Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study.

BACKGROUND: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients. METHODS: A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre. Treatment adherence was evaluated by a validated questionnaire named 'Assessment of Adherence to Antiviral Therapy Questionnaire' (CEAT-HBV) within three yearly periods (2010/2011, 2013/2014 and 2014/2015). RESULTS: CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by non-adherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. 2 years after the first assessment, the CEAT-HBV indicated that 71% (101/143) of subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Long-term evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (P<0.001). CONCLUSIONS: The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV-DNA-negative group.

SUSTAINED VIROLOGIC RESPONSE RATE IN CHRONIC HEPATITIS C PATIENTS THROUGH DIRECT-ACTING ANTIVIRALS THERAPY.

BACKGROUND: In recent years the management of hepatitis C virus infection and the possibility of its eradication have been researched due to the importance that they represent in the health of the world population. Obtaining data that help to cope with this pathology improves the quality of life of those affected by it. The present study evaluated the effectiveness of direct-acting antiviral therapies provided by the Brazilian Ministry of Health in accordance to the Clinical Protocol and Therapeutic Guidelines of 2015. OBJECTIVE: To evaluate the epidemiological profile of patients with chronic hepatitis C and the rate of sustained virologic response using direct-acting antivirals of all individuals that attended the referral service for the treatment of chronic hepatitis C at the Hospital of the Federal University of Rio Grande. METHODS: This was an observational, retrospective/prospective study with all patients with chronic hepatitis C who had their treatments available from December 2015 to August 2017 according to the criteria of the Clinical Protocol and Therapeutic Guidelines of 2015. In the first phase, the clinical and demographic variables of all individuals enrolled in a treatment for hepatitis C were selected and collected from the Reference Service database. In the second phase, treatment data were collected. The outcome variable, sustained virologic response, was defined as an undetectable viral load on the blood test three months after the end of treatment. The descriptive and bivariate analyzes were performed with Pearson's chi-square and Fisher's Exact test, adopting a P value ≤0.05 in the SPSS 20 software. RESULTS: Of the 252 participants in the study, 228 (90.5%) had a sustained virologic response, 55.2% were male with an average age of 58.6 years (SD±9.1). Genotype 1 was the most prevalent, observed in 54.4% of the participants, and 87.4% of the patients had moderate/advanced hepatic fibrosis. After the statistical analysis, it was observed that the individuals with genotype 3 and moderate/advanced hepatic fibrosis had lower sustained virologic response rate (P=0.05 and P=0.04, respectively). CONCLUSION: It was observed that the use of direct-acting antivirals, in comparison to previous therapeutic regimens, increases the sustained virologic response, reaching all patients with mild fibrosis. This study provides information that helps in the hepatitis C treatment by showing that prescribing early treatment for patients without hepatic fibrosis and/or genotype 3 virus could increase therapeutic effectiveness.

Hepatitis C drug prescriptions and Medicaid policies--four states, Indian health care system, USA 2018.

Medicaid, the state-level public insurance in the United States, has widely differing criteria treatment for hepatitis C virus (HCV) such as stage of liver fibrosis, documented sobriety, and specialist consultation. In a rural health network, facilities located in two less restrictive states prescribed HCV drugs at a significantly higher rate than two more restrictive states (rate ratio 4.7, CI 2.6-8.5). Prescription rates per population were highly associated with HCV treatment policies.

Hepatitis C Virus Screening and Care: Complexity of Implementation in Primary Care Practices Serving Disadvantaged Populations.

Background: Hepatitis C virus (HCV) disproportionately affects disadvantaged communities. Objective: To examine processes and outcomes of Screen, Treat, Or Prevent Hepatocellular Carcinoma (STOP HCC), a multicomponent intervention for HCV screening and care in safety-net primary care practices. Design: Mixed-methods retrospective analysis. Setting: 5 federally qualified health centers (FQHCs) and 1 family medicine residency program serving low-income communities in diverse locations with largely Hispanic populations. Patients: Persons born in 1945 through 1965 (baby boomers) who had never been tested for HCV and were followed through May 2018. Intervention: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model guided implementation and evaluation. Test costs were covered for uninsured patients. Measurements: All practices tested patients for anti-HCV antibody (anti-HCV) and HCV RNA. For uninsured patients with chronic HCV in 4 practices, quantitative data also enabled assessment of HCV staging, specialist teleconsultation, direct-acting antiviral (DAA) treatment, and sustained virologic response (SVR). Implementation fidelity and adaptation were assessed qualitatively. Results: Anti-HCV screening was done in 13 334 of 27 700 baby boomers (48.1%, varying by practice from 19.8% to 71.3%). Of 695 anti-HCV-positive patients, HCV RNA was tested in 520 (74.8%; 48.9% to 92.9% by practice), and 349 persons (2.6% of those screened) were diagnosed with chronic HCV. In 4 FQHCs, 174 (84.9%) of 205 uninsured patients with chronic HCV had disease staging, 145 (70.7%) had teleconsultation review, 119 (58.0%) were recommended to start DAA therapy, 82 (40.0%) initiated free DAA therapy, 74 (36.1%) completed therapy (27.8% to 60.0% by practice), and 70 (94.6% of DAA completers) achieved SVR. Implementation was promoted by multilevel practice engagement, patient navigation, and anti-HCV screening with reflex HCV RNA testing. Limitation: No control practices were included, and data were missing for some variables. Conclusion: Despite a similar framework for STOP HCC implementation, performance varied widely across safety-net practices, which may reflect practice engagement as well as infrastructure or cost challenges beyond practice control. Primary Funding Source: Cancer Prevention & Research Institute of Texas and Centers for Medicare & Medicaid Services.

Variation in Hepatitis C Virus Subtype Distribution during 20 Years in Venezuela.

OBJECTIVE: Hepatitis C virus (HCV) infection is a public health problem and a major cause of chronic hepatitis. This virus exhibits a great genetic variability, with 8 genotypes and numerous subtypes. The aim of this study was to evaluate the fluctuations of HCV subtypes during 2 decades in Venezuela. METHODS: HCV genotypes were determined by direct sequencing of the 5'-noncoding region in 392 isolates circulating in patients attended during the years 2014-2015. HCV subtype assignment was confirmed in a subset of samples (n = 24) by partial sequencing of the NS5B region. The genotype distribution was compared with the one observed in a previous study of patients followed up during the years 1994-1996 and 2005-2006. RESULTS: Some variation was observed in the HCV genotype distribution over these 20 years. HCV genotype 1b prevalence was reduced significantly from 1994-1995 to 2004-2005, as previously described, and then remained constant. During the last 10 years, a significant decrease of HCV subtype 2b (36/237 in 2005-2006 vs. 24/392 in 2014-2015, p < 0.001) was observed. Patients infected with HCV G2acj were significantly older than the ones infected with G1 (53 vs. 47 years, p = 0.004), and male sex was significantly more prevalent among G3a-infected patients compared to the other ones (71 vs. 47%, p = 0.047). CONCLUSIONS: Fluctuations in HCV subtype distribution have been observed over 2 decades in Venezuela. Different major mode of transmission and susceptibility to the available HCV treatment during each period might be playing a role in the observed fluctuations in HCV subtype distribution.

Evaluating the centralized purchasing policy for the treatment of hepatitis C: The Colombian CASE.

The high cost of drugs for hepatitis C limits access and adherence to treatment. In 2017, the Colombian health care system decided to design a strategy. It consisted of centralized purchasing, regulations, clinical practice guidelines, and direct observation of the treatment and follow-up of patients. The main objective of this study was to assess the centralized purchasing strategy in Colombia. The study design was a policy implementation assessment. We analyzed the change in prices, the clinical outcomes, and the opinions of stakeholders using data from the Ministry of Health. Additional information about effectiveness came from the Colombian Fund for High-Cost Diseases and semi-structured interviews of the stakeholders. The follow-up was from October, 2017 to October, 2018. The total number of patients reported in the cohort period was 1069. The number that finished 12 weeks of treatment, completed the follow-up for the case closure, and were considered cured through the end of October, 2018 was 563 (53%). The remainder, 506 patients (47%), are currently in treatment. A total of 543 of these treated patients (96%) were cured. After implementing this strategy, the drug prices decreased by more than 90% overall. Before implementation, the total direct cost was $100 102 171.75 dollars. Afterward, the cost was $8 378 747 dollars.

Experiencia cubana en la producción local de medicamentos, transferencia de tecnologías y mejoramiento en el acceso a la salud. Segunda edición

A través de los años, Cuba ha logrado desarrollar exitosamente su capacidad de produc- ción de tecnologías sanitarias para mantener su sistema nacional de salud, reconocido mundialmente por lograr cobertura universal. Esto se evidencia en los indicadores de salud alcanzados, comparables con los de países altamente desarrollados. El nivel de este logro estimula a la imitación por otros países que tratan de establecer un sector farmacéutico nacional sostenible y competitivo. Como resultado, Cuba se ha convertido en un líder mundial en la transferencia sur-sur de tecnología, ayudando a países de bajos ingresos a desarrollar sus propias capacidades biotecnológicas nacionales, proporcionando capacitación técnica y facilitando el acceso a medicamentos vitales a bajo costo, para luchar contra enfermedades como la meningitis B y la hepatitis B.

Detección de anticuerpos contra el virus de la hepatitis C en habitantes de la zona sur de Manabí-Ecuador / Antibodies detection against hepatitis C virus in inhabitants of the South of Manabí-Ecuador

El objetivo de la presente investigación es determinar la presencia de anticuerpos contra el virus de la hepatitis C en la población general de la zona sur de Manabí-Ecuador. Se demostró la ausencia de anticuerpos contra VHC en la población estudiada, se necesitan estudios adicionales que abarquen una población mayor

The objective of this research is to determine the presence of antibodies against hepatitis C virus in the general population of the southern area of Manabí-Ecuador. The absence of HCV antibodies was demonstrated in the studied population, additional studies covering a larger population are needed

Predictors of adverse drug reactions associated with ribavirin in direct-acting antiviral therapies for chronic hepatitis C.

PURPOSE: To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens. METHODS: A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors. RESULTS: A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%. CONCLUSIONS: Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Xiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B.

BACKGROUND: Chronic hepatitis B is associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming at reduction of the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, and improving health-related quality of life. The Chinese herbal medicine formula Xiao Chai Hu Tang has been used to decrease discomfort and replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Xiao Chai Hu Tang formula have never been established with rigorous review methodology. OBJECTIVES: To assess the benefits and harms of Xiao Chai Hu Tang formula versus placebo or no intervention in people with chronic hepatitis B. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and seven other databases to 1 March 2019. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to 1 March 2019. SELECTION CRITERIA: We included randomised clinical trials, irrespective of publication status, language, and blinding, comparing Xiao Chai Hu Tang formula versus no intervention or placebo in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B according to guidelines or as defined by the trialists. We allowed co-interventions when the co-interventions were administered equally to all the intervention groups. DATA COLLECTION AND ANALYSIS: Review authors independently retrieved data from reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risks of bias using risk of bias domains with predefined definitions. We used GRADE methodology to evaluate our certainty in the evidence. MAIN RESULTS: We included 10 randomised clinical trials with 934 participants, but only five trials with 490 participants provided data for analysis. All the trials compared Xiao Chai Hu Tang formula with no intervention. All trials appeared to have been conducted and published only in China. The included trials assessed heterogeneous forms of Xiao Chai Hu Tang formula, administered for three to eight months. One trial included participants with hepatitis B and comorbid tuberculosis, and one trial included participants with hepatitis B and liver cirrhosis. The remaining trials included participants with hepatitis B only. All the trials were at high risk of bias, and the certainty of evidence for all outcomes that provided data for analyses was very low. We downgraded the evidence by one or two levels because of outcome risk of bias, inconsistency or heterogeneity of results (opposite direction of effect), indirectness of evidence (use of surrogate outcomes instead of clinically relevant outcomes), imprecision of results (the CIs were wide), and publication bias (small sample size of the trials). Additionally, 47 trials lacked the necessary methodological information needed to ensure the inclusion of these trials in our review. None of the included trials aimed to assess clinically relevant outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. The effects of Xiao Chai Hu Tang formula on the proportion of participants with adverse events considered 'not to be serious' is uncertain (RR 0.43, 95% CI 0.02 to 11.98; I2 = 69%; very low-certainty evidence). Only three trials with 222 participants reported the proportion of people with detectable hepatitis B virus DNA (HBV-DNA), but the evidence that Xiao Chai Hu Tang formula reduces the presence of HBV-DNA in the blood (a surrogate outcome) is uncertain (RR 0.62, 95% CI 0.45 to 0.85; I2 = 0%; very low-certainty evidence). Only two trials with 160 participants reported the proportion of people with detectable hepatitis B virus e-antigen (HBeAg; a surrogate outcome) (RR 0.72, 95% CI 0.50 to 1.02; I2 = 38%; very low-certainty evidence) and the evidence is uncertain. The evidence is also uncertain for separately reported adverse events considered 'not to be serious'. FUNDING: two of the 10 included trials received academic funding from government or hospital. None of the remaining eight trials reported information on funding. AUTHORS' CONCLUSIONS: The clinical effects of Xiao Chai Hu Tang formula for chronic hepatitis B remain unclear. The included trials were small and of low methodological quality. Despite the wide use of Xiao Chai Hu Tang formula, we lack data on all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The evidence in this systematic review comes from data obtained from a maximum three trials. We graded the certainty of evidence as very low for adverse events considered not to be serious and the surrogate outcomes HBeAg and HBV-DNA. We found a large number of trials which lacked clear description of their design and conduct, and hence, these trials are not included in the present review. As all identified trials were conducted in China, there might be a concern about the applicability of this review outside China. Large-sized, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding are lacking.

Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the ß-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.

Longitudinal migration patterns from an open illicit drug scene among people who use illicit drugs in Vancouver, Canada.

The objective of this study was to identify migration patterns from an open illicit drug scene (the Downtown Eastside [DTES] neighborhood) and describe factors associated with these migration patterns. Data were derived from three cohorts of people who use illicit drugs in Vancouver, Canada. Defined using latent class growth analysis, we identified four distinct migration trajectory groups: 1) consistently living in the DTES (47.8%); 2) early migration out, with a median time of migrating out of DTES of 5.3 months (21.5%); 3) late migration out, with a median time of migrating out of DTES of 38.0 months (20.1%); and 4) frequent revisit back-and-forth to DTES (10.6%). In a multivariable model, compared to the "consistently living in the DTES" group, factors associated with the "frequent revisit" group included being enrolled in non-pharmacological addiction treatment and having an HCV-positive serostatus. Factors associated with the "early migration out" group included being enrolled in detoxification or in other non-pharmacological addiction treatment, later calendar year, being on income assistance, living in a single room occupancy hotel, and having an HCV-positive serostatus. These findings point to the need for appropriate distribution of services in order to meet the needs of this population.

Hepatitis C Virus Infection in Indigenous Populations in the United States and Canada.

American Indian/Alaska Native (AI/AN) and Canadian Indigenous people are disproportionally affected by hepatitis C virus (HCV) infection yet are frequently underrepresented in epidemiologic studies and surveys often used to inform public health efforts. We performed a systematic review of published and unpublished literature and summarized our findings on HCV prevalence in these Indigenous populations. We found a disparity of epidemiologic literature of HCV prevalence among AI/AN in the United States and Indigenous people in Canada. The limited data available, which date from 1995, demonstrate a wide range of HCV prevalence in AI/AN (1.49%-67.60%) and Indigenous populations (2.28%-90.24%). The highest HCV prevalence in both countries was reported in studies that either included or specifically targeted people who inject drugs. Lower prevalence was reported in studies of general Indigenous populations, although in Canada, the lowest prevalence was up to 3-fold higher in Aboriginal people compared with general population estimates. The disparity of available data on HCV prevalence and need for consistent and enhanced HCV surveillance and reporting among Indigenous people are highlighted. HCV affects Indigenous peoples to a greater degree than the general population; thus we recommend tribal and community leaders be engaged in enhanced surveillance efforts and that funds benefitting all Indigenous persons be expanded to help prevent and cover health care expenses to help stop this epidemic.

Reprogramming of cellular metabolic pathways by human oncogenic viruses.

Oncogenic viruses, like all viruses, relies on host metabolism to provide the metabolites and energy needed for virus replication. Many DNA tumor viruses and retroviruses will reprogram metabolism during infection. Additionally, some viral oncogenes may alter metabolism independent of virus replication. Virus infection and cancer development share many similarities regarding metabolic reprogramming as both processes demand increased metabolic activity to produce biomass: cell proliferation in the case of cancer and virion production in the case of infection. This review discusses the parallels in metabolic reprogramming between human oncogenic viruses and oncogenesis.

Hepatitis C Behind and Beyond Bars: Targeting the US Prison Population and Changing North Carolina Prisoner Health Policy.

Prisoners in the United States are disproportionately affected by hepatitis C. Addressing the disease behind bars is crucial for curtailing the epidemic in the greater population. Effective strategies for testing and treatment are elucidated here. Recommendations for changes in hepatitis C health care policy in North Carolina prisons are also described.