Abstract: Objective To investigate the changes and clinical significance of E3 ubiquitin ligase Cbl-b and the related signaling molecules CD28 and CTLA-4 in patients with chronic hepatitis C. Methods 25 patients with chronic hepatitis C and 19 healthy persons were enrolled in this study. Peripheral blood monouclear cells （PBMC）were isolated.The related mRNA expressions of Cbl-b,CD28,and CTLA-4 were measured by RT-PCR; HCV RNA was detected by real-time RT-PCR;Genotyping of HCV was performed using a second generation INNO-LiPA line probe assay. Results The mRNA levels of Cbl-b,CD28,and CTLA-4 were increased in chronic hepatitis C, with 1.38-, 1.90-, and 2.68-time higher than those in healthy controls,respectively;The expressions of Cbl-b and CTLA-4 mRNA were significantly increased in HCV genotype 1b （n=11） than those in HCV genotype 2a （n=14）,with 1.74-and 2.81-time higher,respectively（P<0.05）;There were no correlations between the levels of three molecules and HCV RNA,so as to the associations of those and ALT levels.Conclusion Cbl-b and CTLA-4 may take part in the immune tolerance induced by the HCV infection and play an important role in chronic HCV infection.

Key words: Chronic hepatitis C, Cbl-b, CD28CTLA-4