Tian Meng1, Xiaofeng Shi1, Xuyang Gong1, Haijun Deng1, Yao Huang1, Xuefeng Shan2, Youlan Shan1, Ailong Huang3, Quanxin Long4. 1. Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. 2. Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 3. Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: ahuang1964@163.com. 4. Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: longquanxin@gmail.com.
Abstract
OBJECTIVES: To study the prevalence of drug-resistant HBV in patients with therapy failure in a Chinese tertiary referral liver centre. METHODS: 1223 HBV-infected patients who underwent genotypic resistance testing between 2010-2014 were studied. RESULTS: 3TC genotypic resistance was the most common (46.5%), followed by LdT resistant (46.2%), ETV intermediate (37.9%), ADV resistant (11.4%), TDF intermediate (11.4%) and ETV resistant (1.7%). The 3TC resistance rate increased from 39.8% in 2010 to 56.6% in 2013, before decreasing to 49.5% in 2014, evidence of a lagging effect of l-nucleoside consumption. M204I, N236T and L180M+M204V+V173L/S202G were the most common substitutions for l-nucleoside (3TC and LdT), ADV and ETV genotypic resistant phenotypes, respectively. 3TC-exposed patients showed a high multiple genetic resistance rate (3TC-resistant+LdT-resistant+ETV intermediate; 58.8%). Resistance rates to 3TC, LdT and ETV in HCC patients were significantly higher than in cirrhosis and CHB patients. Resistance rates to different drugs showed no statistical difference between genotype B and C patients, whilst some amino acid substitution showed genotype bias, e.g. N236T incidence in genotype B was significantly higher than in genotype C (43.2% vs. 5.9%; P<0.0001), and genotype C isolates had a significantly higher A181V/T incidence than genotype B (54.9% vs. 19.3%; P<0.0001). CONCLUSIONS: 3TC genotypic resistance was most common in this centre, whilst ETV had the lowest resistance rate. HBV genotypes had no impact on antiviral drug resistance, except for some drug resistance substitutions bias. Optional initial therapy and subsequent rescue treatment should be based on knowledge of nucleos(t)ide analogue resistance.
OBJECTIVES: To study the prevalence of drug-resistant HBV in patients with therapy failure in a Chinese tertiary referral liver centre. METHODS: 1223 HBV-infectedpatients who underwent genotypic resistance testing between 2010-2014 were studied. RESULTS:3TC genotypic resistance was the most common (46.5%), followed by LdT resistant (46.2%), ETV intermediate (37.9%), ADV resistant (11.4%), TDF intermediate (11.4%) and ETV resistant (1.7%). The 3TC resistance rate increased from 39.8% in 2010 to 56.6% in 2013, before decreasing to 49.5% in 2014, evidence of a lagging effect of l-nucleoside consumption. M204I, N236T and L180M+M204V+V173L/S202G were the most common substitutions for l-nucleoside (3TC and LdT), ADV and ETV genotypic resistant phenotypes, respectively. 3TC-exposed patients showed a high multiple genetic resistance rate (3TC-resistant+LdT-resistant+ETV intermediate; 58.8%). Resistance rates to 3TC, LdT and ETV in HCCpatients were significantly higher than in cirrhosis and CHB patients. Resistance rates to different drugs showed no statistical difference between genotype B and C patients, whilst some amino acid substitution showed genotype bias, e.g. N236T incidence in genotype B was significantly higher than in genotype C (43.2% vs. 5.9%; P<0.0001), and genotype C isolates had a significantly higher A181V/T incidence than genotype B (54.9% vs. 19.3%; P<0.0001). CONCLUSIONS:3TC genotypic resistance was most common in this centre, whilst ETV had the lowest resistance rate. HBV genotypes had no impact on antiviral drug resistance, except for some drug resistance substitutions bias. Optional initial therapy and subsequent rescue treatment should be based on knowledge of nucleos(t)ide analogue resistance.
Authors: Jolynne Mokaya; Anna L McNaughton; Phillip A Bester; Dominique Goedhals; Eleanor Barnes; Brian D Marsden; Philippa C Matthews Journal: Wellcome Open Res Date: 2020-06-29