Genotyping of HBV and tracking of resistance mutations in treatment-naïve patients with chronic hepatitis B

Abstract

Background and aimsResistance mutation analogs to nucleos(t)ides have been described in treatment-naïve patients with chronic hepatitis B (CHB), with clinical implications. The aim of this study was to investigate primary resistance mutations and genotypes circulating in patients naïve to chronic hepatitis B, in the Northern and Northeastern regions of Brazil.MethodsWe conducted a study of resistance mutations and genotypic characterization of hepatitis B virus (HBV) in 189 treatment-naïve patients chronically infected with HBV.ResultsDrug resistance-associated mutations located in the RT domain of the P gene (rtHBV) were found in 6% of the treatment-naïve patients from the Northeastern Region. The mutations were rtA194T, rtL180M + rtM204V, rtS202I, rtM204I, and rtA181S. No patient in the Northern Region had the resistance mutation. In the gene S region, the frequency of vaccine escape mutations was 2.4% in the Northeastern Region and 8.6% in the Northern Region.ConclusionThis information before the start of treatment may contribute to clinical decision making, reducing treatment failure and the risk of progression to cirrhosis and hepatocellular carcinoma for CHB.

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

“…The prevalence of potential DR-related variants in the HBV RT region in NAs-untreated CHB patients has been reported in several previous studies but the results are controversial. 6,7,14,17,18 In the present study, potential DRrelated variants were detected in 42.7% (88/206) of untreated CHB patients, and primary and secondary DR variants were found in 7.3% (15/206) patients. Several studies have reported that the prevalence rate of primary and secondary DR variants was low or even zero in untreated patients.…”

“…A study in central China reported that variants associated with DR were detected in 8.9% of untreated patients. 13 Another study recently reported DR variants in 6% of Brazilian treatment-naïve CHB patients, 18 and a meta-analysis showed that the pooled incidence of naturally resistant variants in China was higher than that in other countries (8.00% vs 1.88%). 19 Overall, the incidence of DR variants was closely related to the geographical distribution and epidemic situation of the HBV infection.…”

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

“…Among the 50 studies, 36[ 12 , 20 , 21 , 32 - 58 , 60 - 65 ] used direct PCR sequencing methods, 11[ 22 - 28 , 59 , 66 - 68 ] used the INNO-LiPA line assay, and 3[ 29 - 31 ] detected RT mutations by ultra-deep pyrosequencing (UDPS). Seventeen articles[ 21 , 26 , 27 , 30 , 31 , 34 , 35 , 37 - 39 , 42 , 43 , 46 - 48 , 53 , 58 ] included treatment-naïve patients infected with genotypes B and C, one study[ 32 ] with genotypes A and D, eleven studies[ 22 , 28 , 29 , 36 , 50 , 51 , 55 , 56 , 60 , 63 , 68 ] with genotype D, one study[ 33 ] with genotype C, and fifteen studies[ 20 , 23 - 25 , 40 , 41 , 44 , 45 , 52 , 54 , 57 , 61 , 64 , 65 , 67 ] with more than three genotypes ( e.g ., A, C, and D or A, B, C, and D). In five studies, genotypes of patients were not mentioned.…”

“…Recently, it has been proven through in vitro and in vivo experiments that several putative or pretreatment mutations, including rtL229F, rtS13T, and rtI233V, can also contribute to the development of drug resistance[ 40 , 78 , 79 ]. In addition, several studies have reported that treatment-naïve patients with only putative RT mutations, and without primary or secondary changes, developed drug resistance since treatment initiation[ 41 ]. Our literature based pooled incidence data showed that several putative or pretreatment mutations, including rtI91L, mutations in 6 positions of A-B interdomain (rtY124H, rtY126C/R/H, rtT128I/N, rtD134E/N, rtN139D/E/H/K/Q and rtW153Q/R/E), rtF221Y and rtI224V, were encountered with high frequency from the treatment naïve patients[ 20 , 21 , 33 , 38 , 39 , 42 ].…”

Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients

“…It has become clear that viral resistance originates from mutations in the nucleotide binding motif of HBV RT region [ 3 ]. Phenotypic studies showed that the LMV resistance arising from rtM204V/I in the YMDD motif, could negate sensitivity to LMV by more than 100-fold decrease compared with wild-type [ 4 ].…”