HBsAg Outcome Of Pegylated Interferon-α In The Treatment Of Chronic Hepatitis B

Hepatitis B virus(HBV)infection is prevalent worldwide,and the number of deaths caused by HBV infection each year reaches 900,000.Currently pegylated interferon and nucleoside analogues are the two main drugs against HBV infection.However,in the course of treatment,HBsAg will no longer decline steadily or even fluctuate or rise for a period of time.At this time,the immune adjuvant interleukin 2(IL-2)can be used as an adjuvant therapy to intervene in interferon therapy,but the timing,kinetic model and prognosis of this intervention are still unclear.In the treatment of chronic hepatitis B,the fluctuation of HBsAg is not conducive to the portrayal of disease progression,but the multi-state Markov model is used to divide the treatment process into different states,which can better use the patient data information to analyze the disease development process and explore the possible factors affecting disease progression.The clinical data of patients with chronic hepatitis B from May 2018 to May 2022 in the patient database of the Fourth Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed.The data of 115 patients who were treated with IL-2 in interferon therapy were extracted.The relative change level of HBsAg for four consecutive weeks was used as an index,and PAM(Partitioning Around Medoids)was used to divide it into two dynamic modes : stepwise growth mode and fluctuation mode.Contour analysis showed that there was a statistical difference between the two modes before IL-2 intervention(p < 0.05),but after 2 weeks of IL-2 intervention,the contours of the two showed the same trend.Prognostic correlation analysis showed that CD8 T cells,alanine aminotransferase(ALT),age,natural killer(NK)cells,neutrophils,and course of treatment before IL-2 intervention were the six main indicators affecting the relative decline of HBsAg levels.Using 21031 follow-up records of all 776 patients,univariate cox regression analysis found that gender,age,body mass index BMI,immune status,HBe Ag,HB V DNA,HBsAb and NK cells had significant effects on the average change level of surface antigen.Multivariate cox analysis showed that BMI,immune status and HBV DNA had significant effects on the transformation of disease status.In the multi-state model of three states(decline,stability and rise),it was found that the treatment process of chronic hepatitis B had the longest residence time in the stable state of HBsAg average change level,up to36.4 days.Patients with higher BMI and HBV DNA negative had a greater risk of transfer between HBsAg decline state and rising state,and patients in the immune activity period had a lower risk of transfer between decline and rise.In the multi-state model of four states(rapid decline,stable decline,stable rise,and rapid rise),the patient had the longest duration(28.2 days)in the HBsAg stable decline state and the shortest average stay time(12.7 days)in the rapid rise phase.With the increase of BMI,the risk of patients in the rapid rise-stable rise transfer decreased the most.Patients in the immune activity period had a greater risk of transferring to a better state and a smaller risk of transferring to a worse state,but in the stable rise-rapid rise,rapid rise-rapid decline,rapid rise-stable rise.HBV DNA positive patients had lower risk of metastasis in rapid decline-stable decline,stable decline-stable rise,stable rise-stable decline and rapid rise-rapid decline.For CHB patients receiving Peg-IFN-α continuous treatment,IL-2 intervention should be given as soon as possible when HBsAg levels did not decrease or showed a fluctuating platform pattern for 4 weeks.After intervention,the relative change of HBsAg level can be maintained for more than 4 weeks.CD8 T cells,ALT,NK cells,and neutrophils are baseline indicators closely related to prognosis.In the general treatment of chronic hepatitis B,the relative change of HBsAg is closer to the dynamic model of stable decline or fluctuation.BMI,immune status and HBV DNA are of reference significance for observing and predicting the disease process.