TELBIVUDINE IS ASSOCIATED WITH IMPROVEMENT OF RENAL FUNCTION IN PATIENTS AFTER LIVER TRANSPLANTATION 1 Maria Ioannidou, 1 Evangelos Cholongitas, 2 Themistoklis Vasiliadis, 1 Ioannis Goulis, 1 Georgia Moisidou, 1 Zoe Valari, 1 Parthenis Chalevas, 1 Stergios Soulaidopoulos, 1 Theodora Oikonomou, 1 Evangelos Akriviadis 1 4th Department of Internal Medicine, Hippokration General Hospital of Thessaloniki, Medical School of Aristotle University 2 3rd Internal Medicine Department, Aristotle University of Thessaloniki, Papageorgiou Hospital

Nucleos(t)ide analogues [NA(s)] has evolved the therapeutic manipulation of patients with chronic hepatitis B (CHB) improving the outcome of HBV transplant patients after liver transplantation (LT). NAs have been used, either as monoprophylaxis or in combination with hepatitis B immune globulin (HBIG) after LT. BACKGROUND

During long-term therapy with NAs in CHB patients, minimal rates of GFR decline have been reported, except for telbivudine LT recipients may represent a group of patients, in which the role of telbivudine needs further evaluation, because these patients are considered at high risk for renal dysfunction due to the concomitant use of the calcineurin inhibitors (CNIs) BACKGROUND

OBJECTIVES To evaluate the impact of telbivudine on renal function in liver transplant (LT) recipients

34 recipients were included in this prospective study Inclusion criteria: a) they had no evidence of HBV recurrence, and b) they were under stable immunosuppression regimen without steroids during the last 12 months before baseline MATERIALS & METHODS

In 17 recipients (study group 1) remained on the same NA(s) as before baseline and were followed for 12 months (1 st period). At this time point (month 12), they were switched to telbivudine monoprophylaxis for another 12 months (2 nd period). The rest 17 (group 2) patients continued their original non-telbivudine NA(s) prophylaxis. The changes GFR (ΔGFR) between baseline and after 12 months (1 st period) and between 12 months and 24 months (2 nd period) were evaluated. MATERIALS & METHODS

Tenofovir (N=13), Lamivudine (N=2) Lamivudine + Adefovir (N=2) No-Telbivudine prophylaxis (n=34 ) Baseline 12 months LT 2 nd period1 st period Serum creatinine and GFR Serum creatinine and GFR Serum creatinine and GFR 24 months HBVDNA (-) HBsAg (-) Entecavir (N=5), Tenofovir (N=4), Lamivudine + Adefovir (N=8) Group 2 (n=17) Group 1 (n=17) Telbivudine monoprophylaxis LT: liver transplantation

Variable (unit) Group 1 patients (n=17) Group 2 patients (n=17) P value Age (years)59±654±140.9 Sex, Male n, (%)14 (82) 0.8 Cormobidities after LT, n (%) Diabetes mellitus, n (%) Arterial Hypertension, n (%) 0 (0) 1 (6) 6 (35) 2 (12) Laboratory Creatinine (mean±SD, mg/dL)1.2±0.21.1± Urea (mean±SD, mg/dL)42±1140± MDRD-based GFR (mean±SD, mL/min)72±1882.3± CKD-EPI-based GFR (mean±SD, mL/min)70.9±1580± Immunosuppression CNIs+MMF, n (%) Serum levels of cyclosporine (mean±SD, ng/mL) 12 (71) 43±28 14 (82) 44± Antiviral prophylaxis, n (%) Nucleoside alone Nucleotide ( ±nucleoside) 2 (12) 15 (88) 5 (29) 12 (71) 0.21 Table 1. Baseline characteristics of group 1 patients (n=17) with conversion to telbivudine at 12 months and group 2 patients (n=17) without telbivudine conversion. -

Baseline 12 months 24 months Time after baseline (months) Mean values of GFR in group 1 patients * p=0.025 p=0.017 ml/min * * # # # Evolution of renal function in group 1 patients as calculated by MDRD and CKD-EPI

Baseline 12 months 24 months Time after baseline (months) % of patients with GFR < 60mL/min in group 1 patients % Proportion of patients with GFR < 60mL/min in group 1 patients using the MDRD and CKD-EPI formulae

Time (months) Baseline 12 mo 24 mo GFR (mL/min, MDRD formula) 1 st period2 nd period Tenofovir (N=13) Lamivudine ± Adefovir (N=4) Telbivudine (N=17) Entecavir (N=5), Tenofovir (N=4) Lamivudine + Adefovir (N=8 ) -4.2 mL/min -4.2 mL/min +2.5 mL/min Evolution of renal function in group 1 and 2 patients as calculated by MDRD

CONCLUSIONS We showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, However, this remains to be confirmed in larger well-designed studies