| Objective: Currently, antiviral treatment which is mainly for interferon and nucleos(t)ide analogues is the key to the treatment of CHB, although some results had been seen, but clinical effectiveness is not very satisfactory because of many factors for example the virus, the host and the drugs, so it’s very important to explore its predictors for individualized treatment. The purpose of this study was to provide the basis for optimal treatment by monitoring the change of serum HBs Ag and HBe Ag levels in chronic hepatitis B patients during antiviral therapy.Methods: 213 chronic hepatitis B patients were recruited from the Third Hospital of Hebei Medical University, the Infectious Hospital of Baoding city, the Fifth Hospital of Shijiazhuang city between February 2013 and February 2015. The numbers of HBe Ag positive patients was 109, HBe Ag negative patients was 104. Among them, 88 cases were treated with Pegylated IFN-α 2a 180μg or Pegylated IFN-α 2b 1.5μg/kg(weight) weekly for 48 weeks, the other 125 cases were terated with entecavir 0.5 mg/d orally for 48 weeks. Serum HBs Ag and HBe Ag were determined by electro chemiluminescence immunoassay(ECLIA), Liver and renal function parameters, serum virology and HBV DNA loads were determined at the same time. To observe the levels of HBs Ag and HBe Ag, we defined four groups according to different drugs and different CHB patients,HBe Ag positive patients treated with PEG-IFNα, HBe Ag positive patients treated with ETV, HBe Ag negative patients treated with PEG-IFNα and HBe Ag negative patients treated with ETV, the numbers of them were 45, 64, 43and61, respectively. To assess the antivirol efficacy, we defined complete response groups according to HBVDNA and HBe Ag by treatment week 48,(for HBe Ag positive was defined as HBVDNA undetectable, HBe Ag loss and ALT recovered; for HBe Ag negative was define as HBVDNA undetectable and ALT recovered). Comparison among groups were performed by SPSS 13.0.Results:1 Baseline characteristics of the chronic hepatitis B cohortThere was no significant difference of age, gender, mother-to-infant transmission or not, baseline serum ALT, HBVDNA, HBs Ag, HBe Ag between HBe Ag positive patients treated with PEG-IFNα and ETV, or HBe Ag negative patients treated with PEG-IFNα and ETV(P>0.05). There was significant difference of age, gender, mother-to-infant transmission or not, baseline serum ALT, HBVDNA, HBs Ag, HBe Ag between HBe Ag positive patients and HBe Ag negative patients(P<0.05). The age was higher for HBe Ag negative patients than positive patients, baseline serum ALT, HBVDNA, HBs Ag, HBe Ag levels were lower for HBe Ag negative patients than positive patients.2 The difference of serum HBs Ag and HBe Ag among different groupsSerum HBs Ag and HBe Ag levels were falling during treatment in four groups. But, there was no significant difference for HBe Ag negative patients treated with ETV(0w(3.54±0.35)vs.12w(3.47±0.31)P=0.273;0w(3.54±0.35)vs.24w(3.42±0.32) P=0.054; 0w(3.54±0.35) vs.48w(3.42±0.34) P=0.064), the others, the difference had statistically significant(P<0.05).The decrease of serum HBs Ag had no significant difference between patients treated with PEG-IFNα and ETV for HBe Ag positive in 12w(0.22(-0.5~1.24) vs.0.20(-0.5~0.64) P=0.182), 24w(0.27(-0.25~1.63) vs.0.24(-0.71~0.81) P=0.353), 48w(0.35(-0.82~2.19) vs.0.31(-0.89~1.17) P=0.483). The decrease of serum HBe Ag also had no significant difference between patients treated with PEG-IFNα and ETV for HBe Ag positive in 12w(0.51(0.04~2.4)vs.0.63(-0.04~2.18)P=0.887),24w(1.00(0.01~3.19)vs.1.09(-0.20~3.26) P=0.820),48w(1.33(-0.8~4.51)vs.1.52(-0.02~3.78) P=0.597). There was a higher decrease of serum HBs Ag for HBe Ag negative patients treated with PEG-IFNα then ETV(P<0.05). The decrease of serum HBs Ag for HBe Ag positive patients was higher HBe Ag negative by week 48(P<0.05).3 The prediction of serum HBs Ag and HBe Ag for antiviral therapy3.1 the predictors of treatment effect in HBe Ag positive patientsAmong the 45 patients treated with PEG-IFNα, 9(20%) achieved a complete response(CR). There was no significant difference of age, gender, mother-to-infant transmission or not, baseline serum ALT, HBVDNA, HBs Ag, HBe Ag in the two groups(P>0.05). The serum HBs Ag and HBe Ag levels of patients who achieved a CR was lower than that of non-responder, and the serum HBe Ag reduction rate of patients who achieved a CR was higher than that of non-responder by week 12 and 24(P<0.05). Upon further analysis, it showed HBe Ag<100COI(OR=12.57, P=0.02, PPV=37.5%, NPV=100%) by week 12 or HBe Ag<60COI(OR=16, P=0.01, PPV=40%,NPV=96%)by week 24 were predictors related to a CR.Among the 64 patients treated with ETV, 8(12.5%) achieved a complete response(CR). There was no significant difference of age, gender, mother-to-infant transmission or not, baseline serum ALT, HBVDNA, HBs Ag, HBe Ag in the two groups(P>0.05). The serum HBs Ag levels of patients who achieved a CR was lower than that of non-responder by week 12, and the serum HBe Ag levels of patients who achieved a CR was lower than that of non-responder by week 12 and 24(P<0.05). Upon further analysis, it showed HBs Ag<3100IU/ml(OR=6.99, P=0.02, PPV=36.36%, NPV=92.45%)by week 12,HBe Ag<9COI(OR=45,P<0.001,PPV=71.43%,NPV=94.74%)by week 24 were predictors related to a CR.3.2 the predictors of treatment effect in HBe Ag negation patientsAmong the 43 patients treated with PEG-IFNα, 30(69.76%) achieved a complete response(CR). There was no significant difference of age, gender, mother-to-infant transmission or not, baseline serum ALT in the two groups(P>0.05), but baseline serum HBs Ag and HBVDNA concentration was lower in CR group than in non-responder group(P=0.037). The serum HBs Ag level of patients who achieved a CR was lower than that of non-responder by week12 and 24. Upon further analysis, it showed baseline HBs Ag<4700IU/ml(OR=5.25,P=0.02,PPV=84%,NPV=50%), HBs Ag<3700IU/ml(OR=27.5, P<0.001, PPV=92.59%, NPV=68.75%) by week 12 or HBs Ag<2400IU/ml(OR=15.12, P < 0.001, PPV=91.67%, NPV=57.89%) by week 24 were predictors related to a CR, among them, the threshold of HBs Ag by week12 was a better predictors(AUC=0.856).Among the 61 patients treated with ETV, 55(90.16%) achieved a complete response(CR). There was no significant difference of serum HBs Ag in the two groups(P>0.05), but the HBVDNA concentration was lower in CR group than in non-responder group in all the observation points(P<0.05). Upon further analysis, it showed baseline HBVDNA < 3.5logcopies/ml(OR=26.5, P < 0.001, PPV=96.36%, NPV=66.67%) by week 24 was a predictor related to a CR.Conclusions:1 Serum HBs Ag and HBe Ag levels were falling during treatment. But for HBe Ag negative patients treated with ETV levels was slowly falling.2 Serum HBe Ag levels are dramatically reduced compared to the serum HBs Ag levels in complete response groups, it was a better predictor related to complete response.3 The predictors related to complete response were serum HBs Ag and HBe Ag levels by week 12 and week 24 for HBe Ag positive patients. For HBe Ag negation patients, the serum HBs Ag levels by week12 was a predictor in the group treated with PEG-IFN, serum HBs Ag levels couldn’t predict complete response in the group treated with ETV. |
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