scholarly journals Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study

Gut ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2223-2231 ◽  
Author(s):  
Sharon J Hutchinson ◽  
Heather Valerio ◽  
Scott A McDonald ◽  
Alan Yeung ◽  
Kevin Pollock ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Scale Up ◽  
Sustained Viral Response ◽  
Population Based ◽  
Decompensated Cirrhosis ◽  
Direct Acting Antiviral ◽  
Clinical Databases ◽  
Number Of Patients ◽  
Direct Acting ◽  
The Impact

ObjectivePopulation-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis of population-based data from Scotland.DesignThrough analysis of national surveillance data (involving linkage of HCV diagnosis and clinical databases to hospital and deaths registers), we determined i) the scale-up in the number of patients treated and achieving a sustained viral response (SVR), and ii) the change in the trend of new presentations with HCV-related DC, with the introduction of DAAs.ResultsApproximately 11 000 patients had been treated in Scotland over the 8-year period 2010/11 to 2017/18. The scale-up in the number of patients achieving SVR between the pre-DAA and DAA eras was 2.3-fold overall and 5.9-fold among those with compensated cirrhosis (the group at immediate risk of developing DC). In the pre-DAA era, the annual number of HCV-related DC presentations increased 4.6-fold between 2000 (30) and 2014 (142). In the DAA era, presentations decreased by 51% to 69 in 2018 (and by 67% among those with chronic infection at presentation), representing a significant change in trend (rate ratio 0.88, 95% CI 0.85 to 0.90). With the introduction of DAAs, an estimated 330 DC cases had been averted during 2015–18.ConclusionsNational scale-up in interferon-free DAA treatment is associated with the rapid downturn in presentations of HCV-related DC at the population-level. Major progress in averting HCV-related DC in the short-term is feasible, and thus other countries should strive to achieve the same.

scholarly journals Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis

2020 ◽  
Vol 7 ◽  
Author(s):  
Chao Shen ◽  
Haozhi Fan ◽  
Zhijun Ge ◽  
Weihua Cai ◽  
Jianguo Shao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Publication Bias ◽  
Sustained Viral Response ◽  
The United States ◽  
Comprehensive Analysis ◽  
Bibliographic Databases ◽  
Efficacy And Safety ◽  
Direct Acting Antiviral ◽  
Number Of Patients ◽  
Direct Acting

Background: Since a greater number of hepatitis C virus (HCV) patients have access to direct-acting antiviral (DAA) based therapies, the number of patients not properly responding to prior DAA regimens is increasing. The objective of this comprehensive analysis was to assess the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HCV patients who experienced previous DAA therapy failures.Methods: Bibliographic databases were systematically searched for relevant articles published by November 2020. The main endpoints were sustained viral response after 12 weeks (SVR12), adverse events (AEs; any grade) and severe adverse events (SAEs). Publication bias assessment was performed using funnel plots and the Egger's test.Results: Fourteen studies consisting of a total of 1,294 subjects were included in this study and the pooled estimate of SVR12, AEs and SAEs rates were 96.8% (95%CI: 95.1–98.2), 47.1% (95%CI: 26.0–69.3), and 1.8% (95%CI: 0.7–3.4), respectively. Subgroup analysis showed that pooled SVR12 rates were 97.9% (95%CI: 96.7–98.9) for Japan and 91.1% (95%CI: 87.3–94.3) for the United States; 95.8% (95%CI: 93.9–97.4) for genotype (GT)1 and 100.0% (95%CI: 99.6–100.0) for GT2; 95.3% (95%CI: 92.4–97.2) for cirrhosis and 96.3% (95%CI: 94.2–97.7) for non-cirrhosis cases. There was no publication bias included this study.Conclusion: This comprehensive analysis revealed that GLE/PIB is an effective and secure retreatment option for patients who did not optimally respond to DAA treatment, especially the Asian population with GT1-2.

scholarly journals Liver Pathologic Changes After Direct-Acting Antiviral Agent Therapy and Sustained Virologic Response in the Setting of Chronic Hepatitis C Virus Infection

2020 ◽  
Author(s):  
Romulo Celli ◽  
Saad Saffo ◽  
Saleem Kamili ◽  
Nicholas Wiese ◽  
Tonya Hayden ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Liver Tissue ◽  
Sustained Viral Response ◽  
Antiviral Agent ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Direct Acting Antiviral ◽  
Viral Hepatitis C ◽  
Number Of Patients ◽  
Direct Acting

Context.— Treatment of chronic viral hepatitis C (HCV) infection with direct-acting antiviral agents (DAAs) results in cure, or sustained viral response (SVR), in more than 90% of patients. However, there are subsets of patients who have persistent liver inflammation and fibrosis and develop hepatocellular carcinoma (HCC) despite achieving SVR. A possible reason for these phenomena may be the presence of virus particles in liver tissue but not blood, otherwise defined as occult infection. Objective.— To describe liver histologic findings following successful DAA therapy, test HCV RNA by (liver) tissue polymerase chain reaction in treated cases, and identify predictive markers for HCC development in treated cases. Design.— A total of 96 identified patients were divided into 4 groups, each differentiated by the presence or absence of SVR and HCC. Groups were compared for several clinicopathologic variables, including degree of inflammation and fibrosis, and the ‘directionality' of fibrosis in cirrhotic livers using the novel progressive-indeterminate-regressive scoring system. Results.— Overall, we found a significant decrease in inflammation in SVR patients. None of the patients showed regression of their cirrhosis following treatment. No evidence of occult HCV infection was seen in 40 livers tested, including 21 with HCC. The number of patients who developed HCC was similar in the SVR and non-SVR groups, and increased inflammation and fibrosis were associated with HCC development. Conclusions.— Following DAA-SVR there appears to be an overall decrease in inflammation, but the fibrosis tends to persist, at least in the short term (median follow-up of 20.2 months).

scholarly journals Evolution of Hepatitis C Virus Quasispecies during Repeated Treatment with the NS3/4A Protease Inhibitor Telaprevir

2015 ◽  
Vol 59 (5) ◽  
pp. 2746-2755 ◽  
Author(s):  
Simone Susser ◽  
Mathieu Flinders ◽  
Henk W. Reesink ◽  
Stefan Zeuzem ◽  
Glenn Lawyer ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Treatment Failure ◽  
Deep Sequencing ◽  
Virologic Failure ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Population Based ◽  
Direct Acting Antiviral ◽  
B Virus ◽  
Direct Acting

ABSTRACTIn treating hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, the rapid reselection of resistance-associated variants (RAVs) is well known in patients with repeated exposure to the same class of antiviral agents. For chronic hepatitis C patients who have experienced virologic failure with direct-acting antiviral drugs, the potential for the reselection of persistent RAVs is unknown. Nine patients who received 14 days of telaprevir monotherapy were retreated with telaprevir-based triple therapy 4.3 to 5.7 years later. In four patients with virologic failure with both telaprevir-containing regimens, population-based and deep sequencing (454 GS-FLX) of theNS3protease gene were performed before and at treatment failure (median coverage, 4,651 reads). Using deep sequencing, with a threshold of 1.0% for variant calling, no isolates were found harboring RAVs at the baseline time points. While population-based sequencing uncovered similar resistance patterns (V36M plus R155K for subtype 1a and V36A for subtype 1b) in all four patients after the first and second telaprevir treatments, deep sequencing analysis revealed a median of 7 (range, 4 to 23) nucleotide substitutions on theNS3backbone of the resistant strains, together with large phylogenetic differences between viral quasispecies, making the survival of resistant isolates highly unlikely. In contrast, in a comparison of the two baseline time points, the median number of nucleotide exchanges in the wild-type isolates was only 3 (range, 2 to 8), reflecting the natural evolution of theNS3gene. In patients with repeated direct antiviral treatment, a continuous evolution of HCV quasispecies was observed, with no clear evidence of persistence and reselection but strong signs of independentde novogeneration of resistance. Antiviral therapy for chronic viral infections, like HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV), faces several challenges. These viruses have evolved survival strategies and proliferate by escaping the host's immune system. The development of direct-acting antiviral agents is an important achievement in fighting these infections. Viral variants conferring resistance to direct antiviral drugs lead to treatment failure. For HIV/HBV, it is well known that viral variants associated with treatment failure will be archived and reselected rapidly during retreatment with the same drug/class of drugs. We explored the mechanisms and rules of how resistant variants are selected and potentially reselected during repeated direct antiviral therapies in chronically HCV-infected patients. Interestingly, in contrast to HIV and HBV, we could not prove long-term persistence and reselection of resistant variants in HCV patients who failed protease inhibitor-based therapy. This may have important implications for the potential to reuse direct-acting antivirals in patients who failed the initial direct antiviral treatment. (The phase IIIb study described in this paper is registered at ClinicalTrials.gov under registration number NCT01054573.)

scholarly journals THE USE OF DIRECT-ACTING ANTIVIRALS FOR THE TREATMENT OF CHRONIC HEPATITIS C IN PATIENTS WITH HEMOPHILIA

2020 ◽  
Vol 4 (2) ◽  
pp. 184-188
Author(s):  
D. E. Danilau ◽  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hematological Parameters ◽  
Antiviral Treatment ◽  
Virologic Response ◽  
Direct Acting Antiviral ◽  
Number Of Patients ◽  
Direct Acting ◽  
Alt Activity

Background. Worldwide, prior to 1990, a large number of patients with hemophilia were infected with the hepatitis C virus due to substitution therapy. The mortality rate from chronic liver disease and HCC in patients with HCV and hemophilia is signifcantly higher than in general population. Objective. To assess the results of direct-acting antiviral therapy in patients with hemophilia and chronic hepatitis C. Material and methods. The rate of sustained virologic response after DAA treatment and the dynamics of clinical and laboratory parameters during antiviral treatment were evaluated. Results. All 14 patients achieved sustained virological response after 12 / 24 weeks of treatment. During antiviral treatment, some patients showed an increase in blood urea nitrogen, a decrease in leukocyte count, and increase of ALT activity. All these phenomena were reversible and resolved spontaneously. Conclusion. The DAA regimens available in Belarus are highly effective for the treatment of chronic hepatitis C in patients with hemophilia. These regimens do not signifcantly affect hematological parameters, are well tolerated, and have acceptable safety profle.

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