The Impact Of Nucleos(t)ide Analogues On EGFR In Patients With Chronic HBV Infection

Nucleos(t)ide analogues(NAs),with their high potency of suppression of hepatitis B virus(HBV)replication,are used as a primary antiviral treatment of chronic HBV infection.As in China,chronic HBV infection-associated liver diseases are the most common causes of liver transplantation(LT),combination therapy with a NA and low-dose human HBVimmunoglobulin(HBIG)is a commonly adopted regimen for the prophylaxis of recurrence of HBV infection in post-LT(PLT)population.With the wide application of NAs,increasingly importance has been attached to the impact of NAs on patients' renal function in long-term antiviral treatment.It has been reported that long-term administration of different NAs may have different impacts on renal function.For example,adefovir dipivoxil(ADV)and tenofovir disoproxil fumarate(TDF)may reduce estimated glomerular filtration rate(e GFR)in patients,on the contrary,Telbivudine(Ld T)treatment may be beneficial to patients' e GFR.Till now,most of the researches on the influence of NAs on renal function are focused on patients with chronic hepatitis B or liver cirrhosis,and the study on LT recipients is rare.Our research was composed of two parts.?.The impact of nucleos(t)ide analogues on e GFR in chronic hepatitis B patients.?.The impact of nucleos(t)ide analogues on e GFR in post-liver transplantation patients with chronic HBV infection.Part one:The impact of nucleos(t)ide analogues on e GFR in chronic hepatitis B patientsOBJECTIVE: To observe the influence of nucleos(t)ide analogues monotherapy on e GFR in chronic hepatitis B(CHB)patients.METHODS: A retrospective case control study was conducted in 46 cases who participated in phase ? clinical trials between January 2007 and December 2011 in our department.Twenty-three patients were treated with entecavir(ETV),and other 12 and 11 cases were treated with ADV or Ld T,respectively.Both of the normalization rates of aminotransferase(ALT)and HBV DNA clearance rates were compared among these three groups at week 24 and week 48 on-treatment.Furthermore,the changes of e GFR from baseline to week 48 were also investigated.RESULTS : At week 24 on-treatment,the ALT normalization rates of ADV-treated group,ETV-treated group and Ld T-treated group were 41.7%(5/12),82.6%(19/23)and 63.6%(7/11),respectively.There was no statistic difference among these three groups.And at week 48,the ALT normalization rates of these three groups were 41.7%,86.9% and 72.7%,separately.No significant difference was found among the groups,either.After 24 weeks of treatment,negative rate of HBV DNA in ADV-treated group,ETV-treated group and Ld T-treated group of was 41.7%(5/12),78.3%(18/23)and 72.7%(8/11),respectively.There was no significant difference between the three group.After 48 weeks of treatment,negative rate of HBV DNA in ADV-treated group,ETV-treated group and Ld T-treated group of was 66.7%(8/12),91.3%(21/23)and 81.8%(9/11),respectively.There was no significant difference between the three group.Furthermore,no significant changes was observed from baseline to week 48 on-treatment among these three groups.At week 48,only one case with a ?20% reduction of e GFR from baseline was found in ETV-treated group,but none in ADV-treated group or Ld T-treated group.At the same time-point,2 cases with a ?20% increasing of e GFR from baseline were found in Ld T-treated group,but none in the other two groups.CONCLUSIO: In this study,no significant influence on e GFR in CHB patients treated with ETV,ADV or Ld T were found.All of the 24-week and 48-week ALT normalization rates of ETV or Ld T-treated group were slightly higher than that of ADVtreated group,but there was no significant difference among them.Part two:The impact of nucleos(t)ide analogues on e GFR in post-liver transplantation patients with chronic HBV infectionOBJECTIVE: To investigate the impact of long-term administration of LAM,ETV,Ld T or ADV on estimated glomerular filtration rate(e GFR)in chronic HBV-infected postliver tranplantation(PLT)patients.METHODS: In this prospective clinical real-life cohort study,a total of 177 chronic HBV-infected cases were enrolled from 665 patients underwent liver transplantation(LT)between 1st August 2008 and 31 st October 2014 in our liver transplantation center.The dynamic changes of e GFR(calculated with MDRD and CKD-EPI formulas)betweenbaseline(3 months after LT)and 27 months after LT and the HBV infection recurrence during follow-up among four different NA-treatment subgroups,treated with ETV(n=66),Ld T(n=21),LAM(n=61)or ADV(29),were observed.Risk factors associated with the greater than or equal to 20% decrease or increase of e GFR from baseline at 27 months after LT were analyzed with multivariate logistic regression.RESULTS: There was no significant difference among e GFR at baseline and at 9,15,21 and 27 months after LT in ETV-subgroup.But both in LAM-subgroup and ADVsubgroup,e GFR significantly decreased from the 9th month after LT,and kept its significant downward trend during the 27-month follow-up.On the contrary,e GFR in Ld T-subgroup showed a significant increase trend from the 9th months to 27 months after LT.The number of patients who had a ?20% decrease of e GFR compared to baseline at 27 months after LT in ETV,LAM,ADV and Ld T-treatment subgroups were 3,12,11 and 0,respectively.However,the number of patients who had a ?20% increase of e GFR compared to baseline at 27 months after LT in ETV,LAM,ADV and Ld T-treatment subgroups were 4,0,0 and 9,respectively.Multivariate logistic regression analysis confirmed that LAM and ADV treatment were independent risk factors for the e GFR decrease,and baseline blood urea nitrogen(BUN)level and Ld T treatment were both the independent risk factors for the e GFR increase.The accumulated prevalence of recurrence of HBV infection after LT during the whole follow-up period were as follows: LAMsubgroup,4.1%(9/221);Ld T-subgroup,2.9%(1/35);ETV-subgroup,0%;ADV-subgroup,0%.CONCLUSION: Long-course treatment with LAM or ADV may decrease the e GFR in post liver transplantation patients,but Ld T treatment were beneficial to patients' renal function.Combination therapy with NAs and HBIG were effective in the prophylaxis of HBV reactivation after liver transplantation.