Visceral Fat Accumulation Is Associated with Increased Mortality Rate after Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma


Aim: Transcatheter arterial chemoembolization (TACE) is thought to be a safe and effective treatment for hepatocellular carcinoma (HCC). However, in some HCC patients, it potentially shortens survival due to liver damage. We aimed to identify independent factors to predict overall survival of HCC after TACE. Methods: We included a total of 96 consecutive HCC patients who underwent TACE at Kobe University Hospital. Areas of skeletal muscle and fat tissue were measured by computed tomography (CT) scan before TACE. We divided the patients into two groups in terms of the presence or absence of 1-year mortality after TACE. Factors associated with 1-year mortality after TACE were assessed by multivariate analyses, and the optimal cut-off values were evaluated using a propensity score. Results: Multivariate analyses showed that visceral fat accumulation on CT was an independent factor associated with 1-year mortality after TACE (p = 0.033). There were no differences in skeletal muscle area and subcutaneous and intermuscular fat area between the two groups. Cut-off values for visceral fat area associated with 1-year mortality after TACE were defined as 33.3 cm2/m2 for males and 24.4 cm2/m2 for females. Conclusions: High visceral fat area was a prognostic factor associated with increased mortality rate in HCC patients undergoing TACE. Using this value, 1-year mortality risk after TACE would be better estimated before the day TACE was performed.

Share and Cite:

Saito, M. , Yano, Y. , Hirano, H. , Momose, K. , Kawano, Y. , Yoshida, M. and Azuma, T. (2015) Visceral Fat Accumulation Is Associated with Increased Mortality Rate after Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma. Journal of Cancer Therapy, 6, 1124-1136. doi: 10.4236/jct.2015.613122.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Bronowicki, J.P., Vetter, D., Dumas, F., et al. (1994) Transcatheter Oily Chemoembolization for Hepatocellular Carcinoma. A 4-Year Study of 127 French Patients. Cancer, 74, 16-24.<16::AID-CNCR2820740105>3.0.CO;2-V
[2] Vetter, D., Wenger, J.J., Bergier, J.M., et al. (1991) Transcatheter Oily Chemoembolization in the Management of Advanced Hepatocellular Carcinoma in Cirrhosis: Results of a Western Comparative Study in 60 Patients. Hepatology, 13, 427-433.
[3] Mondazzi, L., Bottelli, R., Brambilla, G., et al. (1994) Transcatheter Oily Chemoembolization for the Treatment of Hepatocellular Carcinoma: A Multivariate Analysis of Prognostic Factors. Hepatology, 19, 1115-1123.
[4] Lo, C.M., Ngan, H., Tso, W.K., et al. (2002) Randomized Controlled Trial of Transarterial Lipiodol Chemoembolization for Unresectable Hepatocellular Carcinoma. Hepatology, 35, 1164-1171.
[5] Llovet, J.M., Real, M.I., Montaňa, X., et al. (2002) Arterial Embolisation or Chemoembolisation versus Symptomatic Treatment in Patients with Unresectable Hepatocellular Carcinoma: A Randomised Controlled Trial. The Lancet, 359, 1734-1739.
[6] Llovet, J.M. and Bruix, J. (2003) Systematic Review of Randomized Trials for Unresectable Hepatocellular Carcinoma: Chemoembolization Improves Survival. Hepatology, 37, 429-442.
[7] Bismuth, H., Morino, M., Sherlock, D., et al. (1992) Primary Treatment of Hepatocellular Carcinoma by Arterial Chemoembolization. The American Journal of Surgery, 163, 387-394.
[8] Yamada, R., Kishi, K., Sonomura, T., et al. (1990) Transcatheter Arterial Embolization in Unresectable Hepatocellular Carcinoma. CardioVascular and Interventional Radiology, 13, 135-139.
[9] Stuart, K., Stokes, K., Jenkins, R., et al. (1993) Treatment of Hepatocellular Carcinoma Using Doxorubicin/Ethiodized Oil/Gelatin Powder Chemoembolization. Cancer, 72, 3202-3209.<3202::AID-CNCR2820721112>3.0.CO;2-4
[10] Bruix, J. and Sherman, R. (2005) Management of Hepatocellular Carcinoma. Hepatology, 42, 1208-1236.
[11] Pugh, R.N., Murray-Lyon, I.M., Dawson, J.L., et al. (1973) Transection of the Oesophagus for Bleeding Oesophageal Varices. British Journal of Surgery, 60, 646-649.
[12] Kamath, P.S., Wiesner, R.H., Malinchoc, M., et al. (2001) A Model to Predict Survival in Patients with End-Stage Liver Disease. Hepatology, 33, 464-470.
[13] Vauthey, J.N., Lauwers, G.Y., Esnaola, N.F., et al. (2002) Simplified Staging for Hepatocellular Carcinoma. Journal of Clinical Oncology, 20, 1527-1536.
[14] Calle, E.E., Rodriguez, C., Walker-Thurmond, K., et al. (2003) Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults. The New England Journal of Medicine, 348, 1625-1638.
[15] Ohki, T., Tateishi, R., Sato, T., et al. (2008) Obesity Is an Independent Risk Factor for Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients. Clinical Gastroenterology and Hepatology, 6, 459-464.
[16] Saito, M., Seo, Y., Yano, Y., et al. (2013) Reduction in Non-Protein Respiratory Quotient Is Related to Overall Survival after Hepatocellular Carcinoma Treatment. PLoS ONE, 8, e55441.
[17] Mathur, A., Hernandez, J., Shaheen, F., et al. (2011) Preoperative Computed Tomography Measurements of Pancreatic Steatosis and Visceral Fat: Prognostic Markers for Dissemination and Lethality of Pancreatic Adenocarcinoma. HPB (Oxford), 13, 404-410.
[18] House, M.G., Fong, Y., Arnaoutakis, D.J., et al. (2008) Preoperative Predictors for Complications after Pancreaticoduodenectomy: Impact of BMI and Body Fat Distribution. Journal of Gastrointestinal Surgery, 12, 270-278.
[19] Kudo, M. and Okanoue, T. (2007) Management of Hepatocellular Carcinoma in Japan: Consensus-Based Clinical Practice Manual Proposed by the Japan Society of Hepatology. Oncology, 72, 2-15.
[20] Mitsiopoulos, N., Baumgartner, R.N., Heymsfield, S.B., et al. (1998) Cadaver Validation of Skeletal Muscle Measurement by Magnetic Resonance Imaging and Computerized Tomography. Journal of Applied Physiology, 85, 115-122.
[21] Kvist, H., Sjostrom, L. and Tylén, U. (1986) Adipose Tissue Volume Determinations in Women by Computed Tomography: Technical Considerations. International Journal of Obesity, 10, 53-67.
[22] Vehmas, T., Kairemo, K.J. and Taavitsainen, M.J. (1996) Measuring Visceral Adipose Tissue Content from Contrast Enhanced Computed Tomography. International Journal of Obesity and Related Metabolic Disorders, 20, 570-573.
[23] Mourtzakis, M., Prado, C.M., Lieffers, J.R., et al. (2008) A Practical and Precise Approach to Quantification of Body Composition in Cancer Patients Using Computed Tomography Images Acquired during Routine Care. Applied Physiology, Nutrition, and Metabolism, 33, 997-1006.
[24] Prado, C.M., Lieffers, J.R., McCargar, L.J., et al. (2008) Prevalence and Clinical Implications of Sarcopenic Obesity in Patients with Solid Tumours of the Respiratory and Gastrointestinal Tracts: A Population-Based Study. The Lancet Oncology, 9, 629-635.
[25] Montano-Loza, A.J., Meza-Junco, J., Prado, C.M., et al. (2012) Muscle Wasting Is Associated with Mortality in Patients with Cirrhosis. Clinical Gastroenterology and Hepatology, 10, 166-173.
[26] Kashihara, H., Lee, J.S., Kawakubo, K., et al. (2009) Criteria of Waist Circumference According to Computed Tomography-Measured Visceral Fat Area and the Clustering of Cardiovascular Risk Factors. Circulation Journal, 73, 1881-1886.
[27] Starley, B.Q., Calcagno, C.J. and Harrison, S.A. (2010) Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection. Hepatology, 51, 1820-1832.
[28] Kopelman, P.G. (2000) Obesity as a Medical Problem. Nature, 404, 635-643.
[29] Regimbeau, J.M., Colombat, M., Mognol, P., et al. (2004) Obesity and Diabetes as a Risk Factor for Hepatocellular Carcinoma. Liver Transplantation, 10, S69-S73.
[30] Gonzalez, L., Blanc, J.F., Sa Cunha, A., et al. (2004) Obesity as a Risk Factor for Hepatocellular Carcinoma in a Noncirrhotic Patient. Seminars in Liver Disease, 24, 415-419.
[31] Nair, S., Mason, A., Eason, J., et al. (2002) Is Obesity an Independent Risk Factor for Hepatocellular Carcinoma in Cirrhosis? Hepatology, 36, 150-155.
[32] Fox, C.S., Massaro, J.M., Hoffmann, U., et al. (2007) Abdominal Visceral and Subcutaneous Adipose Tissue Compartments: Association with Metabolic Risk Factors in the Framingham Heart Study. Circulation, 116, 39-48.
[33] Oka, R., Kobayashi, J., Yagi, K., et al. (2008) Reassessment of the Cutoff Values of Waist Circumference and Visceral Fat Area for Identifying Japanese Subjects at Risk for the Metabolic Syndrome. Diabetes Research and Clinical Practice, 79, 474-481.
[34] Hayashi, T., Boyko, E.J., McNeely, M.J., et al. (2007) Minimum Waist and Visceral Fat Values for Identifying Japanese Americans at Risk for the Metabolic Syndrome. Diabetes Care, 30, 120-127.
[35] Eguchi, Y., Mizuta, T., Ishibashi, E., et al. (2009) Hepatitis C Virus Infection Enhances Insulin Resistance Induced by Visceral Fat Accumulation. Liver International, 29, 213-220.
[36] González-Reimers, E., Castellano-Higuera, A., Alemán-Valls, R., et al. (2009) Relation between Body Fat and Liver Fat Accumulation and Cytokine Pattern in Non-Alcoholic Patients with Chronic HCV Infection. Annals of Nutrition and Metabolism, 55, 351-357.
[37] Ahima, R.S. (2006) Adipose Tissue as an Endocrine Organ. Obesity, 14, 242S-249S.
[38] Vongsuvanh, R., George, J., Qiao, L., et al. (2013) Visceral Adiposity in Gastrointestinal and Hepatic Carcinogenesis. Cancer Letters, 330, 1-10.
[39] Arano, T., Nakagawa, H., Tateishi, R., et al. (2011) Serum Level of Adiponectin and the Risk of Liver Cancer Development in Chronic Hepatitis C Patients. International Journal of Cancer, 129, 2226-2235.
[40] Alexia, C., Fallot, G., Lasfer, M., et al. (2004) An Evaluation of the Role of Insulin-Like Growth Factors (IGF) and of Type-I IGF Receptor Signalling in Hepatocarcinogenesis and in the Resistance of Hepatocarcinoma Cells against Drug-Induced Apoptosis. Biochemical Pharmacology, 68, 1003-1015.
[41] Giovannucci, E. and Michaud, D. (2007) The Role of Obesity and Related Metabolic Disturbances in Cancers of the Colon, Prostate, and Pancreas. Gastroenterology, 132, 2208-2225.
[42] Kaido, T., Ogawa, K., Fujimoto, Y., et al. (2013) Impact of Sarcopenia on Survival in Patients Undergoing Living Donor Liver Transplantation. American Journal of Transplantation, 13, 1549-1556.
[43] Masuda, T., Shirabe, K., Ikegami, T., et al. (2014) Sarcopenia Is a Prognostic Factor in Living Donor Liver Transplantation. Liver Transplantation, 20, 401-407.
[44] Fearon, K.C. (2011) Cancer Cachexia and Fat-Muscle Physiology. The New England Journal of Medicine, 365, 565-567.
[45] Merli, M., Lucidi, C., Giannelli, V., et al. (2010) Cirrhotic Patients Are at Risk for Health Care-Associated Bacterial Infections. Clinical Gastroenterology and Hepatology, 8, 979-985.
[46] Wang, Y., Chen, Y., Ge, N., et al. (2012) Prognostic Significance of Alpha-Fetoprotein Status in the Outcome of Hepatocellular Carcinoma after Treatment of Transarterial Chemoembolization. Annals of Surgical Oncology, 19, 3540-3546.
[47] Tein, I., Bukovac, S.W. and Xie, Z.W. (1996) Characterization of the Human Plasmalemmal Carnitine Transporter in Cultured Skin Fibroblasts. Archives of Biochemistry and Biophysics, 329, 145-155.
[48] Yokogawa, K., Yonekawa, M., Tamai, I., et al. (1999) Loss of Wild-Type Carrier-Mediated L-Carnitine Transport Activity in Hepatocytes of Juvenile Visceral Steatosis Mice. Hepatology, 30, 997-1001.
[49] Kim, Y.J., Kim, K.Y., Kim, M.S., et al. (2008) A Mixture of the Aqueous Extract of Garcinia cambogia, Soy Peptide and L: -Carnitine Reduces the Accumulation of Visceral Fat Mass in Rats Rendered Obese by a High Fat Diet. Genes & Nutrition, 2, 353-358.

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.