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Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

ABSTRACT: Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.

SUBMITTER: Cuypers L

PROVIDER: S-EPMC6059487 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

Cuypers Lize L Pérez Ana Belén AB Chueca Natalia N Aldamiz-Echevarría Teresa T Alados Juan Carlos JC Martínez-Sapiña Ana María AM Merino Dolores D Pineda Juan Antonio JA Téllez Francisco F Espinosa Nuria N Salméron Javier J Rivero-Juarez Antonio A Vivancos María Jesús MJ Hontañón Víctor V Vandamme Anne-Mieke AM García Féderico F

PloS one 20180725 7

Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virolog ...[more]

PMID: 30044871

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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.

Project description:ImportanceDirect-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.ObjectivesTo examine the association of DAA treatment with mortality among Medicare beneficiaries with hepatitis C.Design, setting, and participantsThis 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.ExposuresCompletion of DAA treatment.Main outcomes and measuresTime 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.ResultsA 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 relevanceIn 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.

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Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

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Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

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