Hepatitis C Virus Antivirals Research Articles

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a primary liver cancer predominantly arising in individuals with chronic liver diseases such as cirrhosis or chronic hepatitis B virus (HBV) infection. Accounting for approximately 75% of primary liver tumors, HCC's global epidemiology is significantly influenced by HBV and hepatitis C virus (HCV) infections, alcohol and tobacco use, metabolic syndrome, diabetes, obesity, and aflatoxin B1 exposure. Preventive measures, including HBV vaccination and direct-acting antivirals for HCV, have reduced incidence rates, particularly in younger populations. Early diagnosis through surveillance in high-risk groups is critical, employing imaging modalities like ultrasound, CT, and MRI, alongside biomarkers such as alpha-fetoprotein (AFP). Prognostic assessments utilize scores like Child-Pugh and ALBI. Treatment strategies for HCC are multifaceted, involving surgical resection, locoregional therapies (e.g., transarterial chemoembolization), and systemic therapies, including targeted and immunotherapies. Despite advancements, treatment efficacy remains a challenge, necessitating ongoing research into novel therapeutic approaches and predictive biomarkers to enhance personalized treatment and improve outcomes for HCC patients.

HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation.

The hepatitis C virus (HCV) poses a great risk to pregnant people and their developing fetus, yet no HCV antiviral treatment guidelines have been established. While there has been a substantial increase in the development of HCV antivirals, the effect they have on the developing fetus remains poorly defined. Many of these drugs are metabolized through the cytochrome P450 CYP3A pathway, which is mediated by cytochrome P450 3A7 (CYP3A7) in the fetus and developing infant. In this study, we sought to investigate the effect HCV antivirals have on CYP3A7 metabolism, as this CYP enzyme plays a vital role in proper fetal and neonatal development. Of the 13 HCV antivirals we investigated, 8 (∼62%) inhibited CYP3A7 metabolic activity by 50% or more at a concentration of 20 µM. Furthermore, paritaprevir, asunaprevir, simeprevir, danoprevir, and glecaprevir all had observed half-maximal inhibitory concentrations between the range of 10 and 20 µM, which is physiologically relevant in comparison with the Km of dehydroepiandrosterone-sulfate (DHEA-S) oxidation (reported to be between 5 and 20 µM). We also discovered that paritaprevir is a time-dependent inhibitor of CYP3A7, which shifts the IC50 ∼twofold from 11 µM to 5 µM. Upon further characterization, paritaprevir inactivates DHEA-S metabolism by CYP3A7, with KI and Kinact values of 4.66 µM and 0.00954 minute-1, respectively. Depending on treatment plan and off-label drug use, HCV treatment could adversely affect the fetal-maternal communication axis by blocking fetal CYP3A7 metabolism of important endogenous hormones. SIGNIFICANCE STATEMENT: The prevalence of HCV in pregnant people is estimated at between 1% and 8% of the global population, yet little to no information exists about the risk antiviral treatment poses to the developing fetus. There is a potential risk of drugs adversely affecting mother-fetal communication by inhibiting fetal hepatic CYP3A7, an integral enzyme for estriol production. We discovered that five HCV antivirals inhibited DHEA-S metabolism by CYP3A7, and paritaprevir inactivated the enzyme. Our studies demonstrate the potential threat these drugs pose to proper fetal development.

Real-world Experiences in the Transplantation of Hepatitis C-NAAT-positive Organs.

Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)-positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients with donor-derived HCV infection without significant adverse effects, although variability remains in the timing and duration of antivirals. This retrospective study analyzed all adult HCV-NAAT-negative transplant recipients who received an organ from HCV-NAAT-positive donors from November 24, 2018, to March 31, 2022, at Duke University Medical Center with protocolized delay of DAA initiation until after hospital discharge, with at least 180-d follow-up on all patients. Transplant and HCV-related outcomes were analyzed. Two hundred eleven transplants (111 kidneys, 41 livers, 34 hearts, and 25 lungs) were performed from HCV-NAAT-positive donors to HCV-NAAT-negative recipients. Ninety percent of recipients became viremic within 7 d posttransplant. Ninety-nine percent of recipients were initiated on pangenotypic DAAs in the outpatient setting a median of 52 d posttransplant, most commonly with 12-wk courses of sofosbuvir-velpatasvir (lungs) and glecaprevir-pibrentasvir (heart, kidney, and liver). Ninety-seven percent of recipients had SVR after a first-line DAA; all ultimately achieved SVR at 12 wk after subsequent treatment courses. The median peak HCV RNA for all organ systems was 2 436 512 IU/mL; the median time from antiviral to undetectable RNA was 48 d, although differences were noted between organ groups. No patient deaths or graft losses were directly attributable to HCV infection. One hundred percent of transplant recipients of HCV-NAAT-positive organs ultimately developed SVR without significant adverse effects when HCV antivirals were initiated in the outpatient setting after transplant hospitalization, suggesting that this real-world treatment pathway is a viable option.

Hepatitis C Virus Elimination in Methadone-treated Patients: Implementation of Hepatology Clinic in a Methadone Treatment Program.

Patient ignorance and bureaucratic obstacles prevent initiation of hepatitis C virus (HCV) treatment in patients participating in methadone treatment program. Despite high safety and efficacy of currently available oral medications, the rate of patient-initiated treatment remains low. We evaluated the impact of an interventional program on treatment success rate and factors associated with treatment engagement. An intervention performed from 2018 to 2020 included an on-site Fibroscan and hepatologist evaluation, anti-viral HCV treatment initiation, and close support and follow-up by a dedicated team. Demographic and medical data were collected and comparison between patients who completed vs. patients who did not complete HCV treatment was done. Fifty-nine out of 74 HCV polymerase chain reaction-positive patients (79.7%) were willing and capable of undergoing on-site hepatologist and Fibroscan evaluations. Twelve (25%) of the participants had cirrhosis, 2 of whom were decompensated. Fifty of the 57 patients that got an anti-viral medication prescription (87%) initiated the treatment. Premature treatment discontinuation was rare (3 patients), intention-to-treat sustain virologic response (SVR) rate was 81% and per-protocol SVR rate was 97%. The rate of treatment initiation during the intervention was significantly higher than the patients' self-initiation rate (44 vs 12 patients). The main factors associated with successful completion of the care cascade was full abstinence from street drugs for 6 months before treatment initiation. Installing a hepatology clinic in an methadone treatment program center was associated with a 3-fold increase in the HCV treatment, with high adherence to treatment levels, and a high SVR rate. The main factor associated with low engagement to treatment was ongoing street drug use.

Evaluating the Cardiovascular Risk in an Aging Population of People With HIV: The Impact of Hepatitis C Virus Coinfection.

Background People with HIV (PWH) are at an increased risk of cardiovascular disease (CVD) with an unknown added impact of hepatitis C virus (HCV) coinfection. We aimed to identify whether HCV coinfection increases the risk of type 1 myocardial infarction (T1MI) and if the risk differs by age. Methods and Results We used data from NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) from January 1, 2000, to December 31, 2017, PWH (aged 40-79 years) who had initiated antiretroviral therapy. The primary outcome was an adjudicated T1MI event. Those who started direct-acting HCV antivirals were censored at the time of initiation. Crude incidence rates per 1000 person-years were calculated for T1MI by calendar time. Discrete time-to-event analyses with complementary log-log models were used to estimate adjusted hazard ratios and 95% CIs for T1MI among those with and without HCV. Among 23 361 PWH, 4677 (20%) had HCV. There were 89 (1.9%) T1MIs among PWH with HCV and 314 (1.7%) among PWH without HCV. HCV was not associated with increased T1MI risk in PWH (adjusted hazard ratio, 0.98 [95% CI, 0.74-1.30]). However, the risk of T1MI increased with age and was amplified in those with HCV (adjusted hazard ratio per 10-year increase in age, 1.85 [95% CI, 1.38-2.48]) compared with those without HCV (adjusted hazard ratio per 10-year increase in age,1.30 [95% CI, 1.13-1.50]; P<0.001, test of interaction). Conclusions HCV coinfection was not significantly associated with increased T1MI risk; however, the risk of T1MI with increasing age was greater in those with HCV compared with those without, and HCV status should be considered when assessing CVD risk in aging PWH.

Dispensing of HIV and Hepatitis C Antivirals During COVID-19: An Interrupted Time-Series Analysis of U.S. National Data

IntroductionLittle is known about the potential changes in the dispensation of life-saving hepatitis C virus (HCV) and HIV antivirals after the initial U.S. outbreak of COVID-19. The objective of this study was to describe the immediate and 1-year impacts of the U.S. outbreak of COVID-19 on monthly dispensing of HIV and HCV antivirals, specifically direct-acting antivirals (DAA) to treat HCV, antiretroviral therapy (ART) to treat HIV, and pre-exposure prophylaxis (PrEP) to prevent HIV.MethodsAuthors used interrupted time-series analysis, examining IQVIA National Prescription Audit (includes 92% of U.S. retail pharmacies and 70% of U.S. mail order and long-term care pharmacies) for changes in monthly dispensed prescriptions, 2 years before and 1 year after the initial U.S. COVID-19 outbreak. Fitted linear segmented regression models were used to assess immediate level and slope changes, excluding data from April 2020 as a washout period. Authors stratified analyses by new/refill, age group, payer type, and delivery channel.ResultsAfter the initial outbreak, DAA prescription dispensing declined by almost one third. The COVID-19 outbreak was associated with an immediate-level decrease in total DAA prescriptions, followed by a slope increase in monthly dispensing. However, by April 2021, monthly DAA dispensing had not recovered to prepandemic levels. In contrast, ART and PrEP dispensing changed little over the same time period.ConclusionsU.S. dispensing of DAAs to treat HCV fell at the start of the U.S. COVID-19 outbreak and has yet to fully recover to prepandemic levels. Addressing barriers to care is crucial to reaching national HIV and hepatitis C elimination goals.

Overcoming Bioavailability Challenges of Dasabuvir and Enabling a Triple-Combination Direct-Acting Antiviral HCV Regimen through a Salt of Very Weak Acid for Oral Delivery.

Dasabuvir is a non-nucleoside polymerase inhibitor for the treatment of hepatitis C virus (HCV) infection. It is an extremely weak diacidic drug (pKa = 8.2 and 9.2) and a prolific solvate former. Due to its exceedingly low aqueous solubility (≤0.127 μg/mL at pH 1-6.8, dose number of 1.31 × 104), crystalline dasabuvir free acid exhibited poor oral bioavailability in initial animal pharmacokinetic (PK) assessment. This necessitated the development of enabling formulation for human clinical studies to achieve the required therapeutic in vivo concentration of dasabuvir. While salt formation has been widely used to enhance the solubility and dissolution rate of solids, this approach has rarely been applied to develop oral solid dosage forms for acidic drugs as weak as dasabuvir due to concerns of rapid disproportionation and crystallization of its free acid. In this contribution, we detail our efforts in identifying dasabuvir monosodium monohydrate as a drug substance that is stable, manufacturable, and, most importantly, significantly enhances the dissolution and oral absorption of this poorly soluble drug. The oral delivery of dasabuvir through the salt approach has enabled the commercialization of the triple-combination direct-acting antiviral HCV regimen, Viekira Pak. The methodologies and solutions identified in targeted studies to overcome technical challenges encountered along the way (i.e., incorporation of polymers to inhibit crystallization and disproportionation and species mapping to enable salt manufacturing process, etc.) can be applied to other insoluble compounds.

Direct-acting antiviral regimens and HCV treatment failure and re-treatment in sub-Saharan Africa

Today, most patients chronically infected with hepatitis C virus (HCV) can comfortably clear their infection after a 12-week course of direct-acting antivirals, which are easy to administer, well tolerated, and effective when administered as combination therapies.1 However, treatment failure after the use of direct-acting antivirals for HCV infection, which can be recurrent, is an emerging worldwide problem and a threat to the global elimination of chronic HCV infection. Predictors of failure of direct-acting antiviral treatment include HCV genotypes, subtypes, and viral adaptations.

Reported Barriers to Hepatitis C Treatment among Pregnant and Early-Parenting Mothers Undergoing Substance Use Disorder Treatment in One U.S. State.

Nationwide, the prevalence of the hepatitis C virus (HCV) has risen in recent years. At least 90% of infected persons must be treated to achieve global elimination targets. The current study aimed to explore barriers to, and facilitators of, direct-acting antiviral (DAA) HCV treatment uptake amongst pregnant and early-parenting women undergoing comprehensive substance use treatment. Twenty participants with documented HCV antibody positivity were recruited from two substance use treatment centers in central Kentucky. Semi-structured interviews were conducted to explore knowledge about HCV, previous experiences, and intentions to seek care. Themes were extracted using an inductive analytical approach. Most participants were aware of the dangers posed by HCV infection. However, there was a high degree of misinformation about transmission mechanisms and treatment eligibility requirements. Low priority for HCV treatment also surfaced as a barrier to treatment uptake. Participants reported being unable to seek care due to time and resource limitations in the presence of a highly demanding treatment process. Findings from the current study suggest that more work is needed to eliminate residual barriers that limit access to HCV treatment among pregnant and early-parenting women in treatment for substance use disorder.

Ledipasvir/Sofosbuvir for Patients Coinfected With Chronic Hepatitis C and Hepatitis B in Taiwan: Follow-up at 108 Weeks Posttreatment.

BackgroundFor patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up.MethodsIn Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either less than the lower limit of quantification (LLOQ, 20 IU/mL) to equal to or more than LLOQ or equal to or more than LLOQ to >1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT) >2× upper limit of normal. Factors associated with development of HBV virologic or clinical reactivation were evaluated with logistic regression analysis.ResultsAll patients (100%, 111/111) maintained HCV suppression through 108 weeks after treatment. HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% (10/111). The majority of HBV virologic reactivations (86%, 70/81) occurred by follow-up week 12, whereas clinical reactivation was generally more delayed. Eight (7%, 8/111) initiated HBV therapy. In regression analyses, baseline HBV DNA and hepatitis B surface antigen (HBsAg) levels were associated with HBV virologic reactivation and baseline ALT and HBV DNA, and HBsAg levels were associated with HBV clinical reactivation.ConclusionAmong HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. In most patients, HBV virologic reactivation was asymptomatic; only a small proportion initiated HBV treatment. Notably, clinical reactivation may still occur >3 months after end of therapy.Clinical Trials RegistrationNCT02613871.

From Screening to Therapy: Anti-HCV Screening and Linkage to Care in a Network of General Practitioners and a Private Gastroenterology Practice

(1) Background: Low rates of hepatitis C virus (HCV) diagnosis and sub-optimal linkage to care constitute barriers toward eliminating the infection. In 2012/2013, we showed that HCV screening in primary care detects unknown cases. However, hepatitis C patients may not receive further diagnostics and therapy because they drop out during the referral pathway to secondary care. Thus, we used an existing network of primary care physicians and a practice of gastroenterology to investigate the pathway from screening to therapy. (2) Methods: HCV screening was prospectively included in a routine check-up of primary care physicians who cooperated regularly with a private gastroenterology practice. Anti-HCV-positive patients were referred for further specialized diagnostics and treatment if indicated. (3) Results: Seventeen primary care practices screened 1875 patients. Twelve individuals were anti-HCV-positive (0.6%), six of them reported previous antiviral HCV therapy, and one untreated patient was HCV-RNA-positive (0.05% of the population). None of the 12 anti-HCV-positive cases showed up at the private gastroenterology practice. Further clinical details of the pathway from screening to therapy could not be analyzed. (4) Conclusions: The linkage between primary and secondary care appears to be problematic in the HCV setting even among cooperating partners, but robust conclusions require larger datasets.

Patient-centered HCV care via telemedicine for individuals on medication for opioid use disorder: Telemedicine for Evaluation, Adherence and Medication for Hepatitis C (TEAM-C)

BackgroundTelemedicine has the potential to increase healthcare access especially for vulnerable populations. Telemedicine for Evaluation, Adherence, and Medication for Hepatitis C (TEAM-C) is comparing telemedicine access to specialty medical care to usual care for management of hepatitis C virus (HCV) infection among persons with opioid use disorder (PWOUD). PWOUD have the highest hepatitis C virus (HCV) prevalence and incidence, yet they infrequently receive HCV care. The study objectives are to compare access to specialty care via telemedicine to offsite specialty referral (usual care) on 1) treatment initiation, completion, and sustained virological response, 2) patient satisfaction with health care delivery, and 3) HCV reinfection after successful HCV cure. MethodsTEAM-C is a multi-site, non-blinded, randomized pragmatic clinical trial conducted at 12 opioid treatment programs (OTP) throughout New York State that utilizes the stepped-wedge design. The unit of randomization is the OTP with a total sample size of 624 participants. HCV-infected PWOUD were treated via telemedicine or referral. Telemedicine encounters are conducted onsite in the OTP with co-administration of direct acting antivirals for HCV with medications for opioid use disorder. The primary outcome is undetectable HCV RNA obtained 12 weeks post-treatment cessation. We also follow participants for two years to assess for reinfection. ConclusionsThe study utilizes a rigorous study design to evaluate the effectiveness and implementation of virtual treatment for HCV integrated into behavioral treatment. We demonstrate the feasibility, engagement principles and lessons learned from the initial prospective randomized trial of telemedicine targeted to a vulnerable population.

Association of Medicaid Managed Care Drug Carve Outs With Hepatitis C Virus Prescription Use

Medicaid enrolls a disproportionate share of US adults with hepatitis C virus (HCV), and most receive Medicaid benefits through managed care organizations (MCOs). Medicaid MCOs often impose stricter requirements to access HCV medications than traditional fee-for-service Medicaid, which may inhibit use. Though Medicaid MCOs generally cover prescription drugs, several states have carved out direct-acting antiviral HCV medications from MCO coverage and opted to cover them under fee-for-service. Whether these carve outs were associated with changes in medication use is unknown. To examine the association between Medicaid-covered HCV medication fills and carve outs of these medications from MCO coverage. This cross-sectional study examined changes in fills of Medicaid-covered direct-acting antiviral HCV medications in 4 states (Indiana, Michigan, New Hampshire, and West Virginia) that carved out these drugs from Medicaid MCOs between 2015 and 2017. A synthetic control approach was used to compare changes in HCV prescription fills between states that did and did not carve out these medications from MCO prescription drug coverage. Data of direct-acting antiviral HCV prescription fills were obtained from the Medicaid State Drug Utilization Data files, January 2015 to June 2020. Data analysis was conducted from November 2020 to June 2021. Carve outs of direct-acting antiviral HCV medications from Medicaid MCO prescription drug coverage. Direct-acting antiviral HCV prescriptions filled per 100 000 Medicaid enrollees. In this cross-sectional study, carve outs were associated with a mean quarterly increase of 22.1 (95% CI, 12.7-34.1) HCV prescriptions per 100 000 Medicaid enrollees, a relative increase of 86.3% compared with synthetic control states. Compared with each state's respective synthetic control, HCV prescription fills were associated with an increase of 11.5 (95% CI, 5.1-19.0) HCV prescription fills per 100 000 Medicaid enrollees per quarter in Indiana, 36.6 (95% CI, 23.5-53.9) in Michigan, 20.7 (95% CI, 11.1-32.8) in West Virginia, and 43.6 (95% CI, 25.9-68.4) in New Hampshire. In this cross-sectional study of data from 39 states and the District of Columbia, carve outs of direct-acting antiviral HCV medications from Medicaid MCO prescription drug coverage were associated with significant increases in HCV medication use. Given their clinical benefits, greater uptake of HCV medication may help improve the health of Medicaid enrollees with HCV and reduce the economic burden of untreated HCV on the US health care system.

Medicaid Subscription-Based Payment Models and Implications for Access to Hepatitis C Medications

Hepatitis C virus (HCV) can be cured with direct-acting antiviral medications, but state Medicaid programs often restrict access to these lifesaving medications owing to their high costs. Subscription-based payment models (SBPMs), wherein states contract with a single manufacturer to supply prescriptions at a reduced price, may offer a solution that increases access. Whether SBPMs are associated with changes in HCV medication use is unknown. To estimate changes in Medicaid-covered HCV prescription fills after Louisiana and Washington implemented SBPMs on July 1, 2019. This cross-sectional study examined trends in prescription fills of Medicaid-covered direct-acting antiviral HCV medications in Louisiana and Washington after implementation of SBPMs. A synthetic control approach was used to compare changes in HCV prescription fills between states that did and did not implement SBPMs. The unit of analysis was state-quarter. Outpatient direct-acting antiviral HCV prescription fills from the Medicaid State Drug Utilization Data files were obtained from all 50 US states and the District of Columbia from January 1, 2017, to June 30, 2020. Implementation of SBPMs for Medicaid-covered direct-acting antiviral HCV medications. Direct-acting antiviral HCV prescriptions filled per 100 000 Medicaid enrollees. In the year preceding SBPM implementation, the mean (SD) rate of quarterly HCV prescription fills per 100 000 Medicaid enrollees was 43.1 (8.6) prescriptions in Louisiana and 50.1 (4.1) in Washington. After SBPM implementation, the mean (SD) rate of quarterly HCV prescription fills per 100 000 enrollees was 206.0 (51.2) prescriptions in Louisiana and 53.9 (11.0) in Washington. In synthetic control models, SBPM implementation in Louisiana was associated with an increase of 173.5 (95% CI, 74.3-265.3) quarterly prescription fills per 100 000 Medicaid enrollees during the following year, a relative increase of 534.5% (95% CI, 228.7%-1125.0%). Washington did not experience a significant change in prescription fills following SBPM implementation. In this cross-sectional study, Louisiana experienced substantial increases in HCV medication use among its Medicaid-enrolled population following SBPM implementation, whereas Washington did not. These differences may partially be explained by state-level variation in SBPM implementation, historical restrictions on access to HCV medications, and responses to the COVID-19 pandemic.

"I want to feel young again": experiences and perspectives of young people who inject drugs living with hepatitis C in Vancouver, Canada.

People who inject drugs (PWID) are disproportionately impacted by hepatitis C virus (HCV). Despite the availability and efficacy of direct-acting antiviral (DAA) HCV therapies, treatment rates remain low among PWID. Among PWID, those who are young (under age 30) experience high rates of HCV and also face distinct barriers to care. The objective of this study is to identify facilitators and barriers to navigating various facets of the HCV cascade of care, including DAA treatment access, among young PWID. We draw on data from in-depth, semi-structured interviews conducted between May and November 2019 with a sample of 11 young, street-involved PWID who have lived experience of HCV and who live in Metro Vancouver, Canada. Informed by a social constructivist epistemology, data were thematically analyzed using an equity-oriented theoretical framework. Our analysis yielded two key themes. First, participants described facilitators to HCV care access, including individual factors (e.g., desire to be cured, knowledge of side effects) and healthcare and socio-contextual factors (e.g., peer supports, supportive youth-specific services). Second, participants described a contrasting set of barriers to HCV care access, including concerns over treatment side effects and (in)eligibility, complex healthcare system navigation, substance use- and housing-related stigma, and clinician gatekeeping of DAAs. Findings from this study underscore the need for HCV-related knowledge-building efforts among young PWID and clinicians. Also needed are structural policy interventions to facilitate access to DAAs, including anti-stigma efforts, access to safe housing, and the scale-up of low-barrier youth-specific services and decentralized HCV care.

Predictors of hepatitis C treatment outcomes in a harm reduction-focused primary care program in New York City

BackgroundThe social determinants of health that influence steps in the entire Hepatitis C Virus (HCV) treatment cascade must be identified to achieve HCV elimination goals. This project aimed to evaluate the association of these factors with HCV treatment completion and return for sustained virologic response (SVR) testing.MethodsWe used retrospective cohort data from our primary care-based HCV treatment program that provides comprehensive harm reduction care to those who use or formerly used drugs. Among persons who began direct-acting antiviral HCV treatment between December 2014 and March 2018, we identified two outcomes: HCV treatment completion and return for SVR assessment 12 weeks after treatment end. Several predictors were ascertained including sociodemographic information, substance use, psychiatric symptoms and history, housing instability, and HCV treatment regimen. We then evaluated associations between predictors and outcomes using univariate and multivariable statistical methods.ResultsFrom a cohort of 329 patients treated in an urban primary care center, multivariable analysis identified housing instability as a single significant predictor for HCV treatment completion (odds ratio [OR]: 0.3; 95% confidence interval [CI]: 0.1–0.9). Among patients completing treatment, 226 (75%) returned for SVR assessment; the sole predictor of this outcome was Medicaid as primary insurance (compared to other insurances; OR 0.3; 0.1–0.7).ConclusionsInnovative strategies to help unstably housed persons complete HCV treatment are urgently needed in order to reach HCV elimination targets. Educational and motivational strategies should be developed to promote individuals with Medicaid in particular to return for SVR viral load testing, a critical post-treatment component of the HCV treatment cascade.Trial registration Not applicable.

Transplanting Organs from Donors with HIV or Hepatitis C: The Viral Frontier.

A wide gap between the increasing demand for organs and the limited supply leads to immeasurable loss of life each year. The organ shortage could be attenuated by donors with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). The transplantation of organs from HIV+ deceased donors into HIV+ individuals (HIV D+ /R+) was initiated in South Africa in 2010; however, this practice was forbidden in the USA until the HIV Organ Policy Equity (HOPE) Act in 2013. HIV D+/R+ transplantation is now practiced in the USA as part of ongoing research studies, helping to reduce waiting times for all patients on the waitlist. The introduction of direct acting antivirals for HCV has revolutionized the utilization of donors with HCV for HCV-uninfected (HCV-) recipients. This is particularly relevant as the HCV donor pool has increased substantially in the context of the rise in deaths related to drug overdose from injection drug use. This article serves to review the current literature on using organs from donors with HIV or HCV.

A Population-Based Intervention to Improve Care Cascades of Patients With Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct‐acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population‐based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV‐related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response. Conclusion: A combination of EHR‐based health care system interventions, active linkage to care, and clinician training contributed to a tripling in the number of patients screened and a more than 10‐fold increase of those treated. The interventions are scalable and foundational to the goal of HCV elimination.

Prevalence of Hepatitis C Virus Infection in the Veteran Population Undergoing Total Joint Arthroplasty: An Update

BackgroundIn 2012, we reported on the prevalence of hepatitis C virus (HCV) infection in Veterans Affairs (VA) patients undergoing total joint arthroplasty (TJA) at our center. In this patient population, 8.4% were antibody positive and 4.5% were viremic with HCV. In 2014, the first all-oral direct-acting antiviral treatment for hepatitis C became available. The Department of Veterans Affairs then underwent an aggressive program to eradicate hepatitis C from the veteran population. The purpose of this report is to provide updated information on the prevalence of HCV viremia among patients undergoing primary TJA at the same center. MethodsA retrospective review was performed of all patients undergoing primary TJA at a single VA medical center in 2019. Anti-HCV antibody and HCV viremia prevalence were calculated. Comparisons were made to data from a previously reported cohort of patients who had undergone TJA at the same center from 2007 to 2009. ResultsThirty-three (11.6%) of 285 patients screened preoperatively were positive for the hepatitis C antibody. Only one of the 33 anti-HCV–positive patients was viremic at the time of screening for an overall viremic prevalence of 0.4%. We found no statistically significant difference in the birth year, or anti-HCV antibody–positive rate from the prior cohort, but the prevalence of HCV viremia decreased significantly. ConclusionBecause direct-acting antiviral HCV treatment has become available, HCV viremia among VA patients undergoing TJA has been reduced from 4.5% to 0.4%. Surgeons are still advised to minimize the risk of sharps injury.

Wirelessly Observed Therapy to Optimize Adherence and Target Interventions for Oral Hepatitis C Treatment: Observational Pilot Study.

BackgroundA fixed-dose combination of ledipasvir/sofosbuvir (LDV/SOF) is efficacious in treating chronic hepatitis C virus (HCV) infection; however, objective adherence to prescribed regimens in real-world clinical settings has not been well studied.ObjectiveThis study aimed to evaluate adherence and virologic outcomes in patients with chronic HCV infection treated with LDV/SOF using a novel digital medicine program that directly measures drug ingestion adherence.MethodsThis prospective, observational, open-label, single-arm pilot study was conducted at 2 clinical research sites and followed patients with HCV infection who were prescribed LDV/SOF along with an ingestible sensor. Patients were treated for 8 or 12 weeks. The main outcomes were ingestion adherence, medical interventions, virologic response, safety, and patient satisfaction.ResultsOf the 28 patients (mean 59 years, SD 7), 61% (17/28) were male, 61% (17/28) were non-Caucasian, and 93% (26/28) were treatment naïve. All 28 had genotype 1 HCV, and of these, 27 completed an 8- or 12-week treatment. Patients used the digital medicine program for 92% of the expected days; the overall mean ingestion adherence rate was 97%. Providers used the digital medicine program data for same-day medication therapy management in 39% (11/28) of patients. End-of-treatment response was achieved in all the available 21 of 28 patients. Sustained virologic response at 12 weeks or more was achieved in 26 of 28 patients; of the 2 patients who relapsed, one had less than 90% adherence and the other had greater than or equal to 95% adherence, lending insights into reasons for treatment failure. A total of 4 subjects reported nonserious adverse events, which were resolved.ConclusionsThe findings of this study suggest that digital medicines can be used for wirelessly observed therapy to support adherence to antiviral HCV therapy, reduce unnecessary medication wastage and retreatment costs, and potentially optimize sustained virologic response rates, especially in populations at high risk for nonadherence.