Gender-specific Differences Analysis In Association Between HBV Receptor NTCP Expression And Disease Characteristics And Benefit Of Antiviral Treatment

Part 1Association between NTCP hepatic expression and gender differences of disease characteristics in chronic HBV-infected patientsObjective: To investigate the relationship between the expression of HBV functional receptor NTCP with disease characteristics and gender-specific differences in chronic HBV-infected patients.Methods: Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery.HBV DNA levels and the m RNA and protein expression levels of NTCP in liver tissues were determined.The relationship between NTCP expression and HBV DNA levels,inflammatory activity,fibrosis and gender-specific differences were analyzed.Results: Compared with patients with a METAVIR score of A0-1 or F0-1,patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression.However,the NTCP expression in the A3 or F4 group with the most severe inflammation or fibrosis did not increase but decrease.NTCP levels were positively correlated with HBV DNA levels,with NTCP expression positively correlated with a higher level of HBV DNA in individuals with score A0-2 or score F0-3 and positively correlated with a lower level of HBV DNA in those with score A3 or score F4.The inflammatory activity scores and fibrosis scores of female patients in the < 50 years group were significantly lower than those of female patients ≥ 50 years,and also significantly lower than those of age-matched male patients.Except for individuals with significant liver tissue necrosis or severe fibrosis(METAVIR A3 or F4),in chronic HBV-infected patients with score A0-2 or score F0-3,female patients in the age < 50 years group have lower NTCP expression level compared to the ≥ 50 years group,and were also significantly lower compared to age-matched male patients.Conclusion: The hepatic expression level of NTCP may promote the disease progression of chronic HBV-infected patients by affecting the viral load of HBV.The hepatic expression of NTCP varies between genders and between reproductive women and postmenopausal women in chronic HBV-infected patients,which may be one of the important reasons why male and postmenopausal women are more prone to disease progression than reproductive women.Part 2Benefit analysis of expanded the indications for antiviral treatment in chronic HBV-infected patientsObjective: To analyze the effectiveness,long-term benefits and safety of expanded the indications for antiviral treatment in chronic HBV-infected patients,based on the 2022 guidelines for the prevention and treatment of HBV in China.Methods: Through a long-term cohort study of chronic HBV infected individuals aged 14-30 years selected by our research group in 50 cities/counties in Jilin,China,we compared the changes in clinical characteristics such as biochemical indicators,HBV virological indicators,liver imaging,and LSM between 309 individuals who expanded indications and 417 individuals who met the indications.Results: The undetectable rate of HBV DNA in both groups of chronic HBV-infected patients at 48 weeks can reach over 95%.The HBe Ag clearance rate and HBe Ag seroconversion rate are relatively lower in patients with expanded the indications compared to patients with meet the indications,but there was no significant difference between patients with expanded the indications and ALT normal HBe Ag positive patients with meet the indications.The serum HBs Ag levels of both groups decreased with the prolongation of antiviral treatment.During the antiviral treatment period,the average LSM level of patients with expanded the indications remained at the F0-1 stage,and the average LSM level of patients with meet the indications gradually decreased,but overall remained higher than that of patients with expanded the indications.There were no cases of liver cirrhosis or HCC in patients with expanded the indications followed up for 10 years.The incidence rates of liver cirrhosis and HCC in patients with meet the indications were 1.7% and 0.7%,respectively.The clinical cure rates of long-term antiviral therapy for patients with expanded the indications and those who meet the indications are 5.2% and 6.5%,respectively.There were no cases showed elevated serum creatinine,hypophosphatemic bone disease or bone marrow suppression in both groups.Only one patient with meet the indications showed signs of lactic acidosis.The HBe Ag clearance rate and HBe Ag seroconversion rate are relatively higher in females compared to males in both groups.Conclusion: The effectiveness and safety of expanded the indications for antiviral treatment in chronic HBV-infected patients are magnificent,which can reduce the risk of progression to cirrhosis and HCC.Part of patients with expanded the indications for antiviral treatment can achieve clinical cure.Female HBV-infected patients had better effectiveness in HBe Ag clearance and HBe Ag seroconversion than male patients.