scholarly journals Hepatitis C Virus Variants with Decreased Sensitivity to Direct-Acting Antivirals (DAAs) Were Rarely Observed in DAA-Naive Patients prior to Treatment

2012 ◽  
Vol 87 (3) ◽  
pp. 1544-1553 ◽  
Author(s):  
Doug J. Bartels ◽  
James C. Sullivan ◽  
Eileen Z. Zhang ◽  
Ann M. Tigges ◽  
Jennifer L. Dorrian ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Viral Response ◽  
Allosteric Inhibitors ◽  
Resistant Variant ◽  
Direct Acting Antiviral ◽  
Treatment Naïve ◽  
Variant Frequency ◽  
Direct Acting ◽  
Ns5b Polymerase

ABSTRACTThe prevalence of naturally occurring hepatitis C virus (HCV) variants that are less sensitive to direct-acting antiviral (DAA) inhibitors has not been fully characterized. We used population sequence analysis to assess the frequency of such variants in plasma samples from 3,447 DAA-naive patients with genotype 1 HCV. In general, HCV variants with lower-level resistance (3- to 25-fold increased 50% inhibitor concentration [IC50]) to telaprevir were observed as the dominant species in 0 to 3% of patients, depending on the specific variant, whereas higher-level resistant variants (>25-fold-increased IC50) were not observed. Specific variants resistant to NS5A inhibitors were predominant in up to 6% of patients. Most variants resistant to nucleo(s/t)ide active-site NS5B polymerase inhibitors were not observed, whereas variants resistant to non-nucleoside allosteric inhibitors were observed in up to 18% of patients. The presence of DAA-resistant variants in NS5A, NS5B, or NS3 (including telaprevir-resistant variants), in baseline samples of treatment-naive patients receiving a telaprevir-based regimen in phase 3 studies did not affect the sustained viral response (SVR). Treatment-naive patients with viral populations containing the telaprevir-resistant variants NS3 V36M, T54S, or R155K at baseline achieved a 74% SVR rate, whereas patients with no resistant variants detected prior to treatment achieved a 76% SVR rate. The effect of specific resistant variant frequency on response to various DAA treatments in different patient populations, including interferon nonresponders, should be further studied.

scholarly journals Hepatitis C-vírus-fertőzés és hepatocarcinogenesis

2019 ◽  
Vol 160 (22) ◽  
pp. 846-853
Author(s):  
Evelin Berta ◽  
Anna Egresi ◽  
Anna Bacsárdi ◽  
Zsófia Gáspár ◽  
Gabriella Lengyel ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Primary Liver Cancer ◽  
Antiviral Agents ◽  
Sustained Viral Response ◽  
Abdominal Ultrasound ◽  
Viral Response ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract: Hepatitis C virus infection causes approximately 4 million new infections worldwide, and 399 000 deaths due to its complications, cirrhosis and hepatocellular carcinoma (HCC). Microenvironmental changes, chronic inflammation, oxidative stress, endoplasmic reticulum stress caused by HCV infection, via genetic and epigenetic changes can result in primary liver cancer during decades. The direct oncogenic property of HCV is wellknown. The transforming effect of four HCV proteins (core, NS3, NS4B, NS5A) has been proven. Effective antiviral therapy, sustained viral response decreases the HCV-related general and liver-related mortality. Interferon-based therapy reduces the risk of HCC development. Shorter therapy with direct acting antiviral agents (DAA) has higher efficacy, fewer side-effects. Publications have reported the unexpected effects of DAA. The authors review the articles focusing on the occurrence of HCC in connection with DAA therapies. There is a need for prospective, multicentric studies with longer follow-up to examine the risk of HCC formation. After antiviral therapy, HCC surveillance is of high importance which means abdominal ultrasound every 3–6–12 months in sustained viral response patients as well. Orv Hetil. 2019; 160(22): 846–853.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Fabián Aldunate ◽  
Natalia Echeverría ◽  
Daniela Chiodi ◽  
Pablo López ◽  
Adriana Sánchez-Cicerón ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
South American ◽  
Genotype 1 ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Before And After ◽  
Treatment Naïve ◽  
Direct Acting

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.

Tratamiento de hepatitis crónica por virus de Hepatitis C con drogas antivirales de acción directa en un paciente con fibrosis quística

2021 ◽  
Vol 51 (1) ◽  
Author(s):  
José Daniel Bosia ◽  
María Virginia D´Ascenzo ◽  
Silvia Mabel Borzi ◽  
Ezequiel Barán ◽  
María Cecilia Calzona
Keyword(s):  
Cystic Fibrosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Sustained Viral Response ◽  
Antiviral Drugs ◽  
Hepatitis C Virus Infection ◽  
Direct Acting Antiviral ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting

The development of new direct acting antiviral drugs for the treatment of Hepatitis C virus infection, has made it possible to obtain an excellent cure rate and extend the indications for eradication of Hepatitis C virus to previously very difficult populations to treat like cystic fibrosis, in whom treatment with classic regimens based on pegylated Interferon plus ribavirin could favor worsening lung function. We present a case of a 41-year-old man with cystic fibrosis, diagnosed with Hepatitis C virus infection, genotype 1a, non-cirrhotic, treated with direct acting antiviral drugs for twelve weeks, obtaining a sustained viral response, without adverse effects. One year later, being on the waiting list, underwent a bipulmonary transplant.

scholarly journals Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhanyi Li ◽  
Ying Liu ◽  
Ying Zhang ◽  
Xiaoqiong Shao ◽  
Qiumin Luo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Ns5a Region ◽  
Treatment Naïve ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

Background and Objective. The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4). Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

scholarly journals HIV Coinfection Predicts Failure of Ledipasvir/Sofosbuvir in Treatment-Naïve Noncirrhotic Patients With HCV Genotype 1

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Juan Berenguer ◽  
José Luis Calleja ◽  
María Luisa Montes ◽  
Ángela Gil ◽  
Ana Moreno ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Hiv Infection ◽  
Treatment Failure ◽  
Sustained Viral Response ◽  
Liver Stiffness ◽  
Hcv Rna ◽  
Multivariable Logistic Regression Model ◽  
Direct Acting Antiviral ◽  
Treatment Naïve ◽  
Direct Acting

Abstract Background The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)–monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV. Methods We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV. Results Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27–4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13–4.38; P = .020). Conclusions The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.

Acute hepatitis C virus infection and direct-acting antiviral drugs: Perfect combination to eliminate the epidemic?

2021 ◽  
pp. 095646242110337
Author(s):  
Cristina Gómez-Ayerbe ◽  
Rosario Palacios ◽  
Maria J Ríos ◽  
Francisco Téllez ◽  
Carmen Sayago ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Median Time ◽  
Sustained Viral Response ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Acute Hepatitis C ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Incident Cases

Early diagnosis and treatment of incident cases of hepatitis C virus (HCV) infection is fundamental to eliminate HCV in HIV-positive patients. From January 2016 to December 2019, we attended 40 episodes of acute HCV infection (AHC) in 35 subjects (9 reinfections) who were coinfected with HIV. The patients were treated with direct-acting antiviral agents (DAAs) in seven hospitals in Andalusia, Spain. All were men who have sex with men (MSM), mean age was 42.9 (±8.3) years and median time of HIV infection was 46.6 months (IQR: 20.4–67.2). All received antiretroviral therapy and had undetectable HIV viral load (except 2 with 65 and 68 copies/mL); median CD4 count was 632 cells/mm3 (IQR: 553–896). Over half (74.3%) also had another concomitant sexually transmitted infection, syphilis (48.6%) being the most common. AHC was asymptomatic in 32 cases (80%). Genotypeic distribution was G1a 65%, G4 32.5% and G1b 3%. Median time to DAA was 6 weeks (IQR: 4.3–18.3) and median baseline HCV RNA was 6.1 Log (IQR: 5.6–6.5). DAA regimens were SOF/LDV (19 episodes), SOF/VEL (14), ELB/GZV (5) and GLP/PIB (2). All presented sustained viral response and none discontinued due to adverse effects. In conclusion, early treatment with DAA in AHC patients proved effective and safe. It could be an excellent strategy to eliminate HCV infection in HIV-coinfected MSM.

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