Association of Hepatitis B Virus Polymerase/Surface Gene Overlap Mutations Developed in Nucleos(t)id Analogue Treatments of Chronic Hepatitis B with Hepatocellular Carcinoma

Year 2025, Issue: Early Access

Seda Erem Basmaz , Sadettin Hülagü , Murat Sayan , Yeşim Saliha Gürbüz

https://doi.org/10.18678/dtfd.1526783

Abstract

Aim: Nucleos(t)id analogs (NA) used in hepatitis B virus (HBV) treatment may cause rtA181T and sW172* mutations. sW172* increases progression to hepatocellular carcinoma (HCC). This study aimed to reveal the rtA181T/sW172* mutation in HCC patients on the background of chronic hepatitis B (CHB) to determine its association with NA.
Material and Methods: A total of 90 CHB patients, 42 patients with HCC (DNA of 4 patients could not be analyzed), and 48 patients without HCC as the control group, were included in this study. Patients in the control group were divided into two groups, those who received NA treatment (n=21) and those who did not (n=21). Drug resistance analysis was performed by DNA sequencing.
Results: Among the 42 patients with HCC, the median age was 63 (range, 37-81) years, and the median HBV DNA level was 6.0x106 (range, 30-1.14x108) IU/ml. In the 48 patients included as controls, the median age and HBV DNA level were 46 (range, 20-75) years and 1.41x107 (range, 80-1.70x108) IU/ml in the treatment-naive patients, and 36 (range, 21-50) years and 7.6x106 (range, 15.9x102 - 5.1x107) IU/ml in the NA-treated patients, respectively. sW172* mutation, which causes rtA181T mutation to occur, was identified in only 2 (5.3%) patients in the study group with HCC.
Conclusion: Association between HCC and rtA181T/sW172* mutation suggests that HCC may develop in patients under NA treatment. The rtA181T/sW172* mutation should be screened in patients receiving treatment, and when detected, they should be closely monitored for HCC development.

Keywords

Hepatocellular carcinoma, hepatitis B virus, drug resistance, nucleos(t)id analog

Kronik Hepatit B’nin Nükleoz(t)id Analoğu Tedavilerinde Gelişen Hepatit B Virüsü Polimeraz/Yüzey Geni Çakışma Mutasyonlarının Hepatosellüler Karsinom ile İlişkisi

Abstract

Amaç: Hepatit B virüsü (HBV) tedavisinde kullanılan nükleoz(t)id analogları (NA), rtA181T ve sW172* mutasyonlarına neden olabilir. sW172* hepatosellüler karsinoma (hepatocellular carcinoma, HCC) ilerlemesini artırır. Bu çalışmanın amacı, kronik hepatit B (chronic hepatitis B, CHB) zemininde HCC hastalarında rtA181T/sW172* mutasyonunu ortaya koyarak NA kullanımı ile ilişkisini belirlemektir.
Gereç ve Yöntemler: Bu çalışmaya, 42 HCC'li hasta (4 hastanın DNA'sı analiz edilemedi) ve kontrol grubu olarak 48 HCC'siz hasta olmak üzere toplam 90 CHB hastası dahil edildi. Kontrol grubundaki hastalar, NA tedavisi alanlar (n=21) ve almayanlar (n=27) olmak üzere iki gruba ayrıldı. İlaç direnci analizi DNA sekanslama yöntemi ile gerçekleştirildi.
Bulgular: HCC'li 42 hastada, ortanca yaş 63 (aralık, 37-81) yıl ve ortanca HBV DNA düzeyi 6,0x106 (aralık, 30-1,14x108) IU/ml idi. Çalışmaya kontrol olarak dahil edilen 48 hastada, ortanca yaş ve HBV DNA düzeyi, sırasıyla, tedavi naif hastalarda 46 (aralık, 20-75) yıl ve 1,41x107 (aralık, 80-1,70x108) IU/ml ve NA tedavisi alan hastalarda 36 (aralık, 21-50) yıl ve 7,6x106 (aralık, 15,9x102 - 5,1x107) IU/ml idi. Çalışma grubundaki HCC'li hastaların sadece 2'sinde (%5,3), rtA181T mutasyonunun ortaya çıkmasına neden olan sW172* mutasyonu tespit edildi.
Sonuç: HCC ile rtA181T/sW172* arasındaki ilişki, NA tedavisi alan hastalarda HCC gelişebileceğini düşündürmektedir. Tedavi alan hastalarda rtA181T/sW172* mutasyonu taranmalı ve tespit edildiğinde hastalar HCC gelişimi açısından yakın takip edilmelidir.

Keywords

Hepatosellüler karsinom, hepatit B virüsü, ilaç direnci, nükleoz(t)id analoğu

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