Comparación entre la efectividad y la seguridad renal del tenofovir y el entecavir en pacientes con hepatitis B crónica

Beatriz López Centeno; Roberto Collado Borrell; Montserrat Pérez Encinas; Maria Luisa Gutiérrez García; Patricia Sanmartin Fenollera

doi:10.7399/fh.2016.40.4.10492

Comparación entre la efectividad y la seguridad renal del tenofovir y el entecavir en pacientes con hepatitis B crónica

Beatriz López Centeno, Roberto Collado Borrell, Montserrat Pérez Encinas, Maria Luisa Gutiérrez García, Patricia Sanmartin Fenollera

Resumen

Objetivo: Comparar la efectividad y seguridad renal del tratamiento con tenofovir frente al entecavir en pacientes con hepatitis B cronica. Métodos: Estudio retrospectivo en pacientes con hepatitis B que iniciaron tratamiento con tenofovir o entecavir entre enero 1998-2013. La variable principal de la efectividad fue definida como DNA viral < 20 UI/ml (HBV-DNA) y la de la seguridad renal como variaciones en el filtrado glomerular (eGFR) tras 48 semanas de tratamiento. Resultados: Se analizaron un total de 64 pacientes (1:1), con caracteristicas semejantes excepto por el predominio de pacientes sin tratamiento previo (p=0,036), comorbilidades (p=0,077) y farmacos nefrotoxicos (p=0,088) en el grupo-entecavir, y de pacientes con HBV-DNA < 20 UI/ml (p=0,032) y HBeAg-positivo (p=0,050) en el grupo-tenofovir. Se realizaron analisis estadisticos univariantes y se ajustaron las variables confusoras mediante Propensity score (PS). Los resultados para la variable principal de efectividad (HBV-DNA < 20 UI/ml) denotan una superioridad del tenofovir tras el ajuste por PS con una ORadj= 6,7 (IC95%: 1,2-35,3; p=0,028). Tres pacientes con tenofovir sufrieron seroconversion (p=0,148). Los resultados para la variable principal de seguridad (eGFR < 60ml/min/1.73m2) no mostraron diferencias entre ambas ramas tras el ajuste, obteniendo una ORadj= 0,6 (IC95%: 0,1-2,8; p=0,521). El grupo-tenofovir registro dos casos de suspension por toxicidad renal, con posterior recuperacion, entre ellos un sindrome de Fanconi. Conclusiones: En nuestro estudio existen diferencias significativas entre ambos tratamientos respecto a su efectividad, mostrandose el tenofovir superior. En cuanto a la seguridad renal, no hemos encontrado diferencias significativas, pero dos casos de suspension de tratamiento por toxicidad renal con tenofovir nos llevan a concluir que la decision de tratamiento en los pacientes con alteraciones en la funcion renal deberia incluir un analisis individualizado de cada caso.

Palabras clave

Tenofovir; Entecavir; Hepatitis B cronica; Seguridad renal; Efectividad

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Referencias

European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–42.

Lok ASF, McMahon BJ. Chronic hepatitis B: update 2009 (AASLD Practice Guidelines). Hepatology. 2009;50:661–2.

Morillo Verdugo R, Madrazo Berenguer A, Gil Navarro MV, Suárez García E. Drugs treatment of hepatitis B. Farm Hosp. 2008;32:234–48.

Petersen J, Buti M. Considerations for the long-term treatment of chronic hepatitis B with nucleos(t)ide analogs. Expert Rev Gastroenterol Hepatol. 2012;6:683–94.

Doğan ÜB, Kara B, Gümürdülü Y, Soylu A, Akin MS. Comparison of the efficacy of tenofovir and entecavir for the treatment of nucleos(t)ide-naive patients with chronic hepatitis B. Turk J Gastroenterol. 2012;23:247–52.

Pipili C, Cholongitas E, Papatheodoridis G. Review article: nucleos(t)ide analogues in patients with chronic hepatitis B virus infection and chronic kidney disease. Aliment Pharmacol Ther. 2014;39:35–46.

Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010;51:496–505.

Karras A, Lafaurie M, Furco A, Bourgarit A, Droz D, Sereni D, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis. 2003;36:1070–3.

Krummel T, Parvez-Braun L, Frantzen L, Lalanne H, Marcellin L, Hannedouche T, et al. Tenofovir-induced acute renal failure in an HIV patient with normal renal function. Nephrol Dial Transplant. 2005;20:473–4.

Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559–85.

Fernandez-Fernandez B, Montoya-Ferrer A, Sanz AB, Sanchez-Niño MD, Izquierdo MC, Poveda J, et al. Tenofovir nephrotoxicity: 2011 update. AIDS Res Treat. 2011;2011:354908.

Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, et al. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA. 2012;307:1941–51.

Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118:1094–1101.

Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.

D’Agostino RB. Propensity Score Methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.

Cnaan A, Laird NM, Slasor P. Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med. 1997;16:2349–80.

Gao L, Trinh HN, Li J, Nguyen MH. Tenofovir is superior to entecavir for achieving complete viral suppression in HBeAg-positive chronic hepatitis B patients with high HBV DNA. Aliment Pharmacol Ther. 2014;39:629–37.

Woo G, Tomlinson G, Nishikawa Y, Kowgier M, Sherman M, Wong DKH, et al. Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses. Gastroenterology. 2010;139:1218–29.

Govan L, Wu O, Xin Y, Hutchinson SJ, Hawkins N. Comparative effectiveness of antiviral treatment for hepatitis B: a systematic review and Bayesian network meta-analysis. Eur J Gastroenterol Hepatol. 2015;27:882–94.

Zuo SR, Zuo XC, Wang CJ, Ma YT, Zhang HY, Li ZJ, et al. A meta-analysis comparing the efficacy of entecavir and tenofovir for the treatment of chronic hepatitis B infection. J Clin Pharmacol. 2015;55:288-97.

Güzelbulut F, Ovünç AOK, Oetinkaya ZA, Senates E, Gökden Y, Saltürk AGD, et al. Comparison of the efficacy of entecavir and tenofovir in chronic hepatitis B. Hepatogastroenterology. 2012;59:477–80.

Dakin H, Fidler C, Harper C. Mixed treatment comparison meta-analysis evaluating the relative efficacy of nucleos(t)ides for treatment of nucleos(t)ide-naive patients with chronic hepatitis B. Value Health. 2010;13:934–45.

Ke W, Liu L, Zhang C, Ye X, Gao Y, Zhou S, et al. Comparison of efficacy and safety of tenofovir and entecavir in chronic hepatitis B virus infection: a systematic review and meta-analysis. PloS One. 2014;6:9:e98865.

Maratea D, Fadda V, Trippoli S, Messori A. Letter: First-line monotherapies for chronic hepatitis B - indirect comparison between entecavir and tenofovir. Aliment Pharmacol Ther. 2013;37:584–5.

Gish RG, Clark MD, Kane SD, Shaw RE, Mangahas MF, Baqai S. Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol. 2012;10:941-6.

Nguyen HL, Al-Freah MA, Joe D, Carey I, Boyer T, Suddle A, et al. A single centre, large ‘real-life’ cohort treated with tenofovir versus entecavir: no deterioration in renal function in tenofovir cohort over 12 months of therapy. Hepatology. 2011;54 Suppl 1:604A.

Ridruejo E, Silva MO. Safety of long-term nucleos(t)ide treatment in chronic hepatitis B. Expert Opin Drug Saf. 2012;11:357–60.

Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442–55.

Heathcote EJ, Marcellin P, Buti M, Gane E, De Man RA, Krastev Z, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology. 2011;140:132–43.

Fung J, Seto W-K, Lai C-L, Yuen M-F. Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment. J Gastroenterol Hepatol. 2014;29:428–34.

Nelson MR, Katlama C, Montaner JS, Cooper DA, Gazzard B, Clotet B, et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS Lond Engl. 2007;21:1273–81.

Gracey DM, Snelling P, McKenzie P, Strasser SI. Tenofovir-associated Fanconi syndrome in patients with chronic hepatitis B monoinfection. Antivir Ther. 2013;18:945–48.

Viganò M, Brocchieri A, Spinetti A, Zaltron S, Mangia G, Facchetti F, et al. Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal. J Clin Virol. 2014;61:600–3.

DOI: http://dx.doi.org/10.7399%2Ffh.2016.40.4.10492