J Korean Med Assoc.  2013 Nov;56(11):1001-1011. 10.5124/jkma.2013.56.11.1001.

Management of viral hepatitis in patients with hepatocellular carcinoma

Affiliations
  • 1Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. garden@catholic.ac.kr

Abstract

Globally, viral hepatitis due to hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection is the major cause of advanced liver diseases such as liver cirrhosis and hepatocellular carcinoma (HCC). Chronic inflammation resulting from persistent viral hepatitis is also associated with an increased risk of HCC recurrence. Replication of HBV and/or HCV can reactivate during anti-cancer treatments of HCC and lead to hepatic dysfunction, adversely affecting patient outcomes. The most effective way to prevent chronic viral hepatitis, cirrhosis, or HCC would be the implementation of a vaccine. Unfortunately, a vaccine for HCV is currently not available. For chronically infected patients, antiviral therapy may be the only option that can prevent or retard disease progression. Emerging evidence continues to support direct or indirect benefits from antiviral therapy for preventing liver disease progression to cirrhosis, HCC development, and recurrence after curative treatments in patients with chronic HBV or HCV infection. This paper reviews the literature on the management of viral hepatitis in patients with HCC, focusing on primary and tertiary prevention of HCC.

Keyword

Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Management

MeSH Terms

Carcinoma, Hepatocellular*
Disease Progression
Fibrosis
Hepacivirus
Hepatitis B virus
Hepatitis*
Humans
Inflammation
Liver Cirrhosis
Liver Diseases
Recurrence
Tertiary Prevention

Figure

  • Figure 1 Reported rates of hepatitis B virus (HBV) reactivation during therapies for hepatocellular carcinoma. *The rates of viral reactivation occurring during intensive transarterial chemotherapy.

  • Figure 2 Pooled data from meta-analyses on the preventive effects of interferon therapy on hepatocellular carcinoma (HCC) recurrence after curative treatment of hepatitis C virus-related HCC. IFN, interferon.


Reference

1. Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004; 127:5 Suppl 1. S5–S16.
Article
2. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ. Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002; 347:168–174.
Article
3. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH. REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006; 295:65–73.
Article
4. Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology. 1999; 29:971–975.
Article
5. Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YF. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol. 2007; 46:45–52.
Article
6. Yuen MF, Hui CK, Cheng CC, Wu CH, Lai YP, Lai CL. Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: the effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications. Hepatology. 2001; 34:139–145.
Article
7. Cammà C, Giunta M, Andreone P, Craxi A. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol. 2001; 34:593–602.
Article
8. Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008; 28:1067–1077.
Article
9. Yang YF, Zhao W, Zhong YD, Xia HM, Shen L, Zhang N. Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta-analysis. J Viral Hepat. 2009; 16:265–271.
Article
10. Jin H, Pan N, Mou Y, Wang B, Liu P. Long-term effect of interferon treatment on the progression of chronic hepatitis B: Bayesian meta-analysis and meta-regression. Hepatol Res. 2011; 41:512–523.
Article
11. Lai CL, Yuen MF. Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy. Hepatology. 2013; 57:399–408.
Article
12. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J. Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004; 351:1521–1531.
Article
13. Eun JR, Lee HJ, Kim TN, Lee KS. Risk assessment for the development of hepatocellular carcinoma: according to on-treatment viral response during long-term lamivudine therapy in hepatitis B virus-related liver disease. J Hepatol. 2010; 53:118–125.
Article
14. Papatheodoridis GV, Lampertico P, Manolakopoulos S, Lok A. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010; 53:348–356.
Article
15. Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology. 2006; 43:209–220.
Article
16. Jang JW. Management of patients with hepatitis B virus infection who receive immunosuppressive treatment or chemotherapy. Korean J Med. 2012; 82:149–158.
Article
17. Jang JW, Choi JY, Bae SH, Yoon SK, Chang UI, Kim CW, Cho SH, Han JY, Lee YS. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemolipiodolization. Hepatology. 2006; 43:233–240.
Article
18. Huang L, Li J, Yan J, Sun J, Zhang X, Wu M, Yan Y. Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial. J Viral Hepat. 2013; 20:336–342.
Article
19. Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006; 132:458–465.
Article
20. Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, Fan ST, Wong J. A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg. 2007; 245:831–842.
Article
21. Huang TS, Shyu YC, Chen HY, Yuan SS, Shih JN, Chen PJ. A systematic review and meta-analysis of adjuvant interferon therapy after curative treatment for patients with viral hepatitis-related hepatocellular carcinoma. J Viral Hepat. 2013; 20:729–743.
Article
22. Sun P, Yang X, He RQ, Hu QG, Song ZF, Xiong J, Zheng QC. Antiviral therapy after curative treatment of hepatitis B/C virus-related hepatocellular carcinoma: a systematic review of randomized trials. Hepatol Res. 2013; 04. 02. [Epub]. DOI: 10.1111/hepr.12115.
Article
23. Wong JS, Wong GL, Tsoi KK, Wong VW, Cheung SY, Chong CN, Wong J, Lee KF, Lai PB, Chan HL. Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma. Aliment Pharmacol Ther. 2011; 33:1104–1112.
Article
24. Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS, Lin JT. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA. 2012; 308:1906–1914.
Article
25. Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995; 346:1051–1055.
Article
26. Lok AS, Everhart JE, Wright EC, Di Bisceglie AM, Kim HY, Sterling RK, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Morgan TR. HALT-C Trial Group. Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C. Gastroenterology. 2011; 140:840–849.
Article
27. Bruix J, Poynard T, Colombo M, Schiff E, Burak K, Heathcote EJ, Berg T, Poo JL, Mello CB, Guenther R, Niederau C, Terg R, Bedossa P, Boparai N, Griffel LH, Burroughs M, Brass CA, Albrecht JK. EPIC3 Study Group. Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C. Gastroenterology. 2011; 140:1990–1999.
Article
28. Papatheodoridis GV, Papadimitropoulos VC, Hadziyannis SJ. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis. Aliment Pharmacol Ther. 2001; 15:689–698.
Article
29. Craxì A, Camma C. Prevention of hepatocellular carcinoma. Clin Liver Dis. 2005; 9:329–346.
Article
30. Singal AK, Singh A, Jaganmohan S, Guturu P, Mummadi R, Kuo YF, Sood GK. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol. 2010; 8:192–199.
Article
31. Kimer N, Dahl EK, Gluud LL, Krag A. Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2012; 2:[Epub]. DOI: 10.1136/bmjopen-2012-001313.
Article
32. Miyake Y, Iwasaki Y, Yamamoto K. Meta-analysis: reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C. Int J Cancer. 2010; 127:989–996.
Article
33. Sung PS, Bae SH, Jang JW, Song do S, Kim HY, Yoo SH, Park CH, Kwon JH, Song MJ, You CR, Choi JY, Yoon SK. Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization. Korean J Hepatol. 2011; 17:299–306.
Article
34. Ikeda K, Arase Y, Saitoh S, Kobayashi M, Suzuki Y, Suzuki F, Tsubota A, Chayama K, Murashima N, Kumada H. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer. Hepatology. 2000; 32:228–232.
Article
35. Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Shuto T, Yamazaki O, Shiomi S, Tamori A, Oka H, Igawa S, Kuroki T, Kinoshita H. Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial. Ann Intern Med. 2001; 134:963–967.
Article
36. Shiratori Y, Shiina S, Teratani T, Imamura M, Obi S, Sato S, Koike Y, Yoshida H, Omata M. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med. 2003; 138:299–306.
Article
37. Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, Capussotti L, Calise F, Pellicci R, Belli G, Tagger A, Colombo M, Bonino F, Majno P, Llovet JM. HCC Italian Task Force. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006; 44:1543–1554.
Article
38. Lin SM, Lin CJ, Hsu CW, Tai DI, Sheen IS, Lin DY, Liaw YF. Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors. Cancer. 2004; 100:376–382.
Article
39. Singal AK, Freeman DH Jr, Anand BS. Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma. Aliment Pharmacol Ther. 2010; 32:851–858.
Article
40. Miyake Y, Takaki A, Iwasaki Y, Yamamoto K. Meta-analysis: interferon-alpha prevents the recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. J Viral Hepat. 2010; 17:287–292.
Article
41. Hsu YC, Ho HJ, Wu MS, Lin JT, Wu CY. Postoperative peginterferon plus ribavirin is associated with reduced recurrence of hepatitis C virus-related hepatocellular carcinoma. Hepatology. 2013; 58:150–157.
Article
Full Text Links
  • JKMA
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr