Abstract

BackgroundThere is increasing concern about the potential for nephrotoxicity in patients with chronic hepatitis B (CHB) treated long-term with nucleotide analogs.MethodsWe examined renal dysfunction and its associated risk factors in patients with CHB treated with antiviral regimens containing either nucleosides or nucleotide analogs. We undertook a retrospective cohort study from 2006 to 2014 at the Hospital for Tropical Diseases, Bangkok, Thailand, and analyzed the data of 102 patients with a median follow-up time of 44.5 months (range 4–101 months).ResultsSeventy-three patients were treated with an antiviral regime containing a nucleoside analog, and 29 with a regime containing a nucleotide analog. Abnormally elevated serum creatinine concentration was observed in 12 patients (11.8 %) after 8 years of treatment. Thirty one percent of patients treated with nucleotide analogs had elevated serum creatinine levels and three of these patients (10.3 %) developed nephrotoxicity. In contrast, serum creatinine concentrations were elevated in three of the 73 patients treated with a nucleoside analog (4.1 %), and none developed nephrotoxicity. The incidence of renal dysfunction by the nucleotide analog regimen was cumulative, with 11.1, 21.0, 26.5 and 47.6 % of patients affected after 2, 4, 6 and 8 years, respectively. Univariate and multivariate analysis indicated that a nucleotide analog-based regimen significantly predicted renal dysfunction (odds ratio 10.5, 95 % confidence intervals 2.6–42.4, P <0.001).ConclusionThe long-term use of nucleotide analogs increased the risk of nephrotoxicity in patients with CHB. Thus, the regular assessment of renal function is recommended for all patients with CHB, particularly those treated with a nucleotide analog.

Highlights

  • There is increasing concern about the potential for nephrotoxicity in patients with chronic hepatitis B (CHB) treated long-term with nucleotide analogs

  • There was no significant difference in the proportion of patients positive for hepatitis B e antigen (HBeAg), baseline serum alanine transaminase, hepatitis B virus (HBV) DNA, serum creatinine concentrations, or mean duration of treatment between the nucleoside analog (NSA) and Nucleotide analogs (NTA) groups (Table 1)

  • In summary, we found that the long-term exposure to nucleotide analogs, especially ADV, increased the risk of nephrotoxicity in CHB patients

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Summary

Introduction

There is increasing concern about the potential for nephrotoxicity in patients with chronic hepatitis B (CHB) treated long-term with nucleotide analogs. More than 350 million people are estimated to have chronic hepatitis B virus (HBV) infection. Five oral nucleoside or nucleotide analogs are approved for the treatment of chronic hepatitis B (CHB) by the United States Food and Drug Administration: lamivudine (LAM), entecavir (ETV), telbivudine (LdT), adefovir (ADV) and tenofovir (TDF). All of these antiviral drugs are approved by the Thai FDA for the treatment of CHB. Nucleoside and nucleotide analogs target HBV DNA polymerase protein, a multifunctional protein essential for viral replication [2]

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