DIRECT-ACTING ANTIVIRALS IN THE TREATMENT OF CHRONIC HCV INFECTION IN PATIENTS WITH CIRRHOSIS
Abstract
Chronic hepatitis C is a global healthcare problem. Worldwide, more than 180 million people are infected with hepatitis C virus. Patients with HCV-associated liver damage often present asymptomatic until cirrhosis develops. HCV infection leads to more than 700, 000 deaths annually. In recent years, a new class of direct-acting antivirals for treatment of chronic hepatitis C has been introduced. Being highly effective and generally well-tolerated, the novel interferon-free antiviral treatment demonstrates acceptable safety profile in patients with cirrhosis including those with decompensated liver function. Therefore, antiviral treatment is currently becoming available to the most urgent and atrisk groups, since in most of these patients interferon-based regimens are contraindicated. This article highlights issues concerning antiviral treatment with direct-acting antivirals in patients with chronic HCVassociated cirrhosis. Some of direct-acting antivirals are already available in Belarus with most of them anticipated within the foreseeable future. Information regarding treatment efficacy in special groups of patients with cirrhosis, e.g. those with severe portal hypertension, and HCC, is provided.References
1. Thrift AP, El-Serag HB, Kanwal F. Global epidemiology and burden of HCV infection and HCV-related disease. Nat. Rev. Gastroenterol. Hepatol. 2016;14(2):122-132. doi: 10.1038/ nrgastro.2016.176.
Jacobson IM, Davis GL, El-Serag H, Negro F, Trépo C. Prevalence and challenges of liver diseases in patients with chronic hepatitis C virus infection. Clin. Gastroenterol. Hepatol. 2010;8(11):924-933. doi: 10.1016/j.cgh.2010.06.032.
Petta S, Maida M, Macaluso FS, Barbara M, Licata A, Craxì A, Cammà C. Hepatitis C virus infection is associated with increased cardiovascular mortality: a meta-analysis of observational studies. Gastroenterology. 2016;150(1):145-155. doi: 10.1053/j.gastro.2015.09.007.
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264- 1273. doi: 10.1053/j.gastro.2011.12.061.
D’Amico G, Pasta L, Morabito A, D’Amico M, Caltagirone M, Malizia G, Tinè F, Giannuoli G, Traina M, Vizzini G, Politi F, Luca A, Virdone R, Licata A, Pagliaro L. Competing risks and prognostic stages of cirrhosis: a 25-year inception color study of 494 patients. Aliment. Pharmacol. Ther. 2014;39(10):1180-1193. doi: 10.1111/apt.12721.
American Association for the Study of Liver Diseases. Recommendations for Testing, Managing, and Treating Hepatitis C. Available from: https://www.hcvguidelines.org. (accessed 12.10.2017).
European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2014. Available from: http://www.easl.eu/discover/news/easl-recommendationson-treatment-of-hepatitis-c-2014. (accessed 12.10.2017).
Morgan TR, Ghany MG, Kim HY, Snow KK, Shiffman ML, De Santo JL, Lee WM, Di Bisceglie AM, Bonkovsky HL, Dienstag JL, Morishima C, Lindsay KL, Lok AS; HALT-C Trial Group. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52(3):833-844. doi: 10.1002/hep.23744.
van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Heathcote EJ, Manns MP, Kuske L, Zeuzem S, Hofmann WP, de Knegt RJ, Hansen BE, Janssen HL. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584-2593. doi: 10.1001/jama.2012.144878.
Morisco F, Granata R, Stroffolini T, Guarino M, Donnarumma L, Gaeta L, Loperto I, Gentile I, Auriemma F, Caporaso N. Morisco F. Sustained virological response: a milestone in the treatment of chronic hepatitis C. World J. Gastroenterol. 2013;19(18):2793-2798. doi: 10.3748/wjg.v19. i18.2793.
Iacobellis A, Ippolito A, Andriulli A. Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition. World J. Gastroenterol. 2008;14(42):6467-6472.
Boccaccio V, Bruno S. Management of HCV patients with cirrhosis with direct acting antivirals. Liver Int. 2014;34(suppl. 1):38-45. doi: 10.1111/liv.12391.
Faria R, Woods B, Griffin S, Palmer S, Sculpher M, Ryder SD. Prevention of progression to cirrhosis in hepatitis C with fibrosis: effectiveness and cost effectiveness of sequential therapy with new direct-acting antivirals. Aliment. Pharmacol. Ther. 2016;44(8):866-876. doi: 10.1111/apt.13775.
Reddy KR, Lim JK, Kuo A, Di Bisceglie AM, Galati JS, Morelli G, Everson GT, Kwo PY, Brown RS Jr, Sulkowski MS, Akuschevich L, Lok AS, Pockros PJ, Vainorius M, Terrault NA, Nelson DR, Fried MW, Manns MP; HCV-TARGET Study Group. All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database. Aliment. Pharmacol. Ther. 2017;45(1):115-126. doi: 10.1111/apt.13823.
D’Ambrosio R, Degasperi E, Colombo M, Aghemo A. Direct-acting antivirals: the endgame for hepatitis C? Curr. Opin. Virol. 2017;24:31-37. doi: 10.1016/j.coviro.2017.03.017.
Pawlotsky JM. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016;151(1):70-86. doi: 10.1053/j.gastro.2016.04.003.
Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, Illeperuma A, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Weiland O, Reesink HW, Ferenci P, Hézode C, Esteban R. Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3. N. Engl. J. Med. 2014;370(21):1993-2001. doi: 10.1056/NEJMoa1316145.
Lawitz E, Rodriguez-Torres M, Cornpropst MT, Denning JM, Clemons D, McNair L, Fang L, Berrey MM, Symonds WT. The effect of hepatic impairment on the pharmacokinetics and antiviral activity of PSI-7977 in hepatitis C infected subjects treated for seven days. J. Hepatol. 2012;56(suppl. 2):S445-S446.
Highlights of prescribing information Sovaldi ® (Sofosbuvir) tablets, for oral use Initial U.S. Approval: 2013. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s004lbl.pdf. (accessed: (12.10.2017.)
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, Jacobson IM, Kowdley KV, Nyberg L, Subramanian GM, Hyland RH, Arterburn S, Jiang D, McNally J, Brainard D, Symonds WT, McHutchison JG, Sheikh AM, Younossi Z, Gane EJ. Sofosbuvir for previously untreated chronic hepatitis C infection. N. Engl. J. Med. 2013;368(20):1878-1887. doi: 10.1056/NEJMoa1214853.
Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383(9916):515-523. doi:10.1016/S0140-6736(13)62121-2.
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N. Engl J. Med. 2014;370(20):1889-1898. doi: 10.1056/NEJMoa1402454.
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N. Engl J. Med. 2014;370(16):1483-1493. doi: 10.1056/ NEJMoa1316366.
Poordad F, Hezode C, Trinh R, Kowdley KV, Zeuzem S, Agarwal K, Shiffman ML, Wedemeyer H, Berg T, Yoshida EM, Forns X, Lovell SS, Da Silva-Tillmann B, Collins CA, Campbell AL, Podsadecki T, Bernstein B. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N. Engl. J. Med. 2014;370(21):1973-1982. doi: 10.1056/NEJMoa1402869.
Nelson DR, Cooper JN, Lalezari JP, Lawitz E, Pockros PJ, Gitlin N, Freilich BF, Younes ZH, Harlan W, Ghalib R, Oguchi G, Thuluvath PJ, Ortiz-Lasanta G, Rabinovitz M, Bernstein D, Bennett M, Hawkins T, Ravendhran N, Sheikh AM, Varunok P, Kowdley KV, Hennicken D, McPhee F, Rana K, Hughes EA; ALLY-3 Study Team. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61(4):1127-1135. doi: 10.1002/hep.27726.
Leroy V, Angus P, Bronowicki JP, Dore GJ, Hezode C, Pianko S, Pol S, Stuart K, Tse E, McPhee F, Bhore R, Jimenez-Exposito MJ, Thompson AJ. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+). Hepatology. 2016;63(5):1430-1441. doi: 10.1002/hep.28473.
Li G, De Clercq E. Current therapy for chronic hepatitis C: The role of direct-acting antivirals. Antiviral Res. 2017;142:83-122. doi: 10.1016/j.antiviral.2017.02.014.
Welzel TM, Petersen J, Herzer K, Ferenci P, Gschwantler M, Wedemeyer H, Berg T, Spengler U, Weiland O, van der Valk M, Rockstroh J, Peck-Radosavljevic M, Zhao Y, Jimenez-Exposito MJ, Zeuzem S. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut. 2016;65(11):1861-1870. doi: 10.1136/gutjnl-2016-312444.
FDA Drug Safety Communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie. Available from: http://www.fda.gov/Drugs/DrugSafety/ ucm468634.htm. (accessed: 12.10.2017).
Guarino M, Morisco F, Valvano MR, Ippolito AM, Librandi M, Andriulli N, Greco M, Amoruso A, Iacobellis A, Niro G, Caporaso N, Andriulli A. Systematic review: interferonfree regimens for patients with HCV-related Child C cirrhosis. Aliment. Pharmacol. Ther. 2017;45(9):1193-1200. doi: 10.1111/apt.14017.
Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, Díaz A, Vilana R, Darnell A, Varela M, Sangro B, Calleja JL, Forns X, Bruix J. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J. Hepatol. 2016;65:719-726. doi: 10.1016/j.jhep.2016.04.008.
Kozbial K, Moser S, Schwarzer R, Laferl H, Al-Zoairy R, Stauber R, Stättermayer AF, Beinhardt S, Graziadei I, Freissmuth C, Maieron A, Gschwantler M, Strasser M, Peck-Radosalvjevic M, Trauner M, Hofer H, Ferenci P. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment. J. Hepatol. 2016;65(4):856-858. doi: 10.1016/j.jhep.2016.06.009.
ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CirVir and CO23 CUPILT cohorts). Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts. J. Hepatol. 2016;65(4):734-740. doi: 10.1016/j.jhep.2016.05.045.
Virlogeux V, Pradat P, Hartig-Lavie K, Bailly F, Maynard M, Ouziel G, Poinsot D, Lebossé F, Ecochard M, Radenne S, Benmakhlouf S, Koffi J, Lack P, Scholtes C, Uhres AC, Ducerf C, Mabrut JY, Rode A, Levrero M, Combet C, Merle P, Zoulim F. Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C. Liver Int. 2017;37(8):1122-1127. doi: 10.1111/liv.13456.
Prenner SB, VanWagner LB, Flamm SL, Salem R, Lewandowski RJ, Kulik L. Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with directacting antivirals. J. Hepatol. 2017;66(6):1173-1181. doi: 10.1016/j.jhep.2017.01.020.
Beste LA, Green PK, Berry K, Kogut MJ, Allison SK, Ioannou GN. Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J. Hepatol. 2017;67(1):32-39. doi: 10.1016/j.jhep.2017.02.027.
Bruno S, Di Marco V, Iavarone M, Roffi L, Boccaccio V1, Crosignani A, Cabibbo G, Rossi S, Calvaruso V, Aghemo A, Giacomelli L, Craxì A, Colombo M, Maisonneuve P. Improved survival of patients with hepatocellular carcinoma and compensated HCV-related cirrhosis who attained SVR. Liver Int. 2017;37(10):1526-1534. doi: 10.1111/liv.13452.
Webster DP, Klenerman P, Dusheiko GM. Hepatitis C. Lancet. 2015;385(9973):1124-1135. doi: 10.1016/S0140-6736(14)62401-6.
Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnù L, Mazzella G, Ascione A, Santantonio T, Piccinino F, Andreone P, Mangia A, Gaeta GB, Persico M, Fagiuoli S, Almasio PL; Italian Association of the Study of the Liver Disease (AISF). Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007;45:579-587. doi: 10.1002/hep.21492.
1.png)
