Clinical Study Of Telbivudine Combined With Adefovir To Improve EGFR For HBeAg-positive Chronic Hepatitis B Patients Treated With Adefovir

【Background】Chronic hepatitis B(CHB)is still a global public health problem.About one-third of the world’s people who have been infected with the hepatitis B virus,and nearly 1million people died because of hepatitis B related disease,such as liver failure,decompensated liver cirrhosis,cell cancer.Inhibiting the replication of hepatitis B virus is the key to the treatment of hepatitis B,and it is also the guarantee for improving the quality of life and prolonging the survival time of CHB patients.On the one hand,because of low drug resistance and cheap cost of treatment,ADV is widely used to antiviral therapy for CHB patient in China.On the other hand,ADV may be able to reduce the estimated glomerular filtration rate by inhibiting the replication of mitochondrial DNA in the proximal tubules of the glomeruli.Therefore,how to improve the level of e GFR in CHB patient treated with ADV becomes urgently problem to be solved by the scholars of liver disease.Ld T have strong viral suppression and high rates of HBe Ag seroconversion in the treatment of chronic hepatitis B and there have been a number of studies have demonstrated the role of Ld T significantly improved kidney function in patients with antiviral therapy at the same time.However,there are few clinical studies on whether LDT can improve e GFR in HBe Ag positive CHB patients with ADV-treated.For this reason,a prospective,open,single center randomized controlled trials was proposed to compare the effects of LDT combined ADV and ETV monotherapy on renal function in HBe Ag positive CHB patients with ADV-treated and e GFR light decline.To provide a basis for optimal treatment of CHB patients with ADV-treated and e GFR light descent.【Objective】To investigate the efficacy and safety of an extended course(48-week)of telbivudine combined with adefovir and entecavir therapy for patients with HBe Ag-positive chronic hepatitis B(CHB)who have e GFR decreased(50 ml/min/1.73m~2<e GFR<90 ml/min/1.73m~2)after adefovir treated.【Methods】There were 61 HBe Ag-positive CHB patients who had completed more than half a year of adefovir treated with e GFR decreased,were divided into combination therapy group and monotherapy group using a random number table.The combination therapy group received Ld T(600mg/d)plus ADV(10mg/d)once a day for 48 weeks,while the monotherapy group received ETV(0.5mg/d)once a day for 48 weeks.All patients were tested for conversion to e GFR normalization,alanine aminotransferase(ALT)normalization,HBV DNA clearance,HBe Ag seroconversion,serum phosphate level,drug resistance,and side effects at treatment weeks 48.Inter-group differences were statistically evaluated by t-test or Chi-squared test.【Results】The rate of e GFR normalization were significantly different between the two groups at treatment week 48(60%vs 10%,X~2=16.483,P<0.05),but no different at treatment week 24(20%vs 7%,X~2=2.307,P>0.05).At 48 weeks of treatment,serum phosphorus levels were 1.12±0.045(mmol/L)in the combination therapy group and1.09±0.063(mmol/L)in the monotherapy group.There was a statistically significant difference from baseline(t=-11.151,P<0.05;t=-5.636,P<0.05),but there was no significant difference between the two groups(P>0.05).At week 48,the urinary protein positive rates in the combination therapy group and the monotherapy group were 6.67%and 20%,respectively,and the difference was not statistically significant(X~2=0.129,P>0.05).The rate of ALT normalization were different between the two groups at treatment week 12(70%vs 93.4%,X~2=5.455,P<0.05).The rate of HBV DNA clearance in the monotherapy group at treatment week 12 was 80%,and significantly different than that of the combination group(X~2=4.800,P<0.05).The rate of HBV DNA clearance were no significantly different between the two groups at treatment week 24 and week 48(73.33%vs 86.67%,P>0.05;93.33%vs 96.67%,P>0.05).At treatment week 24 and 48,the rate of HBe Ag seroconversion was significantly higher in the combination group than in the monotherapy group(26.7%vs 6.67%,X~2=4.320,P<0.05;30.0%vs 10.0%,X~2=4.812,P<0.05).At the treatment of 12 weeks,the rate of HBe Ag seroconversion was no significantly different between the two groups(10%vs 3.33%,X~2=1.071,P>0.05).Over the course of treatment,neither group developed drug resistance,nor two therapies had unsafety.【Conclusion】1.For patients with HBe Ag-positive CHB who have e GFR slightly decrease(50ml/min/1.73m~2<e GFR<90 ml/min/1.73m~2)after adefovir treated,ADV plus Ld T has more effective on e GFR improved than monotherapy with ETV.2.ADV plus Ld T has more effective on HBe Ag seroconversion than monotherapy with ETV.