Long‐term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B

Abstract

Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogues is often necessary to achieve durable viral suppression. Therefore, current guidelines recommend the most potent drugs with optimal resistance profiles. Entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line monotherapies for CHB. All of these drugs are highly effective in suppressing viral replication but with slightly different safety profiles. This review provides an overview of the long-term efficacy and safety data that have become available over the 10 years since ETV and TDF were first approved for the treatment of chronic hepatitis, and recent data on TAF in patients with CHB. | SAFETYETV and TDF have been used for more than 10 years for the treatment of CHB, whereas TAF was approved for this indication in 2016.ETV and TDF have been shown to have excellent safety profiles and to be well tolerated by most patients, including those with advanced and decompensated cirrhosis. ETV is a nucleoside analogue, and TDF and TAF are nucleotide analogues. All these agents are given once daily at a fixed oral dose. 9-11 Because ETV and TDF are excreted mainly or completely by the kidneys, dose adjustments are required in patients with an estimated glomerular filtration rate (eGFR) <50 mL/ min/1.73 m 2 . However, no dose adjustment is required for TAF in patients older than 65, patients with liver impairment, renal impairment

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues

“…Both ETV and TDF have been shown to be more effective than low‐ and intermediate‐barrier NAs in phase III trials and real‐life studies studies in CHB patients with or without compensated cirrhosis . No significant differences in antiviral efficacy were detected between these two agents . TDF and ETV therapy leads to high rates of HBV‐DNA suppression (94%‐99% viral suppression with up to 10 years’ follow‐up) in both HBeAg‐positive and ‐negative patients .…”

“…When non‐adherence to therapy has been excluded, a partial response with a plateau in HBV‐DNA levels or a virological breakthrough may be related to emerging resistance. TDF resistance is very unusual and has not been identified in long‐term studies . The resistance rate to ETV in naïve patients can reach 1.2% and rescue therapy with TDF is clinically effective.…”

“…Tubular injury and BMD loss (as well as Fanconi syndrome) seem to be reversible following TDF withdrawal and switching to ETV or TAF . Long‐term ETV has been associated with a low incidence of lactic acidosis (<0.3%) . EASL does not recommend TDF as first‐line treatment because of its safety profile in individuals older than 60 with kidney impairment (CrCl <60 mL/min, albuminuria, serum phosphate <2.5 mmol/dL) or bone disease.…”

“…Serum phosphate evaluations should be included in the follow‐up of TDF‐treated patients. Closer monitoring is required in individuals with risk factors for kidney disease, such as older age, diabetes mellitus, or nephrotoxic treatments, especially patients with ESLD receiving diuretic treatment …”

“…2 No significant differences in antiviral efficacy were detected between these two agents. 6 TDF and ETV therapy leads to high rates of HBV-DNA suppression (94%-99% viral suppression with up to 10 years' follow-up) in both HBeAg-positive and -negative patients. 7,8 However, HBsAg loss is infrequent, with annual rates of <1%.…”