Hepatitis C Virus Mediated Hepatocellular Carcinoma: A Focused Review for a Time of Changing Therapeutic Options

Authors

  • Jesse Civan, MD
  • Hie-Won Hann, MD

Abstract

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality, accounting for approximately 600,000 deaths annually world-wide and 10,000 deaths annually in the United States.  Chronic infection with the hepatitis C virus (HCV) is the leading risk factor for HCC in the United States, and the second leading risk factor for HCC world-wide.  The addition to the anti-HCV treatment armamentarium of boceprevir and telaprevir in 2011, and of simeprevir and sofosbuvir in 2013, mark a transition to a new era.  In this new era, treatment for HCV is becoming so highly effective and tolerable that for the first time eradication of chronic HCV on a population level is realistically foreseeable.  A major reduction in the burden of chronic HCV is likely to translate into a substantial reduction in the incidence of HCC.  Here, we review the epidemiology, pathogenesis, and treatment of HCC with a special focus on hepatocarcinogenesis associated with chronic HCV infection.

References

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a Cancer Journal for Clinicians. 2011;61(2):69-90.

El-Serag HB. Hepatocellular carcinoma: Recent trends in the united states. Gastroenterology. 2004;127(5, Suppl 1):S27-S34.

Sanyal AJ, Yoon SK, Lencioni R. The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist. 2010;15(Suppl 4):14-22.

Szabo E, Paska C, Kaposi Novak P, Schaff Z, Kiss A. Similarities and differences in hepatitis B and C virus induced hepatocarcinogenesis. Pathol Oncol Res. 2004;10(1):5-11.

Gurtsevitch VE. Human oncogenic viruses: Hepatitis B and hepatitis C viruses and their role in hepatocarcinogenesis. Biochemistry (Mosc). 2008;73(5):504-513.

El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264-1273e1.

Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35-$50.

Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332(22):1463-1466.

Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer. 1998;75(3):347-354.

Shi Y, Wu YH, Wu W, Zhang WJ, Yang J, Chen Z. Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: A meta-analysis. Liver Int. 2012;32(2):231-240.

De Mitri MS, Poussin K, Baccarini P, et al. HCV-associated liver cancer without cirrhosis. Lancet. 1995;345(8947):413-415.

Madhoun MF, Fazili J, Bright BC, Bader T, Roberts DN, Bronze MS. Hepatitis C prevalence in patients with hepatocellular carcinoma without cirrhosis. Am J Med Sci. 2010;339(2):169-173.

Bruno S, Silini E, Crosignani A, et al. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: A prospective study. Hepatology. 1997;25(3):754-758.

Stankovic-Djordjevic D, Djordjevic N, Tasic G, Dinic M, Karanikolic A, Pesic M. Hepatitis C virus genotypes and the development of hepatocellular carcinoma. Journal of Digestive Diseases. 2007;8(1):42-47.

Tagger A, Donato F, Ribero ML, et al. Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: The role of HCV genotypes and the synergism with hepatitis B virus and alcohol. brescia HCC study. Int J Cancer. 1999;81(5):695-699.

Nkontchou G, Ziol M, Aout M, et al. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat. 2011;18(10):e516-22.

Hodo Y, Honda M, Tanaka A, et al. Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C. Clinical Cancer Research. 2013;19(7):1827-1837.

Mahmood S, Niiyama G, Kamei A, et al. Influence of viral load and genotype in the progression of hepatitis B-associated liver cirrhosis to hepatocellular carcinoma. Liver International. 2005;25(2):220-225.

Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: Old and new paradigms. Gastroenterology. 2004;127(5 Suppl 1):S56-61.

Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002;2(8):479-486.

Pollicino T, Squadrito G, Cerenzia G, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 2004;126(1):102-110.

Shetty K, Hussain M, Nei L, Reddy KR, Lok AS. Prevalence and significance of occult hepatitis B in a liver transplant population with chronic hepatitis C. Liver Transpl. 2008;14(4):534-540.

Koike K, Kobayashi M, Gondo M, Hayashi I, Osuga T, Takada S. Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients. J Med Virol. 1998;54(4):249-255.

Jilg W, Sieger E, Zachoval R, Schatzl H. Individuals with antibodies against hepatitis B core antigen as the only serological marker for hepatitis B infection: High percentage of carriers of hepatitis B and C virus. J Hepatol. 1995;23(1):14-20.

Raimondo G, Caccamo G, Filomia R, Pollicino T. Occult HBV infection. Semin Immunopathol. 2013;35(1):39-52.

Puoti M, Bruno R, Soriano V, et al. Hepatocellular carcinoma in HIV-infected patients: Epidemiological features, clinical presentation and outcome. AIDS. 2004;18(17):2285-2293.

Brau N, Fox RK, Xiao P, et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: A U.S.-canadian multicenter study. J Hepatol. 2007;47(4):527-537.

Rosenthal E, Poiree M, Pradier C, et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients in france (mortavic 2001 study). AIDS. 2003;17(12):1803-1809.

Garcia-Samaniego J, Rodriguez M, Berenguer J, et al. Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis C. Am J Gastroenterol. 2001;96(1):179-183.

Donato F, Tagger A, Chiesa R, et al. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: A case-control study in italy. brescia HCC study. Hepatology. 1997;26(3):579-584.

Feitelson MA. Hepatitis B virus in hepatocarcinogenesis. J Cell Physiol. 1999;181(2):188-202.

Liang TJ, Heller T. Pathogenesis of hepatitis C-associated hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S62-71.

Bouchard MJ, Navas-Martin S. Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges. Cancer Lett. 2011;305(2):123-143.

Zemel R, Issachar A, Tur-Kaspa R. The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis. 2011;15(2):261-279.

Ahmad J, Eng FJ, Branch AD. HCV and HCC: Clinical update and a review of HCC-associated viral mutations in the core gene. Semin Liver Dis. 2011;31(4):347-355.

El-Serag HB, Rudolph KL. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557-2576.

Yamashita T, Honda M, Kaneko S. Molecular mechanisms of hepatocarcinogenesis in chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2011;26(6):960-964.

Wiemann SU, Satyanarayana A, Tsahuridu M, et al. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J. 2002;16(9):935-942.

Sheikh MY, Choi J, Qadri I, Friedman JE, Sanyal AJ. Hepatitis C virus infection: Molecular pathways to metabolic syndrome. Hepatology. 2008;47(6):2127-2133.

Gong G, Waris G, Tanveer R, Siddiqui A. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci U S A. 2001;98(17):9599-9604.

Okuda M, Li K, Beard MR, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology. 2002;122(2):366-375.

Majumder M, Ghosh AK, Steele R, Ray R, Ray RB. Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. J Virol. 2001;75(3):1401-1407.

Lan KH, Sheu ML, Hwang SJ, et al. HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene. 2002;21(31):4801-4811.

Ishido S, Hotta H. Complex formation of the nonstructural protein 3 of hepatitis C virus with the p53 tumor suppressor. FEBS Lett. 1998;438(3):258-262.

Kittlesen DJ, Chianese-Bullock KA, Yao ZQ, Braciale TJ, Hahn YS. Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. J Clin Invest. 2000;106(10):1239-1249.

Akuta N, Suzuki F, Kawamura Y, et al. Amino acid substitutions in the hepatitis C virus core region are the important predictor of hepatocarcinogenesis. Hepatology. 2007;46(5):1357-1364.

Fishman SL, Factor SH, Balestrieri C, et al. Mutations in the hepatitis C virus core gene are associated with advanced liver disease and hepatocellular carcinoma. Clin Cancer Res. 2009;15(9):3205-3213.

Ura S, Honda M, Yamashita T, et al. Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology. 2009;49(4):1098-1112.

Jain D, Nayak NC, Saigal S. Hepatocellular carcinoma in nonalcoholic fatty liver cirrhosis and alcoholic cirrhosis: Risk factor analysis in liver transplant recipients. Eur J Gastroenterol Hepatol. 2012;24(7):840-848.

Huang JF, Dai CY, Hwang SJ, et al. Hepatitis C viremia increases the association with type 2 diabetes mellitus in a hepatitis B and C endemic area: An epidemiological link with virological implication. Am J Gastroenterol. 2007;102(6):1237-1243.

Hung CH, Wang JH, Hu TH, et al. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World Journal of Gastroenterology. 2010;16(18):2265-2271.

Alberstein M, Zornitzki T, Zick Y, Knobler H. Hepatitis C core protein impairs insulin downstream signalling and regulatory role of IGFBP-1 expression. J Viral Hepat. 2012;19(1):65-71.

Hung CH, Hu TH, Lee CM, et al. Amino acid substitutions in the core region associate with insulin resistance in chronic hepatitis C. Intervirology. 2013;56(3):166-171.

Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer. 2006;6(9):674-687.

Sung WK, Zheng H, Li S, et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet. 2012;44(7):765-769.

Paterlini-Brechot P, Saigo K, Murakami Y, et al. Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene. 2003;22(25):3911-3916.

Saigo K, Yoshida K, Ikeda R, et al. Integration of hepatitis B virus DNA into the myeloid/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma. Hum Mutat. 2008;29(5):703-708.

Murakami Y, Saigo K, Takashima H, et al. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut. 2005;54(8):1162-1168.

Ferber MJ, Montoya DP, Yu C, et al. Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers. Oncogene. 2003;22(24):3813-3820.

Tamori A, Yamanishi Y, Kawashima S, et al. Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA. Clin Cancer Res. 2005;11(16):5821-5826.

Chan C, Wang Y, Chow PK, Chung AY, Ooi LL, Lee CG. Altered binding site selection of p53 transcription cassettes by hepatitis B virus X protein. Mol Cell Biol. 2013;33(3):485-497.

Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: An update. Hepatology. 2011;53(3):1020-1022. doi: 10.1002/hep.24199; 10.1002/hep.24199.

Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: The BCLC update and future prospects. Semin Liver Dis. 2010;30(1):61-74.

European Association For The Study Of The,Liver, European Organisation For Research And Treatment Of,Cancer. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908-943.

Reddy SK, Steel JL, Chen HW, et al. Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology. 2012;55(6):1809-1819.

Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995;346(8982):1051-1055.

Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: A retrospective cohort study. international interferon-alpha hepatocellular carcinoma study group. Lancet. 1998;351(9115):1535-1539.

Imai Y, Kawata S, Tamura S, et al. Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. osaka hepatocellular carcinoma prevention study group. Ann Intern Med. 1998;129(2):94-99.

Valla DC, Chevallier M, Marcellin P, et al. Treatment of hepatitis C virus-related cirrhosis: A randomized, controlled trial of interferon alfa-2b versus no treatment. Hepatology. 1999;29(6):1870-1875.

Fattovich G, Giustina G, Degos F, et al. Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. european concerted action on viral hepatitis (EUROHEP). J Hepatol. 1997;27(1):201-205.

Mazzella G, Accogli E, Sottili S, et al. Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis. J Hepatol. 1996;24(2):141-147.

Benvegnu L, Chemello L, Noventa F, Fattovich G, Pontisso P, Alberti A. Retrospective analysis of the effect of interferon therapy on the clinical outcome of patients with viral cirrhosis. Cancer. 1998;83(5):901-909.

Serfaty L, Aumaitre H, Chazouilleres O, et al. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology. 1998;27(5):1435-1440.

Yoshida H, Shiratori Y, Moriyama 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(3):174-181.

Okanoue T, Itoh Y, Minami M, et al. Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: A retrospective study in 1148 patients. viral hepatitis therapy study group. J Hepatol. 1999;30(4):653-659.

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(5):689-698.

Ng V, Saab S. Effects of a sustained virologic response on outcomes of patients with chronic hepatitis C. Clinical Gastroenterology & Hepatology. 2011;9(11):923-930.

Arase Y, Ikeda K, Suzuki F, et al. Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C. Intervirology. 2007;50(1):16-23.

Bruno S, Stroffolini T, Colombo M, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: A retrospective study. Hepatology. 2007;45(3):579-587.

Coverdale SA, Khan MH, Byth K, et al. Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study. Am J Gastroenterol. 2004;99(4):636-644.

Hung CH, Lee CM, Lu SN, 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(6):409-414.

Kobayashi S, Takeda T, Enomoto M, et al. Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: A multicenter, retrospective cohort study of 1124 patients. Liver Int. 2007;27(2):186-191.

Tanaka H, Tsukuma H, Kasahara A, et al. Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: A retrospective cohort study of 738 patients. Int J Cancer. 2000;87(5):741-749.

Hirakawa M, Ikeda K, Arase Y, et al. Hepatocarcinogenesis following HCV RNA eradication by interferon in chronic hepatitis patients. Intern Med. 2008;47(19):1637-1643.

Cardoso AC, Moucari R, Figueiredo-Mendes C, et al. Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: Incidence and survival in hepatitis C patients with advanced fibrosis. J Hepatol. 2010;52(5):652-657.

Mallet V, Gilgenkrantz H, Serpaggi J, et al. Brief communication: The relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med. 2008;149(6):399-403.

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(5 Pt 1):329-337.

Asahina Y, Tsuchiya K, Tamaki N, et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology. 2010;52(2):518-527.

Hung CH, Lee CM, Wang JH, 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(10):2344-2352.

Kawamura Y, Arase Y, Ikeda K, et al. Diabetes enhances hepatocarcinogenesis in noncirrhotic, interferon-treated hepatitis C patients. Am J Med. 2010;123(10):951-956.e1.

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. Gastroenterology. 2011;140(5, Suppl 1):S-899.

Kurokawa M, Hiramatsu N, Oze T, et al. Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis. Hepatol Res. 2009;39(5):432-438.

Okanoue T, Itoh Y, Kirishima T, 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(1):62-77.

Osaki Y, Ueda Y, Marusawa H, 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(4):444-451.

Pradat P, Tillmann HL, Sauleda S, et al. Long-term follow-up of the hepatitis C HENCORE cohort: Response to therapy and occurrence of liver-related complications. J Viral Hepat. 2007;14(8):556-563.

Sinn DH, Paik SW, Kang P, et al. Disease progression and the risk factor analysis for chronic hepatitis C. Liver Int. 2008;28(10):1363-1369.

Takahashi H, Mizuta T, Eguchi Y, 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(6):790-798.

Tateyama M, Yatsuhashi H, Taura N, 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(1):92-100.

Braks RE, Ganne-Carrie N, Fontaine H, 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(42):5648-5653.

Hasegawa E, Kobayashi M, Kawamura Y, 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(10):793-800.

Morgan TR, Ghany MG, Kim HY, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52(3):833-844.

van der Meer AJP, Hansen BE, Feld JJ, et al. 932 FACTORS ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C PATIENTS WITH ADVANCED LIVER FIBROSIS. J Hepatol. 2012;56, Supplement 2(0):S363-S364.

Velosa J, Serejo F, Marinho R, Nunes J, Gloria H. Eradication of hepatitis C virus reduces the risk of hepatocellular carcinoma in patients with compensated cirrhosis. Dig Dis Sci. 2011;56(6):1853-1861.

Chang CH, Lin JW, Wu LC, Liu CH, Lai MS. National antiviral treatment program and the incidence of hepatocellular carcinoma and associated mortality in taiwan: A preliminary report. Med Care. 2013;51(10):908-913.

Shiratori Y, Shiina S, Teratani T, et al. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med. 2003;138(4):299-306.

Yang T, Lu JH, Zhai J, et al. High viral load is associated with poor overall and recurrence-free survival of hepatitis B virus-related hepatocellular carcinoma after curative resection: A prospective cohort study. Eur J Surg Oncol. 2012;38(8):683-691.

Campsen J, Zimmerman M, Trotter J, et al. Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the united states with hepatitis B immunoglobulin and nucleoside/nucleotide analogues. Liver Transpl. 2013;19(9):1020-1029.

Piao CY, Fujioka S, Iwasaki Y, et al. Lamivudine treatment in patients with HBV-related hepatocellular carcinoma--using an untreated, matched control cohort. Acta Med Okayama. 2005;59(5):217-224.

Kuzuya T, Katano Y, Kumada T, et al. Efficacy of antiviral therapy with lamivudine after initial treatment for hepatitis B virus-related hepatocellular carcinoma. J Gastroenterol Hepatol. 2007;22(11):1929-1935.

Kubo S, Tanaka H, Takemura S, et al. Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus. Hepatol Res. 2007;37(2):94-100.

Kim BK, Park JY, Kim do Y, et al. Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection. Liver Int. 2008;28(3):393-401.

Hann HW, Bergin D, Coben R, DiMarino AJ. Prevention of new hepatocellular carcinoma with concomitant antiviral therapy in chronic hepatitis B patients whose initial tumor was successfully ablated. Int J Cancer. 2011;128(3):739-742.

Chan AC, Chok KS, Yuen WK, et al. Impact of antiviral therapy on the survival of patients after major hepatectomy for hepatitis B virus-related hepatocellular carcinoma. Arch Surg. 2011;146(6):675-681.

Wu CY, Chen YJ, Ho HJ, et al. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA. 2012;308(18):1906-1914.

Hasegawa I, Orito E, Tanaka Y, et al. Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C. Liver Int. 2005;25(2):247-253.

Ikeda K, Kobayashi M, Someya T, et al. Occult hepatitis B virus infection increases hepatocellular carcinogenesis by eight times in patients with non-B, non-C liver cirrhosis: A cohort study. J Viral Hepat. 2009;16(6):437-443.

Miura Y, Shibuya A, Adachi S, et al. Occult hepatitis B virus infection as a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C in whom viral eradication fails. Hepatol Res. 2008;38(6):546-556.

Obika M, Shinji T, Fujioka S, et al. Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease. A prospective study. Intervirology. 2008;51(1):59-68.

Squadrito G, Pollicino T, Cacciola I, et al. Occult hepatitis B virus infection is associated with the development of hepatocellular carcinoma in chronic hepatitis C patients. Cancer. 2006;106(6):1326-1330.

Matsuoka S, Nirei K, Tamura A, et al. Influence of occult hepatitis B virus coinfection on the incidence of fibrosis and hepatocellular carcinoma in chronic hepatitis C. Intervirology. 2008;51(5):352-361.

Adachi S, Shibuya A, Miura Y, Takeuchi A, Nakazawa T, Saigenji K. Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus. Scand J Gastroenterol. 2008;43(7):849-856.

Yotsuyanagi H, Shintani Y, Moriya K, et al. Virologic analysis of non-B, non-C hepatocellular carcinoma in japan: Frequent involvement of hepatitis B virus. J Infect Dis. 2000;181(6):1920-1928.

Kao JH, Chen PJ, Lai MY, Chen DS. Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol. 2002;40(11):4068-4071.

Fang Y, Shang QL, Liu JY, et al. Prevalence of occult hepatitis B virus infection among hepatopathy patients and healthy people in china. J Infect. 2009;58(5):383-388.

Alencar RS, Gomes MM, Sitnik R, et al. Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in brazil. Braz J Med Biol Res. 2008;41(3):235-240.

Branco F, Mattos AA, Coral GP, et al. Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in brazil. Arq Gastroenterol. 2007;44(1):58-63.

Chen CH, Changchien CS, Lee CM, et al. A study on sequence variations in pre-S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non-B, non-C hepatocellular carcinoma patients in taiwan. Int J Cancer. 2009;125(3):621-629.

Tanaka T, Inoue K, Hayashi Y, et al. Virological significance of low-
level hepatitis B virus infection in patients with hepatitis C virus associated liver disease. J Med Virol. 2004;72(2):223-229.

Chang ML, Lin YJ, Chang CJ, et al. Occult and overt HBV co-infections independently predict postoperative prognosis in HCV-associated hepatocellular carcinoma. PLoS One. 2013;8(6):e64891.

Wong SY, Ren XD, Hann HW. Development of hepatocellular carcinoma in patients with chronic hepatitis B long after achieving hbsag seroconversion:  A need for an improved hepatitis B virus DNA assay. Clinical Microbiology: Open Access. 2013;2(6):127.

Ward JW. The epidemiology of chronic hepatitis C and one-time hepatitis C virus testing of persons born during 1945 to 1965 in the united states. Clin Liver Dis. 2013;17(1):1-11.
 

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2014-07-31

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Civan, MD, J., & Hann, MD, H.-W. (2014). Hepatitis C Virus Mediated Hepatocellular Carcinoma: A Focused Review for a Time of Changing Therapeutic Options. North American Journal of Medicine and Science, 7(1). Retrieved from https://www.najms.com/index.php/najms/article/view/134

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