Impact Of Nucleos(t)ide Analogues Therapy On The Metabolic Parameters Of Patients With Chronic Hepatitis B

Background Chronic hepatitis B virus(HBV)infection is a major public health problem worldwide.Entecavir(ETV)and tenofovir disoproxil fumarate(TDF)are first-line medicines for chronic hepatitis B(CHB)patients according to Chinese and international guidelines of hepatitis B.Long-term therapy with these drugs can prevent the progression of liver disease,but the adverse effect of these drugs can not be ignored.With the aging of CHB patients,the effect of long-term treatment with NAs on various metabolic parameters has become a major concern.Objective To evaluate the effect of ETV and TDF treatment on blood lipid,plasma glucose and uric acid in CHB patients by using a retrospective analysis.Methods We enrolled CHB outpatients who visited Department of Infectious Diseases,Nanfang Hospital in 2017.They were divided into treatment-naive and treatment-experienced cohort according to whether antiviral therapy was initiated at the beginning of enrollment.For treatment-naive patients,we collected their clinical information and the data of biochemical tests per 3-6 months during up to 30 months treatment.We observed the dynamic changes of metabolic parameters during the antiviral treatment and compared the difference of them between ETV and TDF group.For treatment-experienced patients,we collected their clinical information and the data of biochemical tests conducted for the first time in 2017,and compare the differences of metabolic parameters among different subgroups divided by drugs and treatment duration.Results A total of 2030 CHB patients were enrolled in the analysis including 122 patients(85 treated with ETV,37 treated with TDF)treatment-naive and 1908 patients(1572 treated with ETV,336 treated with TDF)treatment-experienced.Considering the significant differences in baseline characteristics including age,the proportion of patients with liver cirrhosis and metabolic syndrome,albumin,and high density lipoprotein cholesterol(HDL)between ETV and TDF group in treatment-naive patients,we conducted propensity score matching(PSM)for them.After PSM,there is no significant difference between them.For treatment-naive patients,CHOL,HDL and LDL in TDF group show a descending trend during the antiviral treatment,while these parameters in ETV group do not show a significant tendency.CHOL,HDL and LDL in ETV group is significantly higher than those in TDF group at the Month 6(CHOL:5.33 vs 4.07mmol/l,p=0.001;HDL:1.53 vs 1.13mmol/l,p=0.03;LDL:3.39 vs 2.48mmol/l,p=0.001).CHOL,HDL,LDL and VLDL in ETV group is significantly higher than those in TDF group at Month 12(CHOL:5.20 vs 4.09mmol/l,p<0.001;HDL:1.43 vs 1.11mmol/l,p=0.002;LDL:3.32 vs 2.59mmol/l,p<0.001;VLDL:0.42 vs 0.37mmol/l,p=0.19).The level of plasma glucose and uric acid in treatmentna?ve patients keep relatively stable during the antiviral treatment.Treatment-experienced patients were divided into 3 groups according to the treatment duration,including groups of 1-2 years,2-3 years and 3-5 years.Considering the significant differences in clinical characteristics including age,the proportion of patients with liver cirrhosis and metabolic syndrome,albumin,alanine aminotransferase and total bilirubin between ETV and TDF subgroup in these groups,we conducted propensity score matching(PSM)for them.In groups of 1-2 years,2-3 years and 3-5 years,blood lipid in ETV subgroup is higher than that in TDF subgroup.In 1-2 years group,triglyceride(TG),CHOL,HDL,LDL and VLDL in ETV subgroup is significantly higher than those in TDF subgroup(TG:1.00 vs 0.81mmol/l,p<0.001;CHOL:4.68 vs 3.90mmol/l,p<0.001;HDL:1.25 vs 1.03mmol/l,p<0.001;LDL:2.93 vs 2.51mmol/l,p<0.001;VLDL:0.44 vs 0.40mmol/l,p=0.006).In 2-3 years group,TG,CHOL,HDL and VLDL in ETV subgroup is higher than those in TDF subgroup(TG:1.00 vs 0.90mmol/l,p=0.16;CHOL:4.41 vs 4.10mmol/l,p=0.008;HDL:1.20 vs 1.03mmol/l,p=0.004;VLDL:0.40 vs 0.36mmol/l,p=0.37).In 3-5 years group,TG,CHOL,HDL,LDL and VLDL in ETV subgroup is higher than those in TDF subgroup(TG:0.99 vs 0.90mmol/l,p=0.53;CHOL:4.64 vs 4.37mmol/l,p=0.02;HDL:1.24 vs 1.06mmol/l,p<0.001;LDL:2.91 vs 2.85mmol/l,p=0.24;VLDL:0.44 vs 0.42mmol/l,p=0.67).There is no significant difference in plasma glucose and uric acid between subgroups in some groups of treatment duration.Conclusion CHOL,HDL and LDL in CHB patients with long-term TDF therapy show a descending trend.However,TDF administration exerts no significant influence on plasma glucose and uric acid in CHB patients.It is necessary to explore whether the lipid-lowering effect of TDF therapy can reduce the risk of cardiovascular diseases.