Hepatitis C Virus Direct-acting Antiviral Therapy Research Articles

Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy. Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self-report (≥40 g/day of ethanol), physician-reported history of problematic alcohol use, and anti-craving medication prescription via population-based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician-reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty-three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted-odds ratio 1.69, 95% confidence interval 1.32-2.17) and patients were over-represented for cirrhosis (45.1% vs. 25.6% in no-risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2-year survival (adjusted-hazard ratio 1.98, 95% confidence interval 0.84-4.63) after DAA therapy were not associated with risky alcohol use. Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under-recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this.

A Vermont Statewide Educational Intervention to Improve Access to Hepatitis C Virus Treatment in a Rural State.

Improved knowledge of hepatitis C virus (HCV) screening, linkage to care, and treatment is needed among nonspecialist medical professionals to combat the HCV epidemic. The authors sought to implement and analyze the impact of an HCV curriculum for primary care professionals (PCPs) across the state of Vermont, USA. This investigation was a retrospective analysis of uptake of a Vermont HCV educational curriculum and its impact on HCV direct-acting antiviral (DAA) prescribing rates within the state before and after the study period. The curriculum was delivered online and in-person over 2 years from 2019 to 2020. The primary outcome was health care professional performance on a pre- and post-curriculum short-term knowledge assessment exam. The secondary outcome was assessing the number of unique healthcare professionals within a single payor database prescribing DAA treatment for HCV in Vermont before and after the study intervention, from January 1, 2017 until December 1, 2021. There were 31 unique respondents on the pre- and post-intervention examinations, which represented 9% of known participants. Respondents included physicians (n = 15), nurse practitioners (n = 8), and nurses (n = 8). Pre- and post-intervention knowledge scores increased significantly across all provider groups, from 3.2 (SD 0.6) to 4.5 (SD 0.4) 1 to 5 scale (P = .01). The total number of unique HCV DAA therapy prescribers decreased over the study period, from 17 in 2017 to 9 in 2021. A Vermont statewide HCV curriculum for PCPs was successful at increasing short-term HCV-related knowledge. However, this did not obviously translate to an increase in new professionals treating HCV.

Incidence of primary hepatitis C virus infection among people who inject drugs in Australia pre- and post-unrestricted availability of direct acting antiviral therapies.

The 2016 Global Health Sector Strategy (GHSS) on viral hepatitis aims to reduce new hepatitis C virus (HCV) infections by 80% by 2030, including a 30% reduction by 2020. This study aimed to estimate primary HCV incident infection among a national sample of people who inject drugs (PWID) before and after the introduction of unrestricted access to HCV direct-acting antiviral (DAA) therapy via Australia's Pharmaceutical Benefits Scheme in 2016. A simple deterministic linkage method identified repeat respondents in serial cross-sectional surveys conducted among PWID. Two separate retrospective cohorts of HCV antibody-negative respondents were created, corresponding to the pre- (2010-15) and post- (2016-21) DAA time-periods. This study took place in Australia. Among 757 PWID retained (376 pre-DAA, 381 post-DAA), more than half were male (60%), the majority were heterosexual (80%), the median age was 40 years (interquartile range = 33-46 years) and the predominant drugs last injected were heroin (24%), pharmaceutical opioids (27%) and methamphetamine (41%). The primary outcome was HCV seroconversion, defined as a negative HCV antibody test result followed by a positive HCV antibody result. Time to primary incident HCV infection was estimated using the person-years (PY) method. A total 97 of 376 (2010-15) and 41 of 381 (2016-21) HCV seroconversions were identified. Primary HCV incidence more than halved, from 13.6 per 100 PY [95% confidence intervals (CI) = 11.2, 16.6] in 2010-15 to 5.4 per 100 PY (95% CI =3.9, 7.3) in 2016-21. The decline was independent of observed differences in demographic and drug use characteristics over the two time-periods (adjusted hazard ratio =0.47, 95% CI =0.31-0.69, P<0.001). Australia has had a 53% reduction in primary hepatitis C virus (HCV) incidence among people who inject drugs following unrestricted availability of HCV direct acting antiviral therapy in March 2016. Given that PWID are the predominant population at risk of HCV infection in Australia, findings add to the evidence that Australia has probably met its 2020 Global Health Sector Strategy subtarget of a 30% decline in new infections.

Transient elastography score is elevated during rheumatoid factor-positive chronic hepatitis C virus infection and rheumatoid factor decline is highly variable over the course of direct-acting antiviral therapy.

BackgroundElevated rheumatoid factor (RF) levels and systemic immune activation are highly prevalent during chronic hepatitis C virus (HCV) infection. Direct-acting antiviral (DAA) therapy has been associated with normalization of various soluble immune activation parameters. Whether the RF levels relate to soluble immune activation markers during chronic HCV infection, and over what time frame RF levels normalize during and after DAA treatment is unknown and was investigated here.MethodsIn a longitudinal study, plasma and serum was obtained from HCV infected RF positive (RF+) and RF negative (RF-) participants. The levels of RF, HCV RNA and soluble markers of inflammation were determined before (week 0), during (weeks 4, 8 and 12) and after (week 24) treatment with HCV DAA therapy. In a subset of RF+ participants, the analysis was extended to over 70 weeks after therapy initiation. Hepatic and other clinical parameters were determined at baseline (week 0) in all participants.ResultsBefore therapy, transient elastography (TE) score was greater in RF+ compared to RF- HCV infected participants, while the systemic levels of soluble inflammatory markers were comparable. Following DAA therapy initiation, HCV RNA levels became undetectable within 4 weeks in both the RF+ and RF- groups. RF levels declined in the first 6 months in most RF+ persons but most commonly remained positive. The levels of some soluble inflammatory markers declined, mainly within 4 weeks of DAA therapy start, in both the RF+ and RF- groups. The baseline (week 0) TE score correlated with RF levels before, during and after DAA therapy, while plasma IL-18 levels correlated with RF level after DAA therapy.ConclusionDuring chronic HCV infection, TE score is elevated in RF+ HCV infected individuals and factors other than HCV viremia (including liver stiffness or fibrosis and select markers of inflammation) likely contribute to persistence of RF after treatment of HCV with DAA.

Changes in the gut microbiota after hepatitis C virus eradication

The gut microbiota interacts with infectious diseases and affects host immunity. Liver disease is also reportedly associated with changes in the gut microbiota. To elucidate the changes in the gut microbiota before and after hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 patients who received DAA therapy for HCV. Fecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from fecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not significantly differ between Pre, EOT, and Post24. Principal coordinates analysis showed that for each patient, the values at Pre, EOT, and Post24 were concentrated within a small area. The linear discriminant analysis of effect size showed that the relative abundances of Faecalibacterium and Bacillus increased at EOT, further increased at Post24, and were significantly increased at Post24 compared to Pre. These suggest that changes in the gut microbiota should be considered as among the various effects observed on living organisms after HCV eradication.

Naïve CD4+ T Cell Lymphopenia and Apoptosis in Chronic Hepatitis C Virus Infection Is Driven by the CD31+ Subset and Is Partially Normalized in Direct-Acting Antiviral Treated Persons.

BackgroundThe mechanisms underlying naïve CD4+ lymphopenia during chronic Hepatitis C Virus (HCV) infection are unclear. Whether direct-acting antiviral (DAA) therapy restores peripheral naïve CD4+ T cell numbers and function is unknown.MethodsWe enumerated frequencies and counts of peripheral naïve CD4+, CD4+CD31+ and CD4+CD31- T cells by flow cytometry in a cross sectional analysis comparing chronic HCV infected (n=34), DAA-treated(n=29), and age-range matched controls (n=25), as well as in a longitudinal cohort of HCV DAA treated persons (n=16). The cross-sectional cohort was stratified by cirrhosis state. Cell apoptosis/survival (AnnexinV+7AAD+/BCL-2 labeling) and cell cycle entry (Ki67 expression) of CD31+ and CD31- naïve CD4+ T cells was analyzed directly ex vivo and following 3 and 5 days of in vitro culture with media, interleukin (IL) -7 or CD3/CD28 activator.ResultsIn the cross-sectional cohort, naïve CD4+ proportions were lower in chronic HCV infected persons compared to controls and DAA-treated persons, an effect in part attributed to cirrhosis. Age was associated with naïve cell counts and proportions in HCV infected and treated persons as well. Naïve CD4+ cell proportions negatively correlated with plasma levels of soluble CD14 following therapy in DAA-treated persons. Naïve CD4+ cells from HCV infected persons exhibited greater direct ex vivo apoptosis and cell-cycling compared to cells from DAA-treated persons and controls, and this was localized to the CD4+CD31+ subset. On the other hand, no remarkable differences in expression of BCL-2 or IL-7 Receptor (CD127) at baseline or following in vitro media or IL7 containing culture were observed. In the longitudinal cohort, naïve CD4+CD31+/CD31- ratio tended to increase 24 weeks after DAA therapy initiation.ConclusionsActivation and apoptosis of peripheral naïve CD4+CD31+ T cells appear to contribute to naïve CD4+ lymphopenia in chronic HCV infection, and this defect is partially reversible with HCV DAA therapy. Age and cirrhosis -associated naïve CD4+ lymphopenia is present both before and after HCV DAA therapy. These findings have implications for restoration of host immune function after DAA therapy.

Direct-acting antiviral treatment for Hepatitis C Virus in geriatric patients: a real-world retrospective comparison between early and late elderly patients.

IntroductionChronic hepatitis C virus (HCV) infection rates are high in the geriatric population considering that interferon-based therapy is usually intolerable. With the introduction of oral antiviral therapy for HCV, increased treatment tolerability and good treatment responses have been observed. However, treatment data regarding the geriatric population have been limited. Therefore, this retrospective study aimed to evaluate the efficacy and safety of direct-acting antiviral therapy for HCV in the geriatric population.Materials and MethodsThe primary end point was sustained virologic response (SVR) 12 weeks after treatment completion, whereas the secondary end points were treatment-related side effects and short-term survival rate following treatment.ResultsIn total, 492 patients (median age, 73 years; 43.9% males), including 278 early elderly patients, were enrolled. Among the included patients, 45% had cirrhosis. HCV genotypes 1 (72.4%) and 2 (25.4%) were the most common. The overall SVR rate was 96.7%, with no difference in SVR rates observed between early and late elderly groups (96.8% vs. 96.7%; p = 0.983). Both groups showed similar side effects, including dizziness (11.4%), and fatigue (8.7%), with three patients discontinuing therapy owing to side effects. Both groups had a similar 3-year survival rate. Significant factors associated with post-treatment survival included cirrhosis, albumin, and creatinine level.ConclusionsOur real-world data showed that both early and late elderly patients could undergo direct-acting antiviral treatment for HCV with excellent treatment outcomes.

Addressing HCV Elimination Barriers in Italy: Healthcare Resource Utilization and Cost Impact Using 8Weeks' Glecaprevir/Pibrentasvir Therapy.

IntroductionIn Italy, hepatitis C virus (HCV) elimination is achievable; however, barriers remain to achieving the World Health Organization’s elimination targets, and have become more pronounced with the spread of COVID-19. Glecaprevir/pibrentasvir (G/P) is a direct-acting antiviral therapy for HCV, approved for 8-week treatment in patients without cirrhosis, and with compensated cirrhosis (CC). Previously, 12 weeks of therapy was recommended for patients with CC. Shortened treatment may reduce the burden on healthcare resources, allowing more patients to be treated. This study presents the benefits that 8-week vs 12-week treatment with G/P may have in Italy.MethodsA multicohort Markov model was used to assess the collective number of healthcare visits and time on treatment with 8-week vs 12-week G/P in the HCV-infected population of Italy from 2019 to 2030, using healthcare resource data from post-marketing observational studies of G/P. Increased treatment capacity and downstream clinical and economic benefits were also assessed assuming the reallocation of saved healthcare visits to treat more patients.ResultsModeled outcomes showed that by 2030, 8-week treatment saved 27,006 years on therapy compared with 12-week treatment, with 21,065 fewer hepatologist visits. Reallocating these resources to treat more patients could increase capacity to treat 5064 (1.4%) more patients with 8 weeks of G/P, all with CC. This increased treatment capacity would further avoid 2257 cases of end-stage liver disease, 893 liver-related deaths, and provide net savings to the healthcare system of nearly €70 million.ConclusionThe modeled comparisons between 8- and 12-week treatment with G/P show that shorter treatment duration can lead to greater time and resource savings, both in terms of healthcare visits and downstream costs. These benefits have the potential to enable the treatment of more patients to overcome elimination barriers in Italy through programs aimed to engage and treat targeted HCV populations.

T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy.

BackgroundImmune activation markers associate with morbidity and mortality in HIV and hepatitis C virus (HCV) infection. We investigated how T-cell and monocyte activation are related over the course of HCV direct-acting antiviral (DAA) therapy during HCV/HIV coinfection.MethodsPeripheral blood mononuclear cells from AIDS Clinical Trials Group (ACTG) A5329 participants and a single-site separate cohort treated with DAAs were analyzed for central memory (CM)/effector memory (EM) T-cell subsets, monocyte subsets, and cell activation (CD38 and HLA-DR expression) before, during, and after therapy.ResultsBefore therapy, classical and inflammatory monocyte subset HLA-DR expression positively correlated with absolute counts and frequencies of CD38+HLA-DR+-expressing CD4+ and CD8 T cells and corresponding CM and EM subsets. After therapy initiation, CD38+HLA-DR+ co-expression on CD4+ and CD8+ memory T cells decreased by 12 weeks and 36 weeks, and plasma sCD14 positively correlated with CD38+HLA-DR+ CD4+ and CD4+CM T-cell frequencies. Monocyte subset activation remained similar over time.ConclusionsDuring HCV/HIV coinfection, memory T-cell activation is associated with monocyte subset activation, consistent with related underlying mechanisms. Following therapy initiation, memory T-cell, but not monocyte, activation decreased. Residual CD4+ T-cell activation after therapy completion is associated with sCD14, potentially linking the remaining CD4+ T-cell activation to residual factors driving activation in antiretroviral therapy–controlled HIV.

Patient-reported outcomes 12months after hepatitis C treatment with direct-acting antivirals: Results from the PROP UP study.

The long-term impact of hepatitis C virus (HCV) therapy with all-oral direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) has not been well-described. We characterized changes in PROs from pre-treatment to 12months post-treatment in a real-world cohort. PROP UP was a multi-centre observational cohort study of 1601 patients treated with DAAs at 11 US gastroenterology/hepatology practices from 2015 to 2017. PROs were evaluated pre-treatment (T1) and 12months post-treatment (T5). A minimally important change (MIC) threshold was prespecified as >5% change in PRO scores from T1 to T5. Multivariable analyses identified predictors of change. Three-quarters of patients were 55 or older; 45% were female, 60% were white, 33% were black, nearly half had cirrhosis. The most commonly-prescribed DAA regimens were sofosbuvir-based (83%) and grazoprevir/elbasvir (11%). Study retention was >95%. On average, small improvements were observed at 3months post-treatment in all PROs and sustained at 12months post-treatment among patients with sustained virologic response (SVR). Clinically meaningful improvements were achieved in fatigue (mean change score: -3.7 [-4.2, -3.1]), sleep (mean change score: -3.1 [-3.7, -2.5]), abdominal pain (mean change score: -2.6 [-3.3, -1.9]) and functional well-being (mean change score: -7.0 [-6.0, -8.0]). Symptom improvements were generally not sustained with no SVR (n=52). Patients with cirrhosis and MELD ≥12 had the greatest improvements in functional well-being (-12.9 [-17.6, -8.1]). The improvements in patient-reported outcomes reported by patients who achieved SVR following HCV DAA therapy were durable at 12months post-treatment.

Applying a diffusion of innovations framework to the scale-up of direct-acting antiviral therapies for hepatitis C virus infection: Identified challenges for widespread implementation

Background and AimsInterferon-free, direct-acting antivirals (DAAs) for hepatitis C virus (HCV) offer much promise to achieve World Health Organization targets by 2030. However, impediments at the practitioner and health-system level will continue to obstruct the scale-up of DAAs worldwide unless identified and acted upon. Applying a diffusion of innovations framework, the aim of this study was to identify structural factors impacting practitioner experiences of managing HCV treatment. MethodsIn-depth, semi-structured, telephone interviews took place between September 2018 and April 2019 to investigate barriers and facilitators for engaging in HCV management and DAA therapy amongst general practitioners (GPs) who prescribe opioid agonist therapy and drug and alcohol specialists in Australia. Interviews were transcribed verbatim, de-identified, and coded, and data were analysed with iterative categorisation and thematic analysis using Everett Rogers's diffusion of innovation framework. Resultsamongst 30 participants (12 GPs, 18 drug and alcohol specialists), several structural factors were reported to impede practitioner efforts to deliver optimal HCV care. Two primary themes were explored: contextual factors for the diffusion of DAA therapies, including attempts by participants to shift clinic culture and respond to siloed health structures, and adopter factors. Some participants chose to ‘rock the boat’ by circumventing clinic protocol and HCV guidelines to treat more clients, effectively shifting adopter categories to become greater advocates in HCV care. Also, while a role for GPs as the ‘new adopters’ in HCV management was discussed, many participants expressed uncertainty as to how much GPs should become involved in the diffusion of DAA therapies more widely. ConclusionsReducing the global burden of HCV infection will not be possible without the widespread delivery of HCV treatment amongst practitioners. Practitioners and health workers require leadership and resources from health authorities so that the individual and population-level benefits of DAA therapy are realised.

Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance A 2013 review for the US Preventive Services Task Force (USPSTF) of hepatitis C virus (HCV) screening found interferon-based antiviral therapy associated with increased likelihood of sustained virologic response (SVR) and an association between achieving an SVR and improved clinical outcomes. New direct-acting antiviral (DAA) regimens are available. Objective To update the 2013 review on HCV screening to inform the USPSTF. Data Sources Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through February 2019, with surveillance through September 2019. Study Selection Randomized clinical trials (RCTs) and nonrandomized treatment studies of HCV screening and DAA therapy; cohort studies on screening, antiviral therapy, and the association between an SVR after antiviral therapy and clinical outcomes. Data Extraction and Synthesis One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures Mortality, morbidity, quality of life, screening and treatment harms, and screening diagnostic yield. Results Eight RCTs of DAA therapy vs placebo or an outdated antiviral regimen, 48 other treatment studies, and 33 cohort studies, with a total of 179 230 participants, were included. No study evaluated effects of HCV screening vs no screening. One new study since the 2013 review (n = 5917) found similar diagnostic yield of risk-based screening (sensitivity, 82%; number needed to screen to identify 1 HCV case, 15) and birth cohort screening (sensitivity, 76%; number needed to screen, 29), assuming perfect implementation. Ten open-label studies (n = 3292) reported small improvements in some quality-of-life and functional outcomes (eg, less than 3 points on the 0 to 100 36-Item Short Form Health Survey physical and mental component summary scales) after DAA treatment compared with before treatment. Two cohort studies (n = 24 686) found inconsistent associations of antiviral therapy vs no therapy with risk of hepatocellular carcinoma. Forty-nine treatment studies (n = 10 181) found DAA regimens associated with pooled SVR rates greater than 95% across genotypes, and low short-term rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%). An SVR after antiviral therapy was associated with decreased adjusted risk of all-cause mortality (13 studies, n = 36 986; pooled hazard ratio [HR], 0.40 [95% CI, 0.28-0.56) and hepatocellular carcinoma (20 studies, n = 84 491; pooled HR, 0.29 [95% CI, 0.23 to 0.38]) vs no SVR. Conclusions and Relevance Direct evidence on the effects of HCV screening on clinical outcomes remains unavailable, but DAA regimens were associated with SVR rates greater than 95% and few short-term harms relative to older antiviral therapies. An SVR after antiviral therapy was associated with improved clinical outcomes compared with no SVR.

Direct-acting antiviral therapy for hepatitis C: The initial experience of the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa.

An estimated 600 000 South Africans are chronically infected with hepatitis C virus (HCV). To date, accurate prevalence data are lacking, but emerging data suggest a significant burden in key populations. Historically, pegylated interferon and ribavirin treatment was challenging, with access limited. The advent of all-oral, short-course direct-acting antiviral (DAA) therapy has revolutionised the management of HCV, being well tolerated and highly effective, although initial cost was a prohibitive factor. To report our initial 2-year experience with DAA therapy at the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa (SA). Patients who were viraemic for HCV were offered access to DAA therapy. All relevant demographic, virological, serological and clinical laboratory data were captured in a registry. Liver fibrosis was assessed non-invasively with the FibroScan. DAA regimens were prescribed according to current guidance based on HCV genotype (GT), prior treatment history and degree of fibrosis. On treatment, virological response was recorded and a sustained virological response (SVR) was defined as an undetectable HCV RNA at least 12 weeks after the end of treatment. We report on the first 210 patients treated. Their median (interquartile range (IQR)) age was 52 (42 - 61) years and 65% were male, with men significantly younger than women at 50 (42 - 59) years v. 58 (47 - 67) years, respectively (p=0.001). All GTs were observed, with 1 and 5 most prevalent at 45% and 20%, respectively, and GTs 2, 3 and 4 frequencies of 7%, 11% and 17%, respectively. Extensive subtype diversity for GTs 2 and 4 was present. The median (IQR) HCV viral load was log10 5.9 IU/mL (5.4 - 6.5). A significant proportion of patients (39%) had advanced fibrosis or cirrhosis, with 11% F3 fibrosis and 28% F4. Of those with cirrhosis, 12% were decompensated with Childs-Pugh B or C disease. Of the patients, 19% were HIV co-infected and 2% HBV co-infected. In total, 13% were treatment experienced. The majority of patients were treated with sofosbuvir and ledipasvir (38%), daclatasvir (36%) or velpatasvir (± voxilaprevir, 9%). Less frequent combinations included partitaprevir, ritonavir, ombitasvir ± dasbuvir (11%) and sofosbuvir/ribavirin (5%). The per-protocol SVR was 96% (98% if sofosbuvir/ribavirin is excluded). The majority of treatment failures occurred with GT-4, notably subtype 4r. Mild side-effects were reported in 10% of patients, with none discontinuing therapy. DAA therapy for HCV in a pan-genotypic group of patients, many with advanced liver disease, was highly effective. Our outcomes correspond with existing trial and real-world data for similar treatment. DAA therapy and access need rapid upscaling in SA, especially targeting key populations at point of care.

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir±ribavirin (SOF/LDV±RBV), ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir+ribavirin (SOF+RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV±RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r+DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

362. Hepatitis C Virus (HCV) Co-Infection in Women Living with Human Immunodeficiency Virus (HIV) in Northwest Louisiana

BackgroundHIV and HCV infection are emerging global public health problems. People living with untreated HIV infection have higher HCV viral loads and more rapid HCV disease progression with twice the rates of perinatal HCV transmission. Data are lacking in HCV coinfected women living with HIV. Our study reviewed underrepresented minority group of women living with HIV/HCV in Northwestern Louisiana to better understand epidemiology, risk factors and access to care among this cohort.MethodsWomen with HIV/HCV coinfection aged 18–70 years who presented to an academic medical center between November 2011 and November 2018 were included for analysis. A retrospective chart review was conducted. Data were collected and analyzed on demographics (age, race), risk factors (sexual history, drug use), HIV (viral load, CD4 count, antiretroviral treatment (ART)), and HCV (viral load level and antibody, genotype, alanine transaminase, liver fibrosis, liver cirrhosis, referral, and treatment).ResultsA total of 41 patients met our inclusion criteria. The mean age was 52 years. Of these HIV/ HCV coinfected women, 27 (66%) were African American and 14 (34%) Caucasian. 18 (44%) had history of Injection drug use. Thirty-nine out of 41 (95%) were linked to HIV care and on antiretroviral therapy with 36 (88%) with CD4 count >200. Twenty-three out of 41 (56%) was referred for HCV treatment but only 11 (26%) co-infected patients received treatment for HCV.ConclusionIn this cohort of HCV/HIV coinfected women, only 26% of the women received HCV treatment. Some of the barriers include access to providers, linkage to care and behavioral and socioeconomic factors. The lack of timely appropriate HCV care in this underserved high-risk population is alarming especially in the current era of highly effective direct-acting antiviral therapy for HCV. Despite improved HIV care, further work needs to focus on optimizing HCV screening, linkage and treatment uptake in order to overcome multiple barriers to HCV elimination in this patient population.Disclosures All authors: No reported disclosures.

Is direct acting antiviral therapy for hepatitis c viral infection associated with increased risk of hepatocellular carcinoma before or after liver transplantation?

Direct acting antiviral (DAA) therapy revolutionized the curative therapy for >90% of hepatitis C virus (HCV) infected patients. Initially, in late 2016, concerns were raised by several European centers that DAA therapy may be increasing the incidence of hepatocellular carcinoma (HCC) recurrence or de novo HCC ( Table 1 ). Singal et al . (1) compared the frequency of HCC recurrence in patients who received DAA therapy for HCV versus patients who did not receive DAA, among patients with HCV positive patients associated HCC, cured with complete response by various modalities [resection, trans arterial chemo embolization (TACE), local ablation, stereotactic body radiation therapy (SBRT) or other methods].

Chronic Hepatitis B in US Veterans.

This review summarizes recent data on chronic Hepatitis B virus (HBV) epidemiology, issues in special populations undergoing immunosuppressive and hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy, and describes care delivery, adherence to guideline-recommended care, and barriers to access to care and high-quality care for chronic HBV. Chronic HBV is present in up to 1% of veterans and is more than in the general US population. HBV associated with more advanced liver disease in HCV, HIV, and delta hepatitis co-infection. Recent data on HBV reactivation show a substantial risk of reactivation with anti-CD20 antibodies, no documented cases of reactivation with anti-tumor necrosis factor (anti-TNF) therapy, and a low risk of reactivation with HCV DAA therapy. Adherence to guideline-recommended care for HBV is suboptimal for many quality indicators. Important studies in HBV epidemiology, long-term outcomes and care delivery practices have been conducted in the VA. Future studies should prospectively investigate how to improve guideline-recommended care for HBV.

Pharmacokinetics and important drug-drug interactions to remember when treating advanced chronic kidney disease patients with hepatitis C direct acting anti-viral therapy.

Hepatitis C direct acting antiviral (DAA) therapy has evolved so that infected patients with advanced chronic kidney disease (CKD) can now anticipate the opportunity for sustained virologic response equivalent to that of the broader population of patients with hepatitis C. This has revolutionized the field of transplantation as it relates to renal transplant candidates with hepatitis C and the use of grafts from hepatitis C virus (HCV) viremic donors. In treating this population of patients, special consideration must be given to the timing of anti-viral therapy and drug-drug interactions. Herein we review the pharmacokinetics of HCV DAA therapy in the setting of CKD and chronic renal replacement therapy. Highlighted are drug/drug interactions with special attention to therapies utilized in advanced CKD and immunosuppressants.

Patterns of practice and barriers to care for hepatitis C in the direct-acting antiviral (DAA) era: A national survey of Canadian infectious diseases physicians.

Infectious diseases (ID) physicians are important for hepatitis C virus (HCV) care delivery in Canada. Our study describes their current and intended patterns of practice, attitudes, and barriers to care. The study population includes 372 practicing ID physicians who are members of the Association of Medical Microbiology and Infectious Disease (AMMI) Canada. A random sample from each province was invited to participate in a web-based survey. Our outcome of interest was level of HCV care provided, and related intentions for the next 12 months. Additional survey domains included attitudes toward treatment and perceived barriers to care. Of 205 invitations to complete the survey, 64 (31%) physicians responded to the full survey and 81 to an abbreviated survey on the main outcomes of interest (overall response rate 71%). After adjusting for non-response, we estimate that 38% (95% CI 29% to 46%) are prescribing direct-acting antiviral (DAA) therapy, and 17% (95% CI 9% to 24%) are interested in starting to prescribe. Of full survey respondents, 100% of prescribers and 79% of non-prescribers agreed that people who inject drugs should be offered DAA therapy. Common barriers to care include patients' competing priorities, mental health comorbidities, poor access to harm reduction services, and insufficient physician training. A large proportion of Canadian ID physicians are not currently prescribing DAA therapy for HCV. While some of these physicians are interested in starting to prescribe, we need strategies to improve physician training and address other barriers to care as provincial restrictions on DAA eligibility are being eliminated.

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.