SavedAdd your journal

Journals / Viral Hepatitis Journal / 2021 / Cilt: 27 - Sayı: 3

Molecular Analysis of Hepatitis B Virus Reverse Transcriptase Domain for Mutations Associated with Viral Resistance in Pakistani Patients

Pakistanlı Hastalarda Viral Dirençle İlişkili Mutasyonlar İçin Hepatit B Virüsü Ters Transkriptaz Domaininin Moleküler Analizi

Zia Ur RAHMAN
Majid MAHMOOD
Muhammad Asim ANWAR
Sdia JAMEEL
Pages
153–158
Publication Date
2022-11-06
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

However, no mutation was found to be associated with the viral resistance against tenofovir.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objectives: Current study was designed to screen out the resistant mutations in reverse transcriptase (RT) domain of hepatitis B virus (HBV) genome from non-responder Pakistani patients.
📊
Key Findings & Data:Materials and Methods: A total of 22 patients, receiving different nucleot(s)ide analogues were included in the study.
💡
Conclusion & Impact:However, no mutation was found to be associated with the viral resistance against tenofovir.
🔬Design:Research Article
📍Scope:4 samples
⚙️Variables:Domain Parameters

Abstract

Objectives: Current study was designed to screen out the resistant mutations in reverse transcriptase (RT) domain of hepatitis B virus (HBV) genome from non-responder Pakistani patients. Materials and Methods: A total of 22 patients, receiving different nucleot(s)ide analogues were included in the study. RT domain of the virus from samples of non-responder patients was amplified and sequenced. Sequences were aligned and analyzed for RT domain mutations. Results: After 18 months, 18 patients were responder and 4 were non-responder. Mean alanine aminotransferase (ALT) and viral load of responder patients decreased significantly as compared to those of non-responder patients. Two of the 4 samples from non-responders were successfully sequenced. Mutations rtY135S, rtI169P, rtV173P, rtL180I, rtA181V, rtT184Y and rtM204V were identified from the sample of patient 1, while rtL80V/rtL80G and rtY135S were identified from the sample of patient 2. Conclusion: Mutations rtY135S, rtI169P, rtV173P, rtL180I, rtA181V, rtT184Y, rtM204V, rtL80V/rtL80G, and rtY135S are present in genome of HBV circulating in Pakistani patients. These mutations give resistance to virus against lamivudine, telbivudine, adefovir, and partially resistance against entecavir. However, no mutation was found to be associated with the viral resistance against tenofovir.

Özet

Amaç: Mevcut çalışma, yanıtsız Pakistanlı hastalardan hepatit B virüsü (HBV) genomunun ters transkriptaz (RT) domainindeki dirençli mutasyonları taramak için tasarlanmıştır. Gereç ve Yöntemler: Çalışmaya farklı nükleot(z)id analogları alan toplam 22 hasta dahil edildi. On sekiz ay sonra, 18 hasta yanıt verdi ve 4 hasta yanıt vermedi. Yanıt vermeyen hastaların örneklerinden alınan virüsün RT domaini amplifiye edildi ve dizilendi. Diziler hizalandı ve RT domaini mutasyonları açısından analiz edildi. Bulgular: Yanıt veren hastaların ortalama alanin aminotransferaz (ALT) ve viral yükü, yanıt vermeyen hastalarla karşılaştırıldığında önemli ölçüde azaldı. Yanıt vermeyen hastalardan alınan 4 örnekten 2’si başarıyla sıralandı. Birinci hastanın örneğinden rtY135S, rtI169P, rtV173P, rtL180I, rtA181V, rtT184Y ve rtM204V mutasyonları belirlenirken ikinci hastanın örneğinden rtL80V/rtL80G ve rtY135S mutasyonları belirlendi. Sonuç: Pakistanlı hastalarda saptanan HBV genomunda rtY135S, rtI169P, rtV173P, rtL180I, rtA181V, rtT184Y, rtM204V, rtL80V/rtL80G ve rtY135S mutasyonları mevcuttu. Bu mutasyonlar, virüse lamivudin, telbivudin ve adefovire karşı tam, entecavire karşı kısmen direnç sağlamaktaydı. Bununla birlikte, tenofovire karşı viral dirençle ilişkili hiçbir mutasyon bulunmadı.

🔖

Cite This Article

RAHMAN, Z. U., MAHMOOD, M., ANWAR, M. A., JAMEEL, S. (2022). Molecular Analysis of Hepatitis B Virus Reverse Transcriptase Domain for Mutations Associated with Viral Resistance in Pakistani Patients. Viral Hepatitis Journal, Cilt: 27 - Sayı: 3, 153–158. https://ajindex.com/articles/646320

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (12)

  1. Ganem D, Prince AM. Mechanisms of disease hepatitis B virus infection natural history and clinical consequences. New Eng J Med. 2004;350:1118-1200
  2. Yamada N, Sugiyama R, Nitta S, Murayama A, Kobayashi M, Okuse C, Suzuki M, Yasuda K, Yotsuyanagi H, Moriya K, Koike K, Wakita T, Kato T. Resistance mutations of hepatitis b virus in entecavirrefractory patients. Hepatol Commun. 2017;1:110-122
  3. Choe WH, Kim K, Lee S, Choi Y, Kwon SY, Kim JH, Kim BJ. Tenofovir is a more suitable treatment than entecavir for chronic hepatitis B patients carrying naturally occurring rtM204I mutations. World J Gastroenterol. 2019;25:4985-4998
  4. Tan M, Bhadoria AS, Cui F, Tan A, Holten JV, Easterbrook P, Ford N, Han Q, Lu Y, Bulterys M, Hutin Y. Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and metaanalysis. Lancet Gastroenterol Hepatol. 2021;6:106-119
  5. Madihi S, Syed H, Lazar F, Zyad A, Benani A. A systematic review of the current hepatitis b viral infection and hepatocellular carcinoma situation in mediterranean countries. BioMed Res Int. 2020;7027169
  6. Rantala M, van der Laar MJ. Surveillance and epidemiology of hepatitis B and C in Europe. Euro Surveill. 2008;13:18880
  7. Hua W, Zhang G, Guoc S, Li W, Sun L, Xiang G. Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection. Braz J Infect Dis. 2015;19:291-295
  8. Boesecke C, Wasmuth JC. Distribution and clinical significance of hepatitis B virus genotypes in Pakistan. J Bio Med Cent Gastroenterol. 2012;6:32-35
  9. He X, Wang F, Huang B, Chen P, Zhong L. Detection and analysis of resistance mutations of hepatitis B virus. Int J Clin Exp Med. 2015;8:9630-9639
  10. Bonino F; Hepatitis B virus heterogeneity--a means to personalized care’ steering committee. Introduction to ‘hepatitis B virus heterogeneity- a means to personalized care’. Antivir Ther. 2010;15(Suppl3):1-2
  11. Salpini R, Alteri C, Cento V, Pollicita M, Micheli V, Gubertini G, Visca M, Romano S, Sarrecchia C. Snapshot on drug-resistance rate and profiles in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. J Med Virol. 2013;85:996-1004
  12. Torresi J, Civitico G, Walters T, Lewin SR, Fyfe J. Restoration of replication phenotype of lamivudine resistant hepatitis B virus mutants by compensatory changes in the “fingers” subdomain of the viral po