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

Zhu, Bin; Wang, Tianbao; Wei, Xiaoxia; Zhuo, Ya; Liu, Amin; Zhang, Guangwen

doi:10.17219/acem/63998

Cited by 7 publications

(7 citation statements)

References 31 publications

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“…Zhao et al[ 27 ] also reported similar results showing that 75% of patients with RT mutations were HBeAg-negative and had lower HBV DNA levels (3.92 log 10 IU/mL) whereas 25% of patients with RT mutations were HBeAg-positive with higher HBV DNA loads (5.54 log 10 IU/mL). Similarly, Zhu et al[ 89 ] found that Chinese patients with chronic HBV carrying preexisting RT mutations had significantly decreased serum baseline HBV DNA loads ( P = 0.0363) and blood platelet counts ( P = 0.0181) compared with those without RT mutations.…”

Section: Clinical Factors (Hbeag Serostatus and Hbv Viral Loads) Affementioning

confidence: 90%

“…In addition, the number of RT mutations is associated with the liver disease progression. Zhu et al[ 89 ] revealed that patients with multiple RT mutant sites showed a significantly higher rate of liver fibrosis ( P = 0.0128), suggesting a link between viral mutation and clinical progression of chronic hepatitis, and also highlighting that the natural accumulation of RT mutations is a process involved in viral survival during chronic liver fibrosis.…”

Section: Preexisting Rt Mutations Are Related To the Progression Of Lmentioning

confidence: 99%

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Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression

Choi

Lee

Kim

2018

WJG

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The annual number of deaths caused by hepatitis B virus (HBV)-related disease, including cirrhosis and hepatocellular carcinoma (HCC), is estimated as 887000. The reported prevalence of HBV reverse transcriptase (RT) mutation prior to treatment is varied and the impact of preexisting mutations on the treatment of naïve patients remains controversial, and primarily depends on geographic factors, HBV genotypes, HBeAg serostatus, HBV viral loads, disease progression, intergenotypic recombination and co-infection with HIV. Different sensitivity of detection methodology used could also affect their prevalence results. Several genotype-dependent HBV RT positions that can affect the emergence of drug resistance have also been reported. Eight mutations in RT (rtL80I, rtD134N, rtN139K/T/H, rtY141F, rtM204I/V, rtF221Y, rtI224V, and rtM309K) are significantly associated with HCC progression. HBeAg-negative status, low viral load, and genotype C infection are significantly related to a higher frequency and prevalence of preexisting RT mutations. Preexisting mutations are most frequently found in the A-B interdomain of RT which overlaps with the HBsAg “a” determinant region, mutations of which can lead to simultaneous viral immune escape. In conclusion, the presence of baseline RT mutations can affect drug treatment outcomes and disease progression in HBV-infected populations via modulation of viral fitness and host-immune responses.

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Section: Clinical Factors (Hbeag Serostatus and Hbv Viral Loads) Affementioning

confidence: 90%

Section: Preexisting Rt Mutations Are Related To the Progression Of Lmentioning

confidence: 99%

Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression

Choi

Lee

Kim

2018

WJG

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“…This data was consistent with several other previous studies, indicating that naturally occurring RT variants were associated with decreased HBV-DNA loads. 17,26,29 The reason may be that HBV replication is often impaired by the RT variants, which decreases the activity of polymerase. Although another study indicated that patients with multiple RT variants showed decreased HBV-DNA loads compared with patients with a single RT variant, 29 there was no difference in HBV-DNA loads and other clinical factors (gender, age, genotype, HBeAg, ALT, and AST levels) between the single variant and the multiple variants subgroups, implying that certain single RT variants played a crucial role in viral replication.…”

Section: Discussionmentioning

confidence: 99%

“…17,26,29 The reason may be that HBV replication is often impaired by the RT variants, which decreases the activity of polymerase. Although another study indicated that patients with multiple RT variants showed decreased HBV-DNA loads compared with patients with a single RT variant, 29 there was no difference in HBV-DNA loads and other clinical factors (gender, age, genotype, HBeAg, ALT, and AST levels) between the single variant and the multiple variants subgroups, implying that certain single RT variants played a crucial role in viral replication. It is also worth noting that no classical primary and secondary variants were found in several previous studies, 14,29 which might have influenced the results of the analysis.…”

Section: Discussionmentioning

confidence: 99%

<p>Prevalence of Potential Resistance Related Variants Among Chinese Chronic Hepatitis B Patients Not Receiving Nucleos(T)ide Analogues</p>

Qian

Zou

Fang

et al. 2020

IDR

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Background and Aims: Potential drug resistance (DR) related variants in the hepatitis B virus (HBV) reverse transcriptase (RT) region may be associated with the effectiveness of antiviral drugs and disease progression. The aim of this study was to investigate the prevalence and clinical characteristics of potential DR-related variants in Chinese CHB patients not receiving nucleos(t)ide analogues (NAs). Patients and Methods: Two hundred and six untreated CHB patients from Huzhou Central Hospital in eastern China were recruited for this study. The serum DNA was extracted and the HBV RT region was amplified using nest polymerase chain reaction (nest-PCR). The 42 potential DR-related variants were analyzed by direct sequencing. Results: Among these CHB patients, HBV genotype B and genotype C were identified in 121 (58.7%) and 85 (41.3%) patients, respectively. Potential DR-related variants were detected in 42.7% (88/206) of patients. Primary and secondary DR variants were found in 7.3% (15/206) of patients, including rtL80I/V, rtI169T, rtV173L rtL180M, rtA181T/V, rtM204I/V, and rtN236T. The variants at rt53, rt82, rt221, rt233, rt237, and rt256 were specific for genotype B, and those at rt38, rt84, rt126, rt139, rt153, rt191, rt214, rt238, and rt242 were specific for genotype C. Moreover, the variation frequency in the A-B interdomain (3.96%) was significantly higher than that in the functional domains (1.17%) and non-A-B interdomains (1.11%). Multivariate logistic regression analysis showed that lower HBV-DNA load (<10 6 IU/mL) was an independent factor associated with potential DR-related variants in untreated CHB patients (P <0.05). Conclusion: Potential DR-related variants were frequent and complex in untreated Chinese CHB patients. Furthermore, the variants may contribute to decreased serum HBV-DNA loads. However, the effects of potential DR-related variants on the antiviral therapy and liver disease progression require further study.

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“…HBV pre-existing gene resistance has been confirmed by many studies [15][16][17], and the pre-existing mutation patterns of gene resistance are diverse [15]. However, there is no consensus on HBV genetic resistance testing before NAs antiviral treatment.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of HBV Pre-Existing Mutations and Drug-induced Resistance Mutations in Patients with Hepatitis B Virus-Related Cirrhosis

Wang

Dai

et al. 2019

IGH

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Background: The reported prevalence and necessity of detection of HBV reverse transcriptase (RT) mutation prior to treatment is varied and remains controversial. This study aimed to identify the prevalence of HBV pre-existing gene resistance mutations and compare the difference between pre-existing mutations and drug-induced resistance mutations in patients with hepatitis B virus-related cirrhosis.Methods: 180 patients with hepatitis B virus-related cirrhosis which included 68 patients with virological breakthrough and 112 treatment-naive cirrhosis patients were retrospectively enrolled. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. One-way ANOVA analysis was performed in the comparison among different groups. Ratios difference was compared with the chi-square test.Results: There were 48 patients (48/112, 42.86%) with drug resistance mutations in nucleoside/nucleotide analogues (NAs) treatment-naive group, 59 patients (59/68, 86.76%) showed drug-resistant mutations in the NAs treatment group. The gene resistance mutation patterns in treatment-naive group were mainly rtS213T, rtV214A, 191V/I and rtN/H238T/D, and the types of resistance mutations in the treated group were different. The adefovir (ADV) group: mainly rtA181T/V and rtS213T; lamivudine/ telbivudine (LAM/LDT) group: rtL180M+ rtM204I/V/S and rtM204I/V/S or a complex mutation pattern containing 204 site; entecavir (ETV) group: The drug resistance pattern is the simultaneous presence of multiple site mutations. LAM/LDT sequential ADV group: The variant type was multi-site and resistant to both ADV and LAM.Conclusion: There was a prevalence of pre-existing mutations in RT region of HBV polymerase in patients with hepatitis B virus-related cirrhosis, The mutation pattern is mainly related to LAM and ADV-related compensatory mutations, while the drug-induced mutation pattern is more complicated, mainly related to the antiviral drugs used and there are mainly primary mutations. Patients with cirrhosis should be tested genetic resistance mutation before using antiviral drugs.

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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

Cited by 7 publications

References 31 publications

Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression

Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression

<p>Prevalence of Potential Resistance Related Variants Among Chinese Chronic Hepatitis B Patients Not Receiving Nucleos(T)ide Analogues</p>

Retrospective Analysis of HBV Pre-Existing Mutations and Drug-induced Resistance Mutations in Patients with Hepatitis B Virus-Related Cirrhosis

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