Association between adefovir dipivoxil treatment and the risk of renal insufficiency in patients with chronic hepatitis B: A meta-analysis

Abstract

Abstract. Adefovir dipivoxil (ADV) is an effective antiviral drug against hepatitis B virus. The renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B (CHB) remains controversial. The present meta-analysis was therefore performed to evaluate the renal safety of ADV treatment in patients with CHB. Two independent investigators searched MEDLINE, Embase and China National Knowledge Infrastructure databases for eligible studies published in English or Chinese until June 1, 2014. The Peto odds ratios (Peto ORs) or the rates of each study were analyzed. Seven randomized controlled trials (RCTs), four cohort studies and six single-arm studies were identified. ADV treatment was not associated with a higher incidence of nephrotoxicity in RCTs [Peto OR, 1.781; 95% confidence interval (CI), 0.637-4.979; P=0.271] but appeared to increase nephrotoxicity significantly in cohort studies (Peto OR, 2.682; 95% CI, 1.470-4.894; P=0.001); the significant increase was further observed in CHB patients receiving long-term ADV treatment in cohort studies (Peto OR, 2.275; 95% CI, 1.127-4.593; P=0.022). The analysis based on single-arm studies showed that the rate of renal dysfunction in the ADV-treated patients was 10.6% (95% CI, 0.059-0.185); the subgroup analysis with the standard of createnine levels showed a lower rate (6.9%, 95% CI, 0.013-0.298) than those in the overall studies. In conclusion, although current evidence indicated a positive link between treatment with ADV in CHB patients and an increased risk of renal dysfunction, optimally designed studies are required for definitive conclusions.

Relationship between nephrotoxicity and long-term adefovir dipivoxil therapy for chronic hepatitis B

“…In 5 of the 21 studies included in the analysis, researchers observed that older patients receiving long-term ADV treatment were more likely to suffer renal impairment. [ 3 , 12 , 14 , 23 , 35 ] In total, there were 3123 men and 1009 women in all analyzed studies, but none of the selected researchers noted any correlation between renal impairment and sex. Na et al concluded that sex had no obvious effect in long-term ADV treatment ( P > 0.005, both in univariate and multivariate analysis).…”

“…Yang et al [ 35 ] also discussed the relationship between ADV treatment and renal insufficiency in their recent meta-analysis, and found that the risk of renal dysfunction was related to treatment duration. Yang et al pointed out that long-term ADV therapy is a high risk factor of kidney damage (Peto OR 2.68, 95% CI 1.47–1.47), consistent with the results of this study (Peto OR 1.97, 95% CI 1.4–2.77).…”

Renal Function in Nucleos(t)ide Analog-Treated Patients With Chronic Hepatitis B: A Systematic Literature Review and Network Meta-Analysis

“…Only one meta-analysis has been published in the literature that evaluated the renal safety profile of adefovir in patients with CHB [ 45 ]. The authors concluded that based on currently available evidence, adefovir treatment is associated with an increased risk of renal dysfunction.…”

Adverse effects of oral antiviral therapy in chronic hepatitis B

“…Renal toxicity is the most noticeable side effect of adefovir. It is generally dose- and time-dependent, and reversible with dose-adjustment or discontinuation of the drug[ 15 , 45 , 82 - 84 ]. In the majority of studies, nephrotoxicity was defined as an increase ≥ 0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of < 1.5 mg/dL on two consecutive occasions[ 83 ].…”

“…In a current meta-analysis, including seven randomized controlled trials, four cohort studies and six single-arm studies, adefovir treatment was not found to be associated with increased nephrotoxicity in the randomized controlled trials. However, the cohort studies showed an increased nephrotoxicity risk in patients given adefovir, and the single-arm studies revealed an approximately 1.7-fold increased risk of renal dysfunction in patients given adefovir compared to those treated with all other NAs[ 82 ]. The authors drew attention to the differences between the risk of nephrotoxicity in randomized controlled trials and cohort studies and emphasized that since the randomized controlled trials were small-sized and short observational studies, the safety data may be inadequate and that these studies may have underestimated the adverse events.…”