Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy–Experienced Patients in Europe (CAPRE)

Hermans, Lucas E; Svicher, Valentina; Pas, Suzan D.; Salpini, Romina; Álvarez, Marta; Ari, Ziv Ben; Boland, Greet J.; Bruzzone, Bianca; Coppola, Nicola; Seguin-Devaux, Carole; Dyda, Tomasz; García, Féderico; Kaiser, Rolf; Köse, Şükran; Krarup, Henrik; Lazarević, Ivana; Lunar, Maja M.; Maylin, Sarah; Micheli, Valeria; Mor, Orna; Paraschiv, Simona; Paraskevis, Dimitrios; Poljak, Mario; Puchhammer‐Stöckl, Elisabeth; Simon, François; Stanojević, Maja; Stene‐Johansen, Kathrine; Tihić, Nijaz; Trimoulet, Pascale; Verheyen, Jens; Vince, Adriana; Weis, Nina; Yalçinkaya, Tülay; Lepej, Snježana Židovec; Perno, Carlo Federico; Boucher, Charles A.; Wensing, Annemarie M. J.

doi:10.1093/infdis/jiv363

Cited by 31 publications

(26 citation statements)

References 42 publications

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“…In Europe, HBV/D is the most frequently encountered viral genotype (63%), followed by HBV/A (26%). 24 In East Asia, HBV/B and HBV/C are dominant HBV genotypes, while in North China, the prevalence of HBV/C was significantly higher than HBV/B. 16 In a largest-to-date European survey that involved 1,568 NA-experienced chronic hepatitis B patients, drug resistance was observed in half of the cases, 24 similar with that in our current study (45.1%).…”

Section: Discussionsupporting

confidence: 86%

“…This and other European studies showed that there was a mutational pattern bias of rtM204 V for HBV/A and rtM204I for HBV/D. 24,25 By contrast, no such bias was observed between HBV/B-and HBV/C-infected patients in our current study. In NA-untreated patients, drug-resistant mutations were detected in 2/140 (1.4%) of European patients with HBV/D.…”

Section: Discussioncontrasting

confidence: 70%

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Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China

Liu

Xin

et al. 2017

Microbial Drug Resistance

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The study aimed to investigate the association of prevalent genotypes in China (HBV/C and HBV/B) with HBV drug-resistant mutations. A total of 13,847 nucleos(t)ide analogue (NA)-treated patients with chronic HBV infection from North China were enrolled. HBV genotypes and resistant mutations were determined by direct sequencing and confirmed by clonal sequencing if necessary. HBV/B, HBV/C, and HBV/D occupied 14.3%, 84.9%, and 0.8% across the study population, respectively. NA usage had no significant difference between HBV/B- and HBV/C-infected patients. Lamivudine-resistant mutations were more frequently detected in HBV/C-infected patients, compared with HBV/B-infected patients (31.67% vs. 25.26%, p < 0.01). Adefovir- and entecavir-resistant mutation detection rates were similar, but the mutational pattern was different between the two genotypes. For adefovir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtA181 V (HBV/C 5.29% vs. HBV/B 1.36%, p < 0.01) and a lower detection rate of rtN236T (2.70% vs. 6.54%, p < 0.01). For entecavir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtM204 V/I+T184 substitution or S202G/C (3.66% vs. 2.16%, p < 0.01) and a lower detection rate of rtM204 V/I+M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01). Multidrug-resistant mutations (defined as coexistence of mutation to nucleoside and nucleotide analogues) were detected in 104 patients. HBV/C-infected patients had a higher detection rate of multidrug-resistant mutation than HBV/B-infected patients (0.83% vs. 0.35%, p < 0.05). The study for the first time clarified that HBV/C-infected patients had a higher risk to develop multidrug-resistant mutations, compared with HBV/B-infected patients; and HBV/C- and HBV/B-infected patients had different inclinations in the ETV-resistant mutational pattern.

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Section: Discussionsupporting

confidence: 86%

Section: Discussioncontrasting

confidence: 70%

Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China

Liu

Xin

et al. 2017

Microbial Drug Resistance

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“…The dominant pattern of resistance (71.4%) among treatment-experienced patients with mutated strains (rtM204V + rtL180M) was higher than that in the European multicenter study (29%) [34] and Ghana (47.6%) [23]. The rtV173LtrtL180MtrtM204V triple change has already been described in patients with HIV and HBV co-infection [35], and resulted in codon changes in the surface open reading frame (ORF; sE164D and sI195M, respectively) [22, 24].…”

Section: Discussionmentioning

confidence: 99%

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

Jia

Chen

et al. 2018

Intervirology

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Objectives: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China. Methods: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed. Results: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3–96.7) was significantly higher than that in group 1 (1.4%, 95% CI –1.4 to 4.2; χ² = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 10⁶ copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations. Conclusion: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.

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“…Therefore, rtV191I mutation may be the new resistance site to LAM. Since rt224I/V has never been reported before [13,[22][23][24][25][26], further observation of these patients might address the question whether these mutations are associated with other nucleoside analogue resistance or affect the outcome of the disease.…”

Section: Discussionmentioning

confidence: 96%

Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

Wang

Han

Duan

et al. 2017

J Infect Dev Ctries

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Introduction: Previous studies have indicated that the drug-resistant mutations of hepatitis B virus (HBV) are a major obstacle to antiviral therapy. However, it is still unclear whether there are pre-existent resistance mutations in patients with HBV infection and the relationship between drug-resistant mutation, genotypes, and progression of hepatitis B disease. Methodology: A total of 357 treatment-naïve patients with HBV infection were involved in this retrospective study. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. Results: Lamivudine (LAM) resistance was detected in 8 patients (3.7%) with chronic hepatitis B (CHB), 13 (11.7%) patients with liver cirrhosis (LC), and 6 (21.4%) patients with hepatocellular carcinoma (HCC). Adefovir(ADV)-resistant mutations were detected in 10 (4.6%) patients with CHB, 15 (13.5%) patients with LC and 4 (14.5%) patients with HCC. Both LAM and ADV resistant mutations were detected in 2 patients (0.9%) with CHB, 1 patient (0.9%) with LC and 1 patient (3.6%) with HCC. Significant differences (p <0.01) were observed in the drug-resistance rates among patients with CHB, LC and HCC. Meanwhile, all the drug-resistant mutations were found in patients with HBV genotype C. Conclusions: This study demonstrated higher risk of pre-existing drug-resistant mutations in patients with HBV genotype C comparing to patients with HBV genotype B. Likewise, increasing prevalence of pre-existing drug-resistant mutations was shown, alongside with the progression of the disease.

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Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy–Experienced Patients in Europe (CAPRE)

Abstract: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

Cited by 31 publications

References 42 publications

Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China

Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

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