BACKGROUND: Adefovir and tenofovir are nucleotide analogues used as long-term therapy of chronic hepatitis B. Side effects are few, but prolonged and high-dose therapy has been associated with proximal renal tubular dysfunction (RTD). AIM: To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B. METHODS: A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria. RESULTS: Among 51 patients treated for 1-10 (mean 7.4) years with adefovir (n = 42), tenofovir (n = 4) or adefovir followed by tenofovir (n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10-year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0-3.0 mg/dL), creatinine (1.6-1.1 mg/dL), uric acid (2.7-3.8 mg/dL) and proteinuria. CONCLUSIONS: Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2-9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long-term adefovir and tenofovir therapy. Published 2012. This article is a US Government work and is in the public domain in the USA.
BACKGROUND:Adefovir and tenofovir are nucleotide analogues used as long-term therapy of chronic hepatitis B. Side effects are few, but prolonged and high-dose therapy has been associated with proximal renal tubular dysfunction (RTD). AIM: To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B. METHODS: A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria. RESULTS: Among 51 patients treated for 1-10 (mean 7.4) years with adefovir (n = 42), tenofovir (n = 4) or adefovir followed by tenofovir (n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10-year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0-3.0 mg/dL), creatinine (1.6-1.1 mg/dL), uric acid (2.7-3.8 mg/dL) and proteinuria. CONCLUSIONS:Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2-9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long-term adefovir and tenofovir therapy. Published 2012. This article is a US Government work and is in the public domain in the USA.
Authors: M G Ghany; J J Feld; X Zhao; T Heller; E Doo; Y Rotman; P Nagabhyru; C Koh; D E Kleiner; E C Wright; T J Liang; J H Hoofnagle Journal: Aliment Pharmacol Ther Date: 2012-03-26 Impact factor: 8.171
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Andrea Snow-Lampart; Brandi Chappell; Maria Curtis; Yuao Zhu; Florence Myrick; James Schawalder; Kathryn Kitrinos; Evguenia S Svarovskaia; Michael D Miller; Jeff Sorbel; Jenny Heathcote; Patrick Marcellin; Katyna Borroto-Esoda Journal: Hepatology Date: 2010-12-22 Impact factor: 17.425
Authors: Christian M Girgis; Tang Wong; Meng C Ngu; Louise Emmett; Katherine A Archer; Roger C Y Chen; Markus J Seibel Journal: J Clin Gastroenterol Date: 2011 May-Jun Impact factor: 3.062
Authors: S Manolakopoulos; S Bethanis; S Koutsounas; J Goulis; J Vlachogiannakos; E Christias; A Saveriadis; C Pavlidis; C Triantos; A Christidou; G Papatheodoridis; D Karamanolis; D Tzourmakliotis Journal: Aliment Pharmacol Ther Date: 2007-11-05 Impact factor: 8.171
Authors: C L Lai; R N Chien; N W Leung; T T Chang; R Guan; D I Tai; K Y Ng; P C Wu; J C Dent; J Barber; S L Stephenson; D F Gray Journal: N Engl J Med Date: 1998-07-09 Impact factor: 91.245
Authors: Man Fai Law; Rita Ho; Carmen K M Cheung; Lydia H P Tam; Karen Ma; Kent C Y So; Bonaventure Ip; Jacqueline So; Jennifer Lai; Joyce Ng; Tommy H C Tam Journal: World J Gastroenterol Date: 2016-07-28 Impact factor: 5.742
Authors: Fabien Zoulim; Jolanta Białkowska-Warzecha; Mircea Mihai Diculescu; Adrian Eugen Goldis; Renate Heyne; Tomasz Mach; Patrick Marcellin; Jörg Petersen; Krzysztof Simon; Soumaya Bendahmane; Isabelle Klauck; Wojciech Wasiak; Harry L A Janssen Journal: Hepatol Int Date: 2016-05-20 Impact factor: 6.047