Long‐term adefovir plus lamivudine therapy does not decrease creatinine clearance in HBeAg‐negative chronic hepatitis B patients

Background/Aims As there are concerns about potential nephrotoxicity of nucleotide analogues, we evaluated renal function parameters during long-term adefovir and lamivudine combination therapy. Methods Forty-six HBeAg-negative patients with lamivudine-resistance treated with adefovir and lamivudine for up to 90 months were included. Renal function was assessed by estimated creatinine clearance (eCCR) and compared with a matched control group of untreated inactive hepatitis B virus carriers. Results Serum HBVDNA became undetectable in 39 (85%) patients after a mean of 37 ± 21 months. Three (6.5%) patients developed virological breakthrough. Adefovir resistance was detected in two patients. At the end of follow up, there was a significant decrease in mean eCCR (95 ± 31–83 ± 30 ml/min, P = 0.003) in the treated patients with 16% presenting aeCCR decrease >30%. Similar changes in eCCR were observed in the control group (108 ± 28–96 ± 26 ml/min, P = 0.003). In multiple regression analysis, age and baseline eCCR were independent predictors of eCCR reduction. Conclusions Adefovir and lamivudine combination therapy is not an independent factor for significant renal dysfunction in HBeAg-negative patients with lamivudine-resistance. Baseline age and creatinine clearance are the only independent predictors of worsening renal function.