Effectiveness of directly acting oral antivirals in treatment of chronic HCV infection in children - experience from a tertiary care institute in southern India

Background: Worldwide, an estimated 71 million people are chronically infected with HCV, of which an estimated 2.1- 5.0 million are children aged ≤15 years. Children with chronic HCV infection have fewer treatment options than adults. Very few reports are available on HCV infection, treatment strategies and its outcome particularly in pediatric population. In this background, we evaluated the effectiveness and safety of Sofosbuvir/Ledipasvir in treating HCV infection in children.Methods: In this retrospective study, a total of 33 children with HCV positive status, 12 cases (children above 12 years of age) were selected for treatment. HCV-RNA quantitative assay, genotyping was carried out. Children above 12 years with HCV genotype 1 were treated with tablet ledipasvir-sofosbuvir (90/400 mg) orally once a day as morning dose for 12 weeks. Children with genotype 3 were treated with sofosbuvir 400 mg and weight based ribavirin for 24 weeks. Viral load was repeated after 12 weeks of completion of treatment with antivirals for sustained virological response (SVR 12).Results: Out of the 12 patients 11 patients had genotype 1 (5/11 had subtype-1a and 6/11 had subtype-1b) infection and only 1 patient has genotype 3 (subtype-3a). All of them attained SVR at the end of 12 weeks. The regimen was well tolerated and there were no side effects noted by the children and their caretakers. Drug compliance and the palatability of the drugs were good.Conclusions: Ledipasvir-sofosbuvir combination was highly effective at treating children with chronic HCV genotype 1 infection. The availability of an all oral, direct-acting antiviral regimen for paediatric population with chronic HCV would improve care for patients who currently have limited treatment options.

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R 7128,* a prodrug of a cytidine nucleoside analogue inhibitor of HCV** RNA polymerase, appears to be active in chronic HCV genotype 1 infections,

Inpharma Weekly ◽

10.2165/00128413-200816210-00014 ◽

2008 ◽

Vol &NA; (1621) ◽

pp. 8

Author(s):

&NA;

Keyword(s):

Rna Polymerase ◽

Nucleoside Analogue ◽

Hcv Rna ◽

Genotype 1 ◽

Hcv Genotype ◽

Hcv Genotype 1 ◽

Chronic Hcv

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Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies

Therapeutic Advances in Gastroenterology ◽

10.1177/1756283x16672392 ◽

2016 ◽

Vol 10 (1) ◽

pp. 68-73 ◽

Cited By ~ 14

Author(s):

Miguel Malespin ◽

Tamara Benyashvili ◽

Susan L. Uprichard ◽

Alan S. Perelson ◽

Harel Dahari ◽

...

Keyword(s):

Antiviral Agents ◽

Sustained Viral Response ◽

Hcv Rna ◽

Genotype 1 ◽

Genotype 3 ◽

Hcv Genotype ◽

End Of Treatment ◽

Genotype 2 ◽

Study Population ◽

Hcv Genotype 1

Background: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice. Methods: Data from patients treated with all oral sofosbuvir-based regimens at a university hepatology practice by 1 July 2015 were reviewed retrospectively. Responses were categorized based on virus levels during and post DAA treatment. HCV RNA levels were measured by Abbott RealTime HCV (ART) or by Roche CobasTaqMan v2.0 (RCTM) assays. Results: The study population included 89 patients. Participants were 62% genotype 1, 19% genotype 2 and 19% genotype 3, 54% cirrhotic and 46% treatment-experienced. A total of 45 received sofosbuvir–simeprevir, 38 sofosbuvir–ribavirin and 6 sofosbuvir–ledipasvir. The SVR12 rate was 82%. A total of 5 patients (6%), all with genotype 1, had EOT+ by ART assay and each achieved SVR12&24. Conclusions: A total of 9% of genotype 1 patients (6% overall) treated with DAAs were EOT+ by ART and all EOT+ cases achieved SVR24. EOT+/SVR was not observed with genotype 2 or 3 or by the RCTM assay. In patients treated with DAAs, EOT+ by the ART assay does not indicate treatment failure.

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Bile Acids Promote the Expression of Hepatitis C Virus in Replicon-Harboring Cells

Journal of Virology ◽

10.1128/jvi.00795-07 ◽

2007 ◽

Vol 81 (18) ◽

pp. 9633-9640 ◽

Cited By ~ 40

Author(s):

Kyeong-Ok Chang ◽

David W. George

Keyword(s):

Hepatitis C Virus ◽

Bile Acid ◽

Hepatitis C ◽

Bile Acids ◽

Farnesoid X Receptor ◽

Hcv Rna ◽

Genotype 1 ◽

Hcv Genotype ◽

Hcv Genotype 1 ◽

Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) is a cause of chronic liver disease, with more than 170 million persistently infected individuals worldwide. Although the combination therapy of alpha interferon (IFN-α) and ribavirin is effective for chronic HCV infection, around half of all patients infected with HCV genotype 1 fail to show sustained virologic responses and remain chronically infected. Previously, we demonstrated that bile acids were essential for growth of porcine enteric calicivirus in cell culture in association with down-regulation of IFN responses. Because hepatocytes are exposed to high concentrations of bile acids in the liver, we hypothesized that bile acids have similar effects on HCV replication. We incubated HCV replicon-harboring cells (genotype 1b, Con1) in the presence of various bile acids and monitored the expression of HCV RNA and protein (NS5B). The addition of an individual bile acid (deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, or glycochenodeoxycholic acid) in the medium increased the levels of HCV RNA and proteins up to fivefold at 48 h of incubation. An antagonist of bile acid receptor farnesoid X receptor (FXR), Z-guggulsterone, reduced the bile acid-mediated increase of HCV RNA. When IFN (α or γ) and each bile acid were incubated together, we observed that bile acid significantly reduced the anti-HCV effect of IFN. These results indicated that bile acids are factors in the failure of IFN treatment for certain patients infected with HCV genotype 1. Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering the bile acid-mediated FXR pathway.

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Genetic associations of vitamin D receptor polymorphisms with advanced liver fibrosis and response to pegylated interferon-based therapy in chronic hepatitis C

PeerJ ◽

10.7717/peerj.7666 ◽

2019 ◽

Vol 7 ◽

pp. e7666 ◽

Cited By ~ 3

Author(s):

Kessarin Thanapirom ◽

Sirinporn Suksawatamnuay ◽

Wattana Sukeepaisarnjaroen ◽

Pisit Tangkijvanich ◽

Panarat Thaimai ◽

...

Keyword(s):

Liver Fibrosis ◽

Poor Response ◽

Pegylated Interferon ◽

Hcv Infection ◽

Hcv Rna ◽

Advanced Liver Fibrosis ◽

Chronic Hcv Infection ◽

Pre Treatment ◽

Hcv Genotype 1 ◽

Chronic Hcv

Vitamin D receptor (VDR) modulates host immune responses to infections such as hepatitis C virus (HCV) infection, including interferon signaling. This study aimed to investigate the associations of VDR polymorphisms with advanced liver fibrosis and response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. In total, 554 Thai patients with chronic HCV infection treated with a PEG-IFN-based regimen were enrolled. Six single-nucleotide polymorphisms (SNPs) were genotyped: the IL28B C > T (rs12979860) SNP and five VDR SNPs, comprising FokI T > C (rs2228570), BsmI C > T (rs1544410), Tru9I G > A (rs757343), ApaI C > A (rs7975232), and TaqI A > G (rs731236). In total, 334 patients (60.3%) achieved sustained virological response (SVR), and 255 patients (46%) were infected with HCV genotype 1. The bAt (CCA) haplotype, consisting of the BsmI rs1544410 C, ApaI rs7975232 C, and TaqI rs731236 A alleles, was associated with poor response (in terms of lack of an SVR) to PEG-IFN-based therapy. The IL28B rs12979860 CT/TT genotypes (OR = 3.44, 95% CI [2.12–5.58], p < 0.001), bAt haplotype (OR = 2.02, 95% CI [1.04–3.91], p = 0.03), pre-treatment serum HCV RNA (logIU/mL; OR = 1.73, 95% CI [1.31–2.28], p < 0.001), advanced liver fibrosis (OR = 1.68, 95% CI [1.10–2.58], p = 0.02), and HCV genotype 1 (OR = 1.59, 95% CI [1.07–2.37], p = 0.02) independently predicted poor response. Patients with the bAt haplotype were more likely to have poor response compared to patients with other haplotypes (41.4% vs 21.9%, p = 0.03). The FokI rs2228570 TT/TC genotypes (OR = 1.63, 95% CI [1.06–2.51], p = 0.03) and age ≥55 years (OR = 2.25; 95% CI [1.54–3.32], p < 0.001) were independently associated with advanced liver fibrosis, assessed based on FIB-4 score >3.25. VDR polymorphisms were not associated with pre-treatment serum HCV RNA. In Thai patients with chronic HCV infection, the bAt haplotype is associated with poor response to PEG-IFN-based therapy, and the FokI rs2228570 TT/TC genotypes are risk factors for advanced liver fibrosis.

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Faculty Opinions recommendation of Boceprevir for untreated chronic HCV genotype 1 infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13863968.15301070 ◽

2012 ◽

Author(s):

Jean-Michel Pawlotsky

Keyword(s):

Genotype 1 ◽

Hcv Genotype ◽

Hcv Genotype 1 ◽

Chronic Hcv

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Hepatitis C virus infection and risk of liver-related and non-liver-related deaths: a population-based cohort study in Naples, southern Italy

BMC Infectious Diseases ◽

10.1186/s12879-021-06336-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Pierluca Piselli ◽

Diego Serraino ◽

Mario Fusco ◽

Enrico Girardi ◽

Angelo Pirozzi ◽

...

Keyword(s):

Southern Italy ◽

Population Based ◽

Hcv Infection ◽

Hcv Rna ◽

Risk Of Death ◽

High Prevalence ◽

Specific Mortality ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Related Mortality

Abstract Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.

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