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Vol. 26. Núm. S7.
La hepatitis B en 2008
Páginas 56-65 (Mayo 2008)
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Vol. 26. Núm. S7.
La hepatitis B en 2008
Páginas 56-65 (Mayo 2008)
Acceso a texto completo
Tratamiento del paciente con hepatitis crónica por el virus de la hepatitis B
Clinical management of patients with chronic hepatitis B virus infection
Visitas
2204
Manuel Rodríguez
Autor para correspondencia
manuelrodrig@terra.es

Correspondencia: Servicio de Digestivo. Hospital Universitario Central de Asturias. Celestino Villamil, s/n. 33006 Oviedo. Asturias. España.
, María Luisa González-Diéguez
Servicio de Digestivo. Hospital Universitario Central de Asturias. Oviedo. Asturias. España
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Información del artículo

La hepatitis crónica por virus de la hepatitis B es aún un problema importante de salud pública, agravado por el creciente fenómeno de la inmigración procedente de zonas con elevada prevalencia de infección por este virus. Durante los últimos años se ha producido un avance notable en los métodos diagnósticos, el conocimiento de la historia natural de la enfermedad y las opciones terapéuticas, incluido el trasplante hepático, lo que se ha traducido en una mejoría en la supervivencia de los pacientes. Todo ello ha ido acompañado de un incremento en la complejidad de la toma de decisiones. Actualmente hay 6 tratamientos aprobados para la hepatitis B, incluidas 2 formulaciones de interferón, el estándar y el pegilado, y 4 análogos de nocleótidos/nucleósidos, lamivudina, adefovir, entecavir y telbivudina, y 2 más que se utilizan en pacientes coninfectados con el virus de la inmunodeficiencia humana, tenofovir y emtricitabina. Sin embargo, ninguno de los tratamientos actuales es capaz de erradicar el virus, por lo que con frecuencia es preciso recurrir a tratamientos prolongados, con el consiguiente riesgo de generar variantes del virus resistentes. Por ello y por la heterogeneidad de la historia natural de la enfermedad, aún no se han establecido con claridad las indicaciones de tratamiento y en qué parámetros deben basarse, cuál es el fármaco o la combinación de fármacos ideal o qué criterios deben seguirse para continuar, modificar o interrumpir el tratamiento. Por tanto, a pesar de los enormes progresos realizados, aún persisten numerosas incógnitas que hacen que el tratamiento clínico de estos pacientes constituya un auténtico reto.

Palabras clave:
Hepatitis B
Tratamiento
Biopsia hepática
Trasplante hepático

Chronic hepatitis B is still a major public health problem, aggravated by the growing phenomenon of immigration from areas with a high prevalence of infection with this virus. In the last few years, marked progress has been achieved in diagnostic methods, knowledge of the natural history of the disease and in therapeutic options, including liver transplantation, which has improved survival in these patients. These advances have been accompanied by an increase in the complexity of decision making. Six treatments have currently been approved for hepatitis B, including two interferon formulations – standard and pegylated – and four neucleos(t)ide analogs, lamivudine, adefovir, entecavir and telbivudine, as well as two further drugs that are used in patients coinfected with HIV, tenofovir and emtricitabine.

However, none of the current treatments is able to eradicate the virus and consequently prolonged treatments are often required with the consequent risk of generating resistance. For this reason, as well as the heterogeneity of the natural history of the disease, there is a lack of consensus on the indications for treatment and the parameters in which treatment should be based, the most suitable drug or drug combination, and the criteria to be used to continue, modify or suspend treatment. Therefore, despite the enormous progress made, numerous questions remain that make the clinical management of these patients a major challenge.

Key words:
Hepatitis B
Treatment
Liver biopsy
Liver transplantation
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Bibliografía
[1.]
A. Lok, B. McMahon.
Chronic hepatitis B.
Hepatology, 45 (2007), pp. 507-539
[2.]
M. Bruguera, R. Bañares, J. Córdoba, R. Jardía, J. González, J.M. Ladero, et al.
Documento de consenso de la AEEH sobre el tratamiento de las infecciones por los virus de la hepatitis B y C.
Gastroenterol Hepatol, 29 (2006), pp. 216-230
[3.]
H.L. Janssen, M. Van Zonneveld, H. Senturk, S. Zeuzem, U.S. Akarca, Y. Cakaloglu, et al.
Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.
[4.]
H.C. Kim, C.M. Nam, S.H. Jee, K.H. Han, D.K. Oh, I. Suh.
Normal serum aminotransferase concentration and risk of mortality from liver disease: prospective cohort study.
[5.]
M.F. Yuen, H.J. Yuan, D.K. Wong, J.C. Yuen, W.M. Wong, A.O. Chan, et al.
Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications.
Gut, 54 (2005), pp. 1610-1614
[6.]
D. Prati, E. Taioli, A. Zanella, E.D. Torre, S. Butelli, E. Del Vecchio, et al.
Updated definitions of healthy ranges for serum alanine aminotransferase levels.
Ann Intern Med, 137 (2002), pp. 1-9
[7.]
E.B. Keeffe, D.T. Dieterich, S.H.B. Han, I.M. Jacobson, P. Martin, E.R. Schiff, et al.
A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update.
Clin Gastroenterol Hepatol, 4 (2006), pp. 936-962
[8.]
C.J. Chen, H.I. Yang, J. Su, C.L. Jen, S.L. You, S.N. Lu, et al.
Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.
JAMA, 295 (2006), pp. 65-73
[9.]
U.H. Iloeje, H.I. Yang, J. Su, C.L. Jen, S.L. You, C.J. Chen, et al.
Predicting cirrhosis risk based on the level of circulating hepatitis B viral load.
Gastroenterology, 130 (2006), pp. 678-686
[10.]
C.J. Chu, M. Hussain, A.S. Lok.
Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection.
Hepatology, 36 (2002), pp. 1408-1415
[11.]
E.K. Manesis, G.V. Papatheodoridis, V. Sevastianos, E. Cholongitas, C. Papaioannou, E.J. Hadziyannis.
Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection.
Am J Gastroenterol, 98 (2003), pp. 2261-2267
[12.]
Feld JJ, Ayers M, El-Ashry D, Mazzulli T, Tellier R, Heathcote EJ. Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2007. En prensa.
[13.]
G. Colloredo, M. Guido, A. Sonzogni, G. Leandro.
Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease.
J Hepatol, 39 (2003), pp. 239-244
[14.]
Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group.
Hepatology, 20 (1994), pp. 15-20
[15.]
J. Parkes, I.N. Guha, P. Roderick, W. Rosenberg.
Performance of serum marker panels for liver fibrosis in chronic hepatitis C.
J Hepatol, 44 (2006), pp. 462-474
[16.]
R.P. Myers, M.H. Tainturier, V. Ratziu, A. Piton, Thibault, F. Imbert-Bismut, et al.
Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.
J Hepatol, 39 (2003), pp. 222-230
[17.]
C.T. Wai, C.L. Cheng, A. Wee, Y.Y. Dan, E. Chan, W. Chua, et al.
Non-invasive models for predicting histology in patients with chronic hepatitis B.
Liver International, 26 (2006), pp. 666-672
[18.]
G. Sebastiani, A. Vario, M. Guido, A. Alberti.
Sequential combinig non-invasive markers and biopsy for the assesment of liver fibrosis in chronic hepatitis B.
World J Gastroenterol, 13 (2007), pp. 525-531
[19.]
A.Y. Hui, H.L. Chan, V.W. m Wong, et al.
Identification of chronic hepatitis B patients without significant liver fibrosis by a simple non-invasive predictive model.
Am J Gastroenterol, 100 (2005), pp. 616-623
[20.]
M.D. Zeng, L.G. Lu, Y.M. Mao, et al.
Prediction of significant fibrosis in HBe-Ag-positive patients with chronic hepatitis B by a non-invasive model.
Hepatologyl, 42 (2005), pp. 1437-1445
[21.]
L. Castera, J. Vergniol, J. Foucher, B. Le Bail, E. Chanteloup, M. Haasser, et al.
Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C.
Gastroenterology, 128 (2005), pp. 343-350
[22.]
B. Coco, F. Oliveri, A.M. Maina, P. Ciccorossi, R. Sacco, P. Colombatto, et al.
Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases.
J Viral Hepatitis, 14 (2007), pp. 360-369
[23.]
J.H. Hoofnagle, E. Doo, T.J. Liang, R. Fleischer, A.S.F. Lok.
Management of hepatitis B: summary of a clinical research workshop.
Hepatology, 45 (2007), pp. 1056-1075
[24.]
A.S.F. Lok.
Navigating the maze of hepatitis B treatments.
Gastroenterol, 132 (2007), pp. 1586-1594
[25.]
H.J. Flink, M. Van Zonneveld, B.E. Nanse, R.A. Fe Man, S.W. Schalm, H.L.A. Janssen.
Treatment with Peg-Interferon α-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype.
Am J Gastroenterol, 101 (2006), pp. 297-303
[26.]
E.B. Keeffe, S. Zeuzem, R.S. Koff, D.T. Dietrich, R. Esteban-Mur, E.J. Gane, et al.
Report of an International Workshop: roadmap for management of patients receiving oral antiviral therapy for chronic hepatitis B.
Clin Gastroenterol Hepatol, 5 (2007), pp. 890-897
[27.]
G. Lau, T. Piratvisuth, K.X. Kuo, P. Marcellin, S. Thongsawat, G. Cooksley, et al.
Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.
N Engl J Med, 352 (2005), pp. 2682-2695
[28.]
H.L.Y. Chan, A.Y. Hui, V.W.S. Wong, A.M.L. Chim, M.L. Wong, J.J.Y. Sung.
Long-term follou up pf peginterferon and lamivudine combination treatment in HBeAg-positive chronic hepatitis B.
Hepatology, 41 (2005), pp. 1357-1364
[29.]
P. Marcellin, G.K.K. Lau, F. Bonino, P. Farci, S. Hadziyannis, R. Jin, et al.
Peginterferon alpha-2a alone, lamivudine alone, and the two in combination for HBeAg-negative chronic hepatitis B.
N Engl J Med, 351 (2004), pp. 1206-1217
[30.]
J.J.Y.L.J. Sung, S. Zeuzem, W.C. Chow, E. Heathcote, R. Perrillo, C. Brosgart, et al.
A randomised double-blind phase II study of lamivudine compared to lamivudine plus adefovir dipivoxil for treatment naïve patients with chronic hepatitis B: week 52 analysis [abstract].
J Hepatol, 38 (2003), pp. 25
[31.]
G. Lau, H. Cooksley, R.M. Ribeiro, K.A. Powers, S. Bowden, H. Mommeja-Marin, et al.
Randomized, double-blind study comparing adefovir dipivoxil (ADV) plus emtricitabine (FTC) combination therapy versus ADV alone in HBeAg + chronic hepatitis B: efficacy and mechanisms of treatment response [abstract].
Hepatology, 40 (2004), pp. 272A
[32.]
C.L. Lai, N. Leung, E.K. Teo, M. Tong, F. Wong, H.W. Hann, et al.
A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B.
Gastroenterology, 129 (2005), pp. 528-536
[33.]
I. Rapti, E. Dimou, P. Mitsoula, S.J. Hadziyannis.
Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B.
Hepatology, 45 (2007), pp. 307-313
[34.]
Y.F. Liaw, J.J. Sung, W.C. Chow, G. Farrell, C.Z. Lee, H. Yuen, et al.
Lamivudine for patients with chronic hepatitis B and advanced liver disease.
N Engl J Med, 351 (2004), pp. 1521-1531
[35.]
E.H.C.J. Buster, B.E. Hansen, M. Buti, J. Delwaide, C. Niederau, P.P. Michielsen, et al.
Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis.
Hepatology, 46 (2007), pp. 388-394
[36.]
R. Perrillo, C. Tamburro, F. Regenstein, L. Balart, H. Bodenheimer, M. Silva, et al.
Low-dose, titratable interferon alpha in decompensated liver disease caused by chronic infection with hepatitis B virus.
Gastroenterol, 109 (1995), pp. 908-916
[37.]
R.P. Perrillo, T. Wright, J. Rakela, G. Levy, E. Schiff, R. Gish, et al.
A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver tranaplantation for chronic hepatitis B.
Hepatology, 33 (2001), pp. 424-432
[38.]
R.J. Fontana, H.W.L. Hann, R.P. Perrillo, J.M. Vierling, T. Wright, J. Rakela, et al.
Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy.
Gastroenterol, 123 (2002), pp. 719-727
[39.]
F.Y. Yao, N.A. Terrault, C. Freise, L. Maslow, N.M. Bass.
Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched untreated cohort.
Hepatology, 34 (2001), pp. 411-416
[40.]
E. Schiff, C.L. Lai, S. Hadziyannis, P. Nehaus, N. Terrault, M. Colombo, et al.
Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results.
Liver Transpl, 13 (2007), pp. 349-360
[41.]
D. Samuel, R. Muller, G. Alexander, L. Fassati, B. Ducot, J.P. Banhamou, et al.
Liver transplantation in European patients with the hepatitis B surface antigen.
N Engl J Med, 329 (1993), pp. 1842-1847
[42.]
T. Steinmüller, D. Seehofer, N. Rayes, A.R. Müller, U. Settmacher, S. Jonas, et al.
Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease.
Hepatology, 35 (2002), pp. 1528-1535
[43.]
E.J. Gane, P.W. Angus, S. Strasser, D.H.G. Crawford, J. Ring, G.P. Jeffrey, et al.
Lamivudine plus low-dose immunoglobulin to prevent recurrent hepatitis B following liver transplantation.
Gastroenterol, 132 (2007), pp. 931-937
[44.]
M. Buti, A. Mas, M. Prieto, F. Casafont, A. González, M. Miras, et al.
A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after transplantation.
J Hepatol, 38 (2003), pp. 811-817
[45.]
A. Marzano, S. Gaia, V. Chisetti, S. Carenzi, A. Premoli, W. Debernardi-Venon, et al.
Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.
Liver Transpl, 11 (2005), pp. 402-409
[46.]
A. Marzano, P. Lampertico, V. Mazzaferro, S. Carenzi, M. Vigano, R. Romito, et al.
Prophylaxis of hepatitis B virus recurrence after liver transplantation in carriers of lamivudine-resistant mutants.
Liver Transpl, 11 (2005), pp. 532-538
[47.]
S. Villet, C. Pichoud, J.P. Villeneuve, C. Trepo, F. Zoulim.
Selection of a multiple drug-resistant hepatitis B virus strain in a liver-transplanted patient.
Gastroenterol, 131 (2006), pp. 1253-1261
[48.]
J. Bruix, M. Sherman.
Management of hepatocellular carcinoma.
Hepatology, 42 (2005), pp. 1208-1236
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