Effectiveness Of Nucleoside(Acid) Analogues In HBeAg-Negative Chronic Hepatitis B Patients With Normal Or Mildly Elevated Alanine Aminotransferase

Background:There are inadequate data and no histological evidence regarding the influence of nucleoside(acid)analogues(NAs)on hepatitis B e-antigen(HBeAg)negative chronic hepatitis B(CHB)patients with normal or mildly elevated alanine aminotransferase(CHB).Methods:In this multi-centre retrospective study,our primary study population was CHB patients who attended the liver disease clinics of Southern Hospital and Shunde Hospital of Southern Medical University and were given NAs from 2010 to 2020,and subjects who matched the criteria of inclusion and exclusion for primary treatment were admitted to this study.The case data of the patients were collected retrospectively,which include:age,gender,time of antiviral treatment initiation,type of drugs taken,liver function,HBV(hepatitis B virus)DNA quantification,hepatitis B surface antigen(HBsAg)quantification,HBeAg quantification,and liver stiffness measurements(LSM),significant liver fibrosis(≥F2)was defined as LSM ≥7.3kPa.The difference in virological response,biochemical response and liver fibrosis changes between patients with normal or mildly elevated ALT were compared.We also analysed the pattern of changes in HBV DNA and HBsAg levels during treatment in the two groups.Results:A total of 128 patients were enrolled;74 patients had normal ALT and 54 patients had mildly elevated ALT.The total cumulative rates of viral suppression were 64.06%,81.97%,and 96.39%,at weeks 24,48,and 96,respectively.The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85%vs.58.97%,86.39%vs.76.31%,and 93.13%vs.97.04%at weeks 24,48,and 96,respectively,with no statistical difference in virological response rates between the two groups.The serum HBV DNA levels at week 12 and HBsAg levels at week 24 were significant predictors of the 96-week virological response.A total of 87 of the 128 patients underwent liver fibrosis scans at baseline,of which 54 had normal ALT and 3 3 had mildly elevated ALT.The proportion of patients with significant liver fibrosis was 47.1%(n=41)of the 87 patients.Significant fibrosis was found in 44.4%(n=24)and 51.5%(n=17)of the patients with normal ALT and mildly elevated ALT,respectively.Compared with the values at baseline,LSM and the proportion of significant liver fibrosis decreased significantly at week 48(8.12 kPa vs.6.57 kPa,58.3%vs.30.6%;p<0.001)and week 96(8.87 kPa vs.6.43 kPa,60.8%vs.26.1%;p<0.001),respectively.Conclusions:HBeAg-negative CHB patients with normal or mildly elevated ALT can achieved a satisfactory cumulative virological response rate(96.39%)after 96 weeks of treatment with NAs,and HBV DNA at week 12 and HBsAg at week 24 were predictors of virological response at week 96.In addition,the degree of liver fibrosis was significantly reduced in these patients after antiviral treatment.This study provides evidence-based medical evidence for antiviral therapy in HBeAg-negative chronic hepatitis B patients with normal or mildly elevated ALT.