Safety of long-term nucleos(t)ide treatment in chronic hepatitis B

Seto

et al. 2018

Aliment Pharmacol Ther

SummaryBackgroundSafety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB).AimTo review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues.MethodsRelevant articles related to nucleoside analogue safety were selected for review following extensive language‐ and date‐unrestricted, electronic searches of the literature.ResultsNephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real‐life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real‐life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long‐term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine‐treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy.ConclusionsLong‐term safety profile of nucleoside analogues is now better defined with more data from large real‐life cohorts and clinical trials with long‐term follow‐up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.

Section: 24mentioning

confidence: 99%

Review article: long‐term safety of oral anti‐viral treatment for chronic hepatitis B

Seto

et al. 2018

Aliment Pharmacol Ther

“…Most studies evaluating the role of TDF in renal dysfunction have been conducted in participants living with HIV [5–7,9–12,15–17,19,20,22,24,28], hepatitis B [29–31], and other chronic diseases that may be independently associated with kidney disease [18]. The Iniciativa Profilaxis Pre-Exposición (iPrEx) study offers an opportunity to assess the unique effects of TDF on renal function in HIV-seronegative individuals.…”

Section: Introductionmentioning

confidence: 99%

Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis

Solomon

Lama

Glidden

et al. 2014

Aids

128

127

Objective:Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons.Design and methods:The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft–Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy.Results:There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: −2.4 vs. −1.1 ml/min; P = 0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P = 0.02), and resolved after stopping pre-exposure prophylaxis (mean change: −0.1 vs. 0.0 ml/min; P = 0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy.Conclusions:In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.

“…In patients at high renal risk these tests can be performed every month for the first 3 mo, every 3 mo until the end of the first year and every 6 mo thereafter, in case of no renal adverse events. Closer renal monitoring is required in patients who develop reductions in creatinine clearance < 60 mL/min or reductions in serum phosphate levels < 2 mg/dL [9,10,15,87] .…”

Section: Term Definitionmentioning

confidence: 99%

Antiviral treatment for chronic hepatitis B in renal transplant patients

Ridruejo

2014

WJH

Self Cite

Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some data showing a favorable safety and efficacy profile of nucleos(t)ide analogue (NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC naïve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under antiHBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population. Core tip: Nucleos(t)ide analogue treatment is safe and effective in renal transplant patients. It improves long term patients and graft survival.Ridruejo E. Antiviral treatment for chronic hepatitis B in renal transplant patients.