Letters to the Editor
Letter: renal tubular dysfunction during nucleotide analogue therapy in chronic hepatitis B
Article first published online: 16 OCT 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 36, Issue 10, pages 992–993, November 2012
How to Cite
Manolakopoulos, S., Striki, A. and Papatheodoridis, G. V. (2012), Letter: renal tubular dysfunction during nucleotide analogue therapy in chronic hepatitis B. Alimentary Pharmacology & Therapeutics, 36: 992–993. doi: 10.1111/apt.12065
- Issue published online: 16 OCT 2012
- Article first published online: 16 OCT 2012
- Manuscript Received: 11 SEP 2012
- Manuscript Accepted: 11 SEP 2012
We read with interest the retrospective study on renal tubular dysfunction (RTD) during nucleotide analogue (NA) therapy in chronic hepatitis B (CHB). RTD was diagnosed by a new definition, but all seven patients developed previously evaluated renal dysfunction markers, such as creatinine clearance (CrCl) <60 mL/min (<50 in five cases) and hypohosphataemia ≤2.3 mg/dL (≤2.0 in four cases).
The authors concluded that RTD develops in 15% of CHB patients treated with adefovir/tenofovir for 2–9 years, which is questionable, at least for tenofovir, for several reasons. First, most patients (47/51) started with adefovir, while only 4 started with tenofovir and 5 additional cases switched from adefovir to tenofovir. Similar probabilities of CrCl decrease have been reported for adefovir,[2, 3] whereas large 5-year phase III (n = 490) and 2.5-year real-life cohort (n = 302) studies have reported minimal (<2%) rates of CrCl <50 mL/min and/or hypophosphataemia <2 mg/dL in tenofovir-treated naive CHB patients.[4, 5] Given the small number of tenofovir-treated patients in the study, the confidence intervals for RTD rates are impressively wide (0–49%). Second, the small total patient number (possible type II error) might have hidden an influence of comorbidities reported in 57% and 39% of patients with and without RTD. Third, the authors did not report any adefovir/tenofovir dose modification in case of RTD signs and therefore cannot comment on the outcome of such a strategy. Finally, the probability of clinical bone effects from hypophosphataemia remains unclear, as mild alkaline phosphatase increases were reported in three patients and no bone biopsy was performed.
In conclusion, we agree that appropriate renal monitoring is required for all CHB patients treated with NAs, as suggested by recent guidelines, but we believe that there is still no clear evidence on the probability of tenofovir nephrotoxicity in CHB. Results from large and well-designed long-term studies are awaited.
Declaration of personal interests: Spilios Manolakopoulos has served as a speaker, a consultant and an advisory board member for Bristol-Myers Squibb, Gilead, Merck, Novartis and Roche, and has received research funding from Bristol-Myers Squibb and Roche. Athanasia Striki has nothing to disclose. George Papatheodoridis has served as a speaker, a consultant and an advisory board member for Bristol-Myers Squibb, Gilead, Merck, Novartis and Roche, and has received research funding from Bristol-Myers Squibb, Gilead and Roche. None of the authors is an employee of any pharmaceutical company, owns stocks and shares in any pharmaceutical company or owns any patent. Declaration of funding interests: None.
- 4Five years of treatment with tenofovir DF (TDF) for chronic hepatitis B (CHB) infection is associated with sustained viral suppression and significant regression of histological fibrosis and cirrhosis. Hepatology 2011; 54(Suppl.): 1011A–2A., , , et al.
- 5Tenofovir monotherapy for naive patients with chronic hepatitis B: a multicenter European study in clinical practice in 302 patients followed for 30 months. J Hepatol 2012; 56(Suppl. 2): S208., , , et al.
- 6European Association for the Study of the Liver. EASL Clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol 2012; 57: 167–85.