Establishment Of Prediction Model Of HBeAg Seroconversion In Chronic Hepatitis B And Therapeutic Effect Of Traditional Chinese Medicine

Chronic hepatitis B(HBV) virus infection increases the risk of patients developing cirrhosis, liver failure, liver cancer and even death.When the patients of chronic hepatitis B HBeAg-positivesustainly undetectable HBVDNAduring the treatment.HBeAg seroconversion is a major clinical endpoints. HBeAg seroconversion makes the replication and infectivity of hepatitis B virus decline and a good prognosis. Researches found that the HBeAg seroconversion rate for oral NAs appeared low,ranging from 12%to 22% after 1 year of treatment. Therefore, it is very importantto establish the score model for predicting 1 year HBeAg seroconversion to evaluate long-term efficacy and adjust treatment programs、probe the treatment with integrative Chinese and Western medicine and raise 1 year HBeAg seroconversion rate.ObjectiveIThe paper intends to systematically analyze chronic hepatitis B e antigen-positive patients clinical characteristic,conduct COX univariate and multivariate analyze to probe independent factors of affecting 1 year e antigen seroconversion,establish a noninvasive scoring model and verify its clinical value.2To investigate the effect of Chinese and Western integrate therapy to e antigen seroconversion,liver fibrosis and liver function in patients of chronic hepatitis B HBeAg-positive.Methods1The clinical data of 1014 patients who diagnosed with chronic hepatitis B HBeAg-positive were collected retrospectively from Beijing Ditan Hospital,Capital Medical University.1014 patients were randomly allocated into the model derivation and validation sets at a 7:3 ratio, that is derivation cohort had 710 people, validation cohort had 304 people. In the derivation cohort,19 indicators underwent COX univariate and multivariate regression analysis to screen independent factors and established prediction scoring model of these independent factors occurring 1 year HBeAg seroconversionin chronic hepatitis B patients. We used the area of receiver operating characteristic (ROC) curve to determine boundary value and evaluate the diagnostic value ofmodel.2By a retrospective cohort study,we collected 679 patients with chronic hepatitis B HBeAg-positive,470 cases in Chinese and Western integrate therapy group and 209 cases in Western therapy group.Western therapy group was given only nucleoside analogue,however, Chinese and Western integrate therapy group was treated on the nucleoside analogue basis of plusing one kind of chinese medicine such as Fu fang bie jia ran gan pill, Fu zheng hua yu capsule,Jiu wei gan tai capsule,Yin zhi huang capsule.To observe the change of HBeAg seroconversion, liver fibrosis factors FIB4, APRI and liver serum markers ALT, AST, ALB, thickness of spleen and portal vein before and after treatment in the two groups.Results1By univariate analysis in derivation cohort,we found that ALT.AST, GGT, GLB, ALB, ALP, HBeAg were related to the occurrence of HBeAg seroconversion. With the multivariate regression analysis, only baseline ALT, GGT, GLB and HBeAg levels were independent predictor in CHB patients. In the derivation cohort,we utilize the the sensitivity and specificity of baseline ALT, GGT, GLB, HBeAg in receiver operating characteristic curve (ROC) to determined the Youden index (sensitivity+specificity-1) and stratify the variables such as ALT≥217U/L and ALT<217U/L; GGT≥72U/L and GGT<72U/L; HBeAg≥313S/CO and HBeAg<313S/CO; GLB≥42g/L and GLB<42g/L. The stratificative variable conduct the forward stepwise multivariate COX regression analysis again to determine these four factors in the derivation cohort were four independent predictor of 1 year HBeAg seroconversion.Moreover,we established the score model for predicting e antigen seroconversion in chronic hepatitis B HBeAg-positive patients. The scope of this scoring model is 0 to 6. The AUC of the prediction scoring model is 0.753, when the maximum Youden index, the cutoff point is 3 by the sensitivity and specificity were 64.3% and 73.2%.The sum scores of 0-2 identified patients at a low conversion group, whereas the sum scores of 3-6 at a high conversion group. We verify the ROC of the established scoring model was 0.766 by the validation cohort.2Chinese and Western integrate therapy group and Western therapy group of chronic hepatitis B were comparable before treatment. After one year of treatment, Chinese and Western integrate therapy group occurring 1 year HBeAg seroconversion rate was significantly higher than Western therapy group (p=0.030) at the low score group;However,the two groups occurring 1 year HBeAg seroconversion rate had no significant difference at the high score group.The hepatic fibrosis factors in Chinese and Western integrate therapy group have the better trend and rate of decline than Western therapy group.The integrate therapy group in improving liver function earlier than Western therapy grou.Conclusion1We utilize baseline ALT, GGT, GLB, HBeAg to establish the 1 year HBeAg seroconversion prediction scoring models with chronic hepatitis B have high diagnostic value.2Chinese and Western integrate therapy group helped to make low score group occur HBeAg seroconversion in Chronic Hepatitis B e antigen-positive patients.3 By the studies of APRI and FIB4 suggests that Chinese and Western integrate therapy can make chronic hepatitis b e antigen-positive patients earlier obtain histological improvement.