Mutation Patterns at Codons Rt204 And Rt180 of the HBV PolymeraseGene Associated with Lamivudine Resistance in Treated and UntreatedChronic HBV Patients in Kuwait: A Case Series

Introduction: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication via suppression of the RNAdependent DNA polymerase. However, patients with prolonged therapy were previously detected harboring drugresistant mutants. Such mutants though partially replication defective, confer resistance to lamivudine and can elicit exacerbation of hepatonecro-inflammation. Cases presentation: In this case series, we examined mutations in the YMDD motif gene in five lamivudinetreated patients (60 yr male, 50 yr female, 46 yr male, 36 yr male and 42 yr male) and in four untreated patients (34 yr female, 29 yr male, 29 female and 37 yr male). Rare mutational patterns of rtM204L in conjunction with rtL108M were recognized conferring resistance to lamivudine. The rtL180M compensatory mutation was identified in conjunction with rtM204V/I/L; among which three patients had viral and biochemical breakthrough associated with serum HBV DNA levels exceeding 106 copies/mL. Conclusions: These results indicate that; (i) lamivudine resistant HBV strains are naturally occurring mutants as detected in lamivudine untreated patients and; (ii) New mutational patterns (rtM204L: YLDD and rtL180M) were identified conferring resistance to lamivudine and resulted in biochemical and virological breakthrough. Based on these findings, we propose that such mutations can be used as a marker to predict development of viral breakthrough in the HBV patients whether or not treated with lamivudine.