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Vaccination and anti-viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations. We analysed sequences downloaded from the HBV Database and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution and estimated the age of selected mutations across tree branches. RAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our data set, and a significantly higher rate in genotype C at 5.4% (60/1102, p = 0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p = 0.002) and 1.6% (34/2109; p = 0.009), respectively. Phylogenetic analysis suggested that RAM/VEMs can arise independently of treatment/vaccine exposure. In conclusion, HBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C. Screening for genotype and for resistance-associated mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero‐surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)‐positive) prevalence and HCV exposure (HCV antibody (HCV‐Ab)‐positive) prevalence between two sero‐surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population‐attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2–2.9) in 2007 to 1.1% (95% CI: 0.8–1.3) in 2019, while HCV‐Ab prevalence increased from 5.1% (95% CI: 4.6%–5.5%) to 6.2% (95% CI: 5.6%–6.8%). The age and gender‐adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1–0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3–0.6) among adults over 2007–2019, while HCV‐Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2–0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2–1.7) in adults. HCV‐Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5–0.8) and higher (aOR = 0.5, 95%CI:0.3–0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2–2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9–3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6–2.7), being tattooed (aOR = 1.4, 95% CI: 1.0–1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0–1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7–48.4%). Overall HCV has increased over 2007–2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities. [ABSTRACT FROM AUTHOR]