Objective To investigate the effects of entecavir treatment on serum complement components, C3 and C4, in patients with hepatitis B cirrhosis and to determine their relation with treatment response.Methods Ninety-eight patients with hepatitis B cirrhosis who were treated with entecavir (10 mg orally once daily) for 48 weeks were enrolled in the study, and included 48 patients with decompensated cirrhosis and 50 patients with compensated cirrhosis.Blood samples from healthy blood donors were used as controls.The 98 cirrhosis patients were divided into three groups according to hepatitis B virus (HBV) DNA content at baseline (detected by real-time quantitative PCR) : low-grade (103 to 105 IU/L) ;mid-grade (105 to 107 IU/L) ;high-grade (≥107 IU/L) .Levels of C3 and C4 were detected by immunonephelometry, and of the liver function enzyme alanine aminotransferase (ALT) by automated biochemical analysis.Response to treatment was classified as: complete (ALT normalization, HBV DNA reduced to the lower limit of detection (<1000 U/L) , and hepatitis B e antigen (HBeAg) seroconversion) ;partial (one or two of the complete response items achieved) ;unresponsive (none of the complete response items achieved) .Significance of changes in levels before and after the treatment in the patients were assessed by single-factor analysis of variance;multiple group comparisons were made by least significant difference test, using Tamhane test for data that did not assume unequal variances.Results Treatment nave cirrhosis patients had significantly lower levels of C3 and C4 than healthy controls (P<0.01) .The treatment nave patients with decompensated cirrhosis had significantly lower C3 and C4 levels than their counterparts with compensated cirrhosis (P<0.01) .The treatment nave patients with low-level infection showed the lowest level of C3 (P<0.05) .Twenty-nine patients acheived complete response, 69 achieved partial response, and there were no unresponsive cases.After treatment, the suppressed levels of C3 and C4 were relieved in the cirrhosis patients, but only the increase seen in the compensated cirrhosis patients was significantly different from the before treatment levels (P<0.01) .Patients who achieved complete response had significantly higher C3 and C4 than those who achieved partial response both before and after treatment (P<0.01) .Finally, the patients who achieved partial response only showed significantly increased levels of C3 in response to treatment (P<0.05) .Conclusion Entecavir treatment increases the HBV-suppressed C3 and C4 in patients with cirrhosis, especially those with compensated cirrhosis, which may be related to the extent of suppression of HBV replication.Furthermore, the recovery of complement may be positively related to response to treatment.