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Clinical Drug Investigation
Published in: Clinical Drug Investigation 12/2015

01-12-2015 | Short Communication

Achieving Sustained Virological Response in Hepatitis C Reduces the Long-Term Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis Employing Relative and Absolute Outcome Measures

Authors: Andrea Messori, Brigitta Badiani, Sabrina Trippoli

Published in: Clinical Drug Investigation | Issue 12/2015

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Abstract

Background and Objectives

We studied the effect of achieving sustained virological response (SVR) on the risk of developing hepatocellular carcinoma (HCC) in patients with hepatitis C receiving anti-hepatitis C virus treatment. Avoiding HCC is considered the main long-term benefit of successful antiviral treatment.

Methods

Our literature search extended up to June 2015. We identified all studies that assessed the risk of HCC in patients achieving or not achieving SVR. Meta-analysis was based on a standard random-effect model. The end-point was occurrence of HCC compared between patients with and without SVR; this end-point was expressed as an odds ratio and percent reduction in risk and was also presented separately for patients with and without cirrhosis. All results estimates presented with 95 % confidence intervals (CIs). The presence of any temporal trend in these indexes was investigated by standard meta-regression.

Results

Our search identified 25 observational studies (19,822 patients). The odds ratio of HCC for SVR versus no-SVR was 0.19 (95 % CI 0.15–0.24) in the overall series of 25 studies. The difference in this index between patients with any stage of fibrosis/cirrhosis and those with cirrhosis was small. With regard to risk difference, the 25 studies indicated an overall reduction of 10 % (95 % CI 8.00–12.0); this effect was much less pronounced in the group with any stage of fibrosis/cirrhosis (risk difference 6.7 %) than in the selected group with cirrhosis (risk difference 22 %). Meta-regression showed no temporal trend.

Conclusion

Our analysis was successful in providing an updated overview on this controversial topic. Some pharmacoeconomic assessments are also presented to interpret the clinical results of our analysis.
Literature
1.
Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158:329–37.CrossRefPubMed
2.
Viswanathan M, Berkman ND, Dryden DM, et al. Assessing risk of bias and confounding in observational studies of interventions or exposures: further development of the RTI Item Bank [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013.
3.
4.
5.
Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology. 2010;52:518–27.CrossRefPubMed
6.
Braks RE, Ganne-Carrie N, Fontaine H, Paries J, Grando-Lemaire V, Beaugrand M, et al. Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin. World J Gastroenterol. 2007;13:5648–53.PubMedCentralCrossRefPubMed
7.
Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnù L, Mazzella G, et al. 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;45:579–87.CrossRefPubMed
8.
Cardoso AC, Moucari R, Figueiredo-Mendes C, Ripault MP, Giuily N, Castelnau C, Boyer N, Asselah T, Martinot-Peignoux M, Maylin S, Carvalho-Filho RJ, Valla D, Bedossa P, Marcellin P. Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: incidence and survival in hepatitis C patients with advanced fibrosis. J Hepatol. 2010;52(5):652–7. doi:10.​1016/​j.​jhep.​2009.​12.​028 (Epub 2010 Mar 4).CrossRefPubMed
9.
Dieperink E, Pocha C, Thuras P, Knott A, Colton S, Ho SB. All-cause mortality and liver-related outcomes following successful antiviral treatment for chronic hepatitis C. Dig Dis Sci. 2014;59(4):872–80. doi:10.​1007/​s10620-014-3050-5 (Epub 2014 Feb 15).CrossRefPubMed
10.
Dohmen K, Kawano A, Takahashi K, Shigematsu H, Tanaka H, Haruno M, Yanagita K, Ichiki Y, Mori T, Hayashida K, Shimoda S, Ishibashi H, Nomura H. The incidence and risk factors for the development of hepatocellular carcinoma after peginterferon plus ribavirin therapy for chronic hepatitis C. Hepatogastroenterology 2013;60(128):2034–8.
11.
Harada N, Hiramatsu N, Oze T, Morishita N, Yamada R, Hikita H, Miyazaki M, Yakushijin T, Miyagi T, Yoshida Y, Tatsumi T, Kanto T, Kasahara A, Oshita M, Mita E, Hagiwara H, Inui Y, Katayama K, Tamura S, Yoshihara H, Imai Y, Inoue A, Hayashi N, Takehara T. Risk factors for hepatocellular carcinoma in hepatitis C patients with normal alanine aminotransferase treated with pegylated interferon and ribavirin. J Viral Hepat. 2014;21(5):357–65. doi:10.​1111/​jvh.​12151 (Epub 2013 Aug 25).CrossRefPubMed
12.
Hasegawa E, Kobayashi M, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, et al. Efficacy and anticarcinogenic activity of interferon for hepatitis C virus related compensated cirrhosis in patients with genotype 1b low viral load or genotype 2. Hepatol Res. 2007;37:793–800.CrossRefPubMed
13.
Hung CH, Lee CM, Lu SN, Wang JH, Hu TH, Tung HD, et al. Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. J Viral Hepat. 2006;13:409–14.CrossRefPubMed
14.
Hung CH, Lee CM, Wang JH, Hu TH, Chen CH, Lin CY, et al. Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon-based antiviral therapy. Int J Cancer. 2011;128:2344–52.CrossRefPubMed
15.
Kawamura Y, Arase Y, Ikeda K, Hirakawa M, Hosaka T, Kobayashi M, et al. Diabetes enhances hepatocarcinogenesis in noncirrhotic, interferon-treated hepatitis C patients. Am J Med. 2010;123:951–6.e1.
16.
Kramer JR, Davila JA, Duan Z, Richardson PA, Kanwal F, El-Serag H. Antiviral treatment for hepatitis C virus is associated with a reduced risk of hepatocellular carcinoma in a national cohort of U.S. veterans. Presented at Digestive Disease Week 2011, 7–11 May 2011, Chicago. Gastroenterology. 2011;140(5 Suppl 1):S899.
17.
Kurokawa M, Hiramatsu N, Oze T, Mochizuki K, Yakushijin T, Kurashige N, et al. Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis. Hepatol Res. 2009;39:432–8.CrossRefPubMed
18.
Lee SS, Jeong SH, Jang ES, Kim YS, Lee YJ, Jung EU, Kim IH, Bae SH, Lee HC, Kee MK, Kang C. A prospective cohort study on the outcomes of hepatitis C virus-related cirrhosis in South Korea. J Gastroenterol Hepatol. 2015. doi:10.​1111/​jgh.​12950 (Epub ahead of print).
19.
Morgan TR, Ghany MG, Kim HY, Snow KK, Shiffman ML, De Santo JL, et al.; HALT-C Trial Group. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 2010;52:833–44.
20.
Okanoue T, Itoh Y, Kirishima T, Daimon Y, Toyama T, Morita A, et al. Transient biochemical response in interferon therapy decreases the development of hepatocellular carcinoma for five years and improves the long-term survival of chronic hepatitis C patients. Hepatol Res. 2002;23:62–77.CrossRefPubMed
21.
Osaki Y, Ueda Y, Marusawa H, Nakajima J, Kimura T, Kita R, et al. Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study. J Gastroenterol. 2012;47:444–51.CrossRefPubMed
22.
Pradat P, Tillmann HL, Sauleda S, Braconier JH, Saracco G, Thursz M, et al; HENCORE Group. Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications. J Viral Hepat. 2007;14:556–63.
23.
Rutter K, Stattermayer AF, Beinhardt S, Scherzer TM, Steindl-Munda P, Trauner M, Ferenci P, Hofer H. Successful anti-viral treatment improves survival of patients with advanced liver disease due to chronic hepatitis C. Aliment Pharmacol Ther. 2015;41(6):521–31. doi:10.​1111/​apt.​13085 (Epub 2015 Jan 23).
24.
Sinn DH, Paik SW, Kang P, Kil JS, Park SU, Lee SY, et al. Disease progression and the risk factor analysis for chronic hepatitis C. Liver Int. 2008;28:1363–9.CrossRefPubMed
25.
Takahashi H, Mizuta T, Eguchi Y, Kawaguchi Y, Kuwashiro T, Oeda S, et al. Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C. J Gastroenterol. 2011;46:790–8.CrossRefPubMed
26.
Tateyama M, Yatsuhashi H, Taura N, Motoyoshi Y, Nagaoka S, Yanagi K, et al. Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol. 2011;46:92–100.CrossRefPubMed
27.
Van der Meer AJ, Hansen BE, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Factors associated with hepatocellular carcinoma in chronic hepatitis C patients with advanced liver fibrosis. J Hepatol. 2012;56(S2):S363–4.
28.
Velosa J, Serejo F, Marinho R, Nunes J, Glória H. Eradication of hepatitis C virus reduces the risk of hepatocellular carcinoma in patients with compensated cirrhosis. Dig Dis Sci. 2011;56:1853–61.CrossRefPubMed
29.
Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med. 1999;131:174–81.CrossRefPubMed
30.
31.
Hartwell D, Jones J, Baxter L, Shepherd J. Peginterferon alfa and ribavirin for chronic hepatitis C in patients eligible for shortened treatment, re-treatment or in HCV/HIV co-infection: a systematic review and economic evaluation. Health Technol Assess 2011;15(17):1–210.CrossRef
32.
33.
Cammà C, Cabibbo G, Petta S, Enea M, Iavarone M, Grieco A, Gasbarrini A, Villa E, Zavaglia C, Bruno R, Colombo M, Craxì A, WEF study group, SOFIA study group. Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma. Hepatology. 2013;57(3):1046–54.CrossRefPubMed
34.
Simmons B, Saleem J, Heath K, Cooke GS, Hill A. Long-term treatment outcomes of patients infected with Hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a Sustained Virological Response. Clin Infect Dis. 2015. pii:civ396 [Epub ahead of print].
Metadata
Title
Achieving Sustained Virological Response in Hepatitis C Reduces the Long-Term Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis Employing Relative and Absolute Outcome Measures
Authors
Andrea Messori
Brigitta Badiani
Sabrina Trippoli
Publication date
01-12-2015
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 12/2015
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-015-0338-y

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