Mauro Viganò1, Alessandro Loglio2, Sara Labanca1, Serena Zaltron3, Francesco Castelli3, Pietro Andreone4, Vincenzo Messina5, Roberto Ganga6, Nicola Coppola7, Aldo Marrone8, Maurizio Russello9, Alfredo Marzano10, Alessandra Tucci10, Gloria Taliani11, Massimo Fasano12, Stefano Fagiuoli13, Erica Villa14, Fabrizio Bronte15, Teresa Santantonio16, Giuseppina Brancaccio17, Vincenzo Occhipinti1, Floriana Facchetti2, Glenda Grossi2, Mariagrazia Rumi1, Pietro Lampertico2. 1. U.O. Epatologia, Ospedale San Giuseppe, University of Milan, Milan, Italy. 2. CRC "A. M. e A. Migliavacca", Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. 3. Clinica Malattie Infettive e Tropicali. Spedali Civili Brescia, University of Brescia, Brescia, Italy. 4. Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, Bologna, Italy. 5. U.O.C. Malattie Infettive, A.O. S. Anna e S. Sebastiano, Caserta, Italy. 6. S.C Medicina Interna, Ospedale S. Michele A.O. Brotzu, Cagliari, Italy. 7. Malattie Infettive, Second University of Naples, Dipartimento Salute Mentale e Medicina Preventiva, Naples, Italy. 8. Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Luigi Vanvitelli University of Campania, Naples, Italy. 9. U.O.S. Epatologia e Malattie Gastroenteriche dell'A.R.N.A.S. Garibaldi-Nesima, Catania, Italy. 10. U.O. Gastroenterologia Universitaria, Ospedale San Giovanni Battista, Città della Salute e della Scienza di Torino, Turin, Italy. 11. Unità di Malattie Infettive e Tropicali, Dipartimento di Medicina Clinica, Sapienza University, Rome, Italy. 12. UOC Malattie Infettive Ospedale F. Fallacara, Triggiano, Italy. 13. Dipartimento di Gastroenterologia, Epatologia e Trapianto di Fegato, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 14. Divisione di Gastroenterologia, AOU Policlinico di Modena, University of Modena e Reggio Emilia, Modena, Italy. 15. Unità di Gastroenterologia ed Epatologia, DiBiMIS, University of Palermo, Palermo, Italy. 16. Dipartimento di Medicina Clinica e Sperimentale, University of Foggia, Foggia, Italy. 17. Malattie Infettive, University of Padua, Padua, Italy.
Abstract
BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. METHODS: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFRMDRD ) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter. RESULTS: During 46 (4-115) months of ETV treatment, all patients' renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFRMDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFRMDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV-R. The 5-year cumulative probability of ETV-R was 0% in LMV-naïve patients, and 11% in LMV-R patients (P = 0.018). CONCLUSIONS: Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long-term TDF treatment.
BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. METHODS: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFRMDRD ) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter. RESULTS: During 46 (4-115) months of ETV treatment, all patients' renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFRMDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFRMDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV-R. The 5-year cumulative probability of ETV-R was 0% in LMV-naïve patients, and 11% in LMV-Rpatients (P = 0.018). CONCLUSIONS:Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long-term TDF treatment.