Changes in Use of Hepatitis C Direct-Acting Antivirals After Access Restrictions Were Eased by State Medicaid Programs.

Importance: Direct-acting antivirals (DAAs) are safe and highly effective for curing hepatitis C virus (HCV) infection, but their high cost led certain state Medicaid programs to impose coverage restrictions. Since 2015, many of these restrictions have been lifted voluntarily in response to advocacy or because of litigation. Objective: To estimate how the prescribing of DAAs to Medicaid patients changed after states eased access restrictions. Design, Setting, and Participants: This modified difference-in-differences analysis of 39 state Medicaid programs included Medicaid beneficiaries who were prescribed a DAA from January 1, 2015, to December 31, 2019. DAA coverage restrictions were measured based on a series of cross-sectional assessments performed from 2014 through 2022 by the US National Viral Hepatitis Roundtable and the Center for Health Law and Policy Innovation. Exposure: Calendar quarter when states eased or eliminated 3 types of DAA coverage restrictions: limiting treatment to patients with severe liver disease, restricting use among patients with active substance use, and requiring prescriptions to be written by or in consultation with specialists. States with none of these restrictions at baseline were excluded. Main Outcomes and Measures: Quarterly number of HCV DAA treatment courses per 100 000 Medicaid beneficiaries. Results: Of 39 states, 7 (18%) eliminated coverage restrictions, 25 (64%) eased restrictions, and 7 (18%) maintained the same restrictions from 2015 to 2019. During this period, the average quarterly use of DAAs increased from 669 to 3601 treatment courses per 100 000 Medicaid beneficiaries. After states eased or eliminated restrictions, the use of DAAs increased by 966 (95% CI, 409-1523) treatment courses per 100 000 Medicaid beneficiaries each quarter compared with states that did not ease or eliminate restrictions. Conclusions and Relevance: The results of this study suggest that there was greater use of DAAs after states relaxed coverage restrictions related to liver disease severity, sobriety, or prescriber specialty. Further reductions or elimination of these rules may improve access to a highly effective public health intervention for patients with HCV.

The illness trap: The impact of disability benefits on willingness to receive HCV treatment.

Health care is assumed to be a primary good, implying that patients should always demand or accept treatments that may enhance their life expectancy and quality of life, especially if the risks associated with the treatment are low. We argue that, especially in countries with a well-developed welfare state, treating an invalidating condition may lead to opportunity costs in terms of reduced disability allowances that may represent a barrier to treatment for low-income individuals. We test this hypothesis by applying a recursive bivariate probit approach to population data from an ad hoc administrative database for Liguria (an Italian administrative region). The dataset includes data for more than 8 thousand people affected by hepatitis C Virus (HCV) infection between 2013 and 2020. After the discovery of new direct-acting antivirals (DAAs) in 2014, HCV eradication may now be possible. However, despite the national and international efforts, several patients diagnosed with HCV choose not to undergo drug therapy despite the adverse consequences for their personal health and relevant costs to the national health system. We show that five years after the implementation of the new drugs, approximately 41 % of the diagnosed population in Liguria remains untreated. This percentage increases to 64 % within the subgroup entitled to disability benefits and characterized by lower income levels. The "illness trap" effect is more substantial for older people but also low-income patients. Moreover, we find that this effect is higher in patients with an intermediate range of comorbidities; indeed, these patients are at a higher risk of losing economic benefits if they recover from HCV. These results suggest the need for healthcare policies addressing this distorting effect when designing benefit programs and granting financial benefits to patients.

The Severity of Depressive Symptoms as an Independent Predictor of Sustained Virological Response During Treatment of Hepatitis C With Pegylated Interferon-α2a and Oral Ribavirin.

BACKGROUND: Sustained virological response (SVR) is the best indicator of successful therapy for hepatitis C virus (HCV) infection. Patients with chronic HCV infection treated with pegylated interferon-α and ribavirin (PEG-IFN-α/RBV) can achieve SVR 56% of the time. OBJECTIVES: This study aimed to evaluate baseline predictors of SVR in patients treated with PEG-IFN-α/RBV for HCV chronic infection. METHODS: A total of 101 patients receiving PEG-IFN-α/RBV for chronic HCV infection participated in the prospective cohort study. Symptoms of depression were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) before the treatment. The multivariate regression analysis was applied to determine predictors of SVR. RESULTS: Of a total of 101 patients included, 99 patients reached the primary end point-24 weeks after completing treatment. After the initial analysis of probable predictive variables, the logistic analysis included age, sex, HCV genetic type, and MADRS score. The HCV genotype (odds ratio = 0.22 [confidence interval = 0.073-0.68, p = .008) and MADRS score (OR = 0.88 [confidence interval = 0.80-0.98), p = .013]) predicted an SVR outcome. CONCLUSIONS: The severity of depressive symptoms before treatment and HCV genotype are independent predictors of SVR.

Safety of fixed-dose heparin titration boluses in underweight patients.

INTRODUCTION: At UNC, venous thromboembolism (VTE) patients are treated with a heparin nomogram including fixed-dose titration boluses to correct subtherapeutic heparin correlation values (HCVs). The bolus dose often exceeds the recommended loading dose in underweight patients, therefore raising concern for an increased bleeding risk. This evaluation aims to assess the safety of these titration boluses for underweight patients. MATERIALS AND METHODS: Adult patients receiving intravenous heparin for VTE treatment and requiring at least one titration bolus were included. The underweight patients had a body mass index (BMI) <18.5 kg/m2 while the patients in the control group had a BMI of 18.5-29.9 kg/m2. The primary outcome was the percentage of patients with a supratherapeutic HCV after the first titration bolus. Secondary outcomes included the percentage of patients with a supratherapeutic HCV requiring holding of the infusion, time to stable HCV, and clinically significant bleeding. RESULTS: One hundred fifty-eight patients met inclusion criteria, with similar baseline characteristics between groups. There were 13.9 % of patients in both groups who had a supratherapeutic HCV after the first titration bolus. More underweight patients required holding of heparin. All patients took over 48 h to reach a stable HCV. There was no difference in clinically significant bleeding. CONCLUSIONS: Despite finding no significant difference, there remains clinical concern for increased bleeding risk in underweight patients as this population required heparin to be held due to supratherapeutic HCVs more often. More evidence is needed to evaluate the safety of fixed-dose heparin titration boluses in underweight patients due to the limited scope of this study.

Safety considerations in the management of hepatitis C and HIV co-infection.

INTRODUCTION: Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise. AREAS COVERED: Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023. EXPERT OPINION: The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.

The impact of sofosbuvir/velpatasvir/voxilaprevir treatment on serum hyperglycemia in hepatitis C virus infections: a systematic review and meta-analysis.

BACKGROUND: The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies. AIM: To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection. METHODS: We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109). RESULTS: Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; p < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration. CONCLUSION: Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.

Management of Hepatitis C in Children - A New Paradigm.

INTRODUCTION: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting the recent changes in the management. METHODS: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human, ages 0-18 years, and the English language. RESULTS: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care. CONCLUSION: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate HCV infection in India.

Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

PURPOSE: The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. METHODS: The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. RESULTS: Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). CONCLUSIONS: DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

Treatment of hepatitis C in children and adolescents: how far have we reached?

BACKGROUND: Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. DATA SOURCES: This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. RESULTS: Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. CONCLUSION: The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.

Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal.

OBJECTIVES: Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. METHODS: In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. RESULTS: Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. CONCLUSION: With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Comparison of 8- versus 12-weeks of glecaprevir/pibrentasvir for Taiwanese patients with hepatitis C and compensated cirrhosis in a real-world setting.

Real-world data on the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) for patients with HCV infection and compensated cirrhosis is limited, especially for the 8-week regimen and in an Asian population. This retrospective study enrolled 159 consecutive patients with HCV and compensated cirrhosis who were treated with GLE/PIB at a single center in Taiwan. Sustained virological response (SVR) and adverse events (AEs) were evaluated. Among the 159 patients, 91 and 68 were treated with GLE/PIB for 8 and 12 weeks, respectively. In the per protocol analysis, both the 8- and 12-week groups achieved 100% SVR (87/87 vs. 64/64); and in the evaluable population analysis, 95.6% (87/91) of the 8-week group and 94.1% (64/68) of the 12-week group achieved SVR. The most commonly reported AEs, which included pruritus (15.4% vs. 26.5%), abdominal discomfort (9.9% vs. 5.9%), and skin rash (5.5% vs. 5.9%), were mild for the 8- and 12-week groups. Two patients in the 8-week group exhibited total bilirubin elevation over three times the upper normal limit. One of these two patients discontinued GLE/PIB treatment after 2 weeks but still achieved SVR. Both 8- and 12-week GLE/PIB treatments are safe and effective for patients of Taiwanese ethnicity with HCV and compensated cirrhosis.

[Sustained virologic response in patients with hepatitis C and chronic kidney disease]. / Respuesta viral sostenida en pacientes con hepatitis C y enfermedad renal crónica.

Background: Patients with chronic kidney disease (CKD) have a higher prevalence of hepatitis C virus (HCV) infection compared to the general population, and they also present higher morbidity and mortality if they are not treated. Current treatment is based on different direct-acting antiviral (DAA) schemes, which are available in the Mexican health system. However, the efficacy and safety of DAA treatment in patients with CKD on hemodialysis and HCV infection are unknown in Mexican population. Objective: To determine the efficacy through sustained viral response (SVR) and the safety of DAAs in patients with CKD on hemodialysis and chronic HCV infection in the Mexican population. Material and methods: Real-life cohort study. Patients with CKD on hemodialysis and HCV infection treated with DAAs from a third level hospital were included. Descriptive statistics of the clinical characteristics were performed, efficacy was determined by SVR and safety with the global frequency of adverse effects associated with treatment. Results: 25 patients were included. All of them received treatment with glecaprebir/pibrentasvir for 8 weeks. The mean age was 57.8 years and the median time of CKD on hemodialysis was 5 years. 96% of patients had HCV genotype 1B. 100% of the patients presented SVR and the most frequent adverse effects were headache, nausea and fatigue. Conclusions: In the Mexican population studied, patients with HCV and CKD on hemodialysis presented a sustained viral response of 100% with glecaprevir/pibrentasvir with mild adverse effects.

Introducción: los pacientes con enfermedad renal crónica (ERC) tienen una mayor prevalencia de infección por virus de hepatitis C (VHC) en comparación con la población general y presentan mayor morbimortalidad si no se tratan. El tratamiento actual se basa en diferentes esquemas de antivirales de acción directa (ADD), disponibles en el sistema de salud mexicano; sin embargo, se desconoce su eficacia y seguridad en pacientes con ERC en hemodiálisis e infección por VHC en población mexicana. Objetivo: determinar la eficacia mediante respuesta viral sostenida (RVS) y la seguridad de los AAD en pacientes con ERC en hemodiálisis e infección crónica por VHC en población mexicana. Material y métodos: estudio de cohorte de vida real. Se incluyeron pacientes con ERC en hemodiálisis e infección por VHC tratados con AAD en un hospital de tercer nivel. Se usó estadística descriptiva de las características clínicas, se determinó eficacia mediante RVS y seguridad con la frecuencia global de efectos adversos asociados al tratamiento. Resultados: se incluyeron 25 pacientes. Todos recibieron tratamiento con glecaprebir/pibrentasvir durante ocho semanas. La media de edad fue 57.8 años y la mediana de tiempo de ERC en hemodiálisis fue de 5 años. El 96% de los pacientes presentó genotipo 1B de VHC. El 100% de los pacientes presentaron RVS y los efectos adversos más frecuentes fueron cefalea, náuseas y fatiga. Conclusiones: en la población mexicana estudiada, los pacientes con VHC y ERC en hemodiálisis presentaron respuesta viral sostenida del 100% con glecaprevir/pibrentasvir con efectos adversos leves.

The structure, function, and clinical use of the thrombopoietin receptor agonist avatrombopag.

Thrombopoietin regulates platelet production through activation of the thrombopoietin receptor (TPO-R). TPO-R agonists (TPO-RAs) are available to treat thrombocytopenia in chronic immune thrombocytopenia (ITP), chronic liver disease (CLD) patients who are undergoing a procedure, severe aplastic anemia (SAA), and hepatitis C virus (HCV) infection. There are four TPO-RAs approved in the US and Europe: romiplostim (ITP), eltrombopag (ITP, SAA, HCV), avatrombopag (ITP, CLD), and lusutrombopag (CLD). It is important to understand pharmacological characteristics of these agents when evaluating treatment options. Avatrombopag interacts with the transmembrane domain of the TPO-RA and does not compete with endogenous thrombopoietin for TPO-R binding. Structural differences between avatrombopag and other TPO-RAs may impart differential downstream effects on cell signaling pathways, potentially resulting in clinically relevant differences in outcome. Avatrombopag has a favorable pharmacological profile with similar exposure in Japanese, Chinese, or Caucasian patients and no drug-drug interactions, food interactions, or potential for chelation.

Thyroid gland and direct-acting antivirals (DAAs) used to treat chronic hepatitis C. Is it a safe regimen?

Hepatitis C virus (HCV) infection is widespread in the world and it has a diverse clinical manifestation. As a result of chronic infection, a patient may experience many health complications. Autoimmune thyroid disorders (AITD) occur more often among HCV-infected patients compared with healthy population. HCV treatment has changed over the years. It results from discovering of more and more new drugs. With the advent of the new generation of drugs, the frequent of endocrine adverse effects decreased. The review considers the latest articles on thyroid diseases caused by direct-acting antiviral drugs (DAAs) against HCV. Based on the available literature, we can find out that DAAs are well tolerated by patients and rarely lead to thyroid disorders. The most common thyroid side effect associated with using one of DAAs in the therapeutic regimen is hypothyroidism. It's worth noting that the information collected from past medical history, especially about thyroid disease in the family of patients are very important. Population studies confirm a strong genetic influence on the development of AITD. Physicians should evaluate thyroid hormone parameters before, during and after treatment with using DAAs. In addition, symptoms of hypothyroidism should be quickly detected and then appropriate diagnosis and treatment initiated.

The synthetic opioid fentanyl enhances viral replication in vitro.

The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of synthetic opioids such as fentanyl. Persons with opioid use disorder are at significant risk for transmission of injection-associated infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Commonly abused substances may antagonize immune responses and promote viral replication. However, the impact of synthetic opioids on virus replication has not been well explored. Thus, we evaluated the impact of fentanyl and carfentanil using in vitro systems that replicate infectious viruses. Fentanyl was used in cell lines replicating HBV or HCV at concentrations of 1 ng, 100 ng, and 10 ug. Viral protein synthesis was quantified by ELISA, while apoptosis and cell death were measured by M30 or MTT assays, respectively. HCV replicative fitness was evaluated in a luciferase-based system. RNAseq was performed to evaluate cellular gene regulation in the presence of fentanyl. Low dose fentanyl had no impact on HCV replication in Huh7.5JFH1 hepatocytes; however, higher doses significantly enhanced HCV replication. Similarly, a dose-dependent increase in HCV replicative fitness was observed in the presence of fentanyl. In the HepG2.2.15 hepatocyte cell line, fentanyl caused a dose-dependent increase in HBV replication, although only a higher doses than for HCV. Addition of fentanyl resulted in significant apoptosis in both hepatocyte cell lines. Cell death was minimal at low drug concentrations. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFκB signaling. Collectively, these data suggest that synthetic opioids promote viral replication but may have distinct effects depending on the drug dose and the viral target. As higher viral loads are associated with pathogenesis and virus transmission, additional research is essential to an enhanced understanding of opioid-virus pathogenesis and for the development of new and optimized treatment strategies.

Drug use-related stigma, safer injection norms, and hepatitis C infection among a network-based sample of young people who inject drugs.

BACKGROUND: Identifying risk for hepatitis C (HCV) infection is important for understanding recent increases in HCV incidence among young people who inject drugs (PWID) in suburban and rural areas; and for refining the targeting of effective HCV preventive interventions. Much of the extant research has focused on individual health behaviors (e.g., risky drug injection behaviors) as predictors of HCV infection. The present study examines two social factors (substance use-related stigma and injection-related social norms), and the interaction between these factors, as predictors of HCV infection. METHODS: Baseline data were used from an ongoing longitudinal study of young PWID (N = 279; mean age = 30.4 years) from the Chicago suburbs and their injection risk network members. Adjusted logistic regression models were used to examine relationships among substance use-related stigma, safer injection norms, and HCV infection. RESULTS: Despite a marginal bivariate association between less safe injection norms and HCV infection (OR = 0.74; 95 % CI[0.39, 1.02]; p = .071), a significant stigma X norms interaction (AOR = 0.68; 95 % CI[0.51, 0.90]) suggested that at high levels of stigma, probability of HCV infection was high regardless of injection norms. CONCLUSIONS: Findings suggest that social factors - specifically, substance use-related stigma and injection norms - are important predictors of HCV infection risk. The interaction found between these social factors suggests that intervening only to change injection norms or behaviors is likely insufficient to reduce risk for HCV infection in high-stigma settings or among high-stigma populations. Future research should develop and evaluate stigma-reduction interventions in combination with safer-injection interventions in order to maximize HCV risk reduction.

Responding to global stimulant use: challenges and opportunities.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

Rituximab May Cause Increased Hepatitis C Virus Viremia in Rheumatoid Arthritis Patients Through Declining Exosomal MicroRNA-155.

OBJECTIVE: Several studies have shown that rituximab may enhance hepatitis C virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the host immune response in HCV infection; miRNAs can be packaged into the exosomes and then shuttled by the exosomes to aid biologic functions. However, the role of exosomal miRNAs (exo-miRNAs) in rituximab-related HCV activity enhancement remains unclear. METHODS: The association between rituximab and increased HCV activity was examined using an in vitro cell-based assay. Purified exosomes were confirmed using immunoblotting and flow cytometry and quantified using enzyme-linked immunosorbent assay. Exosomal miRNA-155 (exo-miR-155) levels were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: In vitro data showed that B cell-derived miR-155 could inhibit HCV replication in hepatocytes through exosome transmission. Rituximab could both induce B cell depletion and affect intracellular miR-155 production as well as exo-miR-155 transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum exosome levels were increased in rheumatoid arthritis (RA) patients with HCV infection compared with the levels in RA patients without HCV infection (P < 0.01). The exo-miR-155 levels were significantly increased in RA patients with HCV infection compared with those without infection (P < 0.01). A significantly greater decrement of exo-miR-155 expression was observed after rituximab therapy compared with those observed before therapy (P < 0.01), and hepatitis C viral loads increased simultaneously (P < 0.05). CONCLUSION: Circulating exo-miR-155 levels were negatively correlated with hepatitis C viral loads and subsequently associated with rituximab-related HCV activity enhancement in RA patients. Exo-miR-155 may become a potential diagnostic biomarker or therapeutic target.

Risk for hepatitis B and C virus reactivation in patients with psoriasis on biologic therapies: A retrospective cohort study and systematic review of the literature.

BACKGROUND: Patients with psoriasis on biologic therapies and a history of viral hepatitis carry a risk for reactivation. OBJECTIVE: We evaluated safety of biologic therapies in psoriasis patients seropositive for hepatitis B or C viruses (HBV, HCV). METHODS: A retrospective cohort study design was used. Clinical and laboratory data for 30 patients undergoing biologic therapy who were seropositive for HBV or HCV were evaluated. Next, a systematic review was performed. Primary outcomes were hepatitis and viral reactivation during therapy. Treatment duration and antiviral prophylaxis were also recorded. RESULTS: Serology indicated HCV infection in 4 patients, past HBV infection in 17 patients, isolated core antibody in 8 patients, and chronic HBV infection in 1 patient. During follow-up (mean 4.85 ± 3.1 years), no patients experienced hepatitis or viral reactivation. The systematic review of the literature included 49 studies comprising 312 patients followed for a mean of 30.9 months. Viral reactivation occurred in 2/175 patients who were seropositive for core antibody and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively) compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%). Three of these 8 patients with reactivated HBV infection received antiviral prophylaxis. LIMITATIONS: We pooled heterogeneous studies evaluating different biologic therapies. CONCLUSION: Biologic therapies pose minimal risk for viral reactivation in low-risk patients without hepatitis seropositive for HCV or HBV core antibody but are a considerable risk in patients with chronic HBV infection, highlighting the necessity of antiviral prophylaxis.