Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients
Background: Direct acting antivirals (DAAs) have demonstrated remarkable efficacy, in achieving hepatitis C viral (HCV) elimination rates higher than 90%. One particular concern associated with treatment failure is the emergence of resistance associated substitutions (RASs) in the genome. The occurr...
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Interna Publishing
2024-10-01
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| Series: | Acta Medica Indonesiana |
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| Online Access: | https://actamedindones.org/index.php/ijim/article/view/2625 |
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| author | Juferdy Kurniawan Anugrah Dwi Handayu Gita Aprilicia Darlene Raudhatul Bahri Irsan Hasan |
| author_facet | Juferdy Kurniawan Anugrah Dwi Handayu Gita Aprilicia Darlene Raudhatul Bahri Irsan Hasan |
| author_sort | Juferdy Kurniawan |
| collection | DOAJ |
| description | Background: Direct acting antivirals (DAAs) have demonstrated remarkable efficacy, in achieving hepatitis C viral (HCV) elimination rates higher than 90%. One particular concern associated with treatment failure is the emergence of resistance associated substitutions (RASs) in the genome. The occurrence of RASs highlights the adaptability and resilience of the HCV. This highlights the importance of RASs mutation, enabling the development of new therapeutic strategies to combat these resistant strains. This study aims to determine the presence of early HCV mutations in chronic hepatitis C in Indonesia and the association between this mutation to the efficacy of sofosbuvir-daclatasvir. Methods: We conducted a prospective longitudinal study in naïve hepatitis C patient population. The virus was examined for RAS by RNA sequencing before starting treatment. RAS mutations were determined through the cut-off value of RAS mutations that contributed in the successful therapy. All patients were followed up until 12 weeks after completion of treatment to determine the sustained virological response 12 (SVR12). Results: Out of the 58 patients, 9 patients (15.51%) did not achieve SVR. Only 14 patients was further analyzed to provide the association between the mutation and SVR-12 failure after sofosbuvir-daclatasvir therapy. Specifically, 2 patients with L31 mutation and one patient with L31/Y93 mutation achieved SVR. Only one patient with failure to achieve SVR and the mutation was found in Y93H region. Conclusion: The mutation of Y93H may contribute to treatment failure while L31A may increase the susceptibility to DAAs treatment. |
| format | Article |
| id | doaj-art-59452dccd98c4c60aeaa2f2dec7db80e |
| institution | Kabale University |
| issn | 0125-9326 2338-2732 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Interna Publishing |
| record_format | Article |
| series | Acta Medica Indonesiana |
| spelling | doaj-art-59452dccd98c4c60aeaa2f2dec7db80e2025-01-27T04:12:06ZengInterna PublishingActa Medica Indonesiana0125-93262338-27322024-10-01564692Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C PatientsJuferdy Kurniawan0Anugrah Dwi Handayu1Gita Aprilicia2Darlene Raudhatul Bahri3Irsan Hasan4Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.Background: Direct acting antivirals (DAAs) have demonstrated remarkable efficacy, in achieving hepatitis C viral (HCV) elimination rates higher than 90%. One particular concern associated with treatment failure is the emergence of resistance associated substitutions (RASs) in the genome. The occurrence of RASs highlights the adaptability and resilience of the HCV. This highlights the importance of RASs mutation, enabling the development of new therapeutic strategies to combat these resistant strains. This study aims to determine the presence of early HCV mutations in chronic hepatitis C in Indonesia and the association between this mutation to the efficacy of sofosbuvir-daclatasvir. Methods: We conducted a prospective longitudinal study in naïve hepatitis C patient population. The virus was examined for RAS by RNA sequencing before starting treatment. RAS mutations were determined through the cut-off value of RAS mutations that contributed in the successful therapy. All patients were followed up until 12 weeks after completion of treatment to determine the sustained virological response 12 (SVR12). Results: Out of the 58 patients, 9 patients (15.51%) did not achieve SVR. Only 14 patients was further analyzed to provide the association between the mutation and SVR-12 failure after sofosbuvir-daclatasvir therapy. Specifically, 2 patients with L31 mutation and one patient with L31/Y93 mutation achieved SVR. Only one patient with failure to achieve SVR and the mutation was found in Y93H region. Conclusion: The mutation of Y93H may contribute to treatment failure while L31A may increase the susceptibility to DAAs treatment.https://actamedindones.org/index.php/ijim/article/view/2625hepatitis cdirect acting antiviralresistance associated substitutionsmutationy93h region |
| spellingShingle | Juferdy Kurniawan Anugrah Dwi Handayu Gita Aprilicia Darlene Raudhatul Bahri Irsan Hasan Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients Acta Medica Indonesiana hepatitis c direct acting antiviral resistance associated substitutions mutation y93h region |
| title | Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients |
| title_full | Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients |
| title_fullStr | Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients |
| title_full_unstemmed | Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients |
| title_short | Resistance-Associated Substitutions (RAS) and Clinical Factors as Determinants of Sofosbuvir-Daclatasvir Treatment Outcomes in Chronic Hepatitis C Patients |
| title_sort | resistance associated substitutions ras and clinical factors as determinants of sofosbuvir daclatasvir treatment outcomes in chronic hepatitis c patients |
| topic | hepatitis c direct acting antiviral resistance associated substitutions mutation y93h region |
| url | https://actamedindones.org/index.php/ijim/article/view/2625 |
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