Treatment of hepatitis C virus genotype 4 in the DAA era

Biagio, Antonio Di; Taramasso, Lucia; Cenderello, Giovanni

doi:10.1186/s12985-018-1094-4

Cited by 20 publications

(21 citation statements)

References 45 publications

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“…Moreover, due to the risk of re-activation of hepatitis B virus (HBV) in patients with dual infections and to the risk of drug interactions in human immunodeficiency virus (HIV) co-infected individuals, careful consideration before therapy initiation is needed [6,7]. Notably, less treatment-susceptible genotypes (e.g., 1l, 4r, 3b, 3g, 6u, 6v) is an emerging challenge and DAA treatment failure involves a significant proportion of patients (approximately 1-3% of all HCV patients) [8,9].…”

Section: Introductionmentioning

confidence: 99%

Management and Treatment of Hepatitis C: Are There Still Unsolved Problems and Unique Populations?

Solitano

Torres

Pugliese

et al. 2021

Viruses

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Direct-acting antivirals (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, possibly leading to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients belonging to the so-called unique or special populations are referred to as difficult-to-treat due to unreached sustained virological response, potential drug side effects or interactions or co-morbidities. Several years after the DAA introduction and on the basis of excellent findings in terms of efficacy and safety, some doubts arise around the exact meaning of the special population designation and whether this group of patients actually exists. The aim of this review is to discuss and analyze current evidence on the management and treatment of the so-called “unique populations”. We placed particular emphasis on patients with decompensated cirrhosis, chronic kidney disease (CKD), coinfections, rare genotypes, and previous treatment failure, in order to provide physicians with an updated overview of the actual problems and needs in the current scenario.

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Section: Introductionmentioning

confidence: 99%

Management and Treatment of Hepatitis C: Are There Still Unsolved Problems and Unique Populations?

Solitano

Torres

Pugliese

et al. 2021

Viruses

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“…The importance of understanding the reduced susceptibility to DAA among HCV strains circulating in DRC is to tailor DAA regimens based on the genetic diversity of HCV in SSA, since, in general, clinical trials of DAA for HCV have not been carried out in African countries and infections caused by GT4 other than 4a/4d have been poorly evaluated [ 42 ]. In addition, validated information should be obtained to correctly treat infections caused by 4r/4c/4k subtypes affecting migrant patients in high-income countries.…”

Section: Discussionmentioning

confidence: 99%

HCV Diagnosis and Sequencing Using Dried Blood Spots from Patients in Kinshasa (DRC): A Tool to Achieve WHO 2030 Targets

et al. 2021

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The World Health Organization has established an elimination plan for hepatitis C virus (HCV) by 2030. In Sub-Saharan Africa (SSA) access to diagnostic tools is limited, and a number of genotype 4 subtypes have been shown to be resistant to some direct-acting antivirals (DAAs). This study aims to analyze diagnostic assays for HCV based on dried blood spots (DBS) specimens collected in Kinshasa and to characterize genetic diversity of the virus within a group of mainly HIV positive patients. HCV antibody detection was performed on 107 DBS samples with Vidas® anti-HCV and Elecsys anti-HCV II, and on 31 samples with INNO-LIA HCV. Twenty-six samples were subjected to molecular detection. NS3, NS5A, and NS5B regions from 11 HCV viremic patients were sequenced. HCV seroprevalence was 12.2% (72% with detectable HCV RNA). Both Elecsys Anti-HCV and INNO-LIA HCV were highly sensitive and specific, whereas Vidas® anti-HCV lacked full sensitivity and specificity when DBS sample was used. NS5B/NS5A/NS3 sequencing revealed exclusively GT4 isolates (50% subtype 4r, 30% 4c and 20% 4k). All 4r strains harbored NS5A resistance-associated substitutions (RAS) at positions 28, 30, and 31, but no NS3 RAS was detected. Elecsys Anti-HCV and INNO-LIA HCV are reliable methods to detect HCV antibodies using DBS. HCV subtype 4r was the most prevalent among our patients. RASs found in subtype 4r in NS5A region confer unknown susceptibility to DAA.

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“…All patients with V170I RAS at baseline achieved an SVR after treatment with SOF/DAC except one patient who relapsed, even though he was treated with a regimen not containing a protease inhibitor. This mutation has not yet been associated with resistance in the GT4-infected patients, but this could be due to their low recruitment in clinical trials [16].…”

Section: Discussionmentioning

confidence: 99%

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

Stefano¹,

Ismail²,

Faleo³

et al. 2021

Preprint

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This study aimed to characterize the genetic subtypes of HCV-GT4 and identify the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT4 patients was analyzed. Sequence analysis of NS3, NS5A and NS5B regions was performed by direct sequencing. In addition, phylogenetic analysis was used to determine genetic subtypes, RAS and polymorphisms. Nine patients were infected by a GT4a, one with GT4o, 3 with GT4d. The remaining four patients were infected with a recombinant virus (GT4a+GT4o in three patients, GT4c+GT4d in a patient). Natural RASs were found in six patients (35%), including three infected by GT4a, two by GT4a+GT4o and one patient infected by GT4c+GT4d. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M+M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about a third of patients, but only one of them showed a treatment failure.

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Treatment of hepatitis C virus genotype 4 in the DAA era

Cited by 20 publications

References 45 publications

Management and Treatment of Hepatitis C: Are There Still Unsolved Problems and Unique Populations?

Management and Treatment of Hepatitis C: Are There Still Unsolved Problems and Unique Populations?

HCV Diagnosis and Sequencing Using Dried Blood Spots from Patients in Kinshasa (DRC): A Tool to Achieve WHO 2030 Targets

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

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