Hepatitis B Virus Carrying Drug-resistance Compensatory Mutations in Chronically Infected Treatment-naive Patients

Abstract

ÖZObjective: The prevalence of hepatitis B virus (HBV) is highly variable throughout the world. Geographical regions are classified according to the prevalence of hepatitis B surface antigen in the general population as high (>8%), moderate (2-7%), and low endemicity (<2%). Turkey has a moderate endemicity level of HBV infection which is a serious health problem. Currently, there are various nucleos(t)ide analogues with anti-HBV activity and they are mostly used in the treatment of chronic hepatitis B (CHB) and cirrhosis. The risk of drug resistance increases because these drugs are still being used as monotherapy. It has been reported that HBV drug resistance-related mutations can occur also in patients who are classified as treatment-naive and who have not received any oral anti-HBV treatment. Materials and Methods:This prospective and descriptive epidemiological study aimed to determine the genotype/subgenotypes of HBV and to investigate the drug resistance mutations in treatment-naive CHB patients. The study included 149 CHB patients who had no chronic coinfections, and have not received treatment for CHB infection. In 53 of the samples collected from the patients, the amount of viral DNA was enough for sequence analysis to search for drug resistance. BigDyeTM Terminator Cycle Sequencing Kit (Applied Biosystems, Foster City, Calif., USA) was used for sequencing of the serum samples from these patients and drug resistance mutations were determined and genotype/ subgenotype detection was performed. Results:The mean viral load value was calculated as 9.84x10 6 , and there was no primary drug resistance in any of these 53 samples which were sequenced. There were compensatory resistance-related amino acid changes in 19 samples. Genotype D was determined as HBV in all cases. Conclusion:The early detection of drug resistance-related mutations can be important in determination of treatment protocol, and prevention of unnecessary drug use, complications, and economic loses.

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.…”

Determination of Resistance Mutation in Chronic Hepatitis B Patients Using Antiviral Drugs at Our Hospital

“…Sequencing can be the method of choice to detect other mutations. Altındiş et al (23) revealed compensatory mutations in treatment-naive CHB patients who have received both nucleoside/nucleotide analogues and lamivudine and/or adefovir treatments by sequencing method. rtQ149K, Q215S, Q215H, Q249K and V214A mutations were found to be associated with lamivudine and adefovir treatment; rtL91I mutation was found to be associated only with telbivudine and N238D with only adefovir.…”