Abstract Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population. Background IFNL (IFNL3 IL6 IL (IL-6 (CLD (HDV Amazon Methods Crosssectional Cross sectional 4 2 1 damage PCR (PCR technique method Results rs rs809991 gene groups however OR 142 42 1.4 0.42 042 0 (0.4 4.75 475 75 0556 556 0.55 95% 95 (95 CI. CI . CI) IL6, 6, IL-6 rs180079 C 0.05. 005 0.05 05 0.05) Conclusion TG GC population (IFNL (IL- rs80999 14 1. 0.4 04 (0. 4.7 47 7 055 55 0.5 9 (9 IL- rs18007 00 0.0 (IL rs8099 0. (0 4. 5 ( rs1800 rs809 rs180 rs80 rs18 rs8 rs1