Evidence Of Hepatitis C Virus Infection Research Articles

Feasibility and Acceptability of Antenatal Hepatitis C Screening: A Pilot Study.

Hepatitis C virus (HCV) is not currently included in the United Kingdom routine antenatal screening program, but the latest guidelines from the Centers for Disease Control and Prevention, American Association for the Study of Liver Diseases, and Infectious Diseases Society of America recommend HCV screening for all pregnant women during each pregnancy. The aim of this study was to collect qualitative data on the feasibility and acceptability of antenatal HCV screening in pregnant women at the time of routine antenatal screening at 12 weeks, to estimate patient knowledge about HCV and identify the prevalence of HCV infection in antenatal women. This was a pilot study targeting a single hospital-based antenatal clinic in Birmingham, initially conducted for eight weeks with a further extension of the study period to enhance recruitment to meet the feasibility target of 500 patients. Data collected included demographic and epidemiological details. Pregnant women attending the antenatal unit were given information regarding HCV and antenatal screening for HCV prior to their initial antenatal visit. During the antenatal visit, research nurses provided further information about the study and HCV infection. Consent was obtained for taking part in the study and testing for HCV using blood samples taken at the same time as other routine antenatal screening blood tests. All women who agreed to participate in the study were asked to complete an acceptability and knowledge questionnaire. All women had HCV antibody testing as the primary screening assay. The test result was communicated in writing to the women and their general practitioner. Confirmatory positive antibody tests were followed up with quantitative HCV PCR and genotype analysis. The outcomes of testing were no evidence of HCV infection and evidence of past HCV infection or current HCV infection. Five hundred and forty-nine women were approached in the antenatal clinic; 30 women refused consent while 29 women were excluded from the study (blood tests not performed after consenting, age less than 18 years, and consent form lost). Four hundred and ninety women were included in the study. The median age of the study population was 29 years (range, 18-46). Knowledge about blood-borne viruses was limited; 75% of women had some understanding about antenatal hepatitis B (HBV) and human immunodeficiency virus (HIV) testing. Previous awareness about hepatitis C was reported by 55%. Ninety-one percent of women found the information they were given about hepatitis C helpful. Ninety-six percent of the women included in this study found the counselling they received about HCV useful and felt that the delivery of this information was carried out in an acceptable manner. Once given information about HCV, 99% felt that universal screening for HCV should be implemented. HCV antibody was negative in 489 women. One patient with a positive HCV antibody (prevalence: 0.2%) had a negative HCV PCR. Routine antenatal screening for HCV is not currently recommended in the UK. Our study suggests that antenatal HCV screening would be both feasible and acceptable to most pregnant women attending antenatal clinics. Though the awareness of HCV was low, with appropriate counselling and communication, 99% of pregnant women were in favor of antenatal screening for HCV. Antenatal screening would identify HCV-positive mothers and allow follow-up of their infants so that any infected mothers and infants could be offered effective curative therapy and prevent the progression of liver disease. The inclusion of HCV antenatal screening would complete the blood-borne virus profile and enhance the WHO target to eliminate HCV in the UK.

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk

BackgroundAbout 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group).MethodsWe performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex.Results13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found.ConclusionsHigher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.

Geographic Variation in the Utilization of HCV-viremic Donors into HCV-negative Recipients

We read with great interest the article by Cotter et al1 in which they identified that the practice of liver transplantation (LT) from hepatitis C virus (HCV)-viremic donors to HCV-negative recipients (D HCV+/R−) has increased with notable geographic variation. While the authors should be congratulated on a substantial effort, we wish to place emphasis on several points to place their studies in the proper context. First, the geographic variation is driven by a variety of factors. As the authors described, the rate of acute HCV infections in each geographic region appeared to be concordant with the practice of D HCV+/R−. However, that alone does not account for the variation in geographic utilization. Da et al2 reported a regional difference of 59.7% to 84.2% in conversion rates of HCV donors from the potential to actually used donors, likely reflective of regional experience and institutional policies. In addition, marginal grafts in LT such as those from old donors3 and donation after circulatory death (DCD)4 are known to show geographical and center differences in their utilization. The geographical variation in the practice of D HCV+/R− likely derives from a combination of these factors. Second, “racial disparity” in the practice of D HCV+/R− is prone to be influenced by several factors. The proportion of Caucasian recipients in the D HCV+/R− was significantly higher than other ethnic groups, which “raises the possibility of racial disparity” in authors’ study.1 However, additional demographics are important to take into consideration. The proportions of Caucasians as donors, not only as recipients, in the D HCV+/R− group was significantly higher, which could arise from the geographic variation. In addition, this study examined recipients without evidence of HCV infection. Liver disease cause varies on the waiting list by race: Caucasians make up 93.2% of HCV− LT candidates, whereas African Americans account for 79.8%.5 These characteristics could have influenced the differences of race in the D HCV+/R− practice. Nonetheless, more research is warranted to explore this important observation. Finally, there seems to be a causal relationship between the practice of D HCV+/R− and median Model for End-Stage Liver Disease (MELD) scores. The highly utilizing regions are “among the regions with the lowest median MELD scores.” Among the regions with the lowest rates of the D HCV+/R− practices, “regions 4 and 7 have many of the states with higher waitlist mortality rates.” The authors conclude that higher utilization of D HCV+/R− may improve waitlist mortality and decrease median MELD scores. However, the practice of using other marginal grafts showed different patterns. The majority of elderly donors were used in region 9, where waiting times and MELD scores are among the highest.3 Region 4 has significantly increased the DCD LT utilization.4 These results suggest that factors other than the practice of marginal grafts also play a role in median MELD scores and waiting list mortality. Despite these critiques, LT from HCV-viremic donors is a promising strategy to expand donor pool. Further detailed investigations in long-term outcomes and patient selection criteria would be helpful to further advance the practice of LT from HCV-viremic donors.

No Evidence of Hepatitis C Virus Infection in Individuals with Cardiovascular Disease in Mashhad

Background and Aim: Hepatitis C virus (HCV) infection is one of the leading causes of morbidity and mortality worldwide. It has been hypothesized that a number of bacteria and viruses might be involved in the pathogenesis of cardiovascular disease. The aim of this study was to define the prevalence of HCV in patients with cardiovascular disease in comparison with a control group. Methods: In this study, 281 individuals including 143 cardiovascular patients and 138 healthy controls were assessed for identification of HCV antibodies. The data collection was done between April 2016 and February 2017. The prevalence of HCV antibodies was determined by the enzyme-linked immunosorbent assay (ELISA) method. Results: There was no HCV infection in both patients with or without cardiovascular disease. There was a significant direct correlation between cardiovascular diseases and mean level of FPG (Fasting plasma glucose) (p<0.001). Also the Systolic and Diastolic blood pressures were significantly higher in the patients with cardiovascular disease (p<0.001 and p=0.005, respectively). Conclusion: The results of this study show that no evidence of HCV infection is found among a group of cardiovascular patients in the city of Mashhad. *Corresponding Author: Zahra Meshkat; Email: meshkatz@mums.ac.ir Please cite this article as: Shakeri Hoseinabad M, Aryan E, Ghayour Mobarhan M, Moohebati M, Abolbashari S, Gholoobi A, Houshyar Chechaklou A, Yaghoubi A, Meshkat M, Meshkat Z. No Evidence of Hepatitis C Virus Infection in Individuals with Cardiovascular Disease in Mashhad. Arch Med Lab Sci. 2021;7:1-5 (e13). https://doi.org/10.22037/amls.v7.33445

Epidemiologic features of a large hepatitis C cohort evaluated in a major health system in the western United States

Introduction and aimReal-world epidemiologic data to guide hepatitis C virus (HCV)-related public health initiatives are lacking. The aim of this study was to describe the prevalence and epidemiological characteristics of a large cohort of patients with an HCV diagnosis evaluated in one of the largest health systems in the United States. Materials and methodsDe-identified demographic and clinical data were extracted from the electronic health record for patients actively followed within the Providence Health & Services health care system. Rates of HCV prevalence and co-morbid illnesses among HCV-infected patients were determined. ResultsAmong 2,735,511 active patients, 23,492 (0.86%) were found to have evidence of HCV infection, the majority of which were Caucasian (78.2%) and born between the years 1945 and 1965 (68.3%). In comparison to Caucasians, higher rates of HCV infection were found among Native Americans (2.5% vs. 0.95%, p<0.001). Compared to HCV-negative patients, a greater proportion of HCV-positive patients had diabetes mellitus (18.7 vs. 8.9%, p<0.0001), chronic kidney disease (4.4 vs. 1.8%, p<0.0001), end-stage renal disease necessitating hemodialysis (2.6 vs. 0.6%, p<0.0001), and HIV co-infection (2.4 vs. 0.2, p<0.0001). Nearly two-thirds (62.1%) of HCV patients had government-sponsored insurance, and 93.0% of treated patients resided in urban settings. ConclusionThe prevalence of HCV infection in this large health care system serving the Pacific Northwest, Alaska, and California was lower than prior population-based estimates and may reflect real-world prevalence rates among patients not selected for risk-based screening. Native Americans are disproportionately affected by HCV and may warrant targeted screening.

The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era.

Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.

Increased Risk for Mother-to-Infant Transmission of Hepatitis C Virus Among Medicaid Recipients - Wisconsin, 2011-2015.

State surveillance during the last 10 years reveals a nationwide increase in hepatitis C virus (HCV) infection among young adults (1). The proportion of infants born to HCV-infected women is also increasing nationally (2). To estimate the proportion of infants born to HCV-infected women and the frequency of confirmed HCV infection in their infants, maternal name and date of birth from HCV reports in the Wisconsin Electronic Disease Surveillance System (WEDSS) were linked to Wisconsin Medicaid data for 2011-2015 births. During this period, in the Wisconsin Medicaid population, the proportion of women who had evidence of HCV infection during pregnancy increased 93%, from 1 in 368 pregnancies to 1 in 192. Among 183 infants born to women with evidence of HCV viremia during pregnancy, 34% received recommended HCV testing (3). Mother-to-infant (vertical) transmission was documented in 4% of infants. Improvements in HCV screening practices among pregnant women and infants could enhance identification of infants at risk for vertical transmission of HCV.

The oncologic burden of hepatitis C virus infection: A clinical perspective.

Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.

High Incidence of Hepatitis C Virus (HCV) Infection among an Urban Emergency Department (ED) Patients. 2003–2016.

Background CDC estimated 30,500 new HCV infections in the US in 2014 [or 0.096 per 1,000 person-years (PYs)] and HCV incidence of high-risk groups ranged from 2 to 400 per 1000 PYs. High seroprevalence of HCV antibody, evidence of HCV infection ever, is common among urban emergency department (ED) patients. Little is known regarding incidence of HCV infection in ED patients in recent years.Methods We conducted a retrospective cohort study to determine HCV incidence among ED adult patients. The study ED rolled out an ED-based HCV screening program since November 2015. A secondary data analysis was performed from a seroprevalence study on all adult patients who visited the study ED during December 10, 2015 and January 21, 2016. Patients who had at least two HCV antibody testings from two separate visits at the study hospital from 2003 to 2016 were included for this secondary data analysis. Patients who had reactive HCV antibody result at the first time point were excluded. Follow-up time (PYs) was calculated for each patient by the interval of between two HCV antibody tests. Time of HCV seroconversion was defined as the midpoint between the negative and positive HCV antibody test. Incidence rate ratio (IRR) and corresponding 95% CI was used to present the relative incidence between groups by mid-p exact test.ResultsA total of 302 ED patients were identified. The majority of them were female (60%), African American (79%), aged 35 years and older (60%). Sixty-eight percent of patients were born after 1965 (68%) and 25% born between 1945 and 1965 (birth cohort). Fifty-six percent of patients had commercial insurance payor and 36% had Medicaid or Medicare. Thirty-four (11%) patients had HIV infection and 7 (2%) were injection drug users (IDU). Overall, 6 (2%) had HCV seroconversion during 971.1 PYs, resulting in an HCV incidence of 6.2 per 1,000 PYs (95% CI: 2.5, 12.9 per 1,000 PYs). The incidence was significantly different by race [white: 30.9/1,000 PYs, African American: 2.9/1,000 PYs; RR: 12.3 (2.2, 95.8)] and IDU [IDU: 192.3/1,000 PYs, non-IDU: 4.2/1,000 PYs; RR: 46.2 (5.9, 260.3)] but not by birth cohort or HIV status.Conclusion The HCV incidence in urban ED patients was over 60 times higher than the general US population and even higher in some high-risk groups, indicating ED is a critical venue for identifying high-risk individuals for HCV prevention and detecting HCV-infected Americans for treatment.Disclosures All authors: No reported disclosures.

Efforts at the Frontlines: Implementing a Hepatitis C Testing and Linkage-to-Care Program at the Local Public Health Level.

The national Viral Hepatitis Action Plan recommends strengthening partnerships among health departments, community-based organizations, and health-care providers for hepatitis services. We implemented a hepatitis C virus (HCV) testing and linkage-to-care program through a local health department using similar strategies reported for HIV care. The Durham County Department of Public Health received federal funding to conduct HCV testing and linkage to care in Durham, North Carolina. HCV antibody testing with reflex RNA was offered through a sexually transmitted disease clinic, a county jail, community testing sites (including a residential substance abuse recovery program), and a homeless clinic. People with evidence of HCV infection were linked to care through an HCV bridge counselor who provided education, incentives, and transportation, and scheduled appointments with HCV specialists at nearby academic centers and on-site clinics. From December 2012 through February 2014, we conducted 2,004 HCV tests, of which 326 (16.3%) were HCV antibody positive and 241 (12.0%) had detectable HCV RNA. Among the 241 people with HCV infection, 178 (73.9%) were men, and 133 (55.2%) were born between 1945 and 1965. Of 241 people with chronic HCV infection, 150 (62.2%) reported ever injecting drugs, eight (2.5%) were coinfected with HIV, and 123 (51.0%) were linked to care. At the local public health level, HCV testing and linkage to care can be facilitated with additional funding and by leveraging existing programs and provider networks to deliver a coordinated system of care.

Risk of echocardiographic pulmonary hypertension in individuals with human immunodeficiency virus-hepatitis C virus coinfection.

Human immunodeficiency virus (HIV) infection is a risk factor for pulmonary hypertension (PH). Chronic hepatitis C virus (HCV) infection may have unique or synergistic effects on the pulmonary vasculature, but the prevalence and risk factors for PH in HIV-HCV coinfected persons are not known. To define the prevalence of echocardiographic PH in a cohort of patients with HIV-HCV coinfection, to compare this estimate with the reported prevalence of PH among those with HIV infection alone, and to identify potential risk factors for PH in coinfected individuals. We performed a retrospective study of HIV-HCV coinfected patients followed at our institution from 2003 to 2012 with evidence of HCV infection (positive HCV antibody, measurable HCV ribonucleic acid viral load, and/or genotype) within 6 months of transthoracic echocardiogram. PH was defined by an estimated pulmonary artery systolic pressure (PASP) of greater than or equal to 40 mm Hg or more than moderate right ventricular dysfunction. We excluded those diagnosed with cirrhosis, left ventricular ejection fraction less than 50%, or more than moderate aortic or mitral valve disease. Sixty-eight patients were included, and 43 had adequate estimates of PASP. The median (interquartile range) age was 52 (48-57) years, and 45 (67%) were men. Eight (19%) had PH, and three (7%) had more than moderate right ventricular dysfunction. After age and sex adjustment, interferon (IFN)-based HCV treatment was associated with higher PASP (β, 6.00 mm Hg; 95% confidence interval, 0.09-11.90; P = 0.047) and with the risk of PH (odds ratio, 5.65; 95% confidence interval, 1.07-29.93; P = 0.042). These associations persisted after adjustment for comorbidities but were attenuated by adjustment for duration of HCV diagnosis. The prevalence of echocardiographic PH may be higher in HIV-HCV coinfected individuals than in those with HIV monoinfection. IFN-based HCV treatment and time since HCV diagnosis were associated with the development of PH as assessed by echocardiography. Further studies are needed to examine HIV-HCV coinfection, HCV treatment, and duration of infection as possible causes of pulmonary vascular disease.

The relationship of Hepatitis C and B with diabetes of Yemeni patients

Many of earlier reports suggest a connection betwee n hepatitis C virus (HCV) infection and type2 diabe tes (T2D). However, the results are conflicting. The aim of ou r study was to investigate the seroprevalence of bo th HCV infections and hepatitis B virus (HBV) in type 2 di abetes mellitus (DM) patients in Yemen as well as t he risk of hepatitis for development diabetes mellitus.120 pat ients were enrolled for this study: 50 patients wit h T2D, 70 with chronic hepatitis(29 with HCV,36 with HBV and 5 were infections with HCV and HBV) along with 50 healthy control. Investigated hepatitis C and B patients fo r blood sugar, determined hepatitis B surface antig en (HBsAg) and anti-HCV in both groups, measured by chromatographic and enzyme-linked immunosorbent assay(ELSIA). We found that in T2D-patients 7 out of 50 (14%) detect ed with hepatitis, 5 (10 %) of 50 T2D-patients had evidence of HCV infection compared to 2 (4%) with HBV. The development diabetic mellitus among 70 hepatitis C and B patients 8 out of 70 (11.4%), 3 HBV 36 (8.3%), 4 HCV 29 (13.7%), 1 Co-infection HBV and HCV 5 (20%) compared to 1 (2%) without association in 50 contro l adults. The antibodies levels in T2D-patients wit h HCV viremia were significantly higher than those in HBV patients. HCV viremia, sex, age, family history of diabetes and tobacco use was found to be difference independent risk factors for diabetes.

Two Distinct Functional Patterns of Hepatitis C Virus (HCV)-Specific T Cell Responses in Seronegative, Aviremic Patients

In hepatitis C Virus (HCV) high-risk groups, HCV-specific T cell responses have been detected in seronegative, aviremic persons who have no evidence of HCV infection. Herein, we investigated functional profiles of HCV-specific T-cell responses in seronegative, aviremic patients of a HCV high-risk group. Seventy seven hemodialysis patients with chronic renal disease were analyzed by IFN-γ ELISpot assays, and eight of 71 (11.3%) seronegative, aviremic patients displayed HCV-specific T-cell responses. Their HCV-specific memory T cells were characterized by assessing cytokine polyfunctionality, known to provide antiviral protection. By intracellular staining of IFN-γ, TNF-α, IL-2 and MIP-1β, we identified two distinct populations in the seronegative, aviremic patients: polyfunctional responders and TNF-α-predominant responders. In further analysis, occult HCV infection was excluded as a cause of the HCV-specific T cell response via secondary nested RT-PCR of HCV RNA in peripheral blood mononuclear cell samples. HCV-specific T cells targeted multiple epitopes including non-structural proteins in a single patient, implying that their T cells might have been primed by HCV proteins synthesized within the host. We conclude that HCV-specific memory T cells of seronegative, aviremic patients arise from authentic HCV replication in the host, but not from current occult HCV infection. By functional pattern of HCV-specific T cells, there are two distinct populations in these patients: polyfunctional responders and TNF-α-predominant responders.

Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection

The clinical spectrum, etiologies, and best therapeutic approaches of type II mixed cryoglobulinemia (MC) not associated with hepatitis C virus (HCV) infection have been poorly described to date. We studied the clinical presentation and outcome of patients with type II MC with no evidence of HCV. This was a multicenter retrospective study on the clinical presentation and outcome of patients with type II MC without evidence of HCV infection. Only patients with symptomatic MC were included. Thirty-three patients were included (median followup 67.2 mo). Extensive investigations for associated diseases were performed at presentation. MC was related to an autoimmune disease in 14 patients, to a lymphoid malignancy in 4 patients, and to an infectious disease in 2 patients, while MC was classified as essential (primary) in 13. Essential MC tended to be more severe than secondary disease with, in particular, more frequent renal and peripheral nerve involvement. Most patients were treated with steroid with or without immunosuppressive agents, mainly cyclophosphamide. These treatments were unable to induce sustained remission. One patient was successfully treated with lenalidomide. Seven patients with nonmalignant MC were treated with rituximab; 2 had a sustained complete remission, 3 improved greatly but relapsed within 5 months, and 2 experienced a disease flare. An important proportion of non HCV-related type II MC remains essential. Efforts should be made to find other etiologies than HCV, because treatments with steroid and immunosuppressants are not satisfactory, especially in severe forms. In these situations anti-CD20 therapy may present the best option but should be used with caution. New agents such as lenalidomide remain to be evaluated.

Interleukin‐28B polymorphisms are associated with hepatitis C virus clearance and viral load in a HIV‐1‐infected cohort

Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP) of the interferon-λ3 coding interleukin (IL)-28B gene to study the relationship between IL28B SNPs and outcome of HCV infection. Among 206 HIV-1-infected Europeans with evidence of HCV infection, 47 (23%) individuals had cleared HCV and 159 (77%) had developed chronic infection. The exonic rs8103142 CT, the promoter rs12979860 CT and the intronic rs11881222 AG genotypes were associated with a decreased HCV clearance rate with adjusted odds ratios (aOR) of 0.3 (95% CI, 0.1-0.7), 0.4 (95% CI, 0.2-0.8) and 0.4 (95% CI, 0.2-0.8), respectively. The haplotype block TCG CTA was associated with a decreased HCV clearance rate (aOR 0.4, 95% CI, 0.2-0.8). Further, we found significant differences in HCV RNA levels among individuals chronically infected with HCV genotype 1 for rs8103142 and rs12979860 (P ≤ 0.05). Chronically infected individuals with HCV genotype 3 and with the favourable haplotype block CTA CTA had higher median HCV RNA levels than individuals with unfavourable haplotype blocks (P ≤ 0.05). Our findings suggest that IL28B may account for some differences in HCV outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence the outcome of HCV infection.

Evaluation of Interleukin-8 in Hepatitis C Virus Infection: Relation to Combined peg-interferon Ribavirin Response and Genotype 4

Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). Previous studies have shown that HCV NS5A protein induces expression of the proinflammatory interleukin-8 (IL-8) and this may affect the therapeutic outcome. The aim of the present study was to investigate the relationship among levels of IL-8 in serum of subjects with past exposure to HCV indicated by positive IgG to HCV and negative PCR, patients with chronic HCV infections and in responder to combined alfa IFN and ribavirin therapy.The study included 48 Egyptian subjects with evidence of HCV infection. They were classified according to viremia to patients with chronic hepatitis C with positive viremia and immune subjects with positive HCV IgG alone. Chronic HCV patients were followed after therapy and 16 healthy adults as control group. It was found that viral load was dependent factor for the level of IL 8 (P = 0.003) and there was significant correlation between levels of IL-8 before treatment and after treatment. The present study highlights the kinetic of serum levels of interleukin-8 in patients with chronic hepatitis C genotype 4 before and after therapy with combined alfa interferon and ribavirin. It was demonstrated that HCV infection was associated with higher levels of interleukin-8 in pretreatment and posttreatment period. Moreover, immune subjects also had higher level of interleukin-8, indicating its role in immunity to HCV infection.

HCV infection in patients with primary defects of immunoglobulin production.

We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.

Efficiency of the Ortho VITROS Assay for Detection of Hepatitis C Virus-Specific Antibodies Increased by Elimination of Supplemental Testing of Samples with Very Low Sample-to-Cutoff Ratios

The clinical significance of specimens with low sample-to-cutoff (S/Co) ratios in the Ortho VITROS chemiluminescence assay (CIA) for detection of antibodies to hepatitis C virus (HCV) was evaluated. In one study of 482 CIA-reactive samples, none of the 83 samples with S/Co ratios of < 5 was HCV RNA positive. In a subsequent study, 332 samples with S/Co ratios of between 1 and 20 were tested with the recombinant immunoblot assay (RIBA). None of the 163 samples with S/Co ratios of < 5 was RIBA positive, 83% were RIBA negative, and 28 samples (18%) were RIBA indeterminate. HCV RNA and/or clinical evidence of hepatitis was not found in the 27 indeterminate cases examined. These results show that over 99% of samples with very low S/Co ratios (< or = 5) have no evidence of HCV infection. Therefore, we suggest that the HCV antibody testing algorithm for the VITROS assay might be modified to eliminate supplemental testing of samples with very low S/Co ratios.

Seroprevalence of hepatitis C among a juvenile detention population

The seroprevalence and determinants of hepatitis C virus (HCV) infection among adolescents in juvenile detention centers in Riverside County was assessed. Among 728 participants, 16 (2.2%, 95% CI 1.1%, 3.3%) demonstrated serologic evidence of HCV infection. Adolescents with a history of injection drug use (adjusted OR = 10.8, 95% CI 2.6, 45.3, P < .001) were more likely to be HCV seropositive, however the frequency of reported injection drug use was just 4%, and only 12% of HCV infection could be attributable to injecting drugs in this population. Additional information is needed on risk factors for HCV infection in adolescent populations. The relatively low level of HCV infection observed in this juvenile detention population underscores the opportunity for implementation of targeted intervention efforts.

Hepatitis C infection and type 2 diabetes in American-Indian women.

The aim of this study was to describe the association between hepatitis C virus (HCV) infection and type 2 diabetes among a group of American-Indian women who were screened for both conditions. The study population was a convenience sample of women who were receiving prenatal care. All women were systematically screened for both HCV and diabetes. A total of 426 women were included in the sample. HCV infection was detected in 13 (3.1% [95% CI 1.7-5.0]) and type 2 diabetes in 22 (5.2%, [3.3-7.6]) women. Women diagnosed with type 2 diabetes were more obese and had higher serum alanine aminotransferase activity compared with women without diabetes. Four of 13 (30.8% [10.6-58.7]) HCV-infected women and 18 of 413 (4.4% [2.7-6.7]) women without evidence of HCV infection had type 2 diabetes. (odds ratio 9.8 [95% CI 2.4-34.0], Fisher's exact test P = 0.003). In a logistic regression model, increasing age (10-year increments), obesity (by standard deviations from the mean BMI), and positive HCV status were each independently related to the diagnosis of diabetes. Among American-Indian women, type 2 diabetes is more common in those with than in those without HCV infection. This association and its potential mechanisms may have clinical implications. Investigation into the mechanisms linking HCV infection to the expression of type 2 diabetes may also help to define processes that promote the development of type 2 diabetes in susceptible individuals.