Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Brandão, Ruben; Marcelino, Rute; Gonçalves, Fátima; Diogo, I; Carvalho, Ana Patrícia; Cabanas, Joaquim; Costa, Isabel; Brogueira, Pedro; Ventura, Fernando; Miranda, Ana Cláudia Carvalho de; Kamal, Mehnaz; Gómes, Perpétua

doi:10.3390/v10050223

Cited by 9 publications

(14 citation statements)

References 51 publications

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“…This mutation confers low-level resistance to dasabuvir and has been reported in patients failing treatment with sofosbuvir 85 , 86 . The relatively high prevalence of C316N in our patients is in line with previous reports showing a prevalence of C316N ranging from 11% to 40% in patients with GT1b enrolled in clinical trials, and this mutation was more frequent among European subjects than among those from the United States 87 , 88 . It should be noted that in the AVIATOR trial that evaluated ritonavir-boosted paritaprevir, ombitasvir and dasabuvir, the C316N RAS at baseline had no significant impact on treatment outcome 87 .…”

Section: Discussionsupporting

confidence: 92%

Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

Palladino

Ezeonwumelu

Marcelino

et al. 2018

Sci Rep

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Any successful strategy to prevent and control HCV infection requires an understanding of the epidemic behaviour among the different genotypes. Here, we performed the first characterization of the epidemic history and transmission dynamics of HCV subtypes in Portugal. Direct sequencing of NS5B was performed on 230 direct-acting antiviral drugs (DAA)-treatment naïve patients in Lisbon. Phylogenetic analysis was used for subtyping and transmission cluster identification. Bayesian methods were used to reconstruct the epidemic history of HCV subtypes. Sequences were analysed for resistance-associated substitutions (RAS). The majority of strains were HCV-GT1 (62.6%), GT3 (18.3%, all subtype 3a) and GT4 (16.1%). Among GT1, the most frequent were subtypes 1a (75.5%) and 1b (24.5%). Polyphyletic patterns were found in all but 12 lineages suggesting multiple introductions of the different subtypes in this population. Five distinct epidemics were identified. The first significant HCV epidemic in Portugal occurred between 1930s and 1960s, was caused almost exclusively by GT1b and was likely associated with blood transfusions. Rapid expansion of GT3a occurred in the 1960s and GT1a in the 1980s, associated with intravenous drug use. The most recent epidemics were caused by GT4a and GT4d and seem to be associated with the resurgence of opioid use. The C316N substitution was found in 31.4% of GT1b-patients. Close surveillance of patients bearing this mutation and undergoing dasabuvir-based regimens will be important to determine its impact on treatment outcome.

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Section: Discussionsupporting

confidence: 92%

Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

Palladino

Ezeonwumelu

Marcelino

et al. 2018

Sci Rep

Self Cite

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“…In Uruguay, these therapies became recently available, and although some have been approved for their use by the public health authorities (Viekira pak and sofosbuvir/ledipasvir therapies), they are not currently financially covered, except in specific cases. Despite the high rates of viral response achieved with DAA-based treatments, still 1 to10% of the patients fails to eliminate infection, and in these cases, baseline and emergent resistance variants turn out to be key factors contributing to treatment failure [ 5 , 17 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of substitutions conferring resistance to NS5A inhibitors has been widely reported both in therapy-naïve and in relapser patients from Europe [ 10 , 33 , 35 – 38 ], USA [ 37 , 39 , 40 ], and Asia [ 41 – 43 ]. However, NS5A sequences from South America are poorly analyzed yet [ 9 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

et al. 2018

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Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

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“…Virologic failure with ledipasvir-sofosbuvir has been associated with several NS5A mutations that reduce susceptibility to ledipasvir, most commonly Q30R, Y93H/N, and L31M in subtype 1a virus and Y93H in subtype 1b virus [4]. Approximately 20% of genotype 1 viruses harbor polymorphisms that confer reduced susceptibility to ledipasvir [11]. Mutational analysis testing for NS5A mutations is now commercially available.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular Carcinoma After Successful Treatment of Hepatitis C Virus with Ledipasvir/Sofosbuvir Presenting as Acute Pulmonary Tumor Embolism

Habib¹,

Azam²,

Siddiqui³

et al. 2019

Cureus

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Hepatitis C virus (HCV)-induced cirrhosis is a major cause of hepatocellular carcinoma (HCC) worldwide. HCC is an aggressive malignancy in which tumor thrombus can invade portal vein, hepatic veins and inferior vena cava (IVC) in the later stages. Our case brings to attention, HCV patient population who might need long-term follow-up to ensure HCV clearance. Physicians should ensure appropriate follow-up after treatment of HCV and should emphasize on the ongoing screening for HCC in patients with cirrhosis or advanced fibrosis, regardless of antiviral treatment outcome.

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Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Cited by 9 publications

References 51 publications

Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

Hepatocellular Carcinoma After Successful Treatment of Hepatitis C Virus with Ledipasvir/Sofosbuvir Presenting as Acute Pulmonary Tumor Embolism

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