Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 7, October, p. 1123–1129

doi: 10.17219/acem/63998

Publication type: original article

Language: English

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Accumulation of mutations in reverse transcriptase of hepatitis B virus is associated with liver disease severity in treatment-naïve Chinese patients with chronic hepatitis B

Bin Zhu1,A,E,F, Tianbao Wang1,B, Xiaoxia Wei1,B, Ya Zhuo1,C, Amin Liu1,C, Guangwen Zhang1,D

1 Infectious Disease Department of the First Affiliated Hospital of Xinxiang Medical University, Henan, China

Abstract

Background. Mutations in reverse transcriptase (RT) of the hepatitis B virus (HBV) are demonstrated to be strongly associated with nucleos(t)ide analog resistance, which is supposed to be the biggest obstacle during the long-term anti-viral treatment of chronic hepatitis B. However, the presence of RT mutations in treatment-naïve chronic hepatitis B patients and its clinical significance are not well known.
Objectives. To investigate the significance of mutations in reverse transcriptase of the hepatitis B virus in treatment-naïve Chinese patients with chronic hepatitis B.
Material and Methods. In this study, 288 treatment-naïve chronic HBV patients were recruited and the RT region was sequenced. The results showed that 71 patients (24.65%) were found with RT mutations, within which there were no well-defined primary nucleotide analog-resistant mutations.
Results. There were a total of 28 mutant sites, which formed three dominant mutant clusters: rt124-139, rt191-212 and rt225-229. Among these 71 patients, 63.38% (45/71) of patients had a single mutation while 19.72% (14/71), 12.68% (9/71) and 4.23% (3/71) of patients had 2, 3 or 4 mutations, respectively. Patients with RT mutations showed significantly decreased serum baseline HBV DNA loads (p = 0.0363) and blood platelet count (p = 0.0181) than patients without RT mutations. Patients with multiple mutant sites (≥ 2) had significantly decreased baseline HBV DNA loads (p = 0.0004) and blood platelet count (p = 0.0011) than patients with single mutant site. Moreover, the number of RT mutant sites is significantly associated with severity of liver fibrosis (p = 0.0128).
Conclusion. This study demonstrated that there was a prevalence of RT mutations in treatment-naïve chronic hepatitis B patients, which reflects a tougher liver environment for the virus and deeper liver injury for the host. Accumulation of RT mutations was associated with liver disease severity in treatment-naïve chronic hepatitis B patients.

Key words

hepatitis B virus, mutation, treatment-naïve, reverse transcriptase

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