Article information
Abstract
Background and objectives
Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma.
MethodsA cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy.
ResultsThe mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55%) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3%) vs. 8 (17%) responders and non responders respectively (p = 0.02).
ConclusionPatients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.
Keywords:
hepatocellular carcinoma
HCV interferon
sustained virologic response
cirrhosis
Full text is only aviable in PDF
References
[1.]
J.M. Llovet, A. Burroughs, J. Bruix.
Hepatocellular carcinoma.
Lancet, 362 (2003), pp. 1907-1917
[2.]
K.A. McGlynn, H.B. El Serag.
Global epidemiology of hepatocellular carcinoma.
Hepatocellular Carcinoma, pp. 1-21
[3.]
G. Fattovich, T. Stroffolini, I. Zagni, F. Donato.
Hepatocellular carcinoma in cirrhosis: incidence and risk factors.
Gastroenterology, 127 (2004), pp. S35-S50
[4.]
L. Benvegnu, M. Gios, S. Boccato, A. Alberti.
Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications.
Gut, 53 (2004), pp. 744-749
[5.]
T. Poynard, P. Marcellin, S.S. Lee, et al.
Randomized trial of interferon- alfa-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon-alfa-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus.
Lancet, 352 (1998), pp. 1426-1430
[6.]
J.G. McHutchison, S.C. Gordon, E. Schiff, et al.
Interferon-alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N.
Engl J Med, 339 (1998), pp. 1485-1489
[7.]
M.W. Fried, M.L. Shiffman, K.R. Reddy, et al.
Peginterferon-alfa-2a plus ribavirin for chronic hepatitis C virus infection.
N Engl J Med, 347 (2002), pp. 975-982
[8.]
M.P. Manns, J.G. McHutchison, S.C. Gordon, et al.
Peginterferonalfa-2b plus ribavirin compared with interferon-alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.
Lancet, 358 (2001), pp. 958-965
[9.]
E.J. Heathcote, M.L. Shiffman, W.G. Cooksley, et al.
Peginterferonalfa- 2a in patients with chronic hepatitis C and cirrhosis.
N Engl J Med, 343 (2000), pp. 1673-1680
[10.]
S. Nishiguchi, S. Shiomi, S. Nakatani, et al.
Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis.
Lancet, 357 (2001), pp. 196-197
[11.]
T. Poynard, J. Moussalli, V. Ratziu, et al.
Is antiviral treatment (IFN-alpha and/or ribavirin) justified in cirrhosis related to hepatitis C virus?.
Acta Gastroenterol Belg, 4 (1998), pp. 1-37
[12.]
G.V. Papatheodoridis, V. Papadimitropoulos, S.J. Hadzyiannis.
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 (2001), pp. 689-698
[13.]
C. Cammà, M. Giunta, P. Andreone, A. Craxi.
Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.
J Hepatol, 34 (2001), pp. 593-602
[14.]
A. Craxi, C. Cammà.
Prevention of hepatocellular carcinoma.
Clin Liv Dis, 9 (2005), pp. 329-346
[15.]
P. Bedossa, T. Poynard.
An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.
Hepatology, 24 (1996), pp. 289-293
[16.]
J. Bruix, M. Sherman, Llovet, et al.
Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference.
J Hepatol, 35 (2001), pp. 421-430
[17.]
M. Szklo, F.J. Nieto.
Measuring Associations between Exposures and Outcomes.
Epidemiology: Beyond the Basics, 2nd ed., pp. 77-104
[18.]
S.S. Thorgeirsson, J.W. Grisham.
Molecular pathogenesis of hepatocellular carcinoma.
Nat Genet, 31 (2002), pp. 339-346
[19.]
S. Nishiguchi, T. Kuroki, S. Nakatani, et al.
Randomised trial of effects of interferon-alfa on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.
Lancet, 346 (1995), pp. 1051-1055
[20.]
G. Mazzella, E. Accogli, S. Sottili, et al.
Alpha-interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.
J Hepatol, 24 (1996), pp. 141-147
[21.]
International Interferon-alpha Hepatocellular Carcinoma Study Group.
Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.
Lancet, 351 (1998), pp. 1535-1539
[22.]
Y. Imai, S. Kawata, S. Tamura, et al.
for the Osaka Hepatocellular Carcinoma Prevention Study Group. Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C.
Ann Intern Med, 129 (1998), pp. 94-99
[23.]
SerfatyL, H. Aumaître, O. Chazouillères, et al.
Determinants of outcome of compensated hepatitis C virus-related cirrhosis.
Hepatology, 27 (1998), pp. 1435-1440
[24.]
S. Sofia, A. Casali, E. Buscarini.
Effect of lymphoblastoid IFN in the treatment of liver cirrhosis and prevention of HCC.
Ital. J. Gastroenterol Hepatol, 30 (1998), pp. A31
[25.]
L. Benvegnù, L. Chemello, F. Noventa, et al.
Retrospective analysis of the effect of interferon therapy on the clinical outcome of patients with viral cirrhosis.
Cancer, 83 (1998), pp. 901-909
[26.]
A. Shioda, M. Moriyama, M. Kaneko.
Long-term prognosis of hepatocellular carcinoma developing after treatment of interferon in patients with chronic hepatitis C and liver cirrhosis.
Hepatology, 30 (1999), pp. 268A
[27.]
H. Yoshida, Y. Shiratori, M. Moriyama, 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 (1999), pp. 174-181
[28.]
D. Mura, R. Deliperi, L. Fastame.
Five year follow-up after Interferon therapy in HCV-positive compensated cirrhosis.
Ital J.Gastroenterol Hepatol, 30 (1998), pp. A114
[29.]
D-C. Valla, M. Chevallier, P. Marcellin, et al.
Treatment of hepatitis C virus-related cirrhosis: a randomized controlled trial of interferon-alfa-2b versus no treatment.
Hepatology, 29 (1999), pp. 1870-1875
[30.]
K. Ikeda, S. Saitoh, Y. Suzuki, et al.
Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus.
Cancer, 82 (1998), pp. 827-835
[31.]
A. Kasahara, N. Hayashi, K. Mochizuki, et al.
Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C.
Hepatology, 27 (1998), pp. 1394-1402
[32.]
I. Miyajima, M. Sata, R. Kumashiro, et al.
The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment.
Oncol Rep, 5 (1998), pp. 201-204
[33.]
K. Ikeda, S. Saitoh, I. Koida, et al.
A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis.
Hepatology, 18 (1993), pp. 47-53
[34.]
International Interferon-alpha Hepatocellular Carcinoma Study Group.
Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.
Lancet, 351 (1998), pp. 1535-1539
[35.]
N. Ghebranious, S. Sell.
Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice.
Hepatology, 27 (1998), pp. 383-439
[36.]
Z. Sun, P. Lu, M.H. Gail, et al.
Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1.
Hepatology, 30 (1999), pp. 379-383
Copyright © 2010. Elsevier Editora Ltda.. All rights reserved
