Origin, prevalence and response to therapy of hepatitis C virus genotype 2k/1b chimeras

Susser, S.; Dietz, Julia; Schlevogt, Bernhard; Zuckerman, Eli; Barak, Manouchehr; Piazzolla, Valeria; Howe, Anita Y.M.; Hinrichsen, Holger; Passmann, Sandra; Daniel, Rasha; Cornberg, Markus; Mangia, Alessandra; Zeuzem, Stefan; Sarrazin, Christoph

doi:10.1016/j.jhep.2017.05.027

Cited by 30 publications

(38 citation statements)

References 34 publications

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“…Fourth, we did not assess the potential presence of recombinant HCV 1b/2 in our patients, which may compromise the SVR 12 rate by SOFbased DAA therapies. [40][41][42] In summary, SOF in combination with RBV, DCV, or LDV for 12 weeks offers excellent effectiveness and safety in HCV-2 patients with compensated liver diseases. The rates of fatigue, pruritus, and anemia are more common for patients receiving SOF/RBV than SOF/DCV or SOF/LDV.…”

Section: Discussionmentioning

confidence: 94%

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Sofosbuvir‐based direct acting antiviral therapies for patients with hepatitis C virus genotype 2 infection

Liu

et al. 2019

J of Gastro and Hepatol

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Background and Aim Data regarding the comparative effectiveness and safety of sofosbuvir (SOF) in combination with ribavirin (RBV), daclatasvir (DCV), or ledipasvir (LDV) for hepatitis C virus genotype 2 (HCV‐2) patients were limited. We aimed to evaluate the performance of these regimens in Taiwan. Methods One hundred eighty‐seven HCV‐2 patients with compensated liver diseases receiving SOF in combination with RBV (n = 82), DCV (n = 66), or LDV (n = 39) for 12 weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response 12 weeks off therapy (SVR12). The patient characteristics potentially related to SVR12 were compared. The safety profiles and laboratory abnormalities were assessed. Results The SVR12 rates were 93.9% (95% confidence interval [CI]: 86.5–97.4%), 98.5% (95% CI: 91.9–99.7%), and 100% (95% CI: 91.0–100%) in patients receiving SOF combined with RBV, DCV, and LDV, respectively. All patients tolerated treatment well. The stratified SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline among these regimens. Six (3.2%) patients had serious adverse events which were not related to treatment. The rates of fatigue, pruritus, and anemia tended to be higher in patients receiving RBV (22.0%, 19.5%, and 8.5%) combination than those receiving DCV (10.6%, 6.1%, and 1.5%) or LDV (10.3%, 5.1%, and 0%) combination. Conclusions Sofosbuvir in combination with RBV, DCV, or LDV for 12 weeks is effective and well‐tolerated for HCV‐2 patients. Compared with DCV or LDV combination, the risks of fatigue, pruritus, and anemia are higher in patients receiving RBV combination.

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Section: Discussionmentioning

confidence: 94%

“…Third, the effects of HCV‐2 subgenotypes and the baseline NS5A or NS5B resistance‐associated substitutions on SVR 12 rates were not evaluated in our retrospective study. Fourth, we did not assess the potential presence of recombinant HCV 1b/2 in our patients, which may compromise the SVR 12 rate by SOF‐based DAA therapies …”

Section: Discussionmentioning

confidence: 99%

Sofosbuvir‐based direct acting antiviral therapies for patients with hepatitis C virus genotype 2 infection

Liu

et al. 2019

J of Gastro and Hepatol

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“…A study by Hedskog et al suggests that the antiviral treatment outcome in patients with the HCV RF_ 2/1 genotype with a 12‐16‐week course of sofosbuvir/ribavirin was closer to the response seen with genotype 1 patients than genotype 2 patients . In a very recently published study by Susser et al, a very high rate of virological relapse (93%) occurred in RF1_2k/1b patients treated with a genotype 2 regimen, but excellent results were achieved when patients were either initially treated with a genotype 1 regimen (8 of 9 patients achieved SVR) or were retreated after relapse (13 of 13 patients achieved SVR) …”

Section: Discussionmentioning

confidence: 99%

“…Notably, it has been shown that patients infected with this recombinant virus in the former Soviet Union countries were predominantly injecting drug users (IDU), mainly of Georgian origin . In the light of this, it was predictable that after the collapse of the Soviet Union further migration could increase the rate of RF1_2k/1b in other parts of the world . In a very recent study in which sequence analysis was performed with 442 supposed HCV genotype 2 isolates, it was shown that 61 were actually genotype 2k/1b (n = 59); one was found to be 2a/1b and one 2b/1a .…”

Section: Discussionmentioning

confidence: 99%

Identification of hepatitis C virus 2k/1b intergenotypic recombinants in Georgia

Zakalashvili¹,

Zarkua²,

Weizenegger

et al. 2017

Liver International

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“…These chimeras combine genetic characteristics of different HCV genotypes. The HCV variant 2k/1b, which was first described from a patient in St. Petersburg, Russia, has been infrequently but consistently detected among patients originating from the former Soviet Union (2)(3)(4). This chimera consists of a sequence fragment originating from an HCV genotype 2k strain (coding for the core region [core]ore, E1, E2, p7, and NS2) and a fragment originating from an HCV genotype 1b strain (coding for nonstructural protein [NS] 3, NS4A/B, and NS5A/B).…”

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confidence: 99%

Performance of Three Common Hepatitis C Virus (HCV) Genotyping Assays for Identification of HCV Genotype 2/1 Chimeras

et al. 2019

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Besides seven major hepatitis C virus (HCV) genotypes (GT), a number of intergenotypic recombinant strains have been described. These so-called chimeras combine genetic characteristics of different HCV genotypes. However, correct genotype classification is important, as choice and duration of direct-acting antiviral (DAA) treatment is mainly based on the viral genotype. Therefore, misclassification of chimeras might lead to suboptimal treatment of patients infected with these strains. For example, 2k/1b chimeras are typically described as HCV genotype 2 strains by commercially available hybridization assays, but real-time PCR-based tests recognizing another HCV region might be more suitable for correct chimera detection. In this study, the analytic capacity of the hybridization-assay Versant HCV Genotype 2.0 (LiPA 2.0) and the real-time PCR-based-assays cobas HCV GT and Abbott RealTime HCV Genotype II were tested in a selected cohort of 230 patients infected with HCV genotype 1 (n ϭ 53) and 2 (n ϭ 177) and 48 patients infected with HCV 2/1 chimeric strains. While the Versant HCV Genotype 2.0 (LiPA 2.0) assay failed to identify chimeras in all of the patients (48/48, 100%), cobas HCV GT and Abbott HCV Genotype II assays identified chimeras correctly in 90% (43/48) and 65% (31/48) of the cases, respectively. In conclusion, while the hybridization-based Versant HCV Genotype 2.0 (LiPA 2.0) assay seems to be unsuitable for detection of HCV 2/1 chimeras, use of the real-time PCR-based assays cobas HCV GT and Abbott RealTime HCV Genotype II led to a higher rate of chimera detection . FIG 2 (a) Overview of genotype and subtype determination by the hybridization-based assay Versant HCV Genotype 2.0 and the real-time PCR-based assay cobas HCV GT in comparison to that by population-based sequencing. If genotype or subtype were consistent with sequencing results, calls were termed consistent; otherwise, the subtype was refined by the sequencing analysis. (b and c) Detailed subtype determination by the hybridization-based assay Versant HCV Genotype 2.0 (b) and by the real-time PCR-based-assay cobas HCV GT (c) in comparison to that by population-based sequencing. If subtype was consistent with sequencing results, calls were termed consistent; otherwise, the subtype was refined by the sequencing analysis.

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Origin, prevalence and response to therapy of hepatitis C virus genotype 2k/1b chimeras

Cited by 30 publications

References 34 publications

Sofosbuvir‐based direct acting antiviral therapies for patients with hepatitis C virus genotype 2 infection

Sofosbuvir‐based direct acting antiviral therapies for patients with hepatitis C virus genotype 2 infection

Identification of hepatitis C virus 2k/1b intergenotypic recombinants in Georgia

Performance of Three Common Hepatitis C Virus (HCV) Genotyping Assays for Identification of HCV Genotype 2/1 Chimeras

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