In patients infected with hepatitis B virus (HBV) who had severe renal impairment, entecavir was found to be safe and effective for the treatment of HBV infection and did not have a negative impact on kidney function, according to a report published in Hepatology Research.
The nucleoside analogs tenofovir-disoproxil-fumarate, tenofovir-alafenamide, and entecavir are among the currently recommended first-line HBV therapies available to clinicians. However, the first medication carries known risks for nephrotoxicity, while the second is relatively new and unproven in patients with chronic kidney disease (CKD). This leaves entecavir as a potentially more suitable treatment for individuals infected with HBV who have serious renal dysfunction. Investigators sought to clarify the safety and efficacy of entecavir in this population, given the sparse data and limited evidence offered in the literature.
Between 2006 and 2018, a multicenter retrospective study enrolled 273 patients (median age, 57 years; 53.1% male) >20 years of age who had been treated with entecavir monotherapy (0.5 mg orally, given daily to weekly, depending on renal disease severity) for HBV infection for >1 year. Participants were evaluated at baseline and annually following initiation of therapy.
Primary outcomes included entecavir efficacy — assessed by viral load reduction rates, alanine transaminase normalization and virologic breakthrough rates — as well as renal function changes, according to baseline renal function. Participants were categorized by level of baseline renal dysfunction, with significant differences in baseline demographic and clinical characteristics existing between those with CKD stage G1/G2 and those with CKD stage G3/G4/G5 or who were on hemodialysis. Among all enrolled patients, at baseline there were 25 (9.2%), 5 (1.8%), and 10 (3.7%) people with CKD stage G3, stage G4/G5, and on hemodialysis, respectively. In the remainder of participants, kidney disease was categorized as stage G1/G2, with normal renal function and estimated glomerular filtration rates (eGFR) >60 mL/min/1.73 m2.
At 1, 2, and 3 years following entecavir therapy initiation, 84.2%, 94.0%, and 96.2% of patients, respectively, demonstrated substantial viral load reduction and disappearance of HBV-DNA. In people undergoing hemodialysis, entecavir had 100% efficacy and no virologic breakthrough after 1 year. A total of 7 individuals (2.5%) demonstrated virologic responses during the study. There were similar rates of HBV-DNA disappearance, virologic breakthrough, and alanine transaminase normalization (89.7%) over time seen in those with and without renal impairment.
Regarding impact on renal function, at 5 years after entecavir initiation, participants without baseline renal dysfunction had significant worsening of eGFR over time (P <.001), while those with CKD stage G3/G4/G5 showed nonsignificant improvements and a trend toward restoration of eGFR (P =.184). Entecavir was found to be safe over the course of the study, with no patients undergoing hemodialysis reporting serious adverse events that caused discontinuation.
Study strengths included a long median observation period, analysis of renal impact according to baseline renal function, and inclusion of several patients undergoing hemodialysis. Study limitations included a retrospective design with missing data, inability to track all co-administered medications, significant differences in baseline characteristics between groups, and a potentially insufficient treatment follow-up duration.
“In conclusion, [entecavir] for HBV-infected patients with moderate to severe renal dysfunction, including hemodialysis patients, is highly effective. [Entecavir] is indicated to be safe for patients with renal dysfunction,” noted the authors. They recommended that future research include longer studies involving more patients.
Funding and Conflicts of Interest Disclosures:
This study was supported in part by grants from the Japan Agency for Medical Research and Development (AMED; grant number grant number 19fk0210022h0103, 19fk0210018h0003, 19fk0310101s0503, 19fk0210048s0501, 19fk0210058h0001, 19fk0210047s04010401) and SPS KAKENHI; (Grant Number 19K0845819K08458).
Professor Naoya Sakamoto received lecture fees from Bristol Myers Squibb and Pharmaceutical K.K, grants and endowments from MSD K.K and Chugai Pharmaceutical Co., Ltd, and a research grant from Gilead Sciences, Inc. Dr. Goki Suda received research grants from Bristol Myers Squibb, MSD K.K, and Gilead Sciences. The other authors have nothing to disclose.
Suzuki K, Suda G, Yamamoto Y, et al. Entecavir treatment of hepatitis B virus‐infected patients with severe renal impairment and those on hemodialysis [published online July 1, 2019]. Hepatol Res. doi:10.1111/hepr.13399