Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia

Background: Mutations within the hepatitis B virus (HBV) reverse transcriptase (RT) gene have been associated with drug resistance against nucleos(t)ide analogs (NAs). Objective: This study aimed to identify mutations in the RT gene among patients with chronic hepatitis B (CHB) before receiving...

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Main Authors: Arfianti Arfianti, Fauzia Andrini Djojosugito, Maisaroh Maisaroh, Hendra Asputra, Dita Kartika Sari, Tubagus Odih Rhomdani Wahid
Format: Article
Language:English
Published: Indonesian Society for Biochemistry and Molecular Biology 2022-05-01
Series:Acta Biochimica Indonesiana
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Online Access:https://pbbmi.org/newjurnal/index.php/actabioina/article/view/68
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author Arfianti Arfianti
Fauzia Andrini Djojosugito
Maisaroh Maisaroh
Hendra Asputra
Dita Kartika Sari
Tubagus Odih Rhomdani Wahid
author_facet Arfianti Arfianti
Fauzia Andrini Djojosugito
Maisaroh Maisaroh
Hendra Asputra
Dita Kartika Sari
Tubagus Odih Rhomdani Wahid
author_sort Arfianti Arfianti
collection DOAJ
description Background: Mutations within the hepatitis B virus (HBV) reverse transcriptase (RT) gene have been associated with drug resistance against nucleos(t)ide analogs (NAs). Objective: This study aimed to identify mutations in the RT gene among patients with chronic hepatitis B (CHB) before receiving antiviral therapy and its relationship with the HBV genotypes. Methods: A total of 26 HBV DNA was extracted from the blood plasma of CHB patients. HBV RT gene was amplified and sequenced using the Sanger dideoxy sequencing method. The HBV genotype was determined through phylogenetic analysis using the Maximum Likelihood method. Results: The study subjects comprised 14 CHB patients without complications and 12 CHB patients with cirrhosis/hepatoma. CHB patients with cirrhosis/hepatoma were older than those without complications. The HBV genotypes comprised 15 (57.7%) genotype C and 11 (42.3%) genotype B. All treatment-naïve CHB patients did not demonstrate any classical NA resistance mutations within the RT gene. However, several putative and pretreatment resistance mutations, including F221Y, N238H, and V224I, were high frequency in more than 40% of study subjects. In addition, F221Y and N238H/Q mutations were frequently observed in genotype B, while V224 I was only found in patients infected with genotype C (p=0.000). Conclusions: There was no evidence of classical RT gene mutations associated with NA resistance in treatment-naïve patients with CHB. However, several putative and pretreatment mutations were identified as genotype-specific mutations and may contribute to antiviral resistance against NAs.
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spelling doaj-art-fe77df0453ff41ddba7e44596486bd522025-02-08T03:06:04ZengIndonesian Society for Biochemistry and Molecular BiologyActa Biochimica Indonesiana2654-61082654-32222022-05-015110.32889/actabioina.68Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, IndonesiaArfianti Arfianti0Fauzia Andrini Djojosugito1Maisaroh Maisaroh2Hendra Asputra3Dita Kartika Sari4Tubagus Odih Rhomdani Wahid5Department of Medical Biology, Faculty of Medicine Universitas Riau, Pekanbaru, 28133, Indonesia Department of Microbiology, Faculty of Medicine Universitas Riau, Pekanbaru, 28133, IndonesiaUndergraduate Medical Program, Faculty of Medicine Universitas Riau, Pekanbaru, 28133, IndonesiaDepartment of Internal Medicine, Faculty of Medicine Universitas Riau/RSUD Arifin Achmad Provinsi Riau, Pekanbaru, 28133, IndonesiaDepartment of Anatomy, Faculty of Medicine Universitas Riau, Pekanbaru, 28133, IndonesiaDepartment of Surgery, Faculty of Medicine Universitas Riau/ RSUD Arifin Achmad Provinsi Riau, Pekanbaru, 28133, Indonesia Background: Mutations within the hepatitis B virus (HBV) reverse transcriptase (RT) gene have been associated with drug resistance against nucleos(t)ide analogs (NAs). Objective: This study aimed to identify mutations in the RT gene among patients with chronic hepatitis B (CHB) before receiving antiviral therapy and its relationship with the HBV genotypes. Methods: A total of 26 HBV DNA was extracted from the blood plasma of CHB patients. HBV RT gene was amplified and sequenced using the Sanger dideoxy sequencing method. The HBV genotype was determined through phylogenetic analysis using the Maximum Likelihood method. Results: The study subjects comprised 14 CHB patients without complications and 12 CHB patients with cirrhosis/hepatoma. CHB patients with cirrhosis/hepatoma were older than those without complications. The HBV genotypes comprised 15 (57.7%) genotype C and 11 (42.3%) genotype B. All treatment-naïve CHB patients did not demonstrate any classical NA resistance mutations within the RT gene. However, several putative and pretreatment resistance mutations, including F221Y, N238H, and V224I, were high frequency in more than 40% of study subjects. In addition, F221Y and N238H/Q mutations were frequently observed in genotype B, while V224 I was only found in patients infected with genotype C (p=0.000). Conclusions: There was no evidence of classical RT gene mutations associated with NA resistance in treatment-naïve patients with CHB. However, several putative and pretreatment mutations were identified as genotype-specific mutations and may contribute to antiviral resistance against NAs. https://pbbmi.org/newjurnal/index.php/actabioina/article/view/68chronic hepatitis Bgenitypenucleos(t)ide analoguesreverse transcriptaseresistance muation
spellingShingle Arfianti Arfianti
Fauzia Andrini Djojosugito
Maisaroh Maisaroh
Hendra Asputra
Dita Kartika Sari
Tubagus Odih Rhomdani Wahid
Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia
Acta Biochimica Indonesiana
chronic hepatitis B
genitype
nucleos(t)ide analogues
reverse transcriptase
resistance muation
title Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia
title_full Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia
title_fullStr Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia
title_full_unstemmed Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia
title_short Putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis B patients at Arifin Achmad Regional District Hospital, Riau, Indonesia
title_sort putative and pretreatment drug resistance mutations in reverse transcriptase gene among untreated chronic hepatitis b patients at arifin achmad regional district hospital riau indonesia
topic chronic hepatitis B
genitype
nucleos(t)ide analogues
reverse transcriptase
resistance muation
url https://pbbmi.org/newjurnal/index.php/actabioina/article/view/68
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