Aim. To determine whether there is a correlation of the composition of circulating lymphocyte subpopulations, the serum concentrations of interferon (IFN)-α, IFN-γ, and IFN-λ3, and the lymphocyte expression of types I and II IFN receptors with the species of a disease pathogen and the degree of liver fibrosis (LF) in patients with chronic hepatitis B (CHB) and in those with chronic hepatitis C (CHC). Subjects and methods. The investigation enrolled 44 patients with CHC, 9 patients with CHB, and 13 clinically healthy donors. The degree of LF in the patients was determined using transient elastography. The composition of peripheral blood lymphocyte subpopulations was examined; the concentrations of IFN-α, IFN-γ, and IL-28B were estimated. Results. Lymphocyte counts were higher in patients with CHC and in those with CHB than those in healthy donors; and the number of neutrophils was lower. There were no differences between the groups in the composition of lymphocyte subpopulations with the exception of the number of CD3+CD4+ cells, which in patients with CHC was larger than in those with CHB. In CHC and CHB patients, the counts of CD118+ lymphocytes were higher than those in healthy donors. Patients with CHB and those with CHC did not differ between themselves and from healthy donors in the expression of CD119 on the lymphocytes. In CHC patients, the relative CD119+ cell counts were higher between CD4+ lymphocytes than those in healthy donors. The serum levels of IFN-α and IFN-γ in CHC and CHB patients were similar, but higher in healthy donors. The concentration of IL-28B genotype in patients with CHC was twice as high as in those with CHB, but the differences were statistically insignificant. The number of lymphocytes increased with the progression of fibrosis; that of neutrophils decreased. There was an inverse relationship between platelet counts and LF severity. Multiple comparisons of the clusters of patients with different degrees of LF revealed no differences in the number of major lymphocyte subpopulations. However, the number of CD3+CD16+CD56+ natural killer-like T (NKT) cells correlated with fibrosis severity. Patients with different degrees of LF showed no differences in the proportion of CD118- and CD119 cells between lymphocytes and in the serum levels of IFN-α, IFN-γ, and IL-28B levels. Patients with grade IV LF displayed a higher proportion of CD4+CD119+ lymphocytes between CD45+ cells than did those with grade III LF. Conclusion. Several new clinical and laboratory trends were identified and the nature and extent of previously described hematological and immunological changes were clarified in CHC or CHB patients with various degrees of LF. Some indicators may be used as additional criteria for the prognosis of the above forms of hepatitis, and a number of newly described facts suggest that it is necessary to revise the protective/phlogogenic value of types I, II, and III IFNs in chronic viral hepatitis C and B.