Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.
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ABSTRACT:
SUBMITTER: Cuypers L
PROVIDER: S-EPMC6059487 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The risk of hepatitis C virus (HCV) recurrence after direct-acting antiviral (DAA) treatment is <0.5%. However, the distinction between HCV RNA late relapse and reinfection still represents a challenge in virological diagnostics. The aim of this study was to employ next-generation sequencing (NGS) to investigate HCV RNA recurrence in patients achieving a sustained virologic response (SVR) at least six months post-treatment. NGS was performed on plasma samples from six HCV-positive patients (Pt1-6) treated with DAA. NGS of HCV NS5B was analyzed before treatment (T0), after HCV RNA rebound (T1), and, for Pt3, after a second rebound (T2). Reinfection was confirmed for Pt5, and for the first rebound observed in Pt3. Conversely, viral relapse was observed when comparing T0 and T1 for Pt6 and T1 and T2 for Pt3. Z-scores were calculated and used to predict whether HCV-positive patient samples at different time points belonged to the same quasispecies population. A low Z-score of <2.58 confirmed that viral quasispecies detected at T0 and T1 were closely related for both Pt1 and Pt2, while the Z-score for Pt4 was suggestive of possible reinfection. NGS data analyses indicate that the Z-score may be a useful parameter for distinguishing late relapse from reinfection.
| S-EPMC8235384 | biostudies-literature
Project description:BackgroundHepatitis C virus (HCV) education may be changing following the simplification of HCV treatment and emergence of direct acting antiviral (DAA). We aimed to characterize HCV knowledge among people who recently completed DAA therapy.MethodsThe Per-SVR (Preservation of Sustained Virologic Response) is a prospective cohort of patients who achieved a sustained virologic response upon successful completion of DAA therapy. The per-SVR study provided the sampling frame of participants who completed a psychometrically validated 19-item HCV knowledge scale at cohort entry (n = 227). To score the questionnaire, for each correct response one point was awarded, with no point for incorrect response. We assessed mean HCV knowledge score in the overall sample and mutually exclusive populations: people who inject drug (PWID) (n = 71); people with co-occurring HIV (n = 23); PWID and co-occurring HIV (n = 29), and others (n = 104) Using a latent class analysis based on distal outcome, we identified unobserved subgroups and assessed HCV knowledge amongst them.ResultsTotal mean (SD) percent of correct responses were 83 (11) in the overall sample; 83 (10) in PWID; 79 (12) in people with co-occurring HIV; 81 (10) in PWID and co-occurring HIV, and 84 (11) in rest of the sample Three latent groups were identified: baby boomers who ever experienced homelessness (n = 126); women sex workers who ever experienced homelessness (n = 68); men who inject drug, ever experienced homelessness and had ever diagnosis of mental health disorders (n = 18). Mean percent of correct responses were 85 (8), 82 (11), 85 (10), in latent class 1, 2, and 3, respectively.ConclusionPatients successfully treated with DAAs had a high HCV knowledge. High knowledge and awareness of reinfection among complex patient groups often facing barriers to HCV care is encouraging and emphasizes the positive outcomes of universal access to treatment.
| S-EPMC8942206 | biostudies-literature
Project description:BackgroundHepatitis C virus (HCV) remains under-treated in the United States and treatment by nonspecialist providers can expand access. We compare HCV treatment provision and treatment completion between nonspecialist and specialist providers.MethodsThis retrospective study used claims data from the Healthcare Cost Institute from 2013 to 2017. We identified providers who prescribed HCV therapy between 2013 and 2017, and patients enrolled in private insurance or Medicare Advantage who had pharmacy claims for HCV treatment. We measured HCV treatment completion, determined based on prescription fills for the minimum expected duration of the antiviral regimen. Using propensity score-weighted regression, we compared the likelihood of early treatment discontinuation by the type of treating provider.ResultsThe number of providers prescribing HCV treatment peaked in 2015 and then declined. The majority were gastroenterologists, although the proportion of general medicine providers increased to 17% by 2017. Among the 23,463 patients analyzed, 1008 (4%) discontinued before the expected minimum duration. In the propensity score-weighted analysis, patients treated by general medicine physicians had similar odds of treatment discontinuation compared with those treated by gastroenterologists [odds ratio (OR)=1.00, 95% confidence interval (CI): 0.99-1.01, P=0.45]. Results were similar when comparing gastroenterologists to nonphysician providers (OR=1.00, 95% CI: 0.99-1.01, P=0.53) and infectious diseases specialists (OR=1.00, 95% CI: 0.99-1.01, P=0.71).ConclusionsHCV treatment providers remain primarily gastroenterologists, even in the current simplified treatment era. Patients receiving treatment from general medicine or nonphysician providers had a similar likelihood of treatment completion, suggesting that removing barriers to the scale-up of treatment by nonspecialists may help close treatment gaps for hepatitis C.
| S-EPMC8384709 | biostudies-literature
Project description:Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. We then performed a cost-effectiveness analysis comparing LA-DAAS to DAA alone in various patient groups, including people who inject drugs. Tunable release kinetics of DAAs was enabled for 1 mo with drug-polymer pills in vitro, and the LA-DAAS safely and successfully provided at least month-long release of sofosbuvir in vivo. Temperature and alcohol sensors could interface with external sources for at least 1 mo. The LA-DAAS was cost-effective compared to DAA therapy alone in all groups considered (base case incremental cost-effectiveness ratio $39,800). We believe that the LA-DAA system can provide a cost-effective and patient-centric method for HCV treatment, including in high-risk populations who are currently undertreated.
| S-EPMC7275718 | biostudies-literature
Project description:Around 71 million people are chronically infected with HCV worldwide. HCV antiviral drug development has been remarkable. The availability of pangenotypic direct-acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN-free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8-12 weeks of treatment. Programmes to eliminate HCV must include increased screening (risk-based and universal), linkage to care, as well as increased access to treatment worldwide. In this paper, we will review the available data on recently approved direct-acting antiviral agents, with sustained virological response that reaches almost 100%.
| S-EPMC7713514 | biostudies-literature
Project description:UnlabelledHepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events.ConclusionSVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression.
| S-EPMC4718772 | biostudies-literature
Project description:The first interferon-free regimens have been approved for the treatment of patients with chronic hepatitis C virus (HCV). In the liver transplant (LT) setting, these regimens are expected to have an important effect, because graft loss due to HCV recurrence is a serious problem after LT. The response to the hitherto conventional treatment with pegylated interferon and ribavirin is poor. The significantly better response rates achieved with boceprevir-based and telaprevir-based triple therapy have led to better graft and patient survival rates, but severe drug interactions with immunosuppressants limit the feasibility of this therapy for LT patients. With the approval of sofosbuvir in January 2014, of simeprevir in May 2014, and of daclatasvir in August 2014, three antiviral agents are now available and promise to be applicable without relevant adverse effects or negative interactions with immunosuppressants. Thus, 2014 marks the beginning of a new era of treatment options for HCV recurrence after LT. Although safety and efficacy studies of several interferon-free regimens for patients with HCV recurrence after LT have achieved good preliminary results, reports of clinical experiences with LT patients are scarce. The lack of randomized studies, the small number of enrolled and carefully selected patients, and the heterogeneity of these studies make the results questionable. Real-life experiences are eagerly awaited so that clinicians can estimate the usefulness and the pitfalls of these new regimens. Additionally, the high costs of these agents may limit their accessibility for many patients. The aim of this review is to summarize the current experience with and the expectations of the new direct-acting antiviral agents for LT patients.
| S-EPMC4381175 | biostudies-literature
Project description:Importance: Direct-acting antiviral (DAA) drugs are highly effective in curing hepatitis C virus (HCV) infection. Previous simulations showed extended life as a key health advantage of DAA drugs, but real-world evidence on the association between DAA treatment and reduced mortality is limited.Objectives: To examine the association of DAA treatment with mortality among Medicare beneficiaries with hepatitis C.Design, setting, and participants: This cohort study used Medicare claims data of beneficiaries who sought hepatitis C care for the first time between January 1, 2014, and December 31, 2016, after at least a 1-year washout period. Medicare Part D files were used in identifying DAA therapy initiation and completion. Death dates, demographic data, and indicators of health risks were obtained from the Master Beneficiary Summary Files. Beneficiaries with hepatitis C were considered as patients with DAA treatment if they initiated DAA therapy during the study period. Beneficiaries with hepatitis C who did not initiate DAA therapy during the study period were considered as patients without DAA treatment. Patients without DAA treatment were selected using 1-to-1 propensity score matching. Data were analyzed between September 1, 2019, and March 31, 2020.Exposures: Completion of DAA treatment.Main outcomes and measures: Time to death from the index date of seeking hepatitis C care after at least a 1-year washout period. Cox proportional hazards regression models with time-varying exposure were used to compare mortality rates between propensity score-matched cohorts of patients with DAA treatment and those without DAA treatment. Separate analyses were performed for patients with or without cirrhosis. Heterogeneity in the association between DAA treatment and mortality by sex and dual-eligibility status was examined.Results: A propensity score-matched sample of 51?478 Medicare beneficiaries with a mean (SD) age of 59.4 (11.1) years and 30 473 men (59.2%) was assessed. Of this total, 8240 patients (16.0%) had cirrhosis (5224 men [63.4%]; mean [SD] age, 62.3 [9.7] years) and 43?238 patients (84.0%) had no cirrhosis (25 249 men [58.4%]; mean [SD] age, 58.8 [11.3] years). The adjusted hazard ratio (HR) of dying between patients with DAA treatment and those without DAA treatment in the cirrhosis group was 0.51 (95% CI, 0.46-0.57). The association of DAA treatment with mortality did not differ by sex (women vs men: HR, 0.46 [95% CI, 0.38-0.56] vs HR, 0.53 [95% CI, 0.47-0.60]; P?=?.27) or dual-eligibility status (non-dual-eligible HR, 0.52 [95% CI, 0.43-0.63] vs dual-eligible HR, 0.50 [95% CI, 0.44-0.57]; P?=?.80) in the cirrhosis group. The adjusted HR of dying between patients with DAA treatment and those without DAA treatment among patients without cirrhosis was 0.54 (95% CI, 0.50-0.58). The association of DAA treatment with mortality did not differ by sex (women vs men: HR, 0.53 [95% CI, 0.46-0.60] vs HR, 0.55 [95% CI, 0.50-0.60]; P?=?.66) among patients without cirrhosis. However, the survival advantage associated with DAAs for non-dual-eligible beneficiaries was statistically significantly higher than for dual-eligible beneficiaries among patients without cirrhosis (HR, 0.47 [95% CI, 0.41-0.55] vs HR, 0.57 [95% CI, 0.52-0.62]; P?=?.02).Conclusions and relevance: In this cohort study, DAA treatment appeared to be associated with a decrease in mortality among Medicare beneficiaries with or without cirrhosis. These findings suggest that increasing access to DAA drugs for all patients with HCV infection, regardless of disease progression, could improve population health.
| S-EPMC7737657 | biostudies-literature
Project description:The introduction of small molecules targeting viral functions has caused a paradigm shift in hepatitis C virus (HCV) treatment. Administration of these direct-acting antivirals (DAAs) achieves a complete cure in almost all treated patients with short-duration therapy and minimal side effects. Although this is a major improvement over the previous pegylated interferon plus ribavirin (PEG-IFNα/RBV) standard-of-care treatment for HCV, remaining questions address several aspects of the long-term benefits of DAA therapy. Interferon (IFN)-based treatment with successful outcome was associated with substantial reduction in liver disease-related mortality. However, emerging data suggest a complex picture and several confounding factors that influence the effect of both IFN-based and DAA therapies on immune restoration and limiting liver disease progression. We review current knowledge of restoration of innate and HCV-specific immune responses in DAA-mediated viral elimination in chronic HCV infection, and we identify future research directions to achieve long-term benefits in all cured patients and reduce HCV-related liver disease morbidity and mortality.
| S-EPMC9202797 | biostudies-literature
Project description:AIM:To evaluate the efficacy of direct-acting antivirals (DAAs) in Kanto Rosai Hospital. METHODS:All patients with hepatitis C virus (HCV) who underwent DAA prescription were enrolled in this study. The present study was a single center retrospective analysis using patients infected with HCV genotype 1 or 2. Resistance analysis was performed by using direct sequencing and cycleave PCR in genotype 1 patients treated with interferon (IFN)-free DAA. The primary endpoint was sustained virologic response at 12 wk after therapy (SVR12). RESULTS:A total of 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + IFN + ribavirin and all achieved SVR. Of the 119 patients who received IFN-free DAA (in different combinations), 102 achieved SVR and 9 failed (7/9 were on daclatasvir/asunaprevir and 2/9 on ledipasvir/sofosbuvir). Efficacy analysis was done only for 43 patients who received daclatasvir/asunaprevir. From this analysis, Y93 resistance-associated substitutions were significantly correlated with SVR. CONCLUSION:The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5A resistance-associated substitutions that are selected by HCV NS5A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.
| S-EPMC5787689 | biostudies-literature