Differences In SRD5A2 Gene Expression And Clinical Characteristics Between Genders And Long-term Antiviral Efficacy Between Genders In Chronic HBV-infected Patients

Part OneTwo genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infectionBackground:To examine the expression characteristics of single nucleotide polymorphisms(SNPs)in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus(HBV)infection.Methods:A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors,namely AKR1C2,AKR1C3,HSD17B6,SRD5A1,SRD5A2,and ESR1,were genotyped in 1007 patients from eight counties(cities)in Northeastern China with chronic HBV infection and 1040 healthy controls,and their association with viral replication characteristics and the differences in disease severity between sexes was assessed.Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.Results:Two SNP loci in the SRD5A2 gene(rs12470143 and rs7594951)exhibited significant differences in genotype and allele frequencies between sexes,with the proportion of T alleles significantly higher in males than in females.It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype.Additionally,serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients.Female patients exhibited significantly lower serum DNA levels compared to male patients.Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores.Furthermore,multivariate analysis showed that the two genetic variants in the SRD5A2 gene(rs12470143 C>T,r7594951 C>T),together with the male sex,age>50 years old,HBeAg positive status,elevated serum HBsAg load,high serum HBV DNA load,and HBV genotype C,were independent risk factors for HBV-related liver fibrosis.Conclusions:This study demonstrated that two genetic variants in the SRD5A2 gene(rs12470143 C>T,r7594951 C>T)are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.Part TwoGender differences in disease regression on long-term antiviral therapy in chronic HBV-infected patientsBackground:To compare whether there are differences in response status to long-term antiviral therapy and differences in disease regression between genders after long-term antiviral therapy in chronically HBV-infected patients of different genders.Methods:A cohort study of 1029 chronic HBV-infected patients who met the indications for antiviral therapy was conducted to compare the biochemistry,virology,and liver stiffness values of chronic HBV-infected patients of different genders,and to explore the differences in disease regression between genders.Results:The overall virologic and biochemical response rates of male and female chronic HBV-infected patients did not differ between genders,whereas the virologic and biochemical response rates of female chronic HBV-infected patients aged ≤50 years were significantly higher than those of the female group aged>50 years and of all male patients at antiviral weeks 12 and 24;the rate of conversion/vanishing of HBeAg was significantly higher in female than in male patients,and the rate of conversion/vanishing of HBeAg was significantly higher in female than in male chronic HBV-infected patients of the age-less-than-50 group.The HBeAg conversion/vanishing rate of female patients was significantly higher than that of female patients aged>50 years and all male patients;the overall decrease in HBsAg quantification of female chronic HBV-infected patients was significantly higher than that of male chronic HBV-infected patients aged ≤50 years;the decrease in HBsAg quantification of female chronic HBV-infected patients aged ≤50 years was significantly higher than that of female patients aged>50 years and all male patients;and the degree of improvement of hepatic fibrosis of female patients was significantly The degree of improvement of liver fibrosis in female patients was significantly better than that in male patients.The incidence of hepatocellular carcinoma is higher in men than in women,and the functional cure rate is lower than that in women.Conclusions:Although antiviral therapy can significantly improve the prognosis of chronic HBV-infected patients,the overall efficacy of female chronic HBV-infected patients was significantly better than that of male chronic HBV-infected patients.Based on the findings of this article,it is recommended that the management of antiviral therapy in men be moved further forward and the indications for antiviral therapy in men be further expanded to maximize the prevention of disease progression and improve the prognosis of patients with chronic HBV infection.