| Objective:The purpose of this study was to investigate the therapeutic effect of peginterferon initially combined with entecavir,peginterferon alone and entecavir alone in patients with chronic hepatitis B with high viral load,changes in T lymphocyte subsets,interferon λ3,and adverse reactions during interferon treatment.Futhermore to establish a risk prediction model for the occurrence of myelosuppression in patients with chronic hepatitis B treated with peginterferon,to provide a basis for the rational selection of peginterferon therapy for patients with chronic hepatitis B.Methods:A total of 279 patients with chronic hepatitis B with high viral load treated from December 2019 to December 2021 were selected as the research subjects.According to the assessment of the condition by physicians and the willingness of the enrolled patients,the patients were divided into three groups: entecavir alone,peginterferon alone,peginterferon initially combined with entecavir.The five indicators of hepatitis B and hepatitis B virus DNA were collected before and after treatment,and the changes of immunological indicators and adverse reactions in patients treated with peginterferon.Another 208 patients with chronic hepatitis B who were treated with peginterferon during the same period were selected.The patients were divided into the model group(153 cases)and the validation group(55 cases)according to a ratio of about 3:1.The patients with grade II or above myelosuppression after 1 injection of interferon treatment were defined as the myelosuppression group,and the rest were the normal group.The general data,clinical data,and hematological data of the patients were collected,and the risk factors of myelosuppression were explored through multivariate logistic regression,and the prediction model was established and verified internally.Results:1.After 48 weeks of treatment,the decrease of HBV-DNA in the initial combination group and ETV group was greater than that in the peginterferon group,and the negative conversion rate of HBV-DNA in the initial combination group and ETV group was higher than that in the peginterferon group at the 4th,12 th,24th,and48 th weeks of treatment.There was statistically significant different(P<0.05).However,there was no significant difference in the negative rate of HBV-DNA between the initial combination group and the ETV group(P>0.05).2.After 48 weeks of treatment,the decrease of HBsAg,HBsAg negative rate,and HBeAg negative rate in the initial combination group were greater than those in the peginterferon alone group,and the peginterferon alone group was greater than the ETV group.The differences between the groups were statistically significant(P<0.05).3.The levels of CD4+ in the ETV group after treatment were higher than those before treatment,the levels of CD3+,CD4+,CD4/CD8 in the peginterferon group were higher than those before treatment,and the levels of CD3+,CD4+,CD8+,CD4/CD8 in the initial combination group were higher than those before treatment,The difference was statistically significant before and after treatment(P<0.05);After treatment,there were significant differences in CD3+,CD4+,CD4/CD8 between the initial combination group and the ETV group(P<0.05).4.The level of IFN-λ3 before peginterferon treatment(78.99±14.89 pg/ml)was lower than that after peginterferon treatment(99.77±16.64 pg/ml),and the difference was statistically significant(P<0.001).5.The common adverse reactions in the initial combination group and the peginterferon alone group were fever 81.7% vs 81.2%,alopecia 69.0% vs 74.1%,fatigue 67.6% vs 74.1%,weight loss 67.6% vs 68.2%,gingival bleeding 56.3% vs62.4 %,loss of appetite 54.9% vs 57.6%,myelosuppression(grade II or higher)56.3%vs 42.4%,joint pain 42.3% vs 43.5%,visual impairment 28.2% vs 21.2%,insomnia26.8% vs 17.6%,there was no significant difference between the two groups(P>0.05).6.The results of multivariate logistic regression analysis and prediction model establishment showed that: BMI(OR=0.869,95%CI 0.772-0.979,P=0.021),WBC(OR=0.704,95%CI 0.508-0.976,P=0.035)and GLB(OR=0.904,95%CI 0.823-0.992,P=0.034)were independent influencing factors of myelosuppression in CHB patients treated with peginterferon,calculation formula: Logit(P)=In[P/(1-P)]=-0.14×[BMI(Kg/m2)]-0.351 ×[WBC(x109/L)]-0.101 ×[GLB(g/ L)] + 7.606;The AUC of the validation group was 0.762,P=0.001.Conclusion:1.For patients with chronic hepatitis B with high viral load,the initial combined regimen can exert its respective antiviral advantages to achieve high HBV-DNA negative rate,high serum HBe Ag negative rate and high HBs Ag negative rate,which is helpful for high viral load The ideal goal of clinical cure of hepatitis B in patients with chronic hepatitis B load as soon as possible.2.The initial combination regimen can increase the levels of CD3+,CD4+,CD4/CD8 in CHB patients,and enhance their immune response to better play an antiviral role.3.Pegylated interferon can play an antiviral effect by increasing the level of IFN-λ3 in patients with chronic hepatitis B.4.Decreased levels of BMI,leukocytes and globulin are independent risk factors of the occurrence of myelosuppression in CHB patients treated with pegylated interferon,and its risk prediction model was established to early identify patients who are prone to myelosuppression in clinical work,and to provide some basis for taking active preventive measures. |
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