Search

Background: Undiagnosed cases of hepatitis C virus (HCV) infection result in significant morbidity and mortality, further transmission, and increased public health costs. Testing in emergency departments (EDs) is an opportunity to expand HCV screening. The goal of this project was to increase the proportion of eligible patients screened for HCV in urban areas. Methods: An opportunistic automated HCV screening program was implemented in the EDs of 4 public hospitals in Spain and Portugal at different periods between 2018 and 2023. HCV prevalence was prospectively evaluated, and single-step or reflex testing was used for confirmation in the same sample. Results: More than 90% of the population eligible for testing were screened in the participating centers. We found HCV antibody seroprevalence rates ranging from 0.6 to 3.9%, with between 19 and 53% of viremic individuals. Conclusions: Opportunistic HCV screening in EDs is feasible, does not disrupt ED activities, is highly effective in increasing diagnosis, and contributes to WHO's HCV elimination goals. [ABSTRACT FROM AUTHOR]

Compared with other racial and ethnic groups in the United States, American Indian and Alaska Native (AI/AN) people experience the highest incidence of acute hepatitis c (HCV). Cherokee Nation Health Services (CNHS) implemented a pilot health screening program from January through May 2019 to assess whether conducting HCV and other preventive health screenings at food distribution sites is a feasible, acceptable, and effective strategy to increase health screening among underserved community members. Data were collected among 340 eligible participants. Most (76%) participants reported being very comfortable receiving health screenings at food distribution sites and that getting screened at food distribution sites is very easy (75.4%). Most (92.1%, n = 313) participants received HCV screening, with 11 (3.5%) individuals testing positive for HCV antibodies. Of the 11 HCV seropositive individuals, six were confirmed to have active HCV infection of which four initiated treatment. Most (55.7%) participants exhibited a body mass index in the obese range, 33.1% exhibited high hemoglobin A1C (> 6.0), 24.5% exhibited high (> 200) cholesterol, 44.6% exhibited high blood pressure (> = 140/90), and 54.8% did not have a current primary care provider. This project demonstrated that conducting HCV and other health screenings at food distribution sites within Cherokee Nation was an effective strategy to engage AI/AN people in preventive health screenings. Future programs are needed to scale-up preventive health screenings outside of traditional medical facilities as these types of screenings may help to decrease the HCV disparities among AI/AN people. [ABSTRACT FROM AUTHOR]

We examined gender differences among people who inject drug (PWID) in Hai Phong, Vietnam in term of blood-borne infections, risk behaviors, and access to care. Using respondent-driven-sampling surveys, we recruited 3146 PWID from 2016 to 2018. Inclusion criteria included a positive urine test for heroin and recent injection marks. There were 155 female PWID (4,9%), including 82 at RDS-2016, 32 at RDS-2017 and 38 at RDS-2018. The age mean was 36.3 ± 7.2 years. The majority of female PWID had less than high school education (90.9%) and were unemployed (51.3%). There was no difference in the proportion of HIV and HCV positive by gender. However, women had several significant differences in risk behaviors than men in multivariable logistic regression. Being a woman was independently associated with being unemployed, being a sex worker, having unstable housing, having uses drugs for less than 5 years, more use of methamphetamine, having a partner who ever injected drugs, and less access to methadone treatment. Interventions targeting female PWID are needed, possibly through community organizations and peer educators. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Estimates of the population size of people who inject drugs (PWID) are essential for efficient program planning and for monitoring key targets. Existing estimates in Greece are based on the capture-recapture method applied to drug treatment sources. We aimed to obtain estimates based on data collected from a community-based program addressing PWID in Athens, Greece. The program was implemented in 2012–2013 to increase diagnosis and treatment for HIV among PWID during an HIV outbreak. Five Responden-Driven Sampling (RDS) rounds were used to recruit participants. A unique code was used to identify participants among rounds. Capture-recapture was applied to estimate the population size in 2013 (PWID with injection in the past 12 months; active PWID with injection in the past 30 days). Log-linear models were applied. In 2013, the estimated number of active PWID in Athens was 4,117 [95% confidence interval (CI): 3,728–4,507] (vs. 1,956 [95% CI: 1,525–2,565] the existing population size estimate). Based on this estimate, the coverage of needle and syringe programs in 2013 was 103 syringes/PWID/year (vs. 216 based on the existing estimate). The population prevalence of injecting drug use in Athens (past 12 months) was 0.222% (95% CI: 0.200–0.245). The inclusion of data from community-based programs in the estimation of the PWID population size resulted in 2.1-fold higher estimates, compared to the official estimates obtained from drug treatment data, and indicates the need for re-evaluation of necessary resources for harm reduction and elimination of HIV and hepatitis C in PWID. [ABSTRACT FROM AUTHOR]

We examine syndemic profiles of intimate partner violence, mental health, drug use, incarceration, and infectious diseases (HIV, HCV, and STIs) among a sample of adult Mexican American women who were affiliated with youth street gangs during adolescence through their relationships to boys and men. Latent class analysis included multiple factors along the following dimensions: intimate partner violence, drug use, mental illness, and incarceration. Five unique syndemic profiles were found with varying associations to HIV, HCV, and STI: (1) no syndemic, (2) intimate partner violence, no syndemic, (3) drug use, mental health, and incarceration syndemic, (4) intimate partner violence, drug use (without injection drug use), and mental health syndemic, and (5) intimate partner violence, drug use with injection drug use, mental health, and incarceration syndemic. To successfully prevent HIV, HCV, and STI among gang-involved girls and women, it is necessary to address syndemic factors. [ABSTRACT FROM AUTHOR]

Elite athletes who participate in contact sports are at risk of bleeding injuries, leading to transmission of blood-borne viruses including hepatitis type B, C and D (HBV, HCV and HDV) capable of causing chronic liver disease, liver failure and liver cancer. In view of the significant advances in the viral hepatitis field over the past decade, more structured approaches should be in place to screen for and manage viral hepatitis in elite athletes. HBV status should be assessed in all elite athletes, and those infected should receive nucleos(t)ide analogues for viral suppression, while uninfected individuals should receive HBV vaccination. The all-oral direct acting antivirals for HCV are highly effective and safe, thus the remaining challenge with hepatitis C is case identification and linkage to care. HDV is only found in HBV-infected individuals, which is characterized by rapid disease progression and higher rates of cirrhosis and liver cancer in infected subjects. Pegylated interferon was the mainstay of treatment for HDV infection until bulevirtide, a viral entry inhibitor, was recently approved by the European Union (EMA) and FDA in America, while multiple novel therapies are already in clinical trials as part of the HBV cure program. Overall, awareness of chronic viral hepatitis in athletes should be improved. Prevention remains the cornerstone of the management of viral hepatitis in sport coupled with rigorous disease assessment in infected individuals, and antiviral therapy where indicated. [ABSTRACT FROM AUTHOR]

The objective of this study was to ascertain hepatitis B (HBV) and hepatitis C (HCV) infection rates in individuals toward the early initiation of treatment and prevention of developing hepatocellular carcinoma (HCC). This cross-sectional study was performed on 2084 participants from two subdistricts in Chiang Mai and Lampang provinces, northern Thailand. Screening for viral hepatitis in the general population was conducted at subdistrict health-promoting hospitals in Nong Pa Krang, in the suburb of Chiang Mai city, and Thoenburi, a subdistrict in the rural area of Lampang province, northern Thailand. Ninety-one (4.4%) participants tested positive for either HBV or HCV, with 3.3% of all participants infected with HBV and 1.1% infected with HCV. Treatment follow-up was 29.0% of HBV and 54.5% of HCV. A proactive approach to eliminate viral hepatitis can be carried out at the subdistrict level in Thailand. Success could increase participation in other subdistricts in a cascade-like manner by 2030. The identified factors of success are leadership by the local government supported by the Local Health Fund and Village Health Volunteers. [ABSTRACT FROM AUTHOR]

To compare the willingness for HCV testing, HCV-knowledge, socio economic status, and HCV related risky behavior among male and female Latino offenders. Participants (n = 201) were recruited from the corrections system in Miami and interviewed. Backward stepwise logistic regression was conducted to compare gender-associated risk. Females (n = 81) were more likely to be engaged in risky sexual and drug behavior compared to males (n = 120). Overall, around 70% of the study population were interested to be tested for HCV if offered with no gender difference (OR 1.4, 95% CI 0.4–4.9). However, females were more likely to have lower income (OR 0.6, 95% CI 0.5–0.9) and engage in more HCV related risky sexual behaviors (OR 2.9, 95% CI 1.3–6.2), despite having better HCV related knowledge in five out of six items (OR 1.5–3.2), but had less crime activity (OR 0.6, 95% CI 0.5–0.8). HCV screening among Latino offenders would offer an efficient opportunity to reduce its burden as well as increase knowledge among vulnerable and high-risk population. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: Although the epidemiology of hepatitis C virus (HCV) infection among children may be rapidly changing, few reports have characterized large nationwide cohorts of children with HCV infection. We, therefore, sought to clarify the epidemiology and natural history of HCV infection in Japanese children born over the last three decades.Methods: Sixty-five pediatric centers retrospectively and prospectively recruited consecutive, otherwise-healthy HCV-infected children born during 1986 to 2015.Results: Entry criteria were met by 348 children. Age at initial diagnosis of infection has decreased significantly in recent years. Cirrhosis and hepatocellular carcinoma were not identified. Prevalence of spontaneous clearance and of interferon treatment with/without ribavirin were 9 and 54%, respectively. Maternal transmission has increased significantly, representing over 99% of cases in the last decade. No transfusion-related cases have been seen after 1994. HCV genotype 2 has increased to become the most prevalent in Japanese children. Histopathology examination of liver specimens showed no or mild fibrosis in most children with chronic hepatitis C; none showed cirrhosis.Conclusions: This largest nationwide cohort study of Asian children with HCV infection spanned the last three decades. None of these Japanese children developed cirrhosis or hepatocellular carcinoma. Maternal transmission increased to account for 99% of cases during the last decade. Genotype 2 now is most prevalent in these children. Histopathologically, most children with chronic hepatitis C showed mild fibrosis or none. [ABSTRACT FROM AUTHOR]

Background: The prevalence of HCV infection is higher among prisoners than in the general population. The introduction of HCV direct-acting antivirals (DAA) holds the potential to improve clinical outcomes also in inmates. However, treatment of hepatitis C in inmates has to face several clinical and logistical issues which are peculiar of prison environment. Recommendations on the management of HCV infection specific for the penitentiary setting in the DAA era remain scant. The Italian Society for Penitentiary Medicine and Healthcare has, therefore, issued these recommendations, to provide clinicians with a guide for the comprehensive management of HCV infection in the restriction setting, taking into account its peculiar characteristics. Results: Dedicated diagnostic and treatment procedures should be established in each prison. In particular, the use of DAAs appears crucial to provide patients with an effective therapeutic option, able to overcome the limitations of IFN-based regimens with a short period of treatment. DAA treatment should be initiated as soon as possible in all eligible subjects with the aim to cure the patient, as well as to limit the transmission of HCV infection both inside the penitentiary system and to the free community, once the inmates ends his/her release. Importantly, efforts should be made to open a discussion with regulatory bodies, to define specific regulations aimed to guarantee wide access to effective therapies of all eligible patients, to optimize the management of and the adherence to the HCV treatment, and to ensure the therapeutic continuity after discharge from prison. [ABSTRACT FROM AUTHOR]

Indiana recently passed legislation allowing local governments to establish syringe exchanges. While the effectiveness of syringe exchange programming is established, there is a dearth of studies about associated policy adoption and implementation. This study documents the experiences of 24 Indiana counties engaged in the process of establishing syringe exchange programming under new state law. A mixed method, qualitative, exploratory case study was conducted from May 2015 to April 2016. We observed rapid and widespread policy adoption interest, and yet counties reported significant policy ambiguity, epidemiologic and resource capacity issues. The emergence of health commons involving information and tangible resource sharing networks allowed institutional rearrangement in the midst of resource scarcity; however, such rearrangement appeared to be a central threat to policy adoption and implementation given state structural barriers. The emerging commons could be a critical policy success factor, as it would achieve efficiencies not possible in the current resource environment, and can help achieve institutional rearrangement for the improvement of population health. Several recommendations for improvement are offered. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a global problem due to the difficulties in developing a protective vaccine. In this work, we demonstrated that the ethyl acetate extract of the endophytic fungus Aspergillus versicolor exhibited significant activity against HCV NS3/4A protease with IC value of 30 μg/mL. The fungus was isolated from the Red Sea black sponge Spongia officinalis and identified by its morphology and 18S rDNA. Large-scale fermentation of the fungus followed by chromatographic purification with silica gel, Sephadex LH-20 and semipreparative HPLC of the active extract led to isolation of some known metabolites related to cyclodipeptides and the so-called diketopiperazines (DKPs). The DKP, cyclo(L-Tyr-L-Pro), displayed strong effect as HCV protease inhibitor with IC value of 8.2 μg/mL. A computational docking study of cyclo(L-Tyr-L-Pro) against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compound on the tested enzyme. [ABSTRACT FROM AUTHOR]

Background: Targeted intervention in patients with hepatitis C virus (HCV) closest to end-stage liver disease (ESLD) progression may offer an approach to treatment prioritisation whilst delivering benefits for patients and the healthcare system. In contrast to previous HCV economic analyses, this study aimed to estimate the health economic value of sustained virologic response (SVR) stratified by the patient's propensity to progress to ESLD. Methods: An HCV natural history model was adapted to estimate the value of avoiding ESLD complications following SVR, assessed as cost offsets and quality-adjusted life year (QALY) gains, as a function of time to ESLD at treatment initiation. These outcomes were used to estimate the financial value of achieving SVR, defined as the maximum investment that could be allocated without exceeding a willingness-to-pay threshold of £20,000/QALY. Results: Regardless of time to ESLD onset, achieving SVR was beneficial, resulting in cost offsets and QALY gains, due to avoidance of ESLD complications. The value of achieving SVR was greatest in patients closest to ESLD onset, resulting in increased cost offsets and QALY gains (up to £50,901 and 9.56 QALYs). In patients closest to ESLD onset, the financial value of achieving SVR was £242,051, compared with £127,116 in patients furthest from onset. Conclusions: Standard cost-effectiveness evaluations may underestimate the value of treatment in HCV patients closest to ESLD development. Targeted intervention would promote efficient allocation of limited healthcare resources and reconcile concerns surrounding the affordability of new direct-acting antivirals, by minimising the number-needed-to-treat to maximise health benefit, whilst minimising healthcare expenditure. [ABSTRACT FROM AUTHOR]

There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens. [ABSTRACT FROM AUTHOR]

Background and purpose: Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection. Methods: In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV. The primary outcome measure was sustained virologic response at post-treatment Week 12 (SVR12). Results: Overall, 874 patients were treated: Lambda/RBV, n = 353; Lambda/RBV + DCV, n = 349; alfa/RBV, n = 172. Patients were 65 % white and 33 % Asian, 57 % male, with a mean age of 47 years; 52 % were infected with genotype 2 (6 % cirrhotic) and 48 % with genotype 3 (9 % cirrhotic). In the Lambda/RBV + DCV group, 83 % (95 % confidence interval [CI] 78.5, 86.5) achieved SVR12 (90 % genotype 2, 75 % genotype 3) whereas SVR12 was achieved by 68 % (95 % CI 63.1, 72.9) with Lambda/RBV (72 % genotype 2, 64 % genotype 3) and 73 % (95 % CI 66.6, 79.9) with peginterferon alfa/RBV (74 % genotype 2, 73 % genotype 3). Lambda/RBV + DCV was associated with lower incidences of flu-like symptoms, hematological abnormalities, and discontinuations due to adverse events compared with alfa/RBV. Conclusion: The 12-week regimen of Lambda/RBV + DCV was superior to peginterferon alfa/RBV in the combined population of treatment-naive patients with genotype 2 or 3 infection, with an improved tolerability and safety profile compared with alfa/RBV. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies have revealed several single-nucleotide polymorphisms around interleukin 28B (IL28B) that are strongly associated with hepatitis C virus (HCV) clearance. However, their predictive value is not perfect, which suggests that other genetic factors may also be involved in HCV clearance. We previously reported a wide variation in the length of a thymine-adenine (TA) dinucleotide repeat in the promoter region of IL28B and that the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner.Methods: We determined the length of the TA repeats of 1,060 Japanese and 201 African-American samples to investigate the relation to spontaneous HCV clearance.Results: The distribution of the TA repeats greatly differed between the two ethnicities. The variation ranged from 10 to 18 repeats, and the most frequent allele, 12, accounted for over 80% for Japanese. The African-American data showed a gently sloping distribution, and the allele with six repeats was detected only in the African-American sample. The TA repeats 11 or greater were correlated with spontaneous clearance. Multiple logistic regression analysis extracted the genotype of the TA repeats as an independent factor in both the Japanese [p = 0.0004, odds ratio (OR) = 13.02 95% confidence interval (CI) = 2.59-237.0] and African-American (p = 0.027, OR = 3.70 95% CI = 1.16-11.8) populations.Conclusions: A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. Although its efficacy may be limited in Japanese population because of its allele distribution, this novel genetic factor will be useful for predicting HCV clearance especially for the African Americans. [ABSTRACT FROM AUTHOR]

Development an effective vaccine may offer an alternative preventive and therapeutic strategy against HCV infection. DNA vaccination has been shown to induce robust humoral and cellular immunity and overcome many problems associated with conventional vaccines. In this study, mice were primed with either conventional pVRC-based or suicidal pSC-based DNA vaccines carrying DEC-205-targeted NS3 antigen (DEC-NS3) and boosted with type 5 adenoviral vectors encoding the partial NS3 and core antigens (C44P). The prime boost regimen induced a marked increase in antigen-specific humoral and T-cell responses in comparison with either rAd5-based vaccines or DEC-205-targeted DNA immunization in isolation. The protective effect against heterogeneous challenge was correlated with high levels of anti-NS3 IgG and T-cell-mediated immunity against NS3 peptides. Moreover, priming with a suicidal DNA vaccine (pSC-DEC-NS3), which elicited increased TNF-α-producing CD4+ and CD8+ T-cells against NS3-2 peptides (aa 1245-1461), after boosting, showed increased heterogeneous protective potential compared with priming with a conventional DNA vaccine (pVRC-DEC-NS3). In conclusion, a suicidal DNA vector (pSC-DEC-NS3) expressing DEC-205-targeted NS3 combined with boosting using an rAd5-based HCV vaccine (rAd5-C44P) is a good candidate for a safe and effective vaccine against HCV infection. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV)-induced, end-stage liver disease is a major indication for liver transplantation, but systematic graft reinfection accelerates liver disease recurrence. Transplantation recipients may be ineligible for direct-acting antivirals, owing to toxicity, resistance or advanced liver disease. Adoptive immunotherapy with liver graft-derived, ex vivo-activated lymphocytes was previously shown to prevent HCV-induced graft reinfections. Alternatively, the applicability and therapeutic efficacy of adoptive immunotherapy may be enhanced by 'ready for use' suicide gene-modified lymphocytes from healthy blood donors; moreover, conditional, prodrug-induced cell suicide may prevent potential side effects. Here, we demonstrate that allogeneic suicide gene-modified lymphocytes (SGMLs) could potently, dose- and time-dependently, inhibit viral replication. The effect occurs at effector:target cell ratios that exhibits no concomitant cytotoxicity toward virus-infected target cells. The effect, mediated mostly by CD56+ lymphocytes, is interleukin-2-dependent, IFN-γ-mediated and, importantly, resistant to calcineurin inhibitors. Thus, post-transplant immunosuppression may not interfere with this adoptive cell immunotherapy approach. Furthermore, these cells are indeed amenable to conditional cell suicide; in particular, the inducible caspase 9 suicide gene is superior to the herpes simplex virus thymidine kinase suicide gene. Our data provide in vitro proof-of-concept that allogeneic, third-party, SGMLs may prevent HCV-induced liver graft reinfection. [ABSTRACT FROM AUTHOR]

In this paper, we present a rigorous mathematical analysis of a deterministic model for the transmission dynamics of hepatitis C. The model is suitable for populations where two frequent modes of transmission of hepatitis C virus, namely unsafe blood transfusions and intravenous drug use, are dominant. The susceptible population is divided into two distinct compartments, the intravenous drug users and individuals undergoing unsafe blood transfusions. Individuals belonging to each compartment may develop acute and then possibly chronic infections. Chronically infected individuals may be quarantined. The analysis indicates that the eradication and persistence of the disease is completely determined by the magnitude of basic reproduction number R. It is shown that for the basic reproduction number R < 1, the disease-free equilibrium is locally and globally asymptotically stable. For R > 1, an endemic equilibrium exists and the disease is uniformly persistent. In addition, we present the uncertainty and sensitivity analyses to investigate the influence of different important model parameters on the disease prevalence. When the infected population persists, we have designed a time-dependent optimal quarantine strategy to minimize it. The Pontryagin's Maximum Principle is used to characterize the optimal control in terms of an optimality system which is solved numerically. Numerical results for the optimal control are compared against the constant controls and their efficiency is discussed. [ABSTRACT FROM AUTHOR]

First-generation adenovirus vectors (FG AdVs) expressing short-hairpin RNA (shRNA) effectively downregulate the expressions of target genes. However, this vector, in fact, expresses not only the transgene product, but also virus-associated RNAs (VA RNAs) that disturb cellular RNAi machinery. We have established a production method for VA-deleted AdVs lacking expression of VA RNAs. Here, we showed that the highest shRNA activity was obtained when the shRNA was inserted not at the popularly used E1 site, but at the E4 site. We then compared the activities of shRNAs against hepatitis C virus (HCV) expressed from VA-deleted AdVs or conventional AdVs. The VA-deleted AdVs inhibited HCV production much more efficiently. Therefore, VA-deleted AdVs were more effective than the currently used AdVs for shRNA downregulation, probably because of the lack of competition between VA RNAs and the shRNAs. These VA-deleted AdVs might enable more effective gene therapies for chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Simeprevir (Sovriad TM) is a new direct-acting antiviral drug and a second-generation small-molecule NS3/4A serine protease inhibitor developed by Janssen and Medivir for the oral treatment of adults with genotype 1 and/or genotype 4 chronic hepatitis C virus (HCV) infection (chronic hepatitis C). Simeprevir antiviral activity is achieved by its non-covalent binding to HCV protease, with a fast association and slow dissociation rate. The capsule formulation is approved in Japan and Canada for use in combination with pegylated interferon (peginterferon) and ribavirin for genotype 1 chronic hepatitis C, and has been filed for approval in the US in this indication. In addition, the capsule formulation has been filed for approval in the EU for use in combination with peginterferon and ribavirin for genotype 1 and 4 chronic hepatitis C. Phase III trials of the capsule formulation of simeprevir are underway in several other regions, including China. In the pivotal phase III trials, simeprevir was administered once daily for 12 weeks in combination with peginterferon and ribavirin for 24 or 48 weeks. This article summarizes the milestones in the development of simeprevir leading to this first approval for chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Needle-syringe programs (NSP) have been effective in reducing HIV and hepatitis C (HCV) infection among people who inject drugs (PWID). Achieving sustainable reductions in these blood-borne infections requires addressing structural factors so PWID can legally access NSP services. Systematic literature searches collected information on NSP coverage and changes in HIV or HCV infection prevalence or incidence at the population level. Included studies had to document biomarkers (HIV or HCV) coupled with structural-level NSP, defined by a minimum 50 % coverage of PWID and distribution of 10 or more needles/syringe per PWID per year. Fifteen studies reported structural-level NSP and changes in HIV or HCV infection prevalence/incidence. Nine reported decreases in HIV prevalence, six in HCV infection prevalence, and three reported decreases in HIV incidence. The results support NSP as a structural-level intervention to reduce population-level infection and implementation of NSP for prevention and treatment of HIV and HCV infection. [ABSTRACT FROM AUTHOR]

Background: Post-transplant hepatitis C is a major challenge after liver transplantation (LT). Antiviral therapy is associated with lower efficacy in the post-transplant setting. Aims: The purpose of this study was to determine the safety and effect of intravenous interferon (IFN) during the anhepatic phase of LT on hepatitis C viral load. Methods: Fifteen consecutive subjects undergoing liver transplant for hepatitis C cirrhosis were enrolled in the study, ten of which received study drug and five subjects served as controls. Cases received weight-based ribavirin and subcutaneous IFN at time of incision followed by intravenous IFN at the start of the anhepatic phase. Adverse events and viral levels were recorded. Repeated measures ANOVA was employed to test for differences over time, between the groups, and time by group interaction. Results: All subjects had genotype 1 virus. Hepatitis C viral load was lower at week 4 in cases compared to controls (769,004 ± 924,082 IU/ml and 2,329,896 ± 3,731,749 IU/ml, respectively), but did not reach statistical significance ( p = 0.50). Three subjects developed adverse events related to IFN including pulmonary edema, rejection, and neutropenia. Conclusions: Intravenous IFN administered during the anhepatic phase of liver transplant did not prevent graft reinfection and was associated with manageable adverse events. This regimen could be further studied if direct acting antiviral agents alone are insufficient for treating post-transplant hepatitis C. [ABSTRACT FROM AUTHOR]

The current available treatment for hepatitis C virus (HCV)-the causative of liver cirrhosis and development of liver cancer-is a dual therapy using modified interferon and ribavirin. While this regimen increases the sustained viral response rate up to 40-80 % in different genotypes, unfortunately, it is poorly tolerated by patients. PSI-7977, a prodrug for PSI-7409, is a Non-Structural 5b (NS5b) polymerase nucleoside inhibitor that is currently in phase III clinical trials. The activated PSI-7977 is a direct acting antiviral (DAA) drug that acts on NS5b polymerase of HCV through a coordination bond with the two Mg present at the GDD active site motif. The present work utilizes a molecular modeling approach for studying the interaction between the activated PSI-7977 and the 12 amino acids constituting a 5 Å region surrounding the GDD active triad motif for HCV genotypes 1a, 2b, 3b and 4a. The analysis of the interaction parameters suggests that PSI-7977 is probably a better DAA drug for HCV genotypes 1a and 3b rather than genotypes 2b and 4a. [ABSTRACT FROM AUTHOR]

Background and Objective: In developed countries, injection drug users have the highest prevalence and incidence of hepatitis C virus (HCV) infection. Clinicians and policy makers have several options for reducing morbidity and mortality related to HCV infection, including preventing new infections, screening high-risk populations, and optimizing uptake and delivery of antiviral therapy. Cost-effectiveness analyses provide an estimate of the value for money associated with adopting healthcare interventions. Our objective was to determine the cost effectiveness of hepatitis C interventions (prevention, screening, treatment) targeting substance users and other groups with a high proportion of substance users. Methods: We conducted a systematic search of MEDLINE, EMBASE, CINAHL, HealthSTAR and EconLit, and the grey literature. Studies were critically appraised using the Drummond and Jefferson, Neumann et al. and Philips et al. checklists. We developed and applied a quality appraisal instrument specific to cost-effectiveness analyses of HCV interventions. In addition, we summarized cost-effectiveness estimates using a single currency and year ($US, year 2009 values). Results: Twenty-one economic evaluations were included, which addressed prevention (three), screening (ten) and treatment (eight). The quality of the analyses varied greatly. A significant proportion did not incorporate important aspects of HCV natural history, disease costs and antiviral therapy. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (less costly and more effective) to $US603 352 per QALY. However, many ICERs were less than $US100 000 per QALY. Screening and treatment interventions involving pegylated interferon and ribavirin were generally cost effective at the $US100000 per QALY threshold, with the exception of some subgroups, such as immune compromised patients with genotype 1 infections. Conclusions: No clear consensus emerged from the studies demonstrating that prevention, screening or treatment provides better value for money as each approach can be economically attractive in certain subgroups. More high-quality economic evaluations of preventing, identifying and treating HCV infection in substance users are needed. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Latinos in the US are disproportionately affected by chronic liver disease, which is the sixth most common cause of death among this group. In Mexico, cirrhosis and other liver diseases are the fourth leading cause of general mortality. The objective of this study was to contrast the liver disease risk factors, knowledge, and prevention practices reported among separate samples of Mexicans living in Los Angeles, CA and in Cuernavaca, Mexico. We assessed the prevalence of specific risk factors (body mass index, waist circumference, and alcohol consumption), the level of knowledge about liver disease in general, hepatitis B (HBV), and hepatitis C (HCV), as well as prevention activities such as screening and vaccination. Data were collected from in-person interviews and anthropometric measures obtained from Mexican adults aged 18-70 years. Chi-square and t tests were used to compare the results between groups. Numerous similarities were observed in the bi-national samples, including high prevalence of obesity, abdominal obesity, and high levels of alcohol consumption. Most participants in both countries recognized that excessive alcohol consumption is a risk factor for liver disease, but only 60% correctly identified hepatitis C, being overweight or obese, or having diabetes as risk factors. Few participants reported having been screened for HBV or HCV, vaccinated for HBV, or having the intention of getting screened for HBV or HCV. US participants reported significantly higher levels of prevention activities and screening intentions than those in Mexico. Identifying the specific risk factors, levels of knowledge and prevention activities that affect specific racial/ethnic populations is important in order to effectively target efforts to prevent liver disease. [ABSTRACT FROM AUTHOR]

Purpose The Prevalhep study seeks to determine the prevalence of factors associated with the hepatitis C (HCV) and B (HBV) virus in Spanish prisoners. Methods This was an observational, cross-sectional study which randomly selected 18 Spanish prisons to participate, with 21 prisoners per centre. Results There were 378 prisoners selected, 370 of whom had serological HCV and 342 had HBV data. The HCV population was predominantly male (91.6%), middle age (66.7% ≤ 40 years of age), of Spanish origin (60.5%), with a history of injection drug use (IDU; 23.2%), in prison <5 years (71.2%) and having entered prison after 2006 (51.9%). The prevalence of HCV was 22.7% ( n = 84; 95% CI, 18.3-27.1) and HBV was 2.6% ( n = 9; 95% CI, 0.2-4.9%). Of the patients with HCV, 40.5% were co-infected with HIV, 0.3% co-infected with HBV, and 1.5% with triple virus co-infection (HBV + HCV + HIV). The three markers of HB had been measured in 99 inmates: 32.1% had post-vaccination immunity (antiHBS+) and 30.4% contact status with HBV (HBcAb + and/or HBsAg+), while 37.5% were susceptible to HB. Conclusions The prevalence of HBV and HCV has decreased in the Spanish prison population, probably as a result of decrease in IDU transmission, and an increase in immigrant prisoner population that does not have this risk behaviour. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and tends to be more aggressive. Data on post-transplant HCV genotype 4 treatment is scarce. The aim of this study is to assess the safety and efficacy of pegylated interferon alpha-2a (PEG-IFN) in combination with ribavirin in the treatment of recurrent HCV genotype 4 after LT.Methods: Twenty-five patients infected with HCV genotype 4 were treated with PEG-IFN alpha-2a at a dose of 180 μg/week in addition to 800 mg/day of ribavirin (the dose was adjusted within the tolerated range of 400-1,200 mg). Pretreatment liver biopsies were obtained from all patients. Biochemical and virological markers were assessed before, during, and after treatment.Results: Twenty-two patients (88%) achieved an early virological response (EVR) (12 patients tested negative for HCV-RNA). Fifteen (60%) and 14 patients (56%) achieved an end of treatment virological response (ETVR) and a sustained virological response (SVR), respectively. Five patients had advanced pretreatment liver fibrosis. Pretreatment ALT was elevated in 24 patients (96%). The most common adverse effects were flu-like symptoms and cytopenia. Eighteen patients (72%) required erythropoietin alpha and/or granulocyte-colony stimulating factor as a supportive measure. One patient developed severe rejection complicated by sepsis, renal failure, and death. Other adverse effects included depression, mild rejection, impotence, itching, and vitiligo.Conclusions: Post-transplant treatment with pegylated interferon alpha-2a and ribavirin achieved SVR in 56% of liver transplant recipients with chronic HCV genotype 4 infection. The combination was relatively safe and exhibited a low rate of treatment withdrawal. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C (HCV) knowledge is limited in injection drug users (IDU). Vulnerable populations including IDUs are disproportionally affected by HCV. Effective HCV education can potentially reduce disparity in HCV prevalence and its outcome in this population.Aim: This study aimed to assess the impact of formal HCV education and factors associated with improved HCV knowledge in the vulnerable population.Methods: Over 18 months, 201 HCV-infected patients underwent a 2-h standardized education and completed demographic and pre- and post-education questionnaires.Results: Patient characteristics were: 69% male, mean age 49±10, 49% White (26% AA, 10% Latino), 75% unemployed, 83% high school education and above, 64% were IDU, and 7% were HIV co-infected. On multivariate analysis, baseline knowledge scores were higher in patients with at least a high school education (coef 7.1, p=0.045). Baseline knowledge scores were lower in African Americans (coef -12.3, p=0.004) and older patients (coef -0.7, p=0.03). Following HCV education, the overall test scores improved significantly by 14% (p=0.0001) specifically in the areas of HCV transmission (p=0.003), general knowledge (p=0.02), and health care maintenance (p=0.004). There was a high compliance with liver specialty clinic attendance following education.Conclusions: Formal HCV education is effective in improving HCV knowledge. Although White race, younger age, and higher education were predictors of having more HCV knowledge prior to education, all patients independent of racial background had a significant improvement in their knowledge after education. Therefore, promoting effective HCV education among vulnerable populations may be an important factor in reducing the disparities in HCV disease. [ABSTRACT FROM AUTHOR]

Increasing sterile syringe access for injection drug users (IDUs) is one way to prevent HIV and hepatitis C virus (HCV) transmission in this population. In 2005, California Senate Bill 1159 allowed counties to adopt the Disease Prevention Demonstration Project (DPDP). Where enacted, the DPDP allows pharmacies that register with the county to sell up to ten syringes to adults without a prescription. In the current study, we describe pharmacy participation in nonprescription syringe sales (NPSS) in two counties in California and examine factors associated with NPSS. Telephone and in-person interviews were conducted in Los Angeles (LA) and San Francisco (SF) with 238 pharmacies in 2007 ( n = 67 in SF; n = 171 in LA). Quantitative survey items captured pharmacy registration with the county, pharmacy policies/practices, episodes and conditions of NPSS and refusals to sell, potential negative consequences of NPSS, and staff attitudes regarding HIV and HCV prevention for IDUs. Overall, 42% of pharmacies reported NPSS (28% in LA and 81% in SF), although only 34% had registered with the county (17% in LA and 76% in SF). Many pharmacies required proof of a medical condition (80% in LA and 30% in SF) and refused NPSS if the customer was a suspected IDU (74% in LA, 33% in SF). Few negative consequences of NPSS were reported. In multivariate logistic regression analysis, we found that the odds of NPSS were significantly higher among pharmacists who thought syringe access was important for preventing HIV among IDUs [adjusted odds ratio (AOR) = 2.95; 95% confidence interval (CI) = 1.10–7.92], were chain pharmacies (AOR = 12.5; 95% CI = 4.55–33.33), and were located in SF (AOR = 4.88; 95% CI = 1.94–12.28). These results suggest that NPSS were influenced by pharmacists’ perception. NPSS might be increased through greater educational efforts directed at pharmacists, particularly those in non-chain pharmacies. [ABSTRACT FROM AUTHOR]

Sexually transmitted diseases (STD) are a public health issue in prison. As inmates are eventually released, it is also a community concern. There are very few data on the entire spectrum of STDs, particularly condyloma among prisoners. To determine the prevalence of all STDs: infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), Chlamydia trachomatis, Neisseria gonorrhoea, syphilis, and condyloma among entering inmates. A cross-sectional study was conducted in France from November 2000 to June 2003. Male adults entering a prison remand center in Caen had a medical consultation and physical examination including external genital organs and perianal area for condyloma and herpes infection, a urethral swab for Chlamydia trachomatis and Neisseria gonorrhoea detection, and a blood sample for HBV, HCV, HIV, and syphilis serology. Five hundred and ninety-seven inmates agreed to participate in the study. Sixteen percent had at least one STD: 4.0% had condyloma, 4.0% chlamydia infection, and 4.9% were positive for HCV antibodies. Two had early syphilis and 1 had acute HBV, but no HIV infection, neither genital herpes nor gonorrhea. The analysis of the STD risk behaviors did not show any difference between the infected and uninfected participants, except that HCV-positive participants were more likely to be intravenous drug users. Results suggest that a systematic screening of all STDs should be at least proposed to every entering inmate since no demographic or sexual characteristics are consistently associated with STDs. [ABSTRACT FROM AUTHOR]

Objective:Hepatitis C virus (HCV) infection exerts diverse effects on atherogenesis. We investigated whether malnutrition inflammation score (MIS) is associated with the presence of coronary artery disease (CAD) in anti-HCV-positive hemodialysis (HD) patients.Subjects/Methods:Twenty-two anti-HCV-positive HD patients with CAD and 61 anti-HCV-positive HD patients without CAD (as controls) were included. Data were obtained from hospital records, patients were evaluated for risk factors for CAD. The same physician performed MIS evaluation.Results:MIS of anti-HCV-positive HD patients with CAD were significantly higher than patients without CAD (8.8±4.0 vs 6.5±2.6, P=0.02). In patients with CAD, basal (P=0.002) and peak C-reactive protein (P=0.03) and serum ferritin (P=0.01) concentrations were higher, serum albumin concentrations (P=0.003) were lower than those patients without CAD. MIS was positively correlated with age (r=+0.359, P=0.001) and viral load (r=+0.629, P<0.0001). In univariate logistic regression analysis, advanced age (odds ratios (OR)=1.093, confidence interval (CI): 1.039–1.150, P=0.001), hypertension (OR=3.143, CI: 1.084–9.116, P=0.035), diabetes mellitus (OR=5.344, CI: 1.343–21.269, P=0.017), low triglyceride (OR=0.992, CI: 0.984–0.999, P=0.026) and high MIS (OR=1.259, CI: 1.066–1.488, P=0.007) were associated with the presence of CAD. Multivariate logistic regression analysis identified age (OR=1.090, CI: 1.007–1.179, P=0.033) and MIS as the factors associated with the presence of CAD (OR=1.232, CI: 1.004–1.511, P=0.04).Conclusions:MIS may be associated with CAD in anti-HCV-positive HD patients.European Journal of Clinical Nutrition (2008) 62, 1449–1454; doi:10.1038/sj.ejcn.1602867; published online 1 August 2007 [ABSTRACT FROM AUTHOR]

Although individuals with serious mental illness have been shown to be at increased risk for hepatitis C viral (HCV) infection, there is growing concern regarding limited dissemination of recommended HCV related services to this population. This paper presents rates of receipt of HCV prevention services among a cohort of seriously mentally ill adults and reports rates of recommended follow-up care among the subset who tested HCV positive in a pilot study. Previous HCV screening was low and indicated medical follow-up among those who tested positive was also limited. Results stress the need for increased screening and counseling and delivery of preventive and follow-up medical services. [ABSTRACT FROM AUTHOR]

Although drug users are at elevated risk for hepatitis C virus (HCV) infection, many are uniformed or misinformed about the virus. Drug treatment programs are uniquely situated to provide comprehensive risk-modifying educational programs for decreasing HCV transmission, a strategy advocated in the most recent National Institutes of Health Consensus Development Conference Statement on the Management of Hepatitis C. Given the large proportion of patients that inject drugs in methadone maintenance treatment programs and the high prevalence of HCV among drug injectors, we compared a nationwide sample (N = 246) of methadone maintenance treatment programs and drug-free programs regarding the content and comprehensiveness of HCV education. All of these programs provide HCV education to at least some of their patients. Results indicated that, compared to drug-free programs, methadone maintenance treatment programs cover a significantly greater number of HCV-related topics, and that a significantly greater proportion of the methadone programs cover specific topics (e.g., how to avoid transmitting HCV, the importance of testing for HCV, treatment options if HCV positive). Of special concern is that fewer than three quarters of the drug-free programs address what to do if co-infected with human immunodeficiency virus (HIV) and HCV and how to maintain health if HCV positive, and only about half of the drug-free and methadone maintenance treatment programs educate HCV-positive patients about the importance of obtaining vaccinations for hepatitis A and B. Drug treatment programs need to educate patients about the proactive steps these individuals can take to deal with HCV, provide critically needed HCV services, and encourage patients to make full use of these services. [ABSTRACT FROM AUTHOR]

Current approaches to prevention of blood-borne infections in injection drug users include referral to drug abuse treatment, access to sterile syringes, bleach disinfection of injection equipment, and education about not sharing equipment. However, rates of some blood-borne infections (e.g., hepatitis C virus) remain elevated among injection drug users, especially early after initiation into injection drug use. With lower infection rates in noninjectors and transition into injection drug use occurring most commonly among these noninjectors, prevention of transition into injection drug use as an additional step to reduce risk for acquisition and transmission of blood-borne infections merits closer attention. [ABSTRACT FROM AUTHOR]

Interferon-alpha is the most widely used antiviral drug in chronic hepatitis B and C. Tolerability is usually good and serious adverse effects are rare. Most of the adverse effects are mild or transient and do not necessitate drug withdrawal. More than 90% of patients who are given interferon-alpha achieve 6 months to 1 year of treatment without serious adverse effects. The serious adverse effects usually occur in predisposed patients with pre-existing organ dysfunction. Nevertheless, careful selection of patients for therapy and observation during therapy are recommended. Nucleoside analogues are promising drugs in the treatment of chronic hepatitis B through inhibition of viral DNA polymerase. Lamivudine has been licensed for use in this indication. Its tolerability is excellent even when used for periods of 1 year or more. The main concern is the relatively high incidence of viral resistance resulting in breakthrough during or relapse after therapy. In the treatment of chronic hepatitis C, ribavirin, in combination with interferon-alpha is currently the reference therapy. The main adverse effect is haemolytic anaemia, which necessitates careful monitoring and adjustment of dosage in many cases. Recently, large trials showed the better efficacy of pegylated interferons as compared with standard interferon. The combination of pegylated interferon with ribavirin is under evaluation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail?" by A. G. Singal in the 2013 issue.

Attempts to elucidate the mechanism underpinning the genetic association between IFNL3, previously called IL28B, and clearance of hepatitis C virus have, by and large, been unsuccessful. A study in this issue suggests that a new gene, IFNL4, may be responsible. [ABSTRACT FROM AUTHOR]

The article focuses on the high prevalence of hepatitis C in Egypt. It cites a study which reveals that one out of seven Egyptians were positive of hepatitis C virus (HCV) infection and one in ten individuals is chronically infected which indicates a large viral reservoir that drives the spread of the disease. It also mentions that the increasing prevalence of HCV complicates the task of the Egyptian government of preventing and treating it.

In this article, the author focuses on the need to prioritize interventions to control the epidemic of hepatitis C virus in the U.S. The author mentions some of the strategies to deal with epidemics including community-based health services and and hepatitis C testing in population with high prevalence. The author notes that surveillance systems must be developed and implemented for the benefit of those who are overlooked by existing systems.

The article stresses the need for immediate transition towards safe injection practices. In an effort to curb blood-borne infections, such as HBV, HCV, and HIV, from unsafe injections, a multi-disciplinary approach addressing policies, standards, behavior and technology is suggested. These include reducing frequency by shifting towards oral medications, and increased safety and waste management. A trial is also presented showing the effectiveness of group discussion approach in reducing the frequency of injections.

The article reports on the study by Georg Lauer of Massachusetts General Hospital and colleagues, which found that CD4+ T cells can prevent the development of chronic hepatitis C infection.

A correction to the article "Management and Treatment of Patients With Cirrhosis and Portal Hypertension: Recommendations From the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program," published in the May 19, 2009 issue, is presented.