Abstract
Treatment of patients with hepatitis-B-related or hepatitis-C-related decompensated cirrhosis should focus on controlling the complications of cirrhosis, surveillance for hepatocellular carcinoma and, if applicable, preparation for orthotopic liver transplant. Interferon-based regimens for the treatment of hepatitis C have been somewhat successful in patients with cirrhosis, although treatment of patients with decompensated cirrhosis should be approached with caution. Given the potential for exacerbation of decompensation and poor tolerance of adverse effects, treatment should be reserved for those patients awaiting liver transplantation. Eradication of HCV before liver transplantation reduces the chances of recurrent hepatitis C infection after transplant. HBV can be treated with few adverse effects in patients with decompensated cirrhosis. This treatment is associated with improvement in decompensation in some patients. Hepatocellular carcinoma remains a significant risk in all patients with cirrhosis, and control of or eradication of HBV or HCV does not remove this risk.
Key Points
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Treating patients with hepatitis-B-related or hepatitis-C-related decompensated cirrhosis is challenging
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Interferon-based regimens for the treatment of hepatitis C in patients with decompensated liver disease should be approached with caution
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Eradication of HCV before liver transplantation can potentially prevent recurrence of HCV post-transplantation
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Oral therapy for the treatment of hepatitis B in patients with decompensated cirrhosis is highly effective in suppressing HBV
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Patients with hepatitis B who have a virologic response on oral therapies may experience an improvement in their decompensation after control of the virus
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The risk of developing hepatocellular carcinoma is high for patients with hepatitis B or C and cirrhosis; surveillance should continue even if the virus is effectively controlled
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References
Valla, D. C. et al. Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment. Hepatology 6, 1870–1875 (1999).
Manns, M. P. et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 358, 958–965 (2001).
Hadziyannis, S. J. et al. Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin. Ann. Intern. Med. 140, 346–355 (2004).
Fried, M. W. et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347, 975–982 (2002).
Everson, G. T. et al. Efficacy of interferon treatment for patients with chronic hepatitis C: comparison of response in cirrhotics, fibrotics, or nonfibrotics. Hepatology 30, 271–276 (1999).
Heathcote, E. J. et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N. Engl. J. Med. 343, 1673–1680 (2000).
Helbling, B. et al. HCV-related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferon alfa-2a and ribavirin. J. Viral Hepat. 13, 762–769 (2006).
Di Marco, V. et al. Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension: A randomized controlled trial. J. Hepatol. 47, 484–491 (2007).
Giannini, E. G., Basso, M., Savarino, V. & Picciotto, A. Predictive value of on-treatment response during full-dose antiviral therapy of patients with hepatitis C virus cirrhosis and portal hypertension. J. Intern. Med. 266, 537–546 (2009).
Crippin, J. S. et al. A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation. Liver Transpl. 8, 350–255 (2002).
Forns, X. et al. Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. J. Hepatol. 39, 389–296 (2003).
Everson, G. T. et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 42, 255–262 (2005).
Thomas, R. M. et al. Infection with chronic hepatitis C virus and liver transplantation: a role for interferon therapy before transplantation. Liver Transpl. 9, 905–915 (2003).
Carrión, J. A. et al. Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: a retrospective study. J. Hepatol. 50, 719–728 (2009).
Everhart, J. E. et al. Recurrent and new hepatitis C virus infection after liver transplantation. Hepatology 29, 1220–1226 (1999).
Charlton, M. et al. Predicators of patient and graft survival following liver transplantation for hepatitis C. Hepatology, 28, 823–830 (1998).
Wiesner, R. H., Sorrell, M., Villamil, F. and the International Liver Transplantation Society Expert Panel. Report of the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. Liver Transpl. 9, S1–S9 (2003).
Veldt, B. J. et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann. Intern. Med. 147, 677–684 (2007).
Everson, G. T. et al. Histological benefits of virological response to peginterferon alfa-2a monotherapy in patients with hepatitis C and advanced fibrosis or compensated cirrhosis. Aliment. Pharmacol. Ther. 27, 542–551 (2008).
Di Bisceglie, A. M. et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N. Engl. J. Med. 359, 2429–2441 (2008).
Shiffman, M. L. et al. Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial. Gastroenterology 137, 1986–1994 (2009).
Morgan, T. R. et al. Outcome of sustained virologic responders with histologically advanced chronic hepatitis C. Hepatology 52, 833–844 (2010).
Serfaty, L. et al. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology 27, 1435–1440 (1998).
Hu, K. & Tong, M. J. The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology 29, 1311–1316 (1999).
Fontana, R. J. et al. Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C. Gastroenterology 138, 2321–2331 (2010).
Bruno, S. et al. Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am. J. Gastroenterol. 104, 1147–1158 (2009).
Masuzaki, R., Yoshida, H. & Omata, M. Interferon reduces the risk of hepatocellular carcinoma in hepatitis C virus-related chronic hepatitis/liver cirrhosis. Oncology 78, 17–23 (2010).
Yoshida, H. et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann. Intern. Med. 131, 174–181 (1999).
Papatheodoridis, G. V., Papdimitropoulos, V. C. & Haziyannis, S. J. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta analysis. Aliment. Pharmacol. Ther. 15, 689–698 (2001).
Camma, C. et al. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J. Hepatol. 34, 593–602 (2001).
Scherzer, T. M. et al. Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C. J. Viral. Hepat. 15, 659–665 (2008).
Bacon, B. R. et al. Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology 49, 1838–1846 (2009).
Ge, D. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461, 399–401 (2009).
Tanaka, Y. et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat. Genet. 41, 1105–1109 (2009).
McHutchison, J. G. et al. Telaprevir for previously treated chronic HCV infection. N. Engl. J. Med. 362, 1292–1303 (2010).
Kwo, P. Y. et al. Efficacy of boceprevir, an NS3 protease inhibitor in combination with peginterferon alfa-2b and ribavirin in treatment-naïve patients with genotype 1hepatitis C infection (SPRINT-1): an open label, randomized, multicentre phase 2 trial. Lancet 376, 705–716 (2010).
Sarrazin, C. et al. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon α-2b for genotype 1 nonresponders. Gastroenterology 132, 1270–1278 (2007).
Ghany, M. G., Strader, D. B., Thomas, D. L. & Seeff, L. B. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 49, 1335–1374 (2009).
Nishida, T. et al. A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis. J. Gastroenterol. Hepatol. 23, 794–803 (2007).
Liaw, Y., Lee, C., Chien, R. & Yeh, C. Switching to adefovir monotherapy after emergence of lamivudine-resistant mutations in patients with liver cirrhosis. J. Viral. Hepat. 13, 250–255 (2006).
Schiff, E. et al. Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine resistant hepatitis B: final long-term results. Liver Transpl. 13, 349–360 (2007).
Zoulim, F. et al. Adefovir dipivoxil is effective for the treatment of cirrhotic patients with lamivudine failure. Liver Int. 29, 420–426 (2009).
Shim, J. H. et al. Efficacy of entecavir in treatment-naïve patients with hepatitis B virus-related decompensated cirrhosis. J. Hepatol. 52, 176–182 (2010).
Buster, E. H. et al. Peginterferon alpha-2b is safe and effective in HbeAg-positive chronic hepatitis B patients with advanced fibrosis. Hepatology 46, 388–394 (2007).
Kim, J. D. et al. Hepatitis B virus load in serum does not reflect histologic activity in patients with decompensated cirrhosis. Clin. Gastroenterol. Hepatol. 1, 60–65 (2010).
Yang, J. D. et al. Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma. Clin. Gastroenterol. Hepatol. 9, 64–70 (2010).
Fontana, F. J. et al. Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy. Gastroenterology 123, 719–727 (2002).
Das, K. et al. Course of disease and survival after onset of decompensation in hepatits B virus-related cirrhosis. Liver Int. 7, 1033–1041 (2010).
European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J. Hepatol. 5, 227–242 (2009).
Lok, A. S. F. & McMahon, B. J. Chronic hepatitis B: update 2009. Hepatology 50, 1–36 (2009).
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C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.
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Fink, S., Jacobson, I. Managing patients with hepatitis-B-related or hepatitis-C-related decompensated cirrhosis. Nat Rev Gastroenterol Hepatol 8, 285–295 (2011). https://doi.org/10.1038/nrgastro.2011.57
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DOI: https://doi.org/10.1038/nrgastro.2011.57