Original article
Pancreas, biliary tract, and liver
Effect of Nucleoside and Nucleotide Analogues on Renal Function in Patients With Chronic Hepatitis B Virus Monoinfection

https://doi.org/10.1016/j.cgh.2014.11.021Get rights and content

Background & Aims

There is controversy regarding whether nucleos(t)ide analogues contribute to renal impairment in patients with chronic hepatitis B virus (HBV) infection. We analyzed changes in renal function in patients with chronic HBV infection and whether these were associated with treatment or comorbidities.

Methods

We performed a longitudinal observational study to investigate factors associated with renal function in 214 patients (median age, 43 y; 69.2% men) with compensated chronic HBV monoinfection treated with 343 lines of nucleos(t)ide analogues (210 monotherapies, 133 combinations) between 1990 and 2012 (median time, 2.4 y) in France. A linear mixed-effect model was used to model variations of estimated glomerular filtration rate (eGFR, computed with the Chronic Kidney Disease Epidemiology Collaboration formula), adjusting for age, sex, geographic origin, initial liver fibrosis, level of HBV DNA, and an eGFR less than 90 mL/min/1.73 m2.

Results

The eGFR decreased in patients given adefovir dipivoxil as monotherapy or in a combination (P < .0001 and P < .002, respectively), and remained stable in patients given lamivudine, tenofovir disoproxil fumarate, or entecavir. The eGFR decreased in patients with a baseline eGFR of less than 90 mL/min/1.73 m2, regardless of treatment. The eGFR remained stable or increased, regardless of treatment, in patients with a baseline eGFR of 90 mL/min/1.73 m2 or greater and with an initial HBV DNA level of 100,000 IU/mL or greater. Patients born in areas of high endemicity of HBV were more prone to increases in eGFR with treatment.

Conclusions

In a real-life study, the eGFR remained stable or increased over time in patients with chronic HBV monoinfection with a baseline eGFR of 90 mL/min/1.73 m2 or higher and treated with tenofovir disoproxil fumarate or entecavir. Patients born in an area of high endemicity of HBV who had initial levels of HBV DNA of 100,000 IU/mL or greater were more likely to have increased eGFR with treatment.

Section snippets

Study Design

We selected from an integrated database of 2485 patients with HBV a retrospective cohort of patients with chronic HBV infection who received specific treatment between 1990 and 2012 at a single hepatology unit in a tertiary care center in France (Supplementary Figure 1).

We included patients who met the following criteria: chronic HBV infection treated with NUC; absence of hepatitis C and hepatitis D co-infection; absence of liver-related complication, including ascites, hepatic encephalopathy,

Sample

The cohort comprised 214 patients with chronic HBV infection without co-infection, without immunodepression, and without more than 1 life-threatening condition described in the Charlson–Deyo index, including end-stage liver disease and hepatocellular carcinoma (Supplementary Figure 1). The median age was 43 years; two-thirds were men and one-fourth was of Asian ethnic origin. Approximately 10% of patients had 1 or more risk factors of CKD, including diabetes, obesity, hyperlipidemia, and high

Discussion

The BeSafe observational study was designed to assess renal function variations of chronic HBV patients with first- and second-generation nucleo(s)tide analogue treatment. We used a linear mixed model adjusted for preexisting comorbidities, geographic origin, and initial viral load to measure the individual variations of the eGFR computed with the Chronic Kidney Disease Epidemiology Collaboration formula. Although patients treated with ADV had a decreased eGFR over time, no renal impairment was

Acknowledgments

The authors thank Drs Yacia Benai and Raoudha Akremi for supporting this work, Dr Amel Sahli for her statistical advice, and Dr Philippe Sultanik for fruitful discussions.

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    Reproducible research statement: study protocol, statistical code, and data set are available from Vincent Mallet after establishing written agreement with the authors: e-mail: [email protected].

    Conflicts of interest These authors disclose the following: Stanislas Pol has served as a speaker for GSK, BMS, Boehringer Ingelheim, Janssen, Gilead, Roche, MSD, Sanofi, Novartis, Vertex, and AbbVie, has received grants from BMS, Gilead, Roche, and MSD, and is a board member of GSK, BMS, Boehringer Ingelheim, Janssen, Gilead, Roche, MSD, Sanofi, Novartis, Vertex, and AbbVie; Michael Schwarzinger has received a research grant from Novartis; Philippe Sogni has served as a speaker for BMS, Gilead, Roche, Janssen, and Merck and Co, and has served as a board member of Gilead, Merck and Co, and Janssen; Vincent Mallet has served as a speaker for BMS, Gilead, Roche, Janssen, and Merck and Co, and has served as a board member of Gilead, Merck and Co, and Janssen; Hélène Fontaine has served as a speaker for BMS, Gilead, Abbvie, Roche and Janssen, and has served as a board member for Gilead and BMS; and Anaïs Vallet Pichard has served as a speaker for Gilead, Roche, BMS, Merck and Co, Abbvie, and Janssen. The remaining authors disclose no conflicts.

    Funding The BeSafe study was funded with an unrestricted grant from Bristol-Myers Squibb.

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