Aim. To assess the course of chronic HDV infection during therapy with nucleoside analogs in patients with Gilbert’s syndrome. Materials and methods. The prospective study included 27 patients with chronic hepatitis D (CHD) observed at the Ogurtsov P.P. Liver Research Center (Moscow) from 2018 to 2021. Patients were prescribed antiviral therapy (HTP) — tenofovir 300 mg daily. Depending on Gilbert’s syndrome (GS), patients were divided into two groups. The dynamics of transaminase levels, the amount of HBsAg, HBV viral load, HDV RNA, and liver fibrosis were evaluated. The Wilcoxon, chi-squared, F-test, and odds ratio were used for statistical analysis. Results. In patients with chronic hepatitis D and Gilbert’s syndrome, a statistically significant decrease in the level of transaminas-es (p=0.04), HBsAg concentration (p<0.001), HBV DNA (p<0.001), and the risk of liver fibrosis progression by 2.3 times (OR=2.3, 95% CI 1.147—5.211; p<0.05) were observed after administration of tenofovir 300 mg daily. Conclusion. Gilbert’s syndrome may predict the favorable outcome of tenofovir therapy in patients with HDV infection. © 2022, Media Sphera Publishing Group. All rights reserved.