Hepatitis C Virus-Associated Primary Hepatocellular Carcinoma in Non-cirrhotic Patients
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There is limited literature on hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of cirrhosis.
To investigate the relationship between HCV and HCC in the absence of cirrhosis and to characterize patients with HCV infection presenting with HCC in the absence of cirrhosis.
We identified all adult patients with histological confirmation of HCC between 1994 and 2007 (404 patients). A case–control design (four controls for each case with non-cirrhotic HCC) was chosen to compare characteristics and survival of HCV in HCC patients without (cases) and with (controls) cirrhosis. Conditional logistic regression analysis was used to identify factors independently associated with HCV in non-cirrhotic HCC.
Eighty-seven patients with non-cirrhotic HCC were identified, six (7 %) had HCV infection in comparison with 107 of 317 (55.7 %) with cirrhotic HCC (P < 0.001). Compared with the HCV-associated HCC cirrhotic group, patients with HCV-associated HCC in the absence of cirrhosis were more likely to present with a single nodule (100 vs. 66.7 %), larger nodule size (>5 cm) (100 vs. 16.7 %), and macrovascular invasion (66.7 vs. 17.4 %) at time of diagnosis. Four of six patients with HCV-associated HCC in the absence of cirrhosis where alive at three years (all had resection), which was better survival than for HCC arising in cirrhotic livers of HCV-infected individuals (66.7 vs. 39.1 %).
We found that HCV is responsible for a small minority of non-cirrhotic HCC cases representing an uncommon and poorly defined subgroup of HCC.
- Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001;2:533–543. CrossRef
- Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35–S50. CrossRef
- Evert M, Dombrowski F. Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe. 2008;29:47–52. CrossRef
- Lam CM, Chan AO, Ho P, et al. Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients—implications for screening. Aliment Pharmacol Ther. 2004;19:771–777. CrossRef
- Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ, Cotler SJ. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med. 2008;132:1761–1766.
- Paradis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology. 2009;49:851–859. CrossRef
- Dupont-Bierre E, Compagnon P, Raoul JL, Fayet G, de Lajarte-Thirouard AS, Boudjema K. Resection of hepatocellular carcinoma in noncirrhotic liver: analysis of risk factors for survival. J Am Coll Surg. 2005;201:663–670. CrossRef
- Lang H, Sotiropoulos GC, Brokalaki EI, et al. Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic livers. J Am Coll Surg. 2007;205:27–36. CrossRef
- Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236. CrossRef
- Fattovich G, Giustina G, Degos F, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:463–472. CrossRef
- Hu KQ, Tong MJ. The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology. 1999;29:1311–1316. CrossRef
- Minino AM, Heron MP, Smith BL. Deaths: preliminary data for 2004. Natl Vital Stat Rep. 2006;54:1–49.
- Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345:41–52. CrossRef
- Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med. 1999;341:22–26. CrossRef
- Shintani Y, Yotsuyanagi H, Moriya K, et al. The significance of hepatitis B virus DNA detected in hepatocellular carcinoma of patients with hepatitis C. Cancer. 2000;88:2478–2486. CrossRef
- 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;54:249–255. CrossRef
- De Mitri MS, Poussin K, Baccarini P, et al. HCV-associated liver cancer without cirrhosis. Lancet. 1995;345:413–415. CrossRef
- Herr W, Gerken G, Poralla T, et al. Hepatitis C virus associated primary hepatocellular carcinoma in a noncirrhotic liver. Clin Investig. 1993;71:49–53. CrossRef
- Nash KL, Woodall T, Brown AS, Davies SE, Alexander GJ. Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis. World J Gastroenterol. 2010;16:4061–4065. CrossRef
- Yeh MM, Daniel HD, Torbenson M. Hepatitis C-associated hepatocellular carcinomas in non-cirrhotic livers. Mod Pathol. 2010;23:276–283. CrossRef
- 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;339:169–173. CrossRef
- Yoshida T, Hanada T, Tokuhisa T, et al. Activation of STAT3 by the hepatitis C virus core protein leads to cellular transformation. J Exp Med. 2002;196:641–653. CrossRef
- Sakamuro D, Furukawa T, Takegami T. Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. J Virol. 1995;69:3893–3896.
- Gale M Jr, Kwieciszewski B, Dossett M, Nakao H, Katze MG. Antiapoptotic and oncogenic potentials of hepatitis C virus are linked to interferon resistance by viral repression of the PKR protein kinase. J Virol. 1999;73:6506–6516.
- Hepatitis C Virus-Associated Primary Hepatocellular Carcinoma in Non-cirrhotic Patients
Digestive Diseases and Sciences
Volume 57, Issue 12 , pp 3265-3270
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Hepatocellular carcinoma
- Hepatitis C virus
- Liver neoplasm
- Industry Sectors
- Author Affiliations
- 1. Department of Gastroenterology and Hepatology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA
- 2. Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- 3. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA