Abstract and Introduction
Tenofovir alafenamide fumarate (TAF) has high plasma stability resulting in fewer renal adverse events compared to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. We aimed to study the effectiveness and renal safety of TAF in a real-world setting, in patients with or without compromised kidney function. CHB patients (Nucleos(t)ide Analogue [NA]-naïve or experienced) who received TAF >1 year from 11 academic institutions as part of the Canadian Hepatitis B Network (CanHepB) were included. Kidney function was measured by estimated glomerular filtration rate (eGFR) as per Cockcroft-Gault. Patients were followed for up to 160 weeks. Of 176 patients receiving TAF, 143 switched from NA (88% TDF), and 33(19%) were NA naïve. Majority of NA-naïve patients (75%) achieved undetectable HBV DNA after one year of TAF treatment. Majority of patients with eGFR <60 mL/min who had renal deterioration during TDF (76%) reversed to eGFR increase after one year of TAF (p=0.009). Among patients with stage 2 chronic kidney disease (CKD) (eGFR 60–89), the estimated eGFR decline during TDF was halted after switching to TAF (p=0.09). NA-experienced patients with abnormal ALT before TAF showed a significant decline after switching to TAF: −0.005 [−0.006 – −0.004] log10 ULN U/L/month, p<0.001). In CHB patients, TAF was safe, well-tolerated and effective in this real-world cohort. Switching to TAF led to improved kidney function, particularly in those with stage 2 CKD, which suggests that the indication for TAF in the guidelines could be extended to patients with an eGFR higher than 60 mL/min.
Nucleos(t)ide analogue(NA) therapy can achieve long-term suppression of viral replication, slowing disease progression and reducing the likelihood of developing unfavourable outcomes such as cirrhosis, hepatic decompensation, liver cancer and liver-related death.[1–3]
Tenofovir disoproxil fumarate(TDF) is recommended as a first-line treatment for chronic hepatitis B(CHB).[4–6] TDF is excreted renally and has been associated with renal toxicity and a decrease in bone mineral density in some patients.[7–9] Current European and American guidelines suggest TDF dose adjustment only when patients reach creatinine clearance <50 mL/min.[4,5]
Tenofovir alafenamide(TAF) has recently been approved as NA therapy for the treatment of CHB. TAF has higher plasma stability and intracellular concentrations at a 90% lower dosage than TDF. Phase three studies with highly selected patients receiving TAF showed fewer renal adverse events when compared to TDF.[8,10–14] While TAF showed similar virologic and serologic response to TDF, higher rates of alanine aminotransferase(ALT) normalization were observed in patients randomized to receive TAF after one year of treatment. TAF was approved by the U.S. food and Drug Administration(FDA) and the European Medical Agency(EMA) and is recommended as a first-line therapy option by major guidelines around the globe in patients with HBV mono-infection and HBV/HIV co-infection.[4,5]
Despite the improved safety profile of TAF compared to TDF, little is known about its outcomes in real-world clinical practice where patients are not selected according to strict inclusion and exclusion criteria and may have medical comorbidities. Current guidelines indicate selecting TAF or ETV over TDF among patients with renal alteration such as eGFR <60 ml/min or haemodialysis. Our aim was to investigate whether the indication for TAF can be extended to those with a better kidney function.
Therefore, we compared long-term virological and clinical outcomes, and safety profiles in CHB patients who had not received antiviral treatment before starting TAF (NA-Naïve) and patients treated with TDF or other NAs switching to TAF (NA-experienced), in a real-world setting.
J Viral Hepat. 2021;28(6):942-950. © 2021 Blackwell Publishing