Hepatitis Monthly Hepatitis Monthly Hepat Mon http://www.hepatmon.portal.tools 1735-143X 1735-3408 10.5812/hepatmon en jalali 2019 9 16 gregorian 2019 9 16 17 3
en 10.5812/hepatmon.44774 Diagnostic and Therapeutic Implications in a Case of Mixed Hepatitis C Virus (HCV) Infection Diagnostic and Therapeutic Implications in a Case of Mixed Hepatitis C Virus (HCV) Infection case-report case-report Conclusions

Two main hypotheses were raised: a reinfection with a new subtype 1a virus during the treatment with a wild type strain, which developed RAS after infection or with an already mutated virus; and a pretreatment hidden dual subtype 4d plus 1a infection.

Introduction

Hepatitis C virus (HCV) multiple infections can influence the course of the disease, either by boosting hepatocellular injury or by increasing the frequency of exacerbations. Their prevalence ranges from 5% to 39% in individuals with HCV infection, with a higher impact on injection drug users (IDUs), or in prison settings.

Case Presentation

The current paper reported a case of dual HCV infection in a 31-year-old female, with a referred vertical transmission of HCV infection and also a history of IDU, who harbored a subtype 4d since youth. Treatment failure, after a 24-week course of sofosbuvir/ledipasvir, prompted a reevaluation of present and past HCV status. HCV genotype was determined by INNO-LiPATM HCV II kit (LiPA II) (Innogenetics, Ghent, Belgium) and sequencing of NS5B region (nucleotide 8281 - 8679). Direct-acting antivirals (DAAs) resistance profile was investigated by NS3/4, NS5A and NS5B sequencing with specific primers. The Sentosa® SQ next generation sequencing (NGS) workflow was further performed in the baseline and failure samples. Unexpectedly, a subtype 4d in the pretreatment sample and a subtype 1a in the posttreatment were identified. No resistance associated mutations (RAS) were detected in the subtype 4d, although the 170AV and 174S in the NS3/4 gene, the 30R in the NS5A gene, and the 444D in the NS5B gene were detected in the subtype 1a virus from the failure sample.

Conclusions

Two main hypotheses were raised: a reinfection with a new subtype 1a virus during the treatment with a wild type strain, which developed RAS after infection or with an already mutated virus; and a pretreatment hidden dual subtype 4d plus 1a infection.

Introduction

Hepatitis C virus (HCV) multiple infections can influence the course of the disease, either by boosting hepatocellular injury or by increasing the frequency of exacerbations. Their prevalence ranges from 5% to 39% in individuals with HCV infection, with a higher impact on injection drug users (IDUs), or in prison settings.

Case Presentation

The current paper reported a case of dual HCV infection in a 31-year-old female, with a referred vertical transmission of HCV infection and also a history of IDU, who harbored a subtype 4d since youth. Treatment failure, after a 24-week course of sofosbuvir/ledipasvir, prompted a reevaluation of present and past HCV status. HCV genotype was determined by INNO-LiPATM HCV II kit (LiPA II) (Innogenetics, Ghent, Belgium) and sequencing of NS5B region (nucleotide 8281 - 8679). Direct-acting antivirals (DAAs) resistance profile was investigated by NS3/4, NS5A and NS5B sequencing with specific primers. The Sentosa® SQ next generation sequencing (NGS) workflow was further performed in the baseline and failure samples. Unexpectedly, a subtype 4d in the pretreatment sample and a subtype 1a in the posttreatment were identified. No resistance associated mutations (RAS) were detected in the subtype 4d, although the 170AV and 174S in the NS3/4 gene, the 30R in the NS5A gene, and the 444D in the NS5B gene were detected in the subtype 1a virus from the failure sample.

Multiple Infection;Direct-Acting Antivirals;Hepatitis C Virus;Resistance Profile;Next Generation Sequencing Multiple Infection;Direct-Acting Antivirals;Hepatitis C Virus;Resistance Profile;Next Generation Sequencing http://www.hepatmon.portal.tools/index.php?page=article&article_id=44774 Bianca Bruzzone Bianca Bruzzone Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy; Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy. Tel: +39-105558983, Fax: +39-105556391 Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy; Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy. Tel: +39-105558983, Fax: +39-105556391 Pasqualina De Leo Pasqualina De Leo Infectious Disease Unit, San Paolo Hospital, Savona, 17100, Italy Infectious Disease Unit, San Paolo Hospital, Savona, 17100, Italy Laura Sticchi Laura Sticchi Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy; Department of Health Sciences, University of Genoa, 16132, Italy Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy; Department of Health Sciences, University of Genoa, 16132, Italy Paola Canepa Paola Canepa Department of Health Sciences, University of Genoa, 16132, Italy Department of Health Sciences, University of Genoa, 16132, Italy Emanuela Rappazzo Emanuela Rappazzo Department of Health Sciences, University of Genoa, 16132, Italy Department of Health Sciences, University of Genoa, 16132, Italy Marco Anselmo Marco Anselmo Infectious Disease Unit, San Paolo Hospital, Savona, 17100, Italy Infectious Disease Unit, San Paolo Hospital, Savona, 17100, Italy Giancarlo Icardi Giancarlo Icardi Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy; Department of Health Sciences, University of Genoa, 16132, Italy Hygiene Unit, IRCCS AOU San Martino, IST, Genoa, 16132, Italy; Department of Health Sciences, University of Genoa, 16132, Italy