Virological Factors Associated with Failure to the Latest Generation of Direct Acting Agents (DAA) and Re-Treatment Strategy: A Narrative Review

The availability of all oral direct acting antiviral agents (DAAs) has revolutionized the management of HCV infections in recent years, allowing to achieve a sustained virological response (SVR) in more than 95% of cases, irrespective of hepatitis C Virus (HCV) genotype or staging of liver disease. Although rare, the failure to the latest-generation regimens (grazoprevir/elbasvir, sofosbuvir/velpatasvir, pibrentasvir/glecaprevir) represents a serious clinical problem, since the data available in the literature on the virological characteristics and management of these patients are few. The aim of the present narrative review was to provide an overview of the impact of baseline RASs in patients treated with the latest-generation DAAs and to analyze the efficacy of the available retreatment strategies in those who have failed these regimens.

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

BioMed Research International ◽

10.1155/2017/9849823 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 5

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.

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Postsustained Virological Response Management in Hepatitis C Patients

Seminars in Liver Disease ◽

10.1055/s-0040-1702944 ◽

2020 ◽

Vol 40 (03) ◽

pp. 233-239 ◽

Cited By ~ 1

Author(s):

Chiara Masetti ◽

Ana Lleo ◽

Matteo Colombo ◽

Massimo Colombo ◽

Alessio Aghemo

Keyword(s):

Liver Disease ◽

Hepatitis C ◽

Virological Response ◽

Antiviral Agents ◽

Direct Acting Antiviral ◽

Clinically Significant ◽

Complications Of Cirrhosis ◽

Direct Acting ◽

Cure Rates ◽

Direct Acting Antiviral Agents

AbstractThe introduction of direct-acting antiviral agents (DAA) has revolutionized management and care of patients with chronic hepatitis C virus (HCV) infection, leading to cure rates higher than 90% in patients with advanced liver disease as well. Viral eradication has been associated with longer survival, reduced mortality from both hepatic and extrahepatic causes, improvement in liver function, and reduced incidence of HCV-related extrahepatic diseases. While patients with mild fibrosis can safely be discharged after achievement of a sustained virological response, patients with advanced fibrosis and cirrhosis remain at risk of developing complications of liver disease, thus requiring regular and life-long surveillance. Major complications of cirrhosis that need to be monitored are hepatocellular carcinoma onset and development or progression of clinically significant portal hypertension.

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Impact of direct-acting antiviral agents-induced SVR on the long-term burden of hepatocellular carcinoma in chronic hepatitis C cirrhosis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.230 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 230-230

Author(s):

Prowpanga Udompap ◽

Ajitha Mannalithara ◽

Donghee Kim ◽

W. Ray Kim

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C ◽

Antiviral Agents ◽

Sensitivity Analyses ◽

Old Patients ◽

Direct Acting Antiviral ◽

Direct Acting ◽

The Impact ◽

Direct Acting Antiviral Agents

230 Background: Sustained virological response (SVR) has been associated with decreased morbidity and mortality from hepatitis C virus (HCV) infection. Data are sparse, however, about the long-term benefits of direct-acting antiviral agents (DAAs) in terms of risk reduction for hepatocellular carcinoma (HCC). We estimate the impact of SVR on the HCC incidence in the DAA era when SVR is achieved nearly universally even in patients with advanced fibrosis and cirrhosis. Methods: We constructed a Markovian model of 50-year-old patients with compensated HCV cirrhosis (n=1,000) to model the incidence of HCC over 20-years of follow-up. We compared 2 cohorts: 1) SVR following DAA therapy and 2) no SVR (natural history). In the latter, HCC would develop at an annual rate of 4.2% and patients would die as a result of end stage liver disease (ESLD) according to their MELD (=6 at baseline). In the former, MELD score would not increase, the HCC risk would decrease and, in some patients, cirrhosis would regress. Results: The table summarizes the 20-year outcome in the two cohorts. In the cohort without SVR, HCC would occur in 33% and 63% would die of ESLD. In the SVR cohort, the proportion of HCC would increase to 37% as the number of subjects at HCC risk would increase, as a result of a dramatic reduction in deaths from ESLD. In the univariate sensitivity analyses, the cumulative HCC incidence was mainly influenced by the rate at which the risk of HCC is decreased after SVR, followed by the change in cirrhosis regression rate. Conclusions: Although HCC risk would decrease after SVR in a given individual patient with cirrhosis, on the population level, highly effective DAA therapy may lead to a paradoxical increase in the burden of HCC. These data underscore the important of (1) HCC surveillance in patients with cirrhosis even after SVR and (2) DAA intervention before cirrhosis develops. [Table: see text]

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Statins use corrects the impact of direct acting antiviral agents on lipid profile in hepatitis C virus patients

Journal of Hepatology ◽

10.1016/s0168-8278(20)31682-2 ◽

2020 ◽

Vol 73 ◽

pp. S607

Author(s):

Andrea Dalbeni ◽

Anna Mantovani ◽

Diego Faccincani ◽

Michele Bevilacqua ◽

Filippo Cattazzo ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Lipid Profile ◽

Antiviral Agents ◽

Direct Acting Antiviral ◽

Direct Acting ◽

The Impact ◽

Direct Acting Antiviral Agents

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Treatment of chronic hepatitis C with direct acting antiviral agents in patients with haemophilia, end-stage liver disease and coinfected with HIV

Haemophilia ◽

10.1111/hae.12899 ◽

2016 ◽

Vol 22 (3) ◽

pp. e223-e225

Author(s):

R. Ackens ◽

D. Posthouwer

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Antiviral Agents ◽

Direct Acting Antiviral ◽

End Stage Liver Disease ◽

Direct Acting ◽

End Stage ◽

Direct Acting Antiviral Agents

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Disparities in Initiation of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in an Insured Population

Public Health Reports ◽

10.1177/0033354918772059 ◽

2018 ◽

Vol 133 (4) ◽

pp. 452-460 ◽

Cited By ~ 19

Author(s):

Julia L. Marcus ◽

Leo B. Hurley ◽

Scott Chamberland ◽

Jamila H. Champsi ◽

Laura C. Gittleman ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Agents ◽

Clinical Factors ◽

Factors Associated ◽

Direct Acting Antiviral ◽

Lower Likelihood ◽

Few Data ◽

Direct Acting ◽

Direct Acting Antiviral Agents

Objectives: The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. Methods: We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. Results: Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). Conclusions: Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.

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