Determination of Reverse Transcriptase Inhibitor Nucleoside Analogue Resistance Profile in Pretreatment Phase of Patients with Viral Hepatitis B


MIKROBIYOLOJI BULTENI, vol.53, no.2, pp.156-169, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 53 Issue: 2
  • Publication Date: 2019
  • Doi Number: 10.5578/mb.67796
  • Title of Journal : MIKROBIYOLOJI BULTENI
  • Page Numbers: pp.156-169


HBV is a DNA virus and the causative agent of hepatitis B infection. Hepatitis B is a contagious disease and is still a major health problem all over the world. When the infection become chronic, it may cause serious diseases such as fibrosis, cirrhosis and/or hepatocellular carcinoma. Interferon/pegylated interferon by intravenous route and nucleoside/nucleotide (NA) analogues such as lamivudine, adefovir, entecavir, telbivudine and tenofovir given by oral route are used in the treatment. Antivirals given by oral route are mostly preferred in the treatment. However, because of the replication strategy and biological properties of HBV, mutations that cause antiviral resistance against these drugs can occur at different rates, although they can vary from drug to drug over time. It is possible that drug resistant virus may transmit from patient to healthy individuals. Therefore, there is a possibility of infection with drug-resistant HBV before treatment. Antiviral resistance mutations are divided into four categories; i) Nucleos(t)ide analog resistance (NAr)-related mutations, ii) primary drug resistance mutations, iii) secondary/compensatory mutations, iv) putative antiviral resistance mutations and pre-treatment variations. Recent studies have focused particularly on putative mutations and pre-treatment variations. The aim of this study was to better understanding of the antiviral resistance profiles of chronic hepatitis B (CHB) patients treated and untreated with NA, and help to prevent unnecessary drug use, minimize the side effects and economic damages. A total of 124 patients who have received nucleoside analog (NA) drug treatments (n=72) and patients without NA treatment (n=52) were included in the study. Viral DNA was isolated from the plasma samples of the patients. A DNA fragment, which is 551 bp, was amplified and sequenced including the binding side of all nucleoside analogs containing the B, C and D domains located in the reverse transcriptase region in the HBV genome. Different types of mutations were detected in 13 (18.05%) of 72 treated patients and in 18 (34.61%) of 52 untreated patients (p<0.05). Primary drug resistance mutations such as rtI169T, rtA181T/V, rtT184A/C/F/G/I/L/M/S, rtA194T, rtS202C/G/I, rtM204I/V/S, rtN236T, rt M250I/L/V and rtV173L were not detected in any of the patient samples. However, potential drug resistance mutations such as rtR164R, rtG165D/A, rtG172Q, rtS176N, rtF178V, rtA181G, rtS185N/G/C, rtV207M, rtQ215H/S, rtL231V, rtI233K, rtN238S, rtV253T, rtC256G/S and rtI266R/V were detected in untreated patient samples in B, C, D and D domains of reverse transcriptase region. Our results have suggested that the detection of pretreatment variations could be helpful for choosing the correct antiviral drug for the better treatment management.