Objective To investigate the influence of nonalcoholic fatty liver disease (NAFLD) on the antiviral response of patients with chronic hepatitis B (CHB), and to provide a reference for clinical treatment of such patients. Methods A total of 187 patients who attended Shenzhen Third People's Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients, NAFLD grou p with 41 patients, and CHB + NAFLD group with 103 patients. Related indices were measured at enrollment different time points of follow - up, including body height, body weight, alanine aminotransferase (ALT), aspartate aminotransferase, four blood lipid parameters, four indicators of liver fibrosis, aspartate aminotransferase - to - platelet ratio index, HBsAg, HBeAg, anti - HBe, and HBV DNA quantification, and the CHB patients and the CHB + NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12, 24, 48, 72, and 96 of antiviral therapy. The Kruskal - Wallis H test was used for comparison of non - normally distributed continuous data between multiple groups, and the Wilcoxon rank - sum test was used for comparison between two groups; the chi - square test was used for comparison of categorical data between groups. Results Compared with the NAFLD group at baseline, the CHB group and the CHB + NAFLD group had significantly lower platelet count, ALT, gamma - glutamyl transpeptidase (GGT), alkaline phosphatase, and right lobe of liver oblique diameter (all P <0. 05), and compared with the CHB group, the CHB + NAFLD group had significantly higher body mass index, total cholesterol, and triglyceride and a significantly lower spleen thickness (all P <0. 05), while there were no significant differences in the other indicators between the two groups at baseline (all P > 0. 05). At week 12 of antiviral therapy, there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB + N AFLD group (all P > 0. 05); compared with the CHB + NAFLD group at weeks 24 and 48, the CHB group had significantly greater reductions in ALT (Z = - 2. 128 and -3. 055, both P <0.05) and GGT (Z = - 2. 025 and - 1. 631, both P <0. 05); at week 48, the CHB group and the CHB + NAFLD group had a significant reduction in HBV DNA (Z = -6. 445 and -4. 415, both P < 0. 001), and the CHB group had a significantly greater reduction. The CHB + NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy (x² = 14. 237, 13. 961, 15. 226, 10. 462, and 13. 030, all P < 0. 05). At week 48 of antiviral therapy, the CHB + NAFLD group had a significantly lower HBeAg clearance rate than the CHB group (x² = 5. 309, P =0. 021), while there was no significant difference between the two groups at week 96 (x² = 0. 117, P = 0.732). At weeks 24, 48, 72, and 96 of antiviral therapy, the CHB + NAFLD group had a significantly lower ALT normalization rate than the CHB group (x² = 12. 049, 5. 287, 11. 407, and 11. 375, all P < 0. 05). Conclusion NAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy. [ABSTRACT FROM AUTHOR]