Renally-Impaired Patients with Chronic Hepatitis B Virus Infection Find Success with Low Dose of TDF

A low dose of tenofovir disoproxil fumarate (TDF) may help to preserve renal function and maintain viral suppression in patients with chronic hepatitis B virus infection, even those with advanced liver disease, according to new research.

TDF (Viread, Gilead) is currently approved for the treatment of chronic hepatitis B virus infection in adults and pediatric patients who are 12 years and older. Although the treatment is effective in inhibiting hepatitis B virus replication, it can cause renal impairment. To this end, investigators led by Dr. Kin Seng Liem from the Toronto Centre for Liver Disease and the University Health Network in Toronto, Ontario, Canada, studied renal function and viral breakthrough in a group of 739 patients from a North American hospital who were renally-impaired and treated with TDF. The investigators compared outcomes for those patients on a reduced dose of TDF (due to GFR [Cockcroft-Gault] <50mL/min/1.73m² ± serum phosphate <0.8mmol/L) with outcomes for patients on a full dose.

A total of 67 patients (9%) were on a reduced dose of TDF and 672 (91%) were on the full dose. The mean age of the patients at baseline was 68 (standard deviation [SD] = 11 years) for those on a reduced dose of TDF versus those on the full dose (45; SD = 13 years). Furthermore, patients on the reduced dose were predominantly male (63%), and had a mean duration of 3 years (SD = 2 years) on TDF, versus the patients on the full dose who were 70% male and had a mean duration of 5 years (SD = 3 years on TDF.

Baseline hepatitis B virus DNA for the low-dose patients was 1.4_log (71% undetectable). A total of 75% of patients received TDF doses of 300mg every 48 hours (range 75mg-300mg Q48hr). The mean Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) was 50ml (20ml), and 22% of the patients had hypophosphatemia. A total of 46% had chronic kidney disease stage G3b or worse and 14% had decompensated cirrhosis, according to the study abstract.

All patients across both study groups maintained viral suppression through a mean 3 years of follow-up (SD = 2 years), except for 1 patient who was on a full dose of TDF, who experienced viral breakthrough, but subsequently resolved naturally, and 1 patient who was on dialysis and taking TDF 300mg per week. That patient experienced viral breakthrough (HBV DNA peak 3.6 log) which resolved 4 months after the dosing was increased to Q72 hours without decompensation. Another patient on a reduced dose experienced a transient ALT increase (peak 2x ULN; however, they did not experience a rise in hepatitis B virus DNA, according to the study abstract.

The decline in CKD-EPI observed in patients on the full dose of TDF reversed in “the first year of lower dosing and remained stable thereafter (+2.0 (13) mL at EOF vs baseline; P = .28), with 50 (75%) patients reaching CKD-EPI>50mL and 11/15 (73%) patients normalizing serum phosphate,” study authors wrote.

Based on these results, the study investigators concluded that a lower dose of TDF could be used in patients with chronic hepatitis B virus infection who are renally-impaired, particularly those who are in resource-limited settings.

The study, “Low Dose Tenofovir Disoproxil Fumarate Improves Kidney Function and Sustains Virologic Suppression in Renally Compromised Chronic Hepatitis B Patients,” was presented at the 2018 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 9-13, 2018, in San Francisco, California.