The influence of YMDD mutation patterns on clinical outcomes in patients with adefovir add-on lamivudine combination treatment

Background/Aim: The aim of this study was to assess the patterns of lamivudine (LAM)-resistant mutations and the influence on biochemical and virological responses to adefovir (ADV) add-on LAM combination therapy in patients with LAM-resistant chronic hepatitis B (CHB). Methods: Seventy-eight CHB patients with confirmed genotypic resistance to LAM, who initiated ADV add-on LAM combination treatment, were enrolled at our institution between April 2007 and April 2009. Results: The baseline tyrosine-methionine-aspartate-aspartate (YMDD) mutation patterns were as follows: rtM204I 45 (57.7%); and rtM204V + rtM204I/V 33 (42.3%). The decrease in the mean ± standard deviation (SD) serum log ₁₀HBV-DNA level did not differ between the patients carrying the rtM204I vs. rtM204IV +rtM204I/V mutations at 3, 6 and 12 months after the initiation of ADV add-on LAM combination treatment. The proportion of patients who achieved ALT normalization (<40 IU/L) 12 months after the initiation of ADV add-on LAM combination treatment were significantly higher in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations (39 [86.7%] vs. 22 [66.7%], P = 0.05). The proportion of patients in whom the log ₁₀HBV-DNA decreased <2 log ₁₀ copies/ml, 6 months after the initiation of ADV add-on LAM combination treatment (non-responders), was significantly higher in patients with a rtM204V + rtM204I/V mutations than rtM204I mutation (7 [21.2%] vs. 2 [4.4%], P = 0.032). Conclusion: Biochemical response at 12 months from baseline was better in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations. In addition, early treatment failure was more common in patients with rtM204V+ rtM204I/V mutations than a rtM204I mutation.