Background and Aims: Chronic Hepatitis B (CHB) remains a leading indication for orthotopic liver transplantation (OLT) globally. Common complications following OLT include renal dysfunction secondary to perioperative renal injury and post-operative nephrotoxicity from calcineurin inhibitors; osteoporosis is also observed secondary to preoperative malnutrition and post-operative corticosteroids. Antiviral prophylaxis to prevent recurrent HBV infection with tenofovir alafenamide (TAF) may have advantages over tenofovir disoproxil fumurate (TDF) due to its improved renal and bone safety profile.

Method:In this Phase 2 study (NCT02862548), OLT recipients with ≥stage 2 chronic kidney disease and receiving HBV prophylaxis with TDF were randomized 1:1 to either receive TAF 25mg QD or continue their TDF-containing regimen. The primary efficacy analysis was the percent of patients who maintained viral suppression at Week 24. Key pre-specified secondary safety endpoints were changes in hip and spine bone mineral density, changes in serum creatinine (SCr), estimated GFR by CKD-EPI formula and direct GFR assessment (Chromium- EDTA Renal Scan; Cr-EDTA) over 48 weeks.

Results: 51 patients from a single site in New Zealand were included. Baseline characteristics: mean age 60 years, 75% males, 53% Pacific Islander and mean baseline eGFR_CKD-EPI 52mL/min/1.73m² with 53% of patients with <50mL/min/1.73m². The median baseline surface area corrected GFR_Cr-EDTA was 58 mL/min/1.73m². The median interval since transplantation was ~9 years. 76% of patients were maintained on tacrolimus and 29% remained on long-term prednisone. All patients that have reached Week 12 to date (47 patients, TAF: 25; TDF: 22) maintained viral suppression. There were no treatment discontinuations and serious adverse events were numerically lower with TAF vs TDF. Switching to TAF treatment resulted in a trend toward improved SCr levels (median change: -0.07 for TAF vs. -0.02 mg/dL for TDF; P=0.09) and improved eGFR_CKD-EPI (median change: 2.7 for TAF vs. 0.8 mL/min/1.73m² for TDF; P=0.14) as early as Week 12 ). Complete data including changes in BMD at Week 24 will be available at the time of the presentation.

Conclusion:Early after switching from TDF to TAF in a liver transplant recipient population with a high rate of renal dysfunction, viral suppression is maintained while smaller changes in renal function were observed.

CITATION INFORMATION: Gane E., George B., Munn S., Wang H., Suri V., Gaggar A. Renal and Bone Safety in Post Liver Transplant Patients with Chronic Kidney Disease Receiving Tenofovir Alafenamide for HBV Prophylaxis Am J Transplant. 2017;17 (suppl 3).

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