eGFR Improvement In Chronic Hepatitis B Patients With Telbivudine Treatment Is Independent Of Antiviral Activity

Abstract

Background and Aim: It was shown, that Telbivudine treatment improved renal function assessed by estimated glomerular filtration rate (eGFR) in Chronic Hepatitis B (CHB) patients. We aimed to analyze factors potentially correlated to eGFR improvement with telbivudine.

Methods: eGFR was calculated retrospectively using MDRD formula on overall ITT population (n = 687 telbivudine, n = 680 lamivudine) and subgroup of patients with reduced baseline renal function (eGFR 60–90) (n = 256 telbivudine, n = 234 lamivudine) over 2 years. Efficacy-response based subgroups were analyzed (ANCOVA model) for eGFR change. Stepwise regression (multivariate analysis) was used to model for baseline/week24 factors known to influence antiviral efficacy of telbivudine treatment on eGFR improvement (shift from 60–90 to >90 ml/min/1.72m2 eGFR) at 2 years.

Results: At 2 years eGFR (LSmean) increased from baseline in telbivudine-treated patients by 8.53% compared to −0.52% in lamivudine-treated patients in the overall ITT population

(p<0.001). In the subgroup of patients >50 years, eGFR increased 11.4% in telbivudine compared to -2.4% decrease in lamivudine-treated patients. Patients with baseline eGFR

60–90 ml/min/1.72m2 eGFR increased by 16.8% in telbivudine versus 3.9% n telbivudine versus treated group.

eGFR improvements at 2 years were independent of baseline HBeAg status, markers of virologic response, including HBVDNA undetectable (<300 copies/ml),

HBVDNA suppression (<5 logs) or virologic breakthrough/genotypic resistance at 2 years. Patients who had not achieved on-treatment HBeAg seroconversion (17.6%) or HBeAg loss (18.7%) had higher eGFR increase versus patients with HBeAg seroconversion (7.3%, p =

0.0223) or HBeAg loss (6.2%, p = 0.0035). In the stepwise regression model, no differences were observed for: baseline HBeAg

status, baseline ALT (<2×ULNvs≥2×ULN), baseline HBVDNA (<9vs≥9log for HBeAg+ and <7vs≥7log for HBeAg− patients), Genotype C and undetectable HBVDNA at Week24. Telbivudine treatment (Odds ratio (OR) 2.509 (95% CI=1.663, 3.784) p<0.0001) and age

(continous variable) OR 0.940 (0.923, 0.958), p = 0.0001 were the strongest significant predictors of eGFR increase. Other predictors were Caucasian race (vs Asian), OR 0.338 (0.175, 0.652), p = 0.0012 and Other vs Asian, OR 0.429 (0.183, 1.005), p = 0.0514.

Conclusion: In this subanalysis of the GLOBE study, the strongest predictors of improvement on renal function during antiviral therapy in patients with compensated CHB were age and

telbivudine treatment, the latter effect independent of on-treatment antiviral response.