Background: Prognosis in hepatocellular carcinoma (HCC) is influenced by both liver and tumor factors, which have been considered independent influences. However, recent evidence has shown that the underlying liver also has prognostic information. Aims: To investigate possible relationships between liver function parameters and HCC aggressiveness indices. Methods: A large HCC patient database with baseline clinical information and survival data was retrospectively examined. Results: Data on 756 HCC patients with normal bilirubin were examined for a relationship between serum liver enzymes and 4 HCC aggressiveness indices of maximum tumor diameter, portal vein invasion, tumor multifocality or serum alpha-fetoprotein levels. An association was found between elevated enzyme levels and increased HCC aggressiveness. An aggressiveness index was constructed from the 4 indices and expressed as a sum of their scores, which in turn reflected 3 survival groups. In a Cox model, the hazard ratios for each of the groups were significantly different. Conclusions: Statistically significant correlations were found between standard liver function parameters and HCC aggressiveness. A composite aggressiveness index was constructed, yielding 3 groups with different survival probabilities. These findings support the concept of the importance of the underlying liver in relation to HCC biology.

Okuda K, Ohtsuki T, Obata H, et al: Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Cancer 1985;56:918-928.
The Cancer of the Liver Italian Program (CLIP) Investigators: A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients. Hepatology 1998;28:751-755.
Llovet JM, Bru C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329-338.
Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfie B, Rapaccini GL, Gasbarrini G: Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut 2005;54:411-418.
Tateishi R, Yoshida H, Shiina S, Imamura H, Hasegawa K, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Makuuchi M, Omata M: Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients. Gut 2005;54:419-425.
Carr BI, Buch SC, Kondragunta V, Pacoska P; Branch RA: Tumor and liver determinants of prognosis in unresectable HCC: a case cohort study. J Gastroenterol Hepatol 2008;23:1259-1266.
Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, Fushiya N, Koike K, Nishino H, Matsushima M, Saeki C, Tajiri H: The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma. BMC Cancer 2013;13:52.
Pinato DJ, Stebbing J, Ishizuka M, Khan SA, Wasan HS, North BV, Kubota K, Sharma R: A novel and validated prognostic index in hepatocellular carcinoma: the inflammation based index (IBI). J Hepatol 2012;57:1013-1020.
Utsunomiya T, Shimada M, Morine Y, Tajima A, Imoto I: Specific molecular signatures of non-tumor liver tissue may predict a risk of hepatocarcinogenesis. Cancer Sci 2014;105:749-754.
Hoshida Y, Villanueva A, Kobayashi M, Peix J, et al: Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 2008;359:1995-2004.
Wu SD, Ma YS, Fang Y, Liu LL, Fu D, Shen XZ: Role of the micro-environment in hepatocellular carcinoma development and progression. Cancer Treat Rev 2012;38:218-225.
Yang JD, Nakamura I, Roberts LR: The tumor micro-environment in hepatocellular carcinoma: current status and therapeutic targets. Semin Cancer Biol 2011;21:35-43.
Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM: Role of the micro-environment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology 2013;144:512-527. Review.
Pancoska P, Carr BI, Branch RA: Network-based analysis of survival for unresectable hepatocellular carcinoma. Semin Oncol 2010;37:170-181.
Carr BI, Guerra V, Giannini EG, Farinati F, et al: Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype. Semin Oncol 2014;41:252-258.
Johnson PJ, Berhane S, Kagebayashi C, Satomura S, et al: Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 2015;33:550-558.
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