Abstract
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.
Highlights
Hepatitis B virus (HBV) infection leads to chronic hepatitis B (CHB), cirrhosis and even hepatic carcinoma
When reverse transcription is replicated, base pairing errors are prone to occur. This mismatch rate is much higher than other DNA viruses, which leads to the high mutation of HBV gene, which leads to drug resistance, which may be the cause of pre-existing drug resistance
The question is whether the viral resistance mutations we encounter in our clinic are pre-existing or drug-induced? Since there is the possibility of pre-existing drug resistance, is it necessary to detect HBV gene resistance mutation before application of nucleoside drugs? Is there any difference between pre-existing mutations and drug-induced drug resistance mutations especially in liver cirrhosis patients? Based on these ideas we have established this retrospective research
Summary
Hepatitis B virus (HBV) infection leads to chronic hepatitis B (CHB), cirrhosis and even hepatic carcinoma. When reverse transcription is replicated, base pairing errors are prone to occur This mismatch rate is much higher than other DNA viruses, which leads to the high mutation of HBV gene, which leads to drug resistance, which may be the cause of pre-existing drug resistance. 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. 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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