Absence Of Hepatitis C Virus RNA Research Articles

Impact of the COVID-19 pandemic on hepatitis C outcomes at a health-system specialty pharmacy.

BACKGROUND: The goal of hepatitis C virus (HCV) treatment is to cure the patient of the infection, defined as a nondetectable HCV RNA at least 12 weeks after treatment completion, or sustained virologic response (SVR). The COVID-19 pandemic has presented new barriers to care in the treatment of patients with HCV that resulted in a transition to tele-health services at many health systems to overcome these barriers. OBJECTIVE: To assess the real-world impact of the COVID-19 pandemic and the subsequent shift to a telehealth model on collection of SVR data and other HCV treatment outcomes in a health-system setting. METHODS: Subjects who received a referral for an HCV direct-acting antiviral agent between January 1, 2018, and November 30, 2020, and were aged 18 years or older at time of enrollment were placed in either "pre-COVID-19" or "COVID-19" cohorts based on enrollment date. The primary endpoint of this study evaluated confirmed SVR to treatment determined by the absence of HCV RNA by polymerase chain reaction testing at least 12 weeks after completion of drug therapy. Secondary endpoints evaluated completion of medication therapy and adherence to laboratory appointments. RESULTS: 1,504 patients met study inclusion criteria (pre-COVID-19 cohort, n = 1,230; COVID-19 cohort, n = 274). The COVID-19 cohort demonstrated significantly lower therapy completion rates (P = 0.001), were less likely to obtain SVR laboratory tests (P < 0.001), and had a significantly lower confirmed SVR rate (P < 0.001) compared with the pre-COVID-19 cohort. In a subset of patients who completed therapy and had SVR laboratory tests collected, there were no significant differences observed in the rate of patients who achieved SVR (P = 0.959). CONCLUSIONS: During the COVID-19 pandemic, patients with HCV were significantly less likely to complete therapy or participate in SVR laboratory work. Further studies are needed to determine if offering a telehealth option for our patients in a post-COVID-19 environment would offer any additional advantage in increasing access to care for patients with HCV. DISCLOSURES: No outside funding supported this study. Dr Cooper is an employee of the University of Kentucky whose position was partially funded by Gilead Sciences, Inc.

Clearance of Hepatitis C Virus (HCV) Is Associated With Improved Outcomes in HCV-Associated Lymphoma

BackgroundImproved hepatitis C virus (HCV) clearance due to directly acting antiviral agents has led to remarkably improved outcomes of indolent HCV-associated non-Hodgkin lymphoma (NHL). The impact of directly acting antivirals on the outcomes of aggressive NHL is still under investigation. Characteristics of HCV-associated NHL in black patients are not well characterized. We report outcomes of HCV-associated NHL compared to their HCV-negative counterparts in a predominantly black population. Patients and MethodsPatients with lymphoma between January 2007 and December 2017 were retrospectively studied. Depending on presence or absence of HCV RNA, patients were grouped into HCV positive (HCV+) and HCV negative (HCV−) cohorts. Depending on virologic clearance (VC), HCV+ were classified into HCV+ with VC and HCV+ without VC. Overall response rate (ORR), complete response, overall survival (OS), and progression-free survival (PFS) of HCV+ patients with and without VC were compared to HCV− patients. ResultsOf 397 patients with lymphoma, 40 had HCV. Black comprised 90% of HCV+ patients. Diffuse large B-cell lymphoma was most frequent (47%) in the HCV+ group. HCV+ patients without VC had significantly worse OS and PFS compared to HCV− patients. There were no differences in ORR, complete response, PFS, and OS of HCV+ patients with VC and HCV− patients. These results were consistent in subgroups of diffuse large B-cell lymphoma and aggressive lymphoma. ConclusionHCV clearance is positively associated with lymphoma outcomes in black patients. Patients who clear HCV have noninferior outcomes to HCV− patients, while those who fail to clear HCV have significantly worse outcomes.

Understanding occult hepatitis C infection.

Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum. A literature review was conducted to identify articles that characterized OCI as a disease, including its epidemiology, mode of transmission, pattern of infection, progression, and treatment. OCI patients experience a milder degree of inflammatory and cirrhotic changes than patients with chronic hepatitis C. OCI is transmissible parenterally both in vivo and in vitro, however the duration and outcome of OCI remains unclear. OCI is most consistently found in patients with previous hepatitis C disease and hemodialysis patients. Beyond the at-risk populations, OCI has also been demonstrated among healthy individuals and blood donors. This review summarises our current understanding of OCI and suggests areas for further research to improve our understanding of this phenomenon, including a better understanding of its epidemiology and full clinical course. The current understanding of OCI and its clinical implications remain limited. Further standardized detection methods, ongoing surveillance, and investigation of its potential transmissions are required.

CXCL9 chemokine level is associated with spontaneous clearance and sustained virological response in Egyptian Chronic Hepatitis C patients receiving direct acting antivirals.

Chronic Hepatitis C virus (HCV) infection is associated with progressive liver inflammation which in turn leads to cirrhosis and finally causes hepatocellular carcinoma (HCC). By different escape mechanisms, the virus succeeds to evade the innate and acquired immune responses to establish chronic infection. This study aimed to evaluate the level of chemokine CXCL9 and its correlation with some biochemical parameters in different subjects of HCV patients. A total of 83 persons participated in this study including healthy subjects without both HCV antibodies and HCV RNA (22.9%), HCV treated responders accomplished SVR post treatment, with HCV antibodies and absence of HCV RNA (24.1%), spontaneous or natural clearance patients, with positive HCV antibodies and negative HCV RNA without treatment (26.5%) and chronic HCV-patients, with both positive HCV antibodies and HCV RNA with no treatment (26.5%). HCV RNA was quantitated by real time PCR and serum CXCL9 level was measured by ELISA commercial kit pre-coated with human MIG/CXCL9 antibody. Assessment of biochemical and hematological parameters was carried out. Data showed that, the level of CXCL9 was significantly increased in chronic individuals (627.1 pg/ml) (P< 0.001) than spontaneous clearance (107.76 pg/ml) and responder subjects (117.28 pg/ml) (P⩽ 0.05). No correlation has been found between CXCL9 level and viral load. Furthermore, CXCL9 levels correlated variably with some biochemical and hematological parameters according to each subject. Serum Chemokine CXCL9 level is associated with spontaneous clearance of HCV and response to HCV treatment, which may be identified as a predictive marker among HCV patients.

Analytical performances of simultaneous detection of HIV-1, HIV-2 and hepatitis C- specific antibodies and hepatitis B surface antigen (HBsAg) by multiplex immunochromatographic rapid test with serum samples: A cross-sectional study

BackgroundThe HIV/HCV/HBsAg Triplex consists in manually performed, visually interpreted, lateral flow, immunochromatographic rapid diagnostic test simultaneously detecting in 15min human immunodeficiency virus (HIV)-1 and HIV-2 and hepatitis C virus (HCV)- specific antibodies (Ab) (IgG and IgM) and hepatitis B virus (HBV) surface antigen (HBsAg) in serum, plasma and whole blood. MethodsA hospital-based cross-sectional study was conducted on a prospective panel of serum samples from adult inpatients included from routine analysis irrespectively of age and sex, including 250 sera positive for HIV-1-specific Ab, 250 for HCV-specific Ab, 250 for HBsAg and 250 sera negative for HIV- and HCV- Ab and HBsAg, and from 110 HIV-2-infected patients living in Ivory Coast, according to the results obtained by the reference chemiluminiscent microparticle immunoassay (CMIA) Abbott Architect i2000SR analyzer (Abbott Diagnostic, Chicago, IL, USA). Among HCV-seropositive sera, 187 were positive for HCV RNA (chronic infection), whereas 63 were negative (resolved infection), respectively. Serum samples were further tested blindly by HIV/HCV/HBsAg Triplex according to manufacturers’ recommendations. ResultsHIV/HCV/HBsAg Triplex showed very high sensitivity and specificity, as well as excellent concordance with CMIA Abbott results, as shown in the Table. Lower sensitivity was observed only in individuals who had cleared their HCV infection (presence of HCV-specific Ab in absence of HCV RNA). The mean lower limit of HBsAg detection was 2.38±0.63 IU/ml. Erythrocytes-spiked serum samples gave similar results than serum samples. ConclusionsAdvantages of HIV/HCV/HBsAg Triplex for HIV-1, HIV-2, HCV and HBV include the requirement for less overall specimen volume, fewer finger-sticks if capillary whole blood is used, cost savings through lower cost per virus tested, improved patient flow with results for multiple viruses available at the same time, overall service delivery efficiencies with less time required per infected patient; and patient benefits from fewer visits and lower cost associated with each clinic attendance. The screening of chronic HIV, HCV and HBV by multiplex HIV-1/HIV-2/HCV/HBsAg Triplex may improve the “cascade of screening” and quite possibly linkage-to-care with reduced cost.

The Absence of HCV RNA and NS5A Protein in Peripheral Blood Mononuclear Cells Is a Prognostic Tool for Sustained Virological Response.

Hepatitis C Virus (HCV) infection is a major health concern worldwide. The presence of both HCV viral RNA and NS5A proteins in peripheral blood mononuclear cells (PBMCs) indicate the efficacy of the treatment during sustained virological response (SVR) and end of treatment response (ETR). The main objective of this study was to detect the absence or presence of HCV RNA and NS5A proteins in PBMCs. Blood samples were taken from selected patients (Islamabad, Pakistan) before treatment, at ETR, and during SVR. Two hundred HCV responders to pegylated IFN-α-2a plus ribavirin were selected. HCV RNA was extracted from the patients to determine the viral load by reverse transcription (RT)-polymerase chain reaction before treatment. Out of 200 patients, 152 (76%) and 48 (24%) achieved positive and negative ETR, respectively. Among ETR patients, 134 (88.2%) showed SVR, whereas 18 (11.8%) displayed relapse. The male to female ratio was 92:108 with mean age of 37.4 years. Among 152 ETR-positive patients, 29 (19%) patients' PBMCs were positive for HCV RNA and 27 (17.8%) were positive for NS55A proteins. Patients having HCV RNA in PBMCs showed higher relapse frequency compared with patients lacking it. Similarly, patients having NS5A protein showed significantly higher relapse frequency compared with patients lacking it. All PBMC-positive samples were of genotype 3a. In addition, patients with positive NS5A in their PBMCs showed greater risk of relapse compared with patients having HCV RNA. We conclude that the absence of both viral HCV and proteins can be used as an indicator for diagnosis of SVR in the future.

Assessment of Hepatitis C Virus RNA in Peripheral Blood Mononuclear Cells as a Predictor of Response to Pegylated-Interferon and Ribavirin: A Cohort Study

Background: Sustained virologic response (SVR) to pegylated-interferon (PegIFN) and ribavirin (RBV) in hepatitis C virus (HCV)-infected patients could be predicted by detection of serum HCV RNA whereas detection of HCV RNA in other reservoirs such as peripheral blood mononuclear cells (PBMCs) for prediction of treatment response is still a mystery. Objectives: This study aimed at assessing the prediction of SVR by detection of HCV RNA in PBMCs or serum in patients during treatment. Methods: In a cohort study (2011 to 2014), 100 chronic HCV patients at Tehran Hepatitis Center were treated with PegIFN and RBV. Serum HCV RNA level was measured at baseline, 4, 12, and 24 weeks during treatment and at 24 weeks after termination of treatment. Meanwhile, HCV RNA was evaluated in PBMCs at weeks 4, 12, and 24 during the treatment. Results: Out of 100 patients treated in this study, 91 completed the course of treatment. Most patients were young males infected with HCV genotype 1. Cirrhosis and previous history of treatment was found in 16.5% and 26.5% of patients. Sustained virologic response was achieved in 65 (71.4%) patients. Among baseline parameters, only female gender was significantly associated with SVR. Undetectable serum HCV RNA at week 4 (OR = 4.74) and week 12 (OR = 11.63) of treatment predicted SVR rate while the same was not true for detection of serum HCV RNA at week 24 of treatment. Moreover, detection of HCV RNA in PBMCs at weeks 4 and 12 of treatment was not associated with the rate of SVR, while absence of HCV RNA in PBMCs at week 24 of treatment was associated with SVR (OR = 4.55). Conclusions: Detection of HCV RNA in PBMCs, especially at week 24 of treatment with PegIFN and RBV, could be considered as an additional marker for prediction of treatment response. It is recommended to assess HCV on-treatment kinetic in PBMCs of patients treated with direct-acting antiviral agents for prediction of treatment response.

Dried Blood Spots: A Tool to Ensure Broad Access to Hepatitis C Screening, Diagnosis, and Treatment Monitoring.

With the advent of highly efficient antiviral therapies for hepatitis C virus (HCV) infection, providing broad access to diagnosis and care is needed. The dried blood spot (DBS) technique can be used to collect, store, and ship whole-blood specimens. Our goal was to assess the performance of standardized HCV diagnostic and monitoring tools in the analysis of DBS. Serum specimens and whole-blood specimens collected using the DBS technique from >500 patients were tested for virological markers used to diagnose and monitor HCV infection. Enzyme immunoassay detection of anti-HCV antibodies in specimens from DBS was reliable after establishment of a new signal-to-cutoff ratio. HCV RNA was detected DBS from the vast majority of patients with active replication, but HCV RNA levels were substantially lower than in serum specimens, implying that only the presence or absence of HCV RNA or changes in the HCV RNA level should be taken into consideration for therapy. Detection of HCV core antigen in specimens from DBS was not a sensitive marker of chronic HCV infection. HCV genotype determination was possible in the vast majority of DBS. This study shows that whole-blood specimens collected using the DBS technique can be confidently used to diagnose and monitor HCV infection. DBS could help improve access to care for HCV infection because they are suitable for use in large-scale screening programs, diagnosis, and therapeutic monitoring.

Gene expression profiling to predict and assess the consequences of therapy-induced virus eradication in chronic hepatitis C virus infection.

Systems biology has proven to be a powerful tool to identify reliable predictors of treatment response in chronic hepatitis C virus (HCV) infection. In the present study, we studied patients with chronic HCV infection who responded to interferon (IFN)-based therapy, as evidenced by an absence of HCV RNA at the end of treatment, and focused on two issues that have not received much attention. First, we evaluated whether specific genes or gene expression patterns in blood were able to distinguish responder patients with a viral relapse from responder patients who remained virus negative after cessation of treatment. We found that patients with chronic HCV infection who were sustained responders and relapsers after IFN-based therapy showed comparable baseline clinical parameters and immune compositions in blood. However, at baseline, the gene expression profiles of a set of 18 genes predicted treatment outcome with an accuracy of 94%. Second, we examined whether patients with successful therapy-induced clearance of HCV still exhibited gene expression patterns characteristic of HCV or whether normalization of their transcriptome was observed. We observed that the relatively high expression levels of IFN-stimulated genes (ISGs) in patients with chronic HCV infection prior to therapy were reduced after successful IFN-based antiviral therapy (at 24 weeks of follow-up). These ISGs included the CXCL10, OAS1, IFI6, DDX60, TRIM5, and STAT1 genes. In addition, 1,428 differentially expressed non-ISGs were identified in paired pre- and posttreatment samples from sustained responders, which included genes involved in transforming growth factor beta (TGF-β) signaling, apoptosis, autophagy, and nucleic acid and protein metabolism. Interestingly, 1,424 genes with altered expression levels in responder patients after viral eradication were identified, in comparison to normal expression levels in healthy individuals. Additionally, aberrant expression levels of a subset of these genes, including the interleukin-32 (IL-32), IL-16, CCND3, and RASSF1 genes, were also observed at baseline. Our findings indicate that successful antiviral therapy for patients with chronic HCV infection does not lead to normalization of their blood transcriptional signature. The altered transcriptional activity may reflect HCV-induced liver damage in previously infected individuals. Tools to predict the efficacy of antiviral therapy for patients with HCV infection are important to select the optimal therapeutic strategy. Using a systems biology approach, we identify a set of 18 genes expressed in blood that predicts the recurrence of HCV RNA after cessation of therapy consisting of peginterferon and ribavirin. This set of genes may be applicable as a useful biomarker in clinical decision-making, since the number of genes included in the predictor is small and the correct prediction rate is high (94%). In addition, we observed that the blood transcriptional profile in patients with chronic HCV infection who were successfully treated is not normalized to the status observed in healthy individuals. Even 6 months after therapy-induced elimination of HCV RNA, gene expression profiles in blood are still altered in these patients with chronic HCV infection, strongly suggesting long-term modulation of immune parameters in previously infected patients.

Occult Hepatitis C Virus Infection in Haemodialysis Unit : A Single-Center Experience

Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in the absence of HCV RNA in serum, designated as ‘occult HCV infection’, has been a matter of controversy in the recent years. Occult hepatitis C virus (HCV) infection has not been investigated in haemodialysis patients. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) patients in a single heamodialysis center at Al-Taif, KSA. Methods: We enrolled 84 CHD patients, whose sera are negative for HCV markers. HCV RNA was tested in PBMC using a sensitive commercial real time assay. In this study, real-time PCR was used to test for the presence of genomic HCV-RNA in peripheral blood mononuclear cells of all of these patients. For comparison, 20 patients on HD with evidence of chronic hepatitis C virus infection were included as a control group. Results: In CHD patients, occult HCV infection, determined by the presence of genomic HCV-RNA in peripheral blood mononuclear cells (PBMNCs), was found in 13.4 % of the patients; 83 % of these patients had ongoing HCV replication, indicated by the presence of HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on heamodialysis and had significantly higher mean alanine aminotransferase levels during the 3 months before study entry. Compared to CHCV patients, those with occult HCV have less elevated bilirubin, AST and ALT. Conclusions: The prevalence of occult HCV infection was moderate in our CHD patients, and it did not appear to be clinically relevant. Further studies in other geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups. Abbreviations HCV, Hepatitis C Virus ; antibody against HCV; PBMC, peripheral blood mononuclear cells; rRT-PCR, real time reverse transcriptase polymerase chain reaction; CHD, chronic hemodialysis.

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.

Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study

BackgroundThe effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment.MethodsWe determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis.ResultsThe majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin.ConclusionsThe effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.

Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia.

Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized.

Peginterferon Alfa-2a and Ribavirin in Latino and Non-Latino Whites with Hepatitis C

Race has been shown to be a factor in the response to therapy for hepatitis C virus (HCV) infection, and limited data suggest that ethnic group may be as well; however, Latinos and other ethnic subpopulations have been underrepresented in clinical trials. We evaluated the effect of Latino ethnic background on the response to treatment with peginterferon alfa-2a and ribavirin in patients infected with HCV genotype 1 who had not been treated previously. In a multicenter, open-label, nonrandomized, prospective study, 269 Latino and 300 non-Latino whites with HCV infection received peginterferon alfa-2a, at a dose of 180 microg per week, and ribavirin, at a dose of 1000 or 1200 mg per day, for 48 weeks, and were followed through 72 weeks. The primary end point was a sustained virologic response. We enrolled Latinos whose parents and grandparents spoke Spanish as their primary language; nonwhite Latinos were excluded. Baseline characteristics were similar in the Latino and non-Latino groups, although higher proportions of Latino patients were 40 years of age or younger, had a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of more than 27 or more than 30, and had cirrhosis. The rate of sustained virologic response was higher among non-Latino whites than among Latinos (49% vs. 34%, P<0.001). The absence of HCV RNA in serum was more frequent in non-Latino whites at week 4 (P=0.045) and throughout the treatment period (P<0.001 for all other comparisons). Latino or non-Latino background was an independent predictor of the rate of sustained virologic response in an analysis adjusted for baseline differences in BMI, cirrhosis, and other characteristics. Adherence to treatment did not differ significantly between the two groups. The numbers of patients with adverse events and dose modifications were similar in the two groups, but fewer Latino patients discontinued therapy because of adverse events. Treatment with peginterferon alfa-2a and ribavirin for 48 weeks resulted in rates of sustained virologic response among patients infected with HCV genotype 1 that were lower among Latino whites than among non-Latino whites. Strategies to improve the sustained virologic response in Latinos are needed. (ClinicalTrials.gov number, NCT00107653.)

MBL2and Hepatitis C Virus Infection among Injection Drug Users

BackgroundGenetic variations in MBL2 that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whether MBL2 variants influence the outcome of hepatitis C virus (HCV) infection.MethodsParticipants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms in MBL2. Statistical analyses of European American and African American participants were conducted separately.ResultsThe analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, the MBL2 -289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans.ConclusionThis study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation that MBL2 -289X was associated with the absence of HCV RNA in European Americans requires validation.

Ethnicity and Spontaneous Clearance of Hepatitis C in HIV‐HCV Coinfected Patients

To the Editor: There are limited reports suggesting that ethnic populations differ in their immunological response to infection with hepatitis C virus (HCV), and that host factors influence spontaneous clearance (1). Canadian data (2–5) suggest that Inuit and First Nations people appear to have a higher rate of spontaneous HCV clearance based on the presence of HCV antibody and the absence of HCV RNA. An epidemiological review (6) has demonstrated a high prevalence of HCV coinfection in HIV-infected populations; we wondered whether there may be evidence of a differential rate of spontaneous HCV clearance depending on ethnicity and, specifically, Aboriginal origins in this coinfected population. After obtaining ethics approval through the Health Research Ethics Board of the Faculty of Medicine and Dentistry at the University of Alberta (Edmonton, Alberta), the Northern Alberta HIV Program database was examined to identify all living HIV-infected patients found to be HCV-seropositive between January 2001 and December 2006. In the HIV database, 120 charts of 181 individuals meeting our study entry criteria were accessible and reviewed by one of the two authors. Of the 120 patients reviewed, 74 were men (mean age 43 years; range 23 to 67 years of age). Of HIV-HCV coinfected patients, 52.5% had self-identified as Aboriginal. Of the 120 reviewed charts, 84 contained results of HCV RNA testing, with 46% of these patients being Aboriginal compared with 31% of the total HIV clinic population self-identified as Aboriginal. Assuming that HCV RNA-negative test results reflected spontaneous clearance in the face of HCV seropositivity, 13 of 84 (15%) patients appeared to have had spontaneous clearance of HCV. Of these 13, seven were of Aboriginal origin. This difference was not statistically significant (P=0.17; OR=0.7; 95% CI 0.128 to 8.2). Of the 84 available HCV RNA test results, 71 were positive and interpreted as indicative of ongoing HCV replication. Thirty-two of these positive test results were in self-identified Aboriginal patients, and 39 in non-Aboriginal patients. Of these 71 patients potentially eligible for antiviral therapy, only 10 received antiviral therapy for HCV and only two had a clinical response. Both of these were non-Aboriginal patients, and had genotypes 3A and 1B. The single Aboriginal patient who received anti-HCV therapy had genotype 1A, and did not respond. Spontaneous HCV viral clearance in populations not known to be HIV-infected has ranged from 15% to 45%, with significantly lower rates in those who are HIV-HCV coinfected (7). Because of literature (2–5) suggesting population differences in rates of spontaneous clearance and specifically in the Canadian Aboriginal and Inuit populations, we thought it would be of interest to examine this in Northern Alberta’s HIV population. Unfortunately, the study was retrospective, relatively small in patient number and incomplete in terms of ascertainment of outcome. Nonetheless, we believed the results were of interest. The relatively low uptake of anti-HCV therapy in this population has suggested the potential merits of a systematic, proactive approach in our population. Studies addressing genetic factors suggest a role for immunological host factors being important in HCV clearance, but these differences may be overshadowed by significant immune deficits as seen in patients with HIV infection.

Treatment of chronic hepatitis C in patients with haemophilia: a review of the literature

Chronic hepatitis C is a major cause of morbidity and mortality in haemophilia patients. In contrast to studies in the general population, the studies of antiviral therapy in haemophilia patients are limited and often include small numbers of patients. A review of the literature was performed to assess the efficacy of interferon (IFN)-based therapy for patients with haemophilia chronically infected with hepatitis C virus (HCV). Studies were identified by electronic searches (Medline, Embase) and hand searches in references of key articles. Data of the included studies were pooled, and responses to therapy were stratified according to treatment regimen, HIV co-infection status, and treatment history. The main outcome was a sustained virological response (SVR) defined as absence of HCV RNA both at the end of treatment and 24-week post-treatment. Thirty-five studies were identified that included 1151 patients. After pooling the data of included patients, the SVR in HIV-negative treatment naïve patients was 22% for IFN monotherapy, 43% for IFN and ribavirin, and 57% for pegylated IFN and ribavirin, respectively. Re-treatment with IFN and ribavirin of those who failed to respond to previous IFN monotherapy was successful in 33%. In HCV/HIV-coinfected patients, response to IFN monotherapy was 8% and to IFN combined with ribavirin 39%. Responses to IFN-based therapy in patients with haemophilia have been improved over time and are nowadays approximately 50-60%. However, data on haemophilic HCV/HIV-coinfected patients and in patients who failed to respond to previous therapy are limited and future studies in these specific patient population are necessary.

Medically assisted procreation and transmission of hepatitis C virus: absence of HCV RNA in purified sperm fraction in HIV co-infected patients

The risk of hepatitis C virus (HCV) transmission in medically assisted procreation (MAP) is debated and some researchers have proposed to exclude MAP for HCV-positive infertile patients. The objectives of this study were to assess the presence of viral RNA in the final preparation of density gradient semen fractions collected from men with chronic HCV and HIV co-infection participating in a MAP program, and to assess whether HIV co-infection influences the rate of the presence of HCV RNA in the semen. The study was based on a cohort of 170 HCV-infected male patients (93 HIV co-infected) participating in a MAP program in a French center. Semen samples were subjected to standard MAP sperm preparation, using density-gradient centrifugation with 40 and 90% layers. All aliquots were tested with a commercially available HCV RNA assay (Roche Monitor), adapted for use with semen after a nucleic HCV RNA extraction modification (Organon Technika). Seminal plasma samples from 19 (11%) patients were HCV RNA positive. The positive HCV viral load in semen was less than 600 IU/ml. None of the 90% fractions from HCV-infected patients were HCV RNA positive. Among the 93 co-infected patients, 10 were positive for HCV RNA in semen and three were HIV/HCV RNA positive in semen. Although HCV RNA was found in the semen of 11% of patients, no purified sperm fraction, or spermatozoa used in MAP were HCV RNA positive. The 90% purified sperm fraction discards the virus and must be used with care in MAP.

Etanercept as an adjuvant to interferon and ribavirin in treatment-naive patients with chronic hepatitis C virus infection: a phase 2 randomized, double-blind, placebo-controlled study

Current therapies for patients with chronic hepatitis C virus (HCV) do not achieve sustained viral clearance in most patients, and are associated with severe toxic effects. Our aim was to investigate the efficacy and safety of etanercept as adjuvant to interferon and ribavirin in treatment-naive patients with HCV. Double-blind, randomized, placebo controlled trial. Fifty patients with chronic HCV were randomly assigned to receive interferon alfa-2b and ribavirin with either etanercept or placebo for 24 weeks. The main outcome measure was the absence of HCV RNA at 24 weeks, the on treatment response at the end of the etanercept randomization period. At 24 weeks, HCV RNA was absent in 63% (12/19) etanercept patients compared to 32% (8/25) placebo patients (P=0.04). In addition, patients receiving etanercept had lower frequency of most adverse events categories compared to placebo. Etanercept given for 24 weeks as adjuvant therapy to interferon and ribavirin significantly improved virologic response at the end of the etanercept randomization period among patients with HCV, and was associated with decreased incidence of most adverse effects associated with interferon and ribavirin.

617 Procreation medically assisted (PMA) and transmission of hepatitis C virus (HCV): Absence of HCV RNA in purified sperm fraction in HCV patients with presence of viral RNA in semen

617 Procreation medically assisted (PMA) and transmission of hepatitis C virus (HCV): Absence of HCV RNA in purified sperm fraction in HCV patients with presence of viral RNA in semen