Biomarkers Detect Early Renal Toxicity from NA Monotherapy Post-Transplant
SAN FRANCISCO, CA—Early biomarkers cystatin C and NGAL may facilitate the safe delivery of long-term nucleos(t)ide analogue (NA) therapy for patients who have undergone liver transplantation, according to a study reported at the The Liver Meeting® 2015.
“Early markers of renal dysfunction cystatin C and NGAL had increased in relation to NA therapy in all patients,” reported study coauthor Anna Mrzljak, MD, PhD, of the Institute of Liver Studies, Kings College School of Medicine at King's College Hospital, in London, England, and colleagues. “Overall estimated glomerular filtration (eGFR) did not change and was only declining in patients with renal risks after switching from lamivudine (LAM) with long-term hepatitis B immunoglobulin (HBIg) to NA monotherapy.”
“Switch from long-term hepatitis B immunoglobulin (HBIg) prophylaxis in combination with lamivudine (LAM) to nucleos(t)ide analogue (NA) monotherapy achieves efficient viral control, but long-term renal safety might be a concern in HBV-exposed patients post-liver transplantation (LTx),” explained Dr. Mrzljak. That's why the coauthors conducted a retrospective cross-sectional, single-center study to see if cystatin C and NGAL on-therapy plasma levels can predict early renal toxicity in HBV-exposed patients who have undergone liver transplantation and switched from LAM + HBlg to long-term tenofovir (TDF) or entecavir (ETV).
A total of 47 eligible patients (39 of whom were men), with a median age of 59 years, were identified and followed for a median of 4 years, Dr. Mrzljak reported. Of these, 26 had switched from LAM + HBlg to TDF, and the other 21 had switched to ETV treatment.
“Differences between eGFR and plasma phosphate (PO4) levels were compared 1 year before switch, at switch and then yearly after switch,” explained Mrzljak. “Cystatin C and NGAL plasma levels were measured at same time points by ELISA. Patients were stratified according to preexisting renal risks (RR: hypertension, diabetes, diuretics, preexisting renal dysfunction) and therapeutic regimens.”
Fifty-five percent of patients were determined to have renal risks: 20 had hypertension, 14 had diabetes, 4 had undergone therapy with diuretics; and 9 patients had preexisting renal impairment, Dr. Mrzljak reported.
“Overall eGFR was similar at all time points, but declined significantly only in RR patients after 2 years on NA (switch: 58 vs. Year 1: 56 vs. Year 2: 51 vs. Year 3: 51 and Year 4: 53mL/min; P=0.04),” the team reported.
As ETV was preferentially administered to patients with renal risks, “eGFR was lower at switch and during therapy in patients on ETV than TDF,” Mrzljak noted. “Phosphate levels gradually declined in all patients after 3 years (switch: 0.98 vs. Year 3: 0.88; P=0.02). Cystatin C levels increased in all patients after 2 years post-switch (switch: 1.51 vs. Year 2: 1.71 mg/L; P<0.05). NGAL increased after 1st year post-switch in all patients (switch: 54 vs. Year 1: 63ng/mL; P<0.05.”