Hepatitis C asociada al abuso de sustancias: nunca tan cerca de un tratamiento sin Interferón Hepatitis C associated to substance abuse: ever closer to a treatment without Interferon

Autores/as

  • Roberto Muga Servei de Medicina Interna. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
  • Paola Zuluaga Servei de Medicina Interna. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
  • Arantza Sanvisens Servei de Medicina Interna. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
  • Inmaculada Rivas Centro de Atención y Seguimiento de las Drogodependencias (CAS DELTA) y Bus Intermunicipal de Metadona (BIM). Institut Municipal de Serveis Personals, Badalona.
  • Daniel Fuster Servei de Medicina Interna. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
  • Ferran Bolao Servei de Medicina Interna. Hospital Universitari de Bellvitge, Universitat de Barcelona, L’Hospitalet de Llobregat.
  • Jordi Tor Servei de Medicina Interna. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
  • - Red de Trastornos Adictivos-RTA

DOI:

https://doi.org/10.20882/adicciones.698

Palabras clave:

Abuso de sustancias, hepatitis C, tratamiento, antivirales acción directa. Substance abuse, Hepatitis C, Treatment, Direct antiviral action.

Resumen

La infección por el virus de la hepatitis C (VHC) es un problema de Salud Pública de primera magnitud; cada año ocurren entre 3 y 4 millones de nuevas infecciones y de hecho, la hepatitis crónica C es una de las principales causas de enfermedad hepática en el mundo. Usar drogas por vía parenteral está en el origen de dos de cada tres nuevas infecciones por VHC en el mundo occidental.El tratamiento de la hepatitis C va a cambiar en los próximos años. El cambio es debido a la aparición de los llamados Antivirales de Acción Directa (AAD), unos fármacos que actúan contra proteínas clave del ciclo vital del VHC y que serán más eficaces, mejor tolerados y se administrarán durante menos tiempo. En este sentido, la nueva guía de tratamiento de la OMS en 2014 ya incluye alguno de ellos en sus recomendaciones; los nuevos fármacos se utilizarán en combinación y probablemente se podrá prescindir del Interferón.Con la aparición de más y mejores antivirales contra el VHC es probable que debamos revisar el modelo asistencial vigente y orientarlo hacia uno más ágil e integrador, que trate al mayor número posible de pacientes, incluyendo a aquellos con abuso de sustancias.
With 3-4 million of new infections occurring annually, hepatitis C virus (HCV) infection is a global Public Health problem. In fact, hepatitis C virus infection is one of the leading causes of liver disease in the world; in Western countries, two thirds of  the new HCV infections are associated with injection drug use.The treatment of hepatitis C will change in the coming years with the irruption of new anti-HCV drugs, the so called Direct Antiviral Agents (DAA)  that attack key proteins of the HCV life cycle. The new antiviral drugs are effective, safer and better tolerated. The 2014 WHO HCV treatment guidelines include some of them. The new DAA are used in combination and it is expected that Interferon will be not necessary in future treatment regimens against HCV infection.The irruption of new and potent antivirals mandate the review of the current standards of care in the HCV infected population. More inclusive and proactive treatment policies will be necessary in those individuals with substance use disorders.

Citas

Afdhal, N. H. (2004). The natural history of hepatitis C. Seminars in Liver Disease, 24, 3–8. doi:10.1055/s-2004-832922

Alavi, M., Grebely, J., Micallef, M., Dunlop, A. J., Balcomb, A. C., Day, C. A., … Dore, G. J. (2013). Assessment and treatment of hepatitis C virus infection among people who inject drugs in the opioid substitution setting: ETHOS study. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 57, S62–9. doi:10.1093/cid/cit305

Alter, M. J. (2007). Epidemiology of hepatitis C virus infection. World Journal of Gastroenterology : WJG, 13, 2436–41.

Anand, B. S., Currie, S., Dieperink, E., Bini, E. J., Shen, H., Ho, S. B., & Wright, T. (2006). Alcohol use and treatment of hepatitis C virus: results of a national multicenter study. Gastroenterology, 130, 1607–1616. doi:10.1053/j.gastro.2006.02.023

Aspinall, E. J., Corson, S., Doyle, J. S., Grebely, J., Hutchinson, S. J., Dore, G. J., … Hellard, M. E. (2013). Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 57, S80–89. doi:10.1093/cid/cit306

Asselah, T., & Marcellin, P. (2014). Second-wave IFN-based triple therapy for HCV genotype 1 infection: simeprevir, faldaprevir and sofosbuvir. Liver International : Official Journal of the International Association for the Study of the Liver, 34, 60–68. doi:10.1111/liv.12424

Borroni, G., Andreoletti, M., Casiraghi, M. A., Ceriani, R., Guerzoni, P., Omazzi, B., … Salerno, F. (2008). Effectiveness of pegylated interferon/ribavirin combination in “real world” patients with chronic hepatitis C virus infection. Alimentary Pharmacology & Therapeutics, 27, 790–797. doi:10.1111/j.1365-2036.2008.03657.x

Cartón, J. A., Collazos, J., de la Fuente, B., García-Alcalde, M. L., Suarez-Zarracina, T., Rodríguez-Guardado, A., & Asensi, V. (2011). Factors associated with liver fibrosis in intravenous drug users coinfected with HIV and HCV. Antiviral Therapy, 16, 27–35. doi:10.3851/IMP1708

Chung, R. T. (2012). A watershed moment in the treatment of hepatitis C. The New England Journal of Medicine, 366, 273–275. doi:10.1056/NEJMe1113272

Cornberg, M., Razavi, H. A., Alberti, A., Bernasconi, E., Buti, M., Cooper, C., … Zeuzem, S. (2011). A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver International : Official Journal of the International Association for the Study of the Liver, 31, 30–60. doi:10.1111/j.1478-3231.2011.02539.x

De Ledinghen, V., Douvin, C., Kettaneh, A., Ziol, M., Roulot, D., Marcellin, P., … Beaugrand, M. (2006). Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. Journal of Acquired Immune Deficiency Syndromes (1999), 41, 175–179.

Des Jarlais, D. C., Diaz, T., Perlis, T., Vlahov, D., Maslow, C., Latka, M., … Garfein, R. S. (2003). Variability in the incidence of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection among young injecting drug users in New York City. American Journal of Epidemiology, 157, 467–471.

Dore, G. J., Freeman, A. J., Law, M., & Kaldor, J. M. (2003). Natural history models for hepatitis C-related liver disease: different disease progression parameters for different settings. Antiviral Therapy, 8, 365–372.

Edlin, B. R. (2002). Prevention and treatment of hepatitis C in injection drug users. Hepatology (Baltimore, Md.), 36, S210–219. doi:10.1053/jhep.2002.36809

Freeman, R. B., Steffick, D. E., Guidinger, M. K., Farmer, D. G., Berg, C. L., & Merion, R. M. (2008). Liver and intestine transplantation in the United States, 1997-2006. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 8, 958–976. doi:10.1111/j.1600-6143.2008.02174.x

Gane, E. J., Stedman, C. A., Hyland, R. H., Ding, X., Svarovskaia, E., Subramanian, G. M., … Pang, P. S. (2014). Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A Inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology, 146, 736–743.e1. doi:10.1053/j.gastro.2013.11.007

Gentile, I., Borgia, F., Coppola, N., Buonomo, A. R., Castaldo, G., & Borgia, G. (2013). Daclatasvir: The First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A. Current Medicinal Chemistry, 21, 1391-1404.

Grebely, J., deVlaming, S., Duncan, F., Viljoen, M., & Conway, B. (2008). Current approaches to HCV infection in current and former injection drug users. Journal of Addictive Diseases, 27, 25–35. doi:10.1300/J069v27n02_04

Grebely, J., Prins, M., Hellard, M., Cox, A. L., Osburn, W. O., Lauer, G., … Dore, G. J. (2012). Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine. The Lancet Infectious Diseases, 12, 408–414. doi:10.1016/S1473-3099(12)70010-5

Grebely, J., Raffa, J. D., Lai, C., Krajden, M., Kerr, T., Fischer, B., & Tyndall, M. W. (2009). Low uptake of treatment for hepatitis C virus infection in a large community-based study of inner city residents. Journal of Viral Hepatitis, 16, 352–358. doi:10.1111/j.1365-2893.2009.01080.x

Grebely, J., & Tyndall, M. W. (2011). Management of HCV and HIV infections among people who inject drugs. Current Opinion in HIV and AIDS, 6, 501–507. doi:10.1097/COH.0b013e32834bcb36

Hellard, M., Sacks-Davis, R., & Gold, J. (2009). Hepatitis C treatment for injection drug users: a review of the available evidence. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 49, 561–573. doi:10.1086/600304

Innes, H. A., Hutchinson, S. J., Allen, S., Bhattacharyya, D., Bramley, P., Carman, B., … Hayes, P. (2012). Ranking predictors of a sustained viral response for patients with chronic hepatitis C treated with pegylated interferon and ribavirin in Scotland. European Journal of Gastroenterology & Hepatology, 24, 646–655. doi:10.1097/MEG.0b013e32835201a4

Kramer, J. R., Kanwal, F., Richardson, P., Giordano, T. P., Petersen, L. A., & El-Serag, H. B. (2011). Importance of patient, provider, and facility predictors of hepatitis C virus treatment in veterans: a national study. The American Journal of Gastroenterology, 106, 483–491. doi:10.1038/ajg.2010.430

Lawitz, E., & Gane, E. J. (2013). Sofosbuvir for previously untreated chronic hepatitis C infection. The New England Journal of Medicine, 369, 678–679. doi:10.1056/NEJMc1307641

Link, J. O., Taylor, J. G., Xu, L., Mitchell, M., Guo, H., Liu, H., … Desai, M. C. (2014). Discovery of Ledipasvir (GS-5885): A Potent, Once-Daily Oral NS5A Inhibitor for the Treatment of Hepatitis C Virus Infection. Journal of Medicinal Chemistry, 57, 2033–2046. doi:10.1021/jm401499g

Litwin, A. H., Kunins, H. V, Berg, K. M., Federman, A. D., Heavner, K. K., Gourevitch, M. N., & Arnsten, J. H. (2007). Hepatitis C management by addiction medicine physicians: results from a national survey. Journal of Substance Abuse Treatment, 33, 99–105. doi:10.1016/j.jsat.2006.12.001

Liu, L., Fisher, B. E., Thomas, D. L., Cox, A. L., & Ray, S. C. (2012). Spontaneous clearance of primary acute hepatitis C virus infection correlated with high initial viral RNA level and rapid HVR1 evolution. Hepatology (Baltimore, Md.), 55, 1684–1691. doi:10.1002/hep.25575

Ly, K. N., Xing, J., Klevens, R. M., Jiles, R. B., Ward, J. W., & Holmberg, S. D. (2012). The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Annals of Internal Medicine, 156, 271–278. doi:10.7326/0003-4819-156-4-201202210-00004

Mallet, V., Dhalluin-Venier, V., Roussin, C., Bourliere, M., Pettinelli, M. E., Giry, C., … Pol, S. (2009). The accuracy of the FIB-4 index for the diagnosis of mild fibrosis in chronic hepatitis B. Alimentary Pharmacology & Therapeutics, 29, 409–415. doi:10.1111/j.1365-2036.2008.03895.x

Mauss, S., & Klinker, H. (2013). Drug-drug interactions in the treatment of HCV among people who inject drugs. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 57, S125–128. doi:10.1093/cid/cit299

McHutchison, J. G., Manns, M., Patel, K., Poynard, T., Lindsay, K. L., Trepo, C., … Albrecht, J. K. (2002). Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology, 123, 1061–1069.

Mehta, S. H., Genberg, B. L., Astemborski, J., Kavasery, R., Kirk, G. D., Vlahov, D., … Thomas, D. L. (2008). Limited uptake of hepatitis C treatment among injection drug users. Journal of Community Health, 33, 126–133. doi:10.1007/s10900-007-9083-3

Mehta, S. H., Vogt, S. L., Srikrishnan, A. K., Vasudevan, C. K., Murugavel, K. G., Saravanan, S., … Solomon, S. S. (2010). Epidemiology of hepatitis C virus infection & liver disease among injection drug users (IDUs) in Chennai, India. The Indian Journal of Medical Research, 132, 706–714.

Memon, M. I., & Memon, M. A. (2002). Hepatitis C: an epidemiological review. Journal of Viral Hepatitis, 9, 84–100.

Mohd Hanafiah, K., Groeger, J., Flaxman, A. D., & Wiersma, S. T. (2013). Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology (Baltimore, Md.), 57, 1333–1342. doi:10.1002/hep.26141

Muga, R., Sanvisens, A., Fuster, D., Tor, J., Martinez, E., Perez-Hoyos, S., & Munoz, A. (2012). Unhealthy Alcohol Use, HIV Infection and Risk of Liver Fibrosis in Drug Users with Hepatitis C. Plos One, 7. doi:10.1371/journal.pone.0046810

Nelson, P. K., Mathers, B. M., Cowie, B., Hagan, H., Des Jarlais, D., Horyniak, D., & Degenhardt, L. (2011). Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet, 378, 571–583. doi:10.1016/S0140-6736(11)61097-0

Observatorio Europeo de las Drogas y las Toxicomanías. (2011) Informe anual 2011: el problema de la drogodependencia en Europa. Retrieved from http://www.emcdda.europa.eu/attachements.cfm/att_143743_ES_EMCDDA_AR2011_ES.pdf

Page, K., Hahn, J. A., Evans, J., Shiboski, S., Lum, P., Delwart, E., … Busch, M. P. (2009). Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. The Journal of Infectious Diseases, 200, 1216–1226. doi:10.1086/605947

Page, K., Morris, M. D., Hahn, J. A., Maher, L., & Prins, M. (2013). Injection drug use and hepatitis C virus infection in young adult injectors: using evidence to inform comprehensive prevention. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 57, S32–38. doi:10.1093/cid/cit300

Poynard, T., Bedossa, P., & Opolon, P. (1997). Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet, 349, 825–832.

Raimondi, S., Bruno, S., Mondelli, M. U., & Maisonneuve, P. (2009). Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. Journal of Hepatology, 50, 1142–1154. doi:10.1016/j.jhep.2009.01.019

Ravi, S., Nasiri Toosi, M., Karimzadeh, I., Ahadi-Barzoki, M., & Khalili, H. (2013). Adherence to chronic hepatitis C treatment regimen: first report from a referral center in Iran. Hepatitis Monthly, 13, e11038. doi:10.5812/hepatmon.11038

Reimer, J., & Haasen, C. (2009). Need-adapted HCV-treatment setting for injection drug users. Lancet, 373, 2090–2091. doi:10.1016/S0140-6736(09)60347-0

Rein, D. B., Smith, B. D., Wittenborn, J. S., Lesesne, S. B., Wagner, L. D., Roblin, D. W., … Weinbaum, C. M. (2012). The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Annals of Internal Medicine, 156, 263–270. doi:10.7326/0003-4819-156-4-201202210-00378

Rein, D. B., Wittenborn, J. S., Weinbaum, C. M., Sabin, M., Smith, B. D., & Lesesne, S. B. (2011). Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States. Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 43, 66–72. doi:10.1016/j.dld.2010.05.006

Rivas, I., Sanvisens, A., Bolao, F., Fuster, D., Tor, J., Pujol, R., … Muga, R. (2013). Impact of medical comorbidity and risk of death in 680 patients with alcohol use disorders. Alcoholism, Clinical and Experimental Research, 37, E221–227. doi:10.1111/j.1530-0277.2012.01861.x

Robaeys, G., Grebely, J., Mauss, S., Bruggmann, P., Moussalli, J., De Gottardi, A., … Dore, G. J. (2013). Recommendations for the management of hepatitis C virus infection among people who inject drugs. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 57, S129–137. doi:10.1093/cid/cit302

Sanvisens, A., Fuster, D., Serra, I., Tor, J., Tural, C., Rey-Joly, C., & Muga, R. (2011). Estimated liver fibrosis and its impact on all-cause mortality of HCV-monoinfected and HCV/HIV-coinfected drug users. Current HIV Research, 9, 256–262. doi:10.2174/157016211796320298

Sanvisens, A., Serra, I., Tural, C., Tor, J., Ojanguren, I., Barluenga, E., … Muga, R. (2009). Hyaluronic acid, transforming growth factor-beta1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection. Journal of Viral Hepatitis, 16, 513–518.

Shepard, C. W., Finelli, L., & Alter, M. J. (2005). Global epidemiology of hepatitis C virus infection. The Lancet Infectious Diseases, 5, 558–567. doi:10.1016/S1473-3099(05)70216-4

Sterling, R. K., Lissen, E., Clumeck, N., Sola, R., Correa, M. C., Montaner, J., … Investigators, A. C. (2006). Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology (Baltimore, Md.), 43, 1317–1325. doi:10.1002/hep.21178

Sulkowski, M. S., Gardiner, D. F., Rodriguez-Torres, M., Reddy, K. R., Hassanein, T., Jacobson, I., … Grasela, D. M. (2014). Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection. New England Journal of Medicine, 370, 211–221. doi:10.1056/NEJMoa1306218

Suzuki, Y., Ikeda, K., Suzuki, F., Toyota, J., Karino, Y., Chayama, K., … Kumada, H. (2013). Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. Journal of Hepatology, 58, 655–662. doi:10.1016/j.jhep.2012.09.037

Thomas, D. L., & Seeff, L. B. (2005). Natural history of hepatitis C. Clinics in Liver Disease, 9, 383–398, vi. doi:10.1016/j.cld.2005.05.003

Vallet-Pichard, A., Mallet, V., Nalpas, B., Verkarre, V., Nalpas, A., Dhalluin-Venier, V., … Pol, S. (2007). FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology (Baltimore, Md.), 46, 32–36. doi:10.1002/hep.21669

Wai, C. T., Greenson, J. K., Fontana, R. J., Kalbfleisch, J. D., Marrero, J. A., Conjeevaram, H. S., & Lok, A. S. (2003). A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology (Baltimore, Md.), 38, 518–526. doi:10.1053/jhep.2003.50346

Wendt, A., Adhoute, X., Castellani, P., Oules, V., Ansaldi, C., Benali, S., & Bourlière, M. (2014). Chronic hepatitis C: future treatment. Clinical Pharmacology : Advances and Applications, 6, 1–17. doi:10.2147/CPAA.S30338

Wong, V. W.-S., Vergniol, J., Wong, G. L.-H., Foucher, J., Chan, H. L.-Y., Le Bail, B., … de Lédinghen, V. (2010). Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.), 51, 454–462. doi:10.1002/hep.23312

World Health Organization. (2014). Guidelines for the screening, care and treatment of persons with hepatitis c infection. Retrieved from http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1

Yang, J. D., Kim, W. R., Coelho, R., Mettler, T. A., Benson, J. T., Sanderson, S. O., … Roberts, L. R. (2011). Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association, 9, 64–70. doi:10.1016/j.cgh.2010.08.019

Zeuzem, S., Asselah, T., Angus, P., Zarski, J.-P., Larrey, D., Müllhaupt, B., … Mensa, F. J. (2013). Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results. Antiviral Therapy, 18,1015-1019. doi:10.3851/IMP2567

Descargas

Publicado

2015-06-17

Número

Vol. 27 Núm. 2 (2015)

Sección

Revisión