Objective To evaluate the efficacy and safety of long-term nucleos (t) ide analogue treatment in patients with chronic hepatitis B (CHB).Methods Two hundred and two initially treated patients with CHB admitted in Zhejiang Provincial People's Hospital during March 2013 and August 2016 were enrolled in the study.Patients were divided into six groups according to the different antiviral therapy:adefovir group (ADV,n =43),entecavir group (ETV,n =44),lamivudine group (LAM,n =25),telbivudine group (LDT,n =23),LDT + ADV group (n =22),and LAM + ADV group (n =45).HBV DNA negative conversion rate,HBeAg serological conversion rate and estimated glomerular filtration rate (eGFR) at baseline and at 48th,96th,144th wk of treatment were measured.Chi-square test and repeated measure of ANOVA were used to analyze the data.Multivariate Logistic regression analysis was applied to detect the relevant risk factors of renal dysfunction in CHB patients.Results After treatment for 144 wks,the HBV DNA negative conversion rates in ETV and LDT group were higher than that in ADV group (both P ＜ 0.01),the levels of eGFR in ADV,ETV,LAM and LAM + ADV group were declined with time,while the eGFR levels in LDT and LDT + ADV group were increased with time (Ftime =3.939,Fgroup =3.983,P ＜0.01 or ＜0.05).After treatment for 96 wks and 144 wks,the levels of eGFR were higher in LDT and LDT + ADV group than those in other groups,respectively (all P ＜ 0.05).Multivariate Logistic regression analysis showed that age ≥40 (x2 =16.145,OR =4.452,95 ％ CI 2.149-9.223,P ＜ 0.05),mild abnormality of eGFR at baseline (x2 =16.449,OR =4.336,95％ CI 2.144-8.891,P ＜ 0.05),and ADV treatment (x2 =5.837,OR =5.280,95％ CI 1.369-20.365,P ＜ 0.05) were independent risk factors of renal dysfunction in CHB patients.Conclusion LDT long-term monotherapy or combination with ADV may improve renal function for patients with CHB,which provides a reference for long-term treatment of CHB patients with nucleos(t) ide analogues.