Clinical, Virological Characteristics, and Outcomes of Treatment with Sofosbuvir/Ledipasvir in Two Pediatric Patients Infected by HCV Genotype 4

Direct-acting antiviral drugs to cure infections with Hepatitis C virus (HCV) achieve a sustained virological response (SVR) in more than 90% of adult patients. At present, clinical trials are ongoing and real-life data are still limited in children. Herein, we report two cases of pediatric patients treated with fixed-dose combination of sofosbuvir/ledipasvir, already approved to treat HCV4 genotype. Both young girls achieved SVR even though HCV4 isolates carried L28M and M31L NS5A resistance-associated substitutions (RASs). Therefore, possible effects of these RASs merit further study, especially in children.

[1]  M. Capobianchi,et al.  Hepatitis C Virus Genetic Variability, Human Immune Response, and Genome Polymorphisms: Which Is the Interplay? , 2019, Cells.

[2]  H. El-karaksy,et al.  Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus–infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir , 2018, Journal of pediatric gastroenterology and nutrition.

[3]  G. D'offizi,et al.  Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents , 2018, Infection and drug resistance.

[4]  A. Nafady,et al.  Peripheral lymphocytes analyses in children with chronic hepatitis C virus infection , 2018, European journal of clinical investigation.

[5]  R. Jhaveri,et al.  Unique Challenges of Hepatitis C in Infants, Children, and Adolescents. , 2018, Clinical therapeutics.

[6]  Aijaz Ahmed,et al.  Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C , 2018, Adolescent health, medicine and therapeutics.

[7]  A. Focà,et al.  Structural Modeling of New Polymorphism Clusters of HCV Polymerase Isolated from Direct‐Acting Antiviral Naïve Patients: Focus on Dasabuvir and Setrobuvir Binding Affinity , 2018, ChemistrySelect.

[8]  A. Focà,et al.  Real‐life 3D therapy failure: Analysis of NS5A 93H RAS plus 108 K polymorphism in complex with ombitasvir by molecular modeling , 2018, Journal of medical virology.

[9]  V. Cuervas-Mons,et al.  Baseline NS5A resistance associated substitutions may impair DAA response in real‐world hepatitis C patients , 2018, Journal of medical virology.

[10]  Francesca Ceccherini-Silberstein,et al.  Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018. , 2018, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[11]  M. Buti,et al.  Patterns of Resistance-Associated Substitutions in Patients With Chronic HCV Infection Following Treatment With Direct-Acting Antivirals. , 2017, Gastroenterology.

[12]  C. Stedman,et al.  The emergence of NS5B resistance associated substitution S282T after sofosbuvir‐based treatment , 2017, Hepatology communications.

[13]  P. Rosenthal,et al.  The safety and effectiveness of ledipasvir−sofosbuvir in adolescents 12‐17 years old with hepatitis C virus genotype 1 infection , 2017, Hepatology.

[14]  Guy Baele,et al.  The epidemic dynamics of hepatitis C virus subtypes 4a and 4d in Saudi Arabia , 2017, Scientific Reports.

[15]  S. Kamal.  Advances in Treatment of Hepatitis C , 2017 .

[16]  F. Ceccherini‐Silberstein,et al.  Multiclass HCV resistance to direct‐acting antiviral failure in real‐life patients advocates for tailored second‐line therapies , 2017, Liver international : official journal of the International Association for the Study of the Liver.

[17]  T. Asselah,et al.  Ledipasvir plus sofosbuvir for 12 weeks in patients with hepatitis C genotype 4 infection , 2016, Hepatology.

[18]  A. Vandamme,et al.  Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naïve Patients , 2016, International journal of molecular sciences.

[19]  Jean-Michel Pawlotsky,et al.  Hepatitis C Virus Resistance to Direct-Acting Antiviral Drugs in Interferon-Free Regimens. , 2016, Gastroenterology.

[20]  M. Halasz,et al.  Immunological changes in different patient populations with chronic hepatitis C virus infection. , 2016, World journal of gastroenterology.

[21]  Thomas Lengauer,et al.  Geno2pheno[HCV] – A Web-based Interpretation System to Support Hepatitis C Treatment Decisions in the Era of Direct-Acting Antiviral Agents , 2016, PloS one.

[22]  P. Tovo,et al.  Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. , 2016, World journal of gastroenterology.

[23]  Pieter J. K. Libin,et al.  Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1–6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance , 2015, Viruses.

[24]  C. Yeung,et al.  Vertical transmission of hepatitis C virus: Current knowledge and perspectives. , 2014, World journal of hepatology.

[25]  A. Focà,et al.  Update on different aspects of HCV variability: focus on NS5B polymerase , 2014, BMC Infectious Diseases.

[26]  Glenn Lawyer,et al.  COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification , 2014, Nucleic acids research.

[27]  E. Domingo,et al.  Identification of host and viral factors involved in a dissimilar resolution of a hepatitis C virus infection , 2014, Liver international : official journal of the International Association for the Study of the Liver.

[28]  N. Kamal,et al.  Burden of pediatric hepatitis C. , 2013, World journal of gastroenterology.

[29]  N. Marascio,et al.  Epidemiological features and specificities of HCV infection: a hospital-based cohort study in a university medical center of Calabria region , 2012, BMC Infectious Diseases.

[30]  R. Bruni,et al.  Hepatitis C virus genotype 4d in Southern Italy: Reconstruction of its origin and spread by a phylodynamic analysis , 2012, Journal of medical virology.

[31]  M. Otto,et al.  Genotype and Subtype Profiling of PSI-7977 as a Nucleotide Inhibitor of Hepatitis C Virus , 2012, Antimicrobial Agents and Chemotherapy.

[32]  M. Nei,et al.  MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. , 2011, Molecular biology and evolution.

[33]  M. Ceccarelli,et al.  Pediatric hepatitis C infection: to treat or not to treat...what's the best for the child? , 2011, European review for medical and pharmacological sciences.

[34]  O. Gascuel,et al.  New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. , 2010, Systematic biology.

[35]  Karina Yusim,et al.  The hepatitis C sequence database in Los Alamos , 2007, Nucleic Acids Res..

[36]  Tulio de Oliveira,et al.  An automated genotyping system for analysis of HIV-1 and other microbial sequences , 2005, Bioinform..

[37]  V. de Lédinghen,et al.  Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. , 2005, Gastroenterology.

[38]  Robert C. Edgar,et al.  MUSCLE: a multiple sequence alignment method with reduced time and space complexity , 2004, BMC Bioinformatics.

[39]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .