RNA-positive Patients Research Articles

HCV treatment uptake in people who have injected drugs — observations in a large cohort that received addiction treatment 1970–1984

Objectives. The aim of this study was to document antiviral treatment uptake among former or current people who inject drugs (PWID) with chronic hepatitis C and to explore a possible association between treatment and mortality. Material and methods. This is a longitudinal cohort study of PWID admitted for drug abuse treatment 1970–1984. The 245 hepatitis C virus (HCV) RNA-positive patients alive by the end of 1996 were followed 1997–2012 through linkage to several health registers. Treatment uptake was mainly documented by information on prescription of antiviral medication registered in the Norwegian Prescription Database from 2004. Cox regression, with a time-dependent covariate measuring end-of-treatment, was employed to evaluate mortality after treatment. Results. At the end of the follow-up, median time since HCV exposure was 36 years, and 19.2% (47/245) had been prescribed antiviral treatment for chronic HCV infection. No gender difference was observed. Among those alive at the end of the study period, 27.8% (44/158) had been treated. Relative hazard of death was 0.21 (95% confidence interval [CI] 0.07–0.68), comparing periods for patients after versus before or without treatment. Mortality rate after treatment was 0.8 per 100 person years (95% CI 0.3–2.4) compared to 2.8 (95% CI 2.2–3.5) in untreated patients and before treatment. The most important causes of death among the untreated were drug-related. Conclusions. Among PWID infected with HCV, approximately one-fourth of those still alive at a median of 36 years after exposure had received HCV treatment. Treatment was associated with increased survival, probably mainly due to selection bias.

Impact of Hepatitis C Seropositivity on the Risk of Coronary Heart Disease Events

Chronic infections have been shown to enhance atherogenicity. However, the association between chronic hepatitis C (HCV) and coronary heart disease (CHD) remains controversial. We examined the risk for CHD events in patients with HCV with an emphasis on the risk of CHD events with active infection. We conducted a retrospective cohort study using the Enterprise Data Warehouse at the University of Arkansas for Medical Sciences. HCV positive and negative patients were identified based on serology and incident CHD events were studied. Patient characteristics at entry were compared either by analysis of variance/F-test (continuous variables) or by a Chi-squared test (categorical variables). The joint effect of risk factors for incident CHD was evaluated using logistic regression. A total of 8,251 HCV antibody positive, 1,434 HCV RNA positive and 14,799 HCV negative patients were identified. HCV antibody and RNA positive patients had a higher incidence of hypertension, diabetes mellitus, obesity and chronic lung disease, but lower serum cholesterol levels compared to HCV negative patients (p< 0.001). HCV seropositive patients had a higher incidence of CHD events when compared to controls (4.9% vs. 3.2%, p<0.001). In the HCV cohort, patients with detectable HCV RNA had a significantly higher incidence of CHD events when compared to patients who were only HCV antibody positive with no detectable RNA (5.9% vs. 4.7%, p=0.04). In multivariate logistic regression analysis, both HCV antibody positivity (OR 1.32, 95% CI 1.09-1.60, p<0.001) and HCV RNA positivity (OR 1.59, 95% CI 1.13-2.26, p<0.001) were independent risk factors for incident CHD events. In conclusion, there is increased incidence of CHD events in HCV seropositive patients and the incidence is much higher in patients with detectable HCV RNA when compared to patients with remote infection who are only antibody positive. Lipid profile does not appear to be a good cardiovascular risk stratification tool in HVC patients.

Hepatitis C virus genotype distribution in Turkey remains unchanged after a decade: Performance of phylogenetic analysis of the NS5B, E1, and 5’UTR regions in genotyping efficiency

Hepatitis C virus (HCV) genotyping has a considerable effect on therapy. The aim was to determine the change in prevalence of HCV genotypes in Turkey during the last decade and to compare the performance of DNA sequencing of different targets in the HCV genome (NS5B, E1, and 5'UTR). Five hundred HCV RNA-positive patients (226 males, 274 females) were included in the study. The NS5B, E1, and 5'UTR regions of the HCV genome were amplified by polymerase chain reaction (PCR) in patients where possible. Amplified PCR products were sequenced directly, and phylogenetic analysis was performed. A commonly used database, namely www.hcv.lanl.gov, was also used to determine the genotypes. Phylogenetic analysis of the NS5B, E1, and 5'UTR regions showed that 1b was the most frequent genotype, with percentages of 92.5%, 93.5%, and 87.7%, respectively. Genotype 1a was the second most prevalent genotype, with ratios of 6.7%, 5.6%, and 6.6%, whereas genotype 2a was detected in proportions of 0.4%, 0.2%, and 0.8%, respectively. Genotype 5 or 6 was not detected among patients. The phylogenetic analysis showed discordant results with 18 patients' genotypes for different targets. The phylogenetic analysis showed similar results with the hcv.lanl.gov database for the E1 and NS5B sequences. There has been no change in genotyping profiles of Turkey during the last decade, representing 1b as the most prevalent subtype, followed by 1a. Phylogenetic analysis of HCV indicated high performance compared with the hcv.lanl.gov database when sequences of E1 and NS5B regions were analyzed.

Interleukin 27 polymorphisms in HCV RNA positive patients: is there an impact on response to interferon therapy?

BackgroundInterleukin 27 (IL-27) has pleiotropic properties that can either limit or enhance immune responses. Recent studies revealed that single nucleotide polymorphisms (SNPs) of the IL-27 promoter region modulate the development of infectious diseases and individual's susceptibility to therapeutic response. Little is known about the relationship between IL-27 single nucleotide polymorphisms and therapy response in patients infected by hepatitis C virus (HCV). In this study we have investigated the potential role of SNPs in the promoter region of IL27 p28 gene (alleles rs153109) on the outcome of HCV infected patients.Methodsrs153109, corresponding to position c.-964A>G of the IL-27 locus, was amplified from genomic DNA extracted from 15 patients with chronic hepatitis C stratified by sustained viral response (SVR), relapser and non-responder, after treatment with peginterferon-α (PegIFN- α) combined with ribavirin (RBV). Amplification products were studied by direct sequencing.ResultsThis method has been applied in a preliminary study on patients with chronic hepatitis C to provide information for a standardized assay useful to genotyping of rs153109 SNPs of IL-27p28. The genotype distribution of the c.-964 A>G polymorphism was more present in patients who did not achieve a SVR. By contrast, the genotype G/G was absent in non-responder and relapser patients. Moreover, the analysis of allelic distribution of rs153109 highlighted a predominance of allele A in all genotypes in spite of allele G.ConclusionsOur work provides preliminary information for a standardized method potentially useful for genotyping rs153109, and suggests its utility as a candidate approach to evaluate IL-27 p28 polymorphisms as additional clinical predictors of response to therapies in HCV infected patients.

Update on epidemiology of HCV in Italy: focus on the Calabria Region.

The epidemiological profile of HCV infection is evolving in Europe, as well as in Italy. We have previously showed genotype distributions and their dynamics in 2,153 HCV RNA positive patients living in Calabria, Southern Italy, over 11 years. In this study, we extend and update this information by evaluating a hospital-based cohort of 945 HCV RNA positive patients attending five hospitals in the Calabria Region from January 2011 to August 2013. We assessed rates of HCV genotypes according to age and gender and the dynamics of HCV genotype distribution over the 3-year period studied. Data showed that genotype 1b is the most prevalent, followed by subtypes 2a/2c and genotype 3. Genotype 4 exhibited an increase between 2011 and 2013. Also, we found a significant decrease in the median age of subjects infected with HCV genotype 3 and 4 during the period studied. Since HCV genotypes are important in epidemiology, pathogenesis and response to antiviral therapy, a continuous epidemiological surveillance is needed.

Barriers to care and treatment for patients with chronic viral hepatitis in Europe: a systematic review.

Despite the availability of effective therapies for hepatitis B (HBV) and C virus (HCV), only a minority of these patients receive treatment. We systematically reviewed published data on barriers to management for chronic HBV/HCV patients in Europe. Literature search to identify studies including adult patients with chronic HBV/HCV infection from European countries and data on barriers to treatment. Twenty-five studies including 6253 chronic HBV and 19,014 HCV patients were identified, of which only two were from Eastern Europe. The mean rate of no treatment in HBV patients was 42% being higher in North-Western European countries than Italy (56% vs. 39%, P < 0.001). Immigrants represented the most common barrier to HBV treatment. The mean rate of no treatment in HCV RNA-positive patients was 57%, being highest in Romania (89%), intermediate in France (79%) and lower though still high in other European countries (52%, P < 0.001). The predominant barriers to HCV treatment were lack of financial resources in Romania and direct/indirect limitations of interferon-alfa and/or parenteral drug and alcohol abuse in other countries. The mean rate of no treatment was highest in HCV RNA-positive parenteral drug users (72%) and intermediate in those with HCV-HIV co-infection (64%). A substantial proportion of diagnosed chronic HBV and the majority of diagnosed HCV patients remain untreated. The rates and most importantly the reasons of barriers to treatment in chronic HBV/HCV patients vary widely among European countries supporting the need for country-specific national strategies, resource allocation and implementation of global management policies.

Investigation of Hepatitis B and Hepatitis C Virus Infections by Serological and Molecular Methods in Hemodialysis Patients

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are significant causes of morbidity and mortality in hemodialysis patients, since those patients are highly susceptible to infections due to immune suppression. The aims of this study were to investigate the presence of HBV and HCV infections in chronic hemodialysis patients by serological and molecular methods, and to determine the rate of occult HBV infection and the viral genotypes. A total of 201 patients who were under hemodialysis due to end-stage renal disease, were retrospectively evaluated. The study involved the patients at three different centers in Antalya, Turkey during 2006. HBV and HCV markers in the patients' sera were screened by ELISA method, viral nucleic acids were investigated by real-time polymerase chain reaction (PCR) in patients' plasma and viral genotypes were determined by DNA sequence analysis. Detection of at least one of the HBV markers HBsAg, anti-HBc total, and HBV DNA, was accepted as HBV infection, and detection of anti-HCV and/or HCV RNA was accepted as HCV infection. HBsAg positive patients with negative HBV DNA were considered as occult HBV infection. Of the patients 80 (40%) were female, 121 (60%) were male and the mean age was 51.16 ± 16.28 (range 17-93) years. In our study, sole anti-HBs positivity due to HBV vaccination, was detected in 89 (44.3%) patients. One hundred (50%) patients were found positive in terms of HBV infection and 40 (20%) were positive for HCV infection, while 24 (12%) patients had HBV and HCV co-infections. Eighty-five (42.3%) patients had no HBV and HCV infection. Among the 5 (2.5%) patients who were HBsAg positive, four were also HBV DNA positive. Occult HBV infection was detected in 1 (0.5%) patient. Anti-HCV and HCV RNA were found positive in 37 (18.4%) and in 24 (12%) patients, respectively. Among the HCV-RNA positive patients, 3 (12.5%) were anti-HCV negative. ALT and AST levels were found normal in all of the HBV DNA positive patients, and 62.5% (15/24) of HCV RNA positive patients. All of the HBV isolates were identified as genotype D and HCV isolates as genotype 1b. No statistically significant correlation was detected between the HBV infection and patients' age, duration of hemodialysis and elevation of serum transaminase levels (p> 0.05). On the other hand, HCV infection was seen to increase with age (p= 0.047). HCV infection showed a statistically significant increase with the duration of hemodialysis. HCV infection risk was increased in patients who were under hemodialysis for ≥ 25 months (p< 0.001, OR: 0224, 95% CI= 0089-0562). There was also a statistically significant correlation between the presence of HCV infection (anti-HCV and/or HCV RNA positive) and high levels of serum transaminases (p< 0.001). However, in two of the three cases who were anti-HCV negative and HCV RNA positive, serum transaminase levels were normal while the viral loads were high. Therefore to follow-up HCV infection in the hemodialysis patients, anti-HCV and serum transaminase levels may not be sufficient alone and these patients should be evaluated periodically for HCV RNA. In addition, the detection of occult HBV infection in one of the study patients, indicated that HBV DNA should also be investigated at regular intervals in the hemodialysis patients.

Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients

Detection of hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in absence of HCV RNA in serum, designated as 'occult HCV infection', has been a matter of controversy in recent years. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) and kidney transplant (KTx) patients. We enrolled 417 CHD patients, 417 KTx recipients and 2 control groups - 25 anti-HCV (antibody against HCV)-positive and HCV RNA-positive patients with chronic hepatitis C, and 40 anti-HCV-, HCV RNA-, and HBsAg-negative healthy subjects. HCV RNA was tested in serum and PBMC using a sensitive commercial assay. In CHD patients, the prevalence of anti-HCV was 3.6% (15/417) and of positive serum HCV RNA 2.4% (10/417). HCV RNA was detected in PBMC in 1/407 (0.25%) HCV serum RNA-negative patients ("occult HCV infection"). In KTx recipients, prevalence of anti-HCV was 4.8% (20/417) and of positive serum HCV RNA 4.6% (19/417). Occult HCV infection was found in 2/398 (0.5%) serum HCV RNA-negative patients. On a mean longitudinal follow-up of 30months of the 3 patients with occult HCV infection, there was no clinical or virological evidence of HCV infection. The prevalence of occult HCV infection was very low in our CHD and KTx patients, and it did not appear to be clinically relevant. Further studies in geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups.

Distribution Pattern of HCV Genotype and Its Association with Liver Functioning Enzymes and Viral Load

Background and objectives: Hepatitis C virus (HCV) causes chronic infectious disease called hepatitis C that mainly affects the liver by scaring the liver tissues which ultimately leads to cirrhosis and hepatocellular carcinoma. The viral load and genotyping of the virus was done from patients sample and the functionality of the various liver enzymes was tested by biochemical approaches. Methods: Twenty-nine HCV RNA positive patients were studied. RNA was exacted and quantified and genotyped by RT PCR. Total bilirubin, S.G.O.T, S.G.P.T, total protein, and alkaline phosphatase were analyzed by biochemical approaches. Result: 53.57% are genotype 1, 24.13 % are genotype 3 and 20.68 % are other than genotype 1, 2, 3, 4. The SGOT level in genotype 1 showed significant difference with reference to standard deviation and mean. Interpretation: The present study revealed that HCV genotype 1 accounted for 53.57% and have the HCV infection in Kolkata and surrounding areas.

Marijuana use in hepatitis C infection does not affect liver biopsy histology or treatment outcomes.

Marijuana smoking is prevalent among hepatitis C virus-infected patients. The literature assessing the influence of marijuana on liver disease progression and hepatitis C virus antiviral treatment outcomes is conflicting. The authors evaluated hepatitis C virus RNA-positive patients followed at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) from 2000 to 2009. Using The Ottawa Hospital Viral Hepatitis Clinic database and charts, information regarding demographics, HIV coinfection, alcohol use, liver biopsy results, treatment outcomes and self-reported marijuana use was extracted. Biopsy characteristics and hepatitis C virus antiviral treatment outcomes were assessed for association with categorized marijuana use by adjusted logistic regression; covariates were specified according to clinical relevance a priori. Information regarding marijuana use was available for 550 patients, 159 (28.9%) of whom were using marijuana at the time of first assessment. Biopsy fibrosis stage and marijuana use data were available for 377 of these 550 (F0-2 = 72.3%). Overall, marijuana use did not predict fibrosis stage, inflammation grade or steatosis. Sustained virological response and marijuana use data were available for 359 of the 550 cohort participants; a total of 211 (58.8%) achieved a sustained virological response. Marijuana use was not associated with premature interruption of therapy for side effects, the likelihood of completing a full course of therapy or sustained virological response. Marijuana use did not influence biopsy histology or alter key hard outcomes of hepatitis C virus antiviral therapy.

Large Human Outbreak of West Nile Virus Infection in North-Eastern Italy in 2012

Human cases of West Nile virus (WNV) disease have been reported in Italy since 2008. So far, most cases have been identified in north-eastern Italy, where, in 2012, the largest outbreak of WNV infection ever recorded in Italy occurred. Most cases of the 2012 outbreak were identified in the Veneto region, where a special surveillance plan for West Nile fever was in place. In this outbreak, 25 cases of West Nile neuroinvasive disease and 17 cases of fever were confirmed. In addition, 14 WNV RNA-positive blood donors were identified by screening of blood and organ donations and two cases of asymptomatic infection were diagnosed by active surveillance of subjects at risk of WNV exposure. Two cases of death due to WNND were reported. Molecular testing demonstrated the presence of WNV lineage 1 in all WNV RNA-positive patients and, in 15 cases, infection by the novel Livenza strain was ascertained. Surveillance in other Italian regions notified one case of neuroinvasive disease in the south of Italy and two cases in Sardinia. Integrated surveillance for WNV infection remains a public health priority in Italy and vector control activities have been strengthened in areas of WNV circulation.

Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/HCV dual infection

The purpose of this investigation was to evaluate the role of IL28-B polymorphism in the clearance of hepatitis C virus (HCV) in chronic hepatitis B virus (HBV)/HCV coinfection during a long-term follow-up. Thirty-four consecutive patients with HBV surface antigen (HBsAg)-positive/anti-HCV-positive chronic hepatitis were retrospectively enrolled at their first liver biopsy (LB). For all patients, a documented clinical, serological and virological follow-up of at least 3 years (range 3-16 years) after LB and a sample of whole blood for genetic evaluation were available. Of the 24 patients with detectable serum HBV-DNA and HCV-RNA at their first observation, three cleared both HBV-DNA and HCV-RNA, 12 HCV-RNA and five HBV-DNA. Of the seven HBV DNA-positive/HCV RNA-negative patients at enrolment, three cleared HBV-DNA and one remained HBV DNA-positive and became HCV RNA-positive. All three HBV DNA-negative/HCV RNA-positive patients remained unchanged. Compared with the 12 patients with HCV persistence, the 15 patients who cleared HCV were younger, had lower serum alanine aminotransferase (ALT), HCV load, and histological activity index (HAI) and fibrosis score, more frequently had IL28-B CC variant, had been receiving an interferon-based treatment and less frequently cleared serum HBV-DNA. To investigate the relationship between the IL28-B variants and clearance of HCV, excluding the confounding effect of interferon-based treatment, the Mantel-Haenszel test was used, which indicated an association between HCV clearance and IL28-B variants (p = 0.009). In chronic HBV/HCV coinfection, a long-term follow-up showed a frequent spontaneous or treatment-related clearance of active replication of one or both viruses and identified the IL28-B CC genotype as an independent predictor of HCV clearance.

Molecular detection of HCV infection in suspected liver disease patients of District Mardan, Khyber PuhktoonKhwa

Chronic hepatitis is a common cause of liver related problem due to different viruses concerned with liver, where Hepatitis C (HCV) has been documented as the major cause and lead to many complications. A total of 1500 (54% Male and 46% Female) suspected liver disease patients were selected for the study. Confirmation was carried out by ICT, ELISA and q-PCR. Age wise and gender wise and Tehsil wise distribution of the data was carried by statistical analysis. HCV RNA was detected in 438 (29.2%) samples out of total 1500 samples of suspected liver disease patients via q-PCR. Out of 438 patients, 210 (47.94%) were male and 228 (52.06 %) were female patients. In age group 41-60 years there were 210 (47.94%) HCV RNA positive patients. In age group 21-40 years it was 104 (23.74%), in >60 years it was 95 (21.68%) and in <20 years 29 (6.62%) was observed. In Tehsil wise distribution it was noted that 228 (52.05%) HCV RNA positive samples were from Tehsil Mardan and 115 (26.25%) and 95 (21.68%) from Takhtbhai and Kattlang respectively. This study concludes that the most specific, sensitive and reliable test use for detection of HCV is q-PCR. Female infectivity rate with HCV is relatively higher then male in District Mardan. Age group 41-60 years was found the most susceptible group to HCV infection in this study. Among the three Tehsil of District Mardan, the highest number of HCV infected patients was found in Tehsil Mardan with 228 (52.05%) patients.

Cyclin D1—a prognostic marker in oropharyngeal squamous cell carcinoma that is tightly associated with high-risk human papillomavirus status

Human papillomavirus-related oropharyngeal squamous cell carcinoma has a unique biology and improved prognosis. A new focus is to identify prognostic biomarkers specifically in this human papillomavirus-positive cohort. We analyzed cyclin D1 immunostaining on a tissue microarray of patients with known clinical follow-up and p16 and human papillomavirus status (by E6/E7 RNA in situ hybridization). Cyclin D1 staining was read visually and digitally. Cutoffs of 5%, 10%, and 30% were separately analyzed as was linear intensity data derived from the image analysis. For the 202 tumors, cyclin D1 expression was > 10% in 25.7% (visual) and 35.5% (digital) of the cases. It was > 30% in 15.8% (visual) and 16.5% (digital) of the cases. High cyclin D1 by both methods, cutoffs, and expression intensity was associated with poorer overall, disease-free, and disease-specific survival in univariate analysis. However, low cyclin D1 expression was also tightly associated with human papillomavirus RNA (P < 1.0 × 10(-18) for all cutoffs) and p16 positivity (P < 1.0 × 10(-14) for all cutoffs). In multivariate analysis using the digital 30% cutoff (the strongest cyclin D1 assessment method), only T stage, p16 status, smoking, and treatment approach associated with survival. Intensity of cyclin D1 expression did, however, significantly substratify the human papillomavirus RNA-positive patients into prognostic subgroups independent of other variables. In summary, cyclin D1 overexpression correlates strongly with patient survival in oropharyngeal squamous cell carcinoma, but its relationship with human papillomavirus status is very tight, and the complex nature of this correlation likely limits any clinical application for cyclin D1 assessment.

Natural history of hepatitis C in thalassemia major: a long‐term prospective study

Transfusion-acquired hepatitis C virus (HCV) remains an important problem among patients with thalassemia. In this study, we evaluated the natural history of post-transfusional hepatitis C in thalassemia major, paying special attention to spontaneous viral clearance, to factors influencing the chronicity rate and fibrosis progression. A prospective study to evaluate the incidence and etiology of transfusion-related hepatitis was started in 1980. In patients who developed hepatitis C, HCV RNA, ALT, and ferritin were measured over time. The correlation between interleukin-28B gene polymorphisms and viral clearance was also analyzed. Seventy-three of 135 patients (62.2%) acquired HCV. An extended follow-up (22 to 30 yr) with HCV RNA assessment was available in 52 patients. Of them, 23 (44.2%) cleared the virus. The proportion of IL-28B genotypes was different between the subjects who cleared the virus and the subjects who did not. Fibrosis progression was similar in HCV RNA-positive and HCV RNA-negative patients. Liver iron was the only factor associated with the fibrosis. In thalassemia patients with HCV infection, liver iron does not play a major role in influencing the chronicity rate, whereas it is significantly associated with the fibrosis.

Frequent Transient Hepatitis C viremia without Seroconversion among Healthcare Workers in Cairo, Egypt

BackgroundsWith 10% of the general population aged 15–59 years chronically infected with hepatitis C virus (HCV), Egypt is the country with the highest HCV prevalence worldwide. Healthcare workers (HCWs) are therefore at particularly high risk of HCV infection. Our aim was to study HCV infection risk after occupational blood exposure among HCWs in Cairo.Methodology/Principal FindingsThe study was conducted in 2008–2010 at Ain Shams University Hospital, Cairo. HCWs reporting an occupational blood exposure at screening, having neither anti-HCV antibodies (anti-HCV) nor HCV RNA, and exposed to a HCV RNA positive patient, were enrolled in a 6-month prospective cohort with follow-up visits at weeks 2, 4, 8, 12 and 24. During follow-up, anti-HCV, HCV RNA and ALT were tested. Among 597 HCWs who reported a blood exposure, anti-HCV prevalence at screening was 7.2%, not different from that of the general population of Cairo after age-standardization (11.6% and 10.4% respectively, p = 0.62). The proportion of HCV viremia among index patients was 37%. Of 73 HCWs exposed to HCV RNA from index patients, nine (12.3%; 95%CI, 5.8–22.1%) presented transient viremia, the majority of which occurred within the first two weeks after exposure. None of the workers presented seroconversion or elevation of ALT.Conclusions/SignificanceHCWs of a general University hospital in Cairo were exposed to a highly viremic patient population. They experienced frequent occupational blood exposures, particularly in early stages of training. These exposures resulted in transient viremic episodes without established infection. These findings call for further investigation of potential immune protection against HCV persistence in this high risk group.

Non-structural 3 protein expression is associated with T cell protein tyrosine phosphatase and viral RNA levels in chronic hepatitis C patients

The hepatitis C virus (HCV) non-structural 3 (NS3) protein plays key roles in both the viral life cycle and in the modulation of intrahepatic signaling and immunity. We recently showed that NS3 cleaves the T cell protein tyrosine phosphatase (TCPTP).To better understand the inactivation of TCPTP in HCV-infected humans, we investigated whether there is an association between TCPTP cleavage, NS3 protein levels and clinical parameters in hepatitis C patients.Liver biopsies were obtained from 69 HCV RNA positive patients with confirmed chronic HCV infection and 16 control patients. Hepatic NS3 and TCPTP protein levels were determined and correlated to viral load or clinical parameters for the severity of liver disease.We found a positive correlation between the viral load and the intrahepatic NS3 protein levels in patients infected with HCV. HCV-infected patients had significantly lower intrahepatic TCPTP levels than non-infected control patients. In HCV-infected patients both intrahepatic NS3 expression and the viral load were inversely correlated with the intrahepatic TCPTP protein levels. Detection of NS3 did not associate with any other clinical parameters such as liver damage, the grade of liver inflammation or fibrosis stage.This is the first study reporting a detailed analysis of HCV NS3 and TCPTP protein levels in the liver. It demonstrates a clear link between HCV viral load, NS3 expression in the liver and intrahepatic TCPTP levels. Thus, the association between TCPTP cleavage and viral replication may have important consequences for the HCV life cycle and HCV-induced liver diseases.

Türkiye’deki Kırm Kongo Kanamalı Ateşi Virüslerinin Kısmi M-segmentlerinin Genetik Analizi

Crimean-Congo hemorrhagic fever (CCHF) is a fatal tick-borne zoonosis extensively common in Africa, Asia, Eastern Europe and the Balkan Peninsula. CCHF has been reported in Turkey with high frequency since 2002. Genetic diversity of CCHF virus (CCHFV) isolates circulating in Turkey were studied by two recent studies from 2006 to the end of 2010. Since CCHFV disease has been an important public health concern in Turkey, it is necessary to continue genetic analysis of CCHFV viruses for the assessment of future patterns of disease. The aim of the present study was to genetic analysis of CCHFV isolates derived from infected patients over a two-year period (2011 and 2012) in several provinces of Turkey. Serum samples (n=10) were selected from CCHFV RNA positive patients and subjected to sequence analysis of the gene region encoding partial M segment. The nucleotide sequence alignments of the 10 partial M segments of CCHFV isolates showed that the nucleic acid relatedness of CCHFV isolates ranged from 94.4% to 100%. Phylogenetic analysis of M segment sequences revealed that CCHFV isolates circulating in Turkey belonged to the European lineage I and were closely related to the viruses previously found in Turkey and in the Eastern European-Russian and Balkan Peninsula. The results of the present study indicated the genetic stability and the lack of the genetic diversity of CCHFV isolates circulating in Turkey.

Age and Gender Distribution of Hepatitis C Virus Genotypes in the Metropolitan Area of Naples

Objective: To assess any time-related variations in the distribution of hepatitis C virus (HCV) genotypes in the metropolitan area of Naples, Italy. Methods: HCV genotypes were analysed in 255 HCV RNA-positive patients with chronic HCV infection, observed from 2009 to 2011, and compared with data pertaining to a sample of 176 HCV RNA-positive patients observed from 2006 to 2008. Results: In both periods of analysis, genotype 1b was predominant (51.8 and 48.3%, respectively), followed by genotype 2 (27.9 and 31.7%, respectively). These HCV genotypes were particularly prevalent in older patients, whereas genotypes 3a and 1a were observed more frequently in the younger population. Genotype 1b was particularly common in females compared to males in both study periods (39.3% of 89 males vs. 64.3% of 87 females in the 3-year period 2006-2008, p < 0.001; 41.5% of 118 males vs. 54.0% of 137 females in the period 2009-2011, p < 0.05). The prevalence of patients with genotype 1b in the age range 51-60 years was higher in the 2006-2008 period than in 2009-2011 (76.9 vs. 37.7%; p < 0.0005) and lower in the over 60 year olds (55.1 vs. 59.6%; p = 0.5). Conclusion: Genotype 1b, historically the most prevalent in Italy, is still predominant; however, when comparing the two time periods, a cohort effect evidencing the increasing prevalence of genotype 1b among elderly patients was revealed.

Detection of enterovirus in the thyroid tissue of patients with graves' disease

The etiology and pathogenesis of Graves' disease (GD) are still unknown, although it is thought that both genetic and environmental factors are important. Some indirect evidence implies that a viral infection may be a possible etiologic factor in autoimmunity. The main objective of this study was to examine direct evidence of the presence of enteroviruses (EVs) in the thyroid tissue of patients with GD. Thyroid tissue from 22 patients with newly diagnosed GD was obtained by core needle biopsy, while tissue from 24 patients with chronic GD and 24 control subjects without any autoimmune thyroid diseases was collected during neck surgery. Formalin-fixed, paraffin-embedded thyroid tissue samples were examined for the presence of enterovirus capsid protein using immunohistochemistry and for enterovirus RNA using in situ hybridization. Enterovirus capsid protein was detected in 17 (37%) patients and in 4 (17%) control subjects (P = 0.103). Enterovirus RNA was identified in thyroid tissue from nine (20%) patients, but in none of the control subjects (P = 0.016). Eight (90%) of the nine virus RNA positive patients were also positive for enterovirus protein. This is the first study to analyze thyroid tissue for EVs, including patients with untreated, newly diagnosed GD. The results suggest that EVs are more frequently present in thyroid tissue of patients than controls. Further studies are indicated to explore this association to find out if a low-grade chronic enteroviral infection might be involved in the pathogenesis of GD and if this could offer new therapeutic and preventive opportunities.