Efficacy Of Antiviral Therapy In Patients With Chronic HBV Infection In Indeterminate Stage

Background and Aims:It is generally pointed out in the hepatitis B treatment guidelines of the Chinese Association for the Study of the liver,the American Association for the Study of Liver Diseases（AASLD）,European Association for the Study of the Liver（EASL）and Asian-Pacific Association for the Study of the Liver（APASL）that patients with immune activation and immune reactivation with abnormal ALT should be given antiviral treatment.Patients are in the stage of immune tolerance or immune control with chronic HBV infection,the disease is not easy to progress or the antiviral efficacy is poor,and the risk of virological breakthrough is high.Therefore,antiviral treatment is not recommended.However,some patients can not be divided into the existing immune stages（immune tolerance stage,immune active stage,inactive stage and response stage）.For these patients who do not meet the existing standards,they are regarded as the disease stage can not be determined,or they are named as indeterminate stage.These patients are often chronic HBV infected patients with normal ALT and low HBV DNA level,But there are many patients in this part.because the pathological tissues of these patients have inflammation and even cirrhosis,they may develop into hepatocellular carcinoma（HCC）.Therefore,it is of great clinical significance to start treatment for patients in indeterminate period.Here,we introduced the situation of hepatitis B immunization staging briefly:immune stage of patients is staged according to the established guidelines.Liver biopsy is the basis for the determination of the patients who fail to stage the disease.This study relaxed the standard of this group of patients,and did not rely on liver biopsy,after excluding the patients who had been included in the period,the rest were classified as non phased patients,or named as patients in indeterminate stages.In the present study,we evaluated the disease stage of patients with chronic HBV infection,found out the patients who could not be staged according to the current guidelines,and treated these patients with nucleoside（T）analogues（NAs）anti-viral therapy.The patients who should be treated according to the guidelines were used as the control group to analyze the virological response after treatment.This study aims to explore the feasibility of these patients by observing the clinical efficacy of patients in indeterminate stage,in order to provide evidence for the expansion of indications for treatment of chronic hepatitis B.Methods:Some patients with naive treatment of chronic HBV infection without cirrhosis and/or HCC were selected from the outpatient department of hepatobiliary medicine of the first hospital of Jilin University from October2020 to February 2022.The demographic information,liver biochemistry,antigen and antibody index associated with hepatitis B,liver stiffness,blood routine and imaging of patients were collected,and the results of quantitative detection of HBV DNA and HBs Ag and other serological and liver biochemical tests rechecked every 3-6 months after treatment.To evaluate the immune stages of 186 treatment-naive chronic HBV patients and to analyze their virological response after antiviral treatment.Then selected the patients with chronic HBV infection in indeterminate stage into the study,and took the patients who should be treated in accordance with the guidelines as the control group to compare their curative effects and according to the baseline HBV DNA with a cutoff value of 2000IU/m L,it was divided into low viral load（HBV DNA<2×10~3IU/m L）and high viral load（HBV DNA≥2×10~3IU/m L）to compare the virological response between the two groups,and further divided into subgroups to analyze the virological response rate of different HBs Ag levels and first-line treatment drugs.Results:Among 186 treatment-naive chronic HBV patients,Up to 53.2%～63.9%of patients could not be clearly staged according to the currently recognized guidelines.This study relaxed the criteria of these patients,and the patients who did not rely on liver biopsy as the basis of diagnosis in the indeterminate period were as high as 88.7%～91.4%of patients could not be staged.The negative rate of HBV DNA of patients with ALTS,that is,they can obtain an ideal virological response.Subgroup analysis showed that the baseline HBs Ag level（Ig IU/ml）and the type of first-line medication did not affect the virological response rate.Logistic regression model showed that low baseline HBV DNA（Ig IU/ml）level is an independent predictor of virological response and when the baseline HBV DNA value was 3.5 Ig IU/ml,the best virological response can be obtained by starting antiviral treatment.it was found that the liver hardness was improved compared with that before treatment,but the decrease the level of HBs Ag was not very obvious.Conclusion:Among outpatients with chronic HBV infection,up to 53.2%～91.4%of patients could not be staged.Patients with chronic HBV infection in indeterminate stage can obtain ideal virological response after anti-viral treatment with NAs,but the decrease of HBs Ag level is not very obvious.