Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon-lambda 3 induction in chronic hepatitis B patients

Background & Aims: Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon-lambda3 (IFN-lambda 3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN-lambda 3 levels in chronic hepatitis B (CHB) patients. Methods: A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN-lambda 3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5 years post-therapy. Results: The change (mean +/- standard deviation) in serum HBsAg levels from baseline to year five was -0.38 +/- 0.46 and -0.84 +/- 0.64 log(10) IU/ml in ETV and ADV/TDF groups, respectively (p = 0.0004). Higher serum IFN-lambda 3 levels were observed in ADV/TDF group compared with ETV group during treatment (p < 0.001). Serum IFN-lambda 3 levels showed negative correlation with HBsAg reduction in ADV/TDF group (r = -0.386, p = 0.038) at week 48. Nucleotide analogs (ADV/ TDF) treatment has associated factors with -0.3 log HBsAg decline at 1 year, -0.5 log HBsAg decline at 3 years, and -0.8 log HBsAg decline at 5 years after NAs treatment on multivariate analysis. Conclusions: Nucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN-lambda 3 induction.