required to further investigate the clinical importance of HHpgV-1.

Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy

Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy. We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients. A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level. The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure.

Antiretroviral therapy does not affect response to chronic hepatitis C therapy in HIV-coinfected patients.

Many patients coinfected with the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are using highly active antiretroviral therapy (HAART) and HCV therapy with peginterferon (PEG-IFN) and ribavirina (RBV) because the use of direct-acting antivirals is not a reality in some countries. To know the impact of such medications in the sustained virological response (SVR) during HCV treatment is of great importance. This was a retrospective cohort study of 215 coinfected HIV/HCV patients. The patients were treated with PEG-IFN and RBV between 2007 and 2013 and analyzed by intention to treat. Treatment-experienced patients to HCV and carriers of hepatitis B were excluded. Demographic data (gender, age), mode of infection, HCV genotype, HCV viral load, hepatic fibrosis, HIV status, and type of PEG were evaluated. One hundred eighty-eight (87.4%) patients were using HAART. SVR was achieved in 55 (29.3%) patients using HAART and in 9 (33.3%) patients not using HAART (p = 0.86). There was no difference in SVR between different HAART medications and regimens using two reverse transcriptase inhibitor nucleosides (NRTIs) or the use of protease inhibitors and non-NRTIs (27.1% versus 31.5%; p = 0.61). The predictive factors for obtaining SVR were low HCV viral load, non-1 genotype, and the use of peginterferon-α2a. The use of HAART does not influence the SVR of HCV under PEG-IFN and RBV therapy in HIV/HCV coinfected patients.

Association of ATP-Binding Cassette Transporter (ABC) Gene Polymorphisms with Viral Load in Patients with Genotype 1 Hepatitis C Virus Infection.

ATP-binding cassette transporters (ABC) gene polymorphisms are associated with various biological functions, including hepatitis C virus (HCV) infection. This study aims to explore the impact of ABC transporters polymorphisms on HCV viral load in chronic treatment-naïve hepatitis C patients. We recruited 347 Chinese Han patients chronically infected with genotype 1 HCV in this study. Ten single nucleotide polymorphism (SNPs) in ABCA1, ABCB5, ABCB11, ABCG2, ABCG5, ABCG10 were analyzed by custom chip from Illumina. Allele frequency analysis and genotype frequency analysis were performed. Patients were categorized according to pretreatment HCV viral load (VL) with a cutoff level 600 000 IU/mL. No significant variations on gender and age were observed in the two groups. G allele of rs3890182 and C allele of rs1883025 in ABCA1 gene were significantly associated with lower HCV viral load (p = 0.013 and p = 0.006) in allele frequency analysis. GG genotype of rs3890182 and CC genotype of rs1883025 in ABCA1 gene were significantly associated with lower HCV viral load (p = 0.027 and p = 0.013) in genotype frequency analysis. Quantitative analysis showed significantly lower viral load in patients with CC genotype of rs1883025 (p = 0.012). Allele associated lower HCV viral load was reported to be associated with higher HDL cholesterol level. Our finding suggests that ABCA1 gene polymorphism in rs1883025 is significantly associated with HCV VL in patients infected with HCV genotype 1.

Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C.

AIMTo determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients.METHODSOne hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems).RESULTSOf the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P < 0.001), urban residence (P = 0.004), IL28B CC genotype (P < 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P < 0.001) and early virological response (P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P < 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%.CONCLUSIONHCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian patients.

Prior assessment of insulin resistance by HOMA-IR is emerging as an important milestone in the treatment of patients with chronic hepatitis C. This cost-effective tool is recommended to individualize treatment duration, or to exclude those with low insulin sensitivity from being treated until ameliorating their state of insulin resistance (IR). The present work aims to elucidate further the effect IR state on early viral kinetic response to Chronic hepatitis C virus (HCV) therapy and the impact of HCV treatment and viral eradication on insulin sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All enrolled patients were treated with a dual therapy (pegylated interferon-alpha plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic response as well as the impact of treatment on insulin sensitivity throughout the early period of therapy. Of a total 392 chronic HCV cases, early virologic response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV patient of which 73.4% responded to treatment. Early virologic response among patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA-IR values ≤2.18 (P < 0.0001). IR was significantly associated with high baseline BMI. Steatosis and fibrosis correlated with IR but neither independently predicted early virologic response. Pretreatment IR < 2.18, low fasting blood glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were independent factors associated with early virologic response. IR interferes with early virologic response to the antiviral care. Clinical application of pretreatment HOMA-IR assessment could help in predicting early treatment outcome and thus enable treatment regimens to be optimized and individually tailored.

Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection

Background and AimChronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management.MethodsIn this cross-sectional observational study, treatment-naïve Han ethnic adults with recently confirmed chronic HCV infection were enrolled at 28 hospitals across China. HCV genotype and host interleukin 28B (IL28B) genotypes were determined and compared with patient demographic parameters and medical status.ResultsAmong the 997 HCV-positive patients analyzed, 56.8% were infected with HCV genotype 1b, followed in prevalence by genotypes 2, 3, and 6, with substantial regional variation. Overall, 84.1% of patients were IL28B genotype CC (rs12979860), with little regional variation. Cirrhosis was reported in 10.1% of patients and was significantly associated with hepatitis B virus coinfection, low HCV viral load, low serum alanine aminotransferase, high serum aspartate aminotransferase, diabetes, and high pickled food consumption. Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6.ConclusionsMost HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes.

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus.

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC). A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n=160) and those infected with other genotypes (n=39). With a comparable median HCV viral load (6.0 vs. 5.8 log10 IU/mL, p=0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20%, p=0.65) and the 5-year overall survival (OS) rates (72 vs. 65%, p=0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log10 IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p=0.003) and the other genotypes (p=0.037) at HCV viral load of 5.3 log10 IU/mL. The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.

In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use

Among patients with hepatitis C virus (HCV) monoinfection, 25-hydroxyvitamin D [25(OH)D] concentrations are positively associated with a response to peg-interferon/ribavirin. Data on the relation between 25(OH)D concentrations and HCV treatment response in HIV-infected patients are limited. The objective was to determine whether baseline 25(OH)D concentrations predict virologic response in HIV/HCV co-infected patients and to examine variables associated with 25(OH)D concentrations ≥30 ng/mL. Data and samples from 144 HCV genotype 1, treatment-naive patients from a completed HCV treatment trial were examined in this retrospective study. Early virologic response (EVR) was defined as ≥2 log10 reduction in HCV RNA and/or HCV RNA <600 IU/mL at week 12 of peg-interferon/ribavirin treatment. Baseline 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Compared with the non-EVR control group (n = 68), the EVR group (n = 76) was younger, had fewer cirrhotic subjects, had a higher proportion with the IL28B CC genotype, had a higher albumin concentration, and had a lower HCV viral load at baseline (P ≤ 0.05). The difference in baseline 25(OH)D concentrations between EVR and non-EVR patients was not statistically significant (median: 25 ng/mL compared with 20 ng/mL; P = 0.23). Similar results were found for sustained virologic response (SVR). In multivariable analysis, white and Hispanic race-ethnicity (OR: 6.26; 95% CI: 2.47, 15.88; P = 0.0001) and ritonavir use (OR: 2.68; 95% CI: 1.08, 6.65; P = 0.033) were associated with higher 25(OH)D concentrations (≥30 ng/mL). Baseline 25(OH)D concentrations did not predict EVR or SVR. Because ritonavir impairs the conversion of 25(OH)D to the active metabolite, utilization of 25(OH)D may have been impaired in subjects taking ritonavir. This trial was registered at www.clinicaltrials.gov as NCT00078403.

Effect of human leukocyte antigen class I and II alleles on hepatitis C viral load among chronic hepatitis C patients in Southern Taiwan

The viral load of hepatitis C virus (HCV) in chronic hepatitis C patients affects clinical outcomes and response to interferon treatment. Various factors may be involved in determining the viral load, including host genetic factors. The aim of this study was to investigate the relationship between HCV viral load and human leukocyte antigen (HLA) class I and class II alleles. One hundred and six HCV RNA positive subjects were enrolled, and viral load was measured. HLA-A, -B, -C, -DR, and -DQ loci were determined by sequence-based genotyping. Univariate analysis indicated that HLA-B(*)40 and HLA-C(*)07 alleles had significantly higher HCV RNA levels (P<0.05). Patients with the HLA-C(*)15 allele exhibited a trend toward a lower HCV viral load (P=0.06). After controlling for confounding factors, multivariate analysis revealed that only HLA-C(*)15 allele was identified as a significant determinant for HCV-RNA level (slope=-0.91, 95% CI: -1.58, -0.24; Holm's P<0.01). Patients expressing the HLA-C(*)15 allele had significantly lower HCV RNA levels. HCV genotype 1 was significantly associated with high HCV RNA levels (P<0.05 by Mann-Whitney U test). In conclusion, HLA-C(*)15 is an important host immunogenetic factor with an inverse association to HCV viral load in CHC patients in Taiwan. HCV genotype 1 is the viral factor that associated with high viral load.

Factors associated with guideline‐based hepatitis C virus (HCV) treatment initiation in HIV/HCV‐coinfected patients: role of comorbidities and physicians' perceptions

Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Low Hepatitis C Viral Load Predicts Better Long-Term Outcomes in Patients Undergoing Resection of Hepatocellular Carcinoma Irrespective of Serologic Eradication of Hepatitis C Virus

Hepatitis C virus (HCV) infection has been recognized as a potent risk factor for the postoperative recurrence of hepatocellular carcinoma (HCC). However, little is known about the impact of HCV viral load on surgical outcomes. The study objective was to investigate clinical significance of HCV viral load on long-term outcomes of HCC. Three hundred seventy patients who were classified as Child-Pugh class A and underwent curative liver resections for HCV-related HCC were divided into low and high viral load groups (≤ or > 5.3 log(10)IU/mL) based on the results of a minimum P value approach to predict moderate to severe activity of hepatitis; the clinical outcomes were then compared. The 5-year recurrence-free survival rate was 36.1% in the low viral load group and 12.4% in the high viral load group (P < .001). The 5-year overall survival rate was 76.6% in the low viral load group and 57.7% in the high viral load group (P < .001). Multivariate analysis confirmed significant correlation between high viral load and tumor recurrence with a hazard ratio of 1.87 (95% CI, 1.41 to 2.48; P < .001). Subanalysis revealed that the favorable results in the low viral load group were not attributed to whether or not serologic eradication of HCV was obtained both in primary and recurrent lesions. Low HCV viral load predicts better long-term surgical outcomes in patients with HCC regardless of the serologic eradication of HCV.

IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection

Chronic hepatitis C virus (HCV) infection patients exhibit different sustained virological responses (SVRs) following the treatment with pegylated interferon-α (IFN-α) and ribavirin. Genome-wide association studies consistently linked SVR of IFN-α-based therapy to the IL28B single-nucleotide polymorphisms (SNPs) on chromosome 19q.13 in various populations. This study was undertaken to investigate the association of IL28B SNPs with SVR in a cohort of Taiwanese chronic HCV patients. Ten SNPs of IL28B were genotyped in 728 chronic HCV patients and 960 healthy controls. Genotype distributions, allele frequencies and haplotypes were tested for SVR and susceptibility in Taiwanese chronic HCV patients. Non-genotype 1 infection (adjusted P=3.3 × 10−12, odds ratio (OR) 0.179; 95% confidence interval (CI): 0.110–0.290) and low HCV viral load (<400 000 IU ml–1) (adjusted P=3.5 × 10−9, OR 0.299; 95% CI: 0.200–0.446) were two major factors identified for high SVR. Notably, eight IL28B SNPs including previously described disease-associated SNPs (Trend test P=0.005) were significantly associated with SVR. Our data indicate that IL28B polymorphisms are the essential contributing factors for high SVR in Taiwanese chronic HCV patients. Combination of virus genotyping and host genetic data may be used to select the optimal treatment regimes in IFN-based therapy.

Association of Human Leucocyte Antigen Class I (HLA-A and HLA-B) With Chronic Hepatitis C Virus Infection in Egyptian Patients

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, ranging from 6% to 28% with an average of approximately 13.8% in the general population. It has been reported that human leucocyte antigen (HLA) alleles are associated with the outcome of HCV infection, but this associations showed ethnic and geographical differences. The objective of this study is to investigate the association between the frequencies of HLA Class I and chronic HCV infection in Egyptian patients and to find out whether there is a relation between certain HLA Class I antigens and HCV viral load, degree of fibrosis, activity and alanine aminotransferase (ALT) level. A case control study was conducted on 100 patients with chronic HCV infection and 150 healthy controls. HLA-A and HLA-B typing by complement-dependent micro-lympho-cytotoxicity assay was performed for both groups. HLA-A11 antigen was significantly increased in patients with chronic HCV infection versus controls (OR 3.98; 95% CI = 1.85-8.89; P = 0.001; and Pc = 0.021). HLA-B12, HLA-B13, HLA-B17 and HLA-B40 were higher in patients, and HLA-A32 and HLA-B14 were higher in controls, although the significance was lost after correction for multiple testing. HLA-A9 was significantly associated with low viral load (P = 0.008, Pc = 0.048). The results of this work implicate that HLA-A11 antigen may influence chronic HCV infection and may play a role in viral persistence. Different HLA Class I antigens are not associated with degree of liver fibrosis, grades of activity or level of ALT. However, HLA-A9 is associated with low HCV viral load in chronic HCV Egyptian patients.

Distribution of HCV genotypes and HCV RNA viral load in different regions of Mexico

Background and aim. To identify the geographic distribution of hepatitis C virus (HCV) genotypes and HCV RNA viral load in a large number of HCV-infected carriers in Mexico.Methods. Patients with chronic hepatitis C (n = 8,802) were studied to identify HCV genotype using an immune line probe assay in samples shown previously to be positive for viral RNA by an RT-PCR test. Baseline HCV RNA was also evaluated.Results. Genotype 1 accounted for 70.3%, genotype 2 for 21.8%, genotype 3 for 7.2%, genotype 4 for 0.3%, and genotype 5 for 0.1% of all cases; coinfection was present in 0.3%. Overall, Genotype 1 was the most prevalent Genotype. Regionally, genotype 1 occurred more frequently in the North-East, North, and Center-East regions of Mexico; genotype 2 was more prevalent in the South, East, and Peninsula regions; and genotype 3 was more prevalent in the North and North-West regions. Only 22.4% of patients with genotype 1 were classified in the low HCV RNA viral load category, and the distribution of this genotype did not differ significantly between regions.Conclusion. The prevalence of HCV genotypes and viral load in Mexico was 70.3% for genotype 1, but only 22.4% of these patients had a low HCV viral load. Distribution was not uniform in Mexico, with greater frequency of genotype 2 in South, East and Peninsula Regions and Genotype 3 in North and North-West Regions.

Acute hepatitis C in HIV-infected patients: rare spontaneous clearance correlates with weak memory CD4 T-cell responses to hepatitis C virus

To explore the parameters of specific immunity to hepatitis C virus (HCV) associated with virus clearance during acute HCV infection in HIV coinfection. HIV-infected patients without prior HCV infection were prospectively enrolled for acute hepatitis C and followed up over 15 months. HCV-specific T cells were assessed by proliferation, ELISpot, intracellular cytokine staining and pentamer assays. Pegylated-interferon-alpha and ribavirin were proposed if HCV persisted at M3. Thirty eight acutely HCV-infected HIV-positive patients were enrolled. HCV genotypes were predominantly 4 and 1. Five patients (13%) showed spontaneous clearance and 20 initiated treatment, of whom 13 (65%) showed sustained virologic responses. Before M3, HCV-specific proliferative responses observed in 35% cases, were associated with lower HCV viral load (P = 0.04) and predictive of spontaneous clearance (P = 0.02), particularly anti-NS4 responses (P = 0.03). These HCV-specific proliferative responses were associated with HIV-p24-specific responses (P = 0.002) independently from the HIV stage. Interferon-gamma-producing T cells specific for HCV were detectable ex vivo in 81% cases but at low intensity (<150 spot forming cells/10 peripheral blood mononuclear cells) and were independent of the HCV outcome. Low frequencies of pentamer-positive HCV-specific CD8 cells (0.01-0.05%) detected in nine of 12 patients were mainly effector-memory PD-1-negative T cells. Twelve days of HCV-specific in-vitro culture induced amplification of CD4 T cells coproducing interleukin-2 and interferon-gamma but rarely of CD8 T cells. Acute HCV infection in HIV-coinfected patients is characterized by a low rate of spontaneous clearance and weak HCV-specific memory T cells, not strictly related to HIV-induced immune defects, and which correlate with virus clearance.

Role of rapid virological response in prediction of sustained virological response to Peg‐IFN plus ribavirin in HCV / HIV co‐infected individuals

The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24-48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV-HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.

High hepatitis C virus viral load in HIV/hepatitis C virus-co-infected patients: a different influence of protease inhibitor and non-protease inhibitor-based HAART?

We examined the possible relationships between hepatitis C virus (HCV) viral load and host factors, viral factors, and anti-HIV therapy in 379 HIV/HCV-co-infected patients. Multiple linear regression analysis identified two independent factors associated with higher HCV viral load, HCV genotype 1 or 4 infection and protease inhibitor-based antiretroviral therapy. Antiretroviral therapy in general was independently associated with lower HCV viral load. This suggests that HCV viral load kinetics could differ according to the choice of HAART regimen.