Información del artículo
La infección por el virus de la hepatitis B (VHB) es una causa significativa de morbimortalidad, sobre todo por la evolución a cirrosis y hepatocarcinoma. La prevalencia y la distribución genotípica del VHB tienen marcadas diferencias geográficas. La infección por el VHB es un proceso muy dinámico, con una fase de inmunotolerancia y alta replicación viral, seguida del aclaramiento del antígeno e de la hepatitis B (HBeAg), no siempre acompañado de remisión de la replicación viral. Es el caso de la hepatitis HBeAg negativa, que representa un grupo relativamente resistente al tratamiento. Los tres fármacos aprobados para el tratamiento del VHB (interferón alfa, lamivudina y adefovir) tienen eficacia limitada. Las recidivas son más frecuentes con lamivudina y adefovir, requiriendo frecuentemente tratamientos prolongados. Mientras la selección de mutaciones de resistencia a lamivudina es frecuente, adefovir tiene una barrera genética alta. La infección por virus de la inmunodeficiencia humana (VIH) tiene una repercusión negativa sobre el VHB, por lo que son necesarias estrategias que atiendan simultáneamente a ambas infecciones.
Palabras clave:
Hepatitis crónica B
Tratamiento anti-VHB
VIH
Infection by the hepatitis B virus (HBV) is a significant cause of morbidity and mortality, mainly due to evolvement to cirrhosis and hepatocellular carcinoma. The prevalence and genotypic distribution of HBV infection has marked geographic differences. HBV infection is a very dynamic process, with a phase of immune tolerance and high viral replication, followed by HBeAg clearance, not always accompanied by complete suppression of HBV replication. The latter situation corresponds to negative HBeAg hepatitis, which represents a group relatively resistent to therapy. The three approved drugs for the treatment of HBV infection (interferon alpha, lamivudine and adefovir) have limited efficacy. Relapses are more common with lamivudine and adefovir, requiring often long-term treatment. While the selection of lamivudine resistance mutations is frequent, adefovir has a high genetic barrier. HIV infection negatively impacts on HBV disease, requiring these coinfected patients strategies aimed to manage both viruses.
Key words:
Chronic hepatitis
Anti-HBV therapy
HIV
El Texto completo está disponible en PDF
Bibliografía
[1.]
D. Lavanchy, B. Hepatitis.
virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures: a review.
J Viral Hepat, 11 (2004), pp. 97-107
[2.]
C. Lai, V. Ratziu, M. Yuen, T. Poynard.
Viral hepatitis B.
Lancet, 362 (2003), pp. 2089-2094
[3.]
M. Alter.
Epidemiology and prevention of hepatitis B.
Semin Liver Dis, 23 (2003), pp. 39-46
[4.]
Shaw T, Locarnini S. Hepatitis B. En: Encyclopedia of Gastroenterology. Elsevier, 2004.
[5.]
G. Fattovich.
Natural history and prognosis of hepatitis B.
Semin Liver Dis, 23 (2003), pp. 47-58
[6.]
D. Ganem, A. Prince.
Hepatitis B virus infection. Natural History and clinical consequences.
N Engl J Med, 350 (2004), pp. 1118-1129
[7.]
C. Chu, M. Hussain, A. Lok.
Quantitative serum HBV-DNA levels during different stages of chronic hepatitis B infection.
Hepatology, 36 (2002), pp. 1408-1415
[8.]
A. Geier, C. Dietrich, C. Gartung.
Antiviral therapy in HBeAg-positive hepatitis B with normal aminotransferase levels.
Hepatology, 37 (2003), pp. 712-713
[9.]
A. Lok, B. McMahon.
Chronic hepatitis B.
Hepatology, 34 (2001), pp. 1225-1241
[10.]
H. Mommeja-Marin, E. Mondou, M.R. Blum, F. Rousseau.
Serum HBV-DNA as a marker of efficacy during therapy for chronic HBV infection: analysis and review of the literature.
Hepatology, 37 (2003), pp. 1309-1319
[11.]
E. Keeffe, D. Dieterich, S. Han, et al.
A treatment algorithm for the management of chronic hepatitis B virus infection in the United States.
Clinical Gastroenterol Hepatol, 2 (2004), pp. 87-106
[12.]
W. Cooksley, T. Piratvisuth, S. Lee, et al.
Peginterferon alfa-2a (40KD): An advance in the treatment of HBeAg-Positive Chronic Hepatitis B.
J Viral Hepat, 10 (2003), pp. 298-305
[13.]
M. Brunetto, F. Oliveri, P. Colombatto, B. Coco, P. Ciccorossi, F. Bonino.
Treatment of HBeAg-negative chronic hepatitis B with interferon or pegylated interferon.
J Hepatol, 39 Suppl 1 (2003), pp. 164-167
[14.]
I. Tatulli, R. Francavilla, G. Rizzo, et al.
Lamivudine and alpha-interferon in combination long-term for precore mutant chronic hepatitis B.
J Hepatol, 35 (2001), pp. 805-810
[15.]
E. Schiff, S. Karayalcin, J. Dienstag, et al.
Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon non-responders.
J Hepatol, 38 (2003), pp. 818-826
[16.]
G. Barbaro, F. Zechini, A. Pellicelli, et al.
Long-term efficacy of interferon alpha-2b and lamivudine combination compared to lamivudine monotherapy in patients with chronic hepatitis B. An Italian multicenter randomized trial.
J Hepatol, 35 (2001), pp. 406-411
[17.]
J. Sung, H. Chan, A. Hui, V. Wong, C. Liew, A. Chim, et al.
Combination of peginterferon alfa-2b and lamivudine is superior to lamivudine alone in the treatment of chronic hepatitis B [abstract 410].
Gastroenterology, 126 Suppl 2 (2004), pp. A-682
[18.]
M. Peters, H. Hann, P. Martin, et al.
Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B.
Gastroenterology, 126 (2004), pp. 91-101
[19.]
Y. Liaw, N. Leung, T. Chang, et al.
Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B.
Gastroenterology, 119 (2000), pp. 172-180
[20.]
N. Leung, C. Lai, T. Chang, et al.
Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy.
Hepatology, 33 (2001), pp. 1527-1532
[21.]
C. Westland, J. Villeneuve, N. Terrault, F. Zoulim, C. Brosgart, M. Wulfsohn, et al.
Resistance surveillance of liver transplantation patients with lamivudine-resistant hepatitis B virus (HBV) after 96 weeks of adefovir dipivoxil treatment [abstract #10].
Hepatology, 38 Suppl 1 (2003), pp. 160A
[22.]
T. Chang, S. Hadziyannis, J. Cianciara, M. Rizzeto, G. Schiff, G. Pastore, et al.
Sustained viral load and ALT reduction following 48 weeks of entecavir treatment in subjects with chronic hepatitis B who have failed lamivudine [abstract 550].
Hepatology, 36 (2002), pp. 300A
[23.]
F. Kanwal, B. Spiegel, G. Dulai, P. Martin, T. Bralnek, et al.
Adefovir salvage therapy is cost-effective in chronic hepatitis B [abstract 6].
Gastroenterology, 126 Suppl 2 (2004), pp. A-661
[24.]
V. Soriano, L. Martín-Carbonero, J. García-Samaniego, M. Puoti.
Mortality due to viral liver disease among patients infected with human immunodeficiency virus.
Clin Infect Dis, 33 (2001), pp. 1793-1794
[25.]
C. Thio, E. Seaberg, R. Skolasky, et al.
HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS.
Lancet, 360 (2002), pp. 1921-1926
[26.]
F. Laure, D. Zagury, A. Saimont, et al.
Hepatitis B virus DNA sequences in lymphoid cells from patients with AIDS and AIDS-related complex.
Science, 229 (1985), pp. 561-563
[27.]
Gómez-Gonzalo M, Carretero M, Rullas J, et al. The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals. J Biol Chem 276;38:35435-43.
[28.]
R. Gilson, A. Hawkins, M. Beecham, et al.
Interaction between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection.
AIDS, 11 (1997), pp. 597-606
[29.]
M. Puoti, M. Airoldi, R. Bruno, et al.
Hepatitis B virus co-infection in HIV-infected subjects.
AIDS Clin Rev, 4 (2002), pp. 27-35
[30.]
A. Eskil, P. Magnus, G. Petersen, et al.
Hepatitis B antibodies in HIV-infected homosexual men are associated with more rapid progression to AIDS.
AIDS, 6 (1992), pp. 571-574
[31.]
I. Weller, A. Brown, B. Morgan, et al.
Spontaneous loss of HBeAg and the prevalence of HTLV-III / LAV infection in a cohort of homosexual hepatitis B virus carriers and the implication for antiviral therapy.
J Hepatol, 3 Suppl 2 (1986), pp. 9-16
[32.]
J. Colin, D. Cazals-Hatem, A. Loriot, et al.
Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men.
Hepatology, 29 (1999), pp. 1306-1310
[33.]
M. Núñez, P. Ríos, M. Pérez-Olmeda, V. Soriano.
Lack of “occult” hepatitis B virus infection in HIV-infected patients.
AIDS, 16 (2002), pp. 2099-2101
[34.]
N. Bodsworth, B. Donovan, B. Nightingale.
The effects of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men.
J Infect Dis, 160 (1989), pp. 577-582
[35.]
R. Perrillo, F. Regenstein, S. Roodman.
Chronic hepatitis B in asymptomatic homosexual men with antibody to the human immunodeficiency virus.
Ann Intern Med, 105 (1986), pp. 382-383
[36.]
M. Bonacini, S. Govindarajan, A. Redeker.
Human immunodeficiency virus infection does not alter serum transaminases and hepatitis B virus (HBV) DNA in homosexual patients with chronic HBV infection.
Am J Gastroenterol, 86 (1991), pp. 570-573
[37.]
C. Housset, S. Pol, F. Carnot, et al.
Interactions between human immunodeficiency virus-1, hepatitis delta and hepatitis B virus infection in 260 chronic carriers of hepatitis B virus.
Hepatology, 15 (1992), pp. 578-583
[38.]
D. Wong, A. Cheung, C. O’Rourke Naylor, A. Detsky, J. Heathcote.
Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.
Ann Intern Med, 119 (1993), pp. 312-323
[39.]
V. Di Martino, T. Thevenot, J. Colin, et al.
Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B.
Gastroenterology, 123 (2002), pp. 1812-1822
[40.]
J. Dore, D. Cooper, C. Barret, et al.
Dual efficacy of lamivudine treatment in human immunodeficiency virus hepatitis B coinfected persons in a randomized, controlled study (CAESAR.
J Infect Dis, 180 (1999), pp. 607-613
[41.]
Y. Benhamou, M. Bochet, V. Thibault, et al.
Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus infected patients.
Hepatology, 30 (1999), pp. 1303-1306
[42.]
J. Hoff, F. Bani-Sadr, M. Gassin, et al.
Evaluation of chronic hepatitis B virus (HBV) infection in co-infected patients receiving lamivudine as component of anti-human immunodeficiency virus regimen.
Clin Infect Dis, 32 (2001), pp. 963-969
[43.]
M. Bessesen, D. Ives, L. Condreay, S. Lawrence, K. Sherman.
Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine.
Clin Infect Dis, 285 (1999), pp. 1032-1035
[44.]
G. Dore, D. Cooper, A. Pozniak, et al.
Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naïve and -experienced patients coinfected with HIV-1 and hepatitis B virus.
J Infect Dis, 189 (2004), pp. 1185-1192
[45.]
F. Van Bömmel, T. Wünsche, D. Schürmann, T. Berg.
Tenofovir treatment in patients with lamivudine-resistant hepatitis B mutants strongly affects viral replication.
Hepatology, 36 (2002), pp. 507-508
[46.]
M. Núñez, M. Pérez-Olmeda, B. Díaz, P. Ríos, J. González-Lahoz, V. Soriano.
Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine.
AIDS, 16 (2002), pp. 2352-2354
[47.]
M. Ristig, J. Crippin, J. Aberg, et al.
Tenofovir disoproxil fumarate therapy for chronic hepatitis B in human immunodeficiency virus/hepatitis B virus-coinfected individuals for whom interferon-α and lamivudine therapy have failed.
J Infect Dis, 186 (2002), pp. 1844-1847
[48.]
M. Nelson, S. Portsmouth, J. Stebbing, et al.
An open-label study of tenofovir in HIV-1 and hepatitis B virus co-infected individuals.
AIDS, 17 (2003), pp. F7-F10
[49.]
Y. Benhamou, R. Tubiana, V. Thibault.
Tenofovir disoproxil fumarate in patients with HIV and lamivudine-resistant hepatitis B virus.
N Engl J Med, 348 (2003), pp. 177-178
[50.]
Y. Benhamou, M. Bochet, V. Thibault, et al.
Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine resistant hepatitis B virus: an open-label pilot study.
Lancet, 358 (2001), pp. 718-723
[51.]
R. Gish, N. Leung, C. Wang, L. Corey, S. Sacks, N. Fried, et al.
Antiviral activity, safety and incidence of resistance in chronically infected hepatitis B patients (CHB) given once daily emtricitabine for 2 years [abstract 383].
Hepatology, 36 (2002), pp. 372A
[52.]
M. Brook, R. Gilson, E. Wilkins.
British HIV Association. BHIVA guidelines: co-infection with HIV and chronic hepatitis B virus.
HIV Med, 4 Suppl 1 (2003), pp. 142-151
[53.]
V. Soriano, J. Miró, J. García-Samaniego, et al.
Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.
J Viral Hepat, 11 (2004), pp. 2-17
[54.]
The EASL Jury.
EASL International Consensus Statement Conference on Hepatitis B. J Hepatol, 38 (2003), pp. 533-540
Copyright © 2004. Elsevier España, S.L.. Todos los derechos reservados
