Current Practice of Hepatocellular Carcinoma Surveillance

Imelda Maria Loho, Lianda Siregar, Agus Sudiro Waspodo, Irsan Hasan


Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. This is due to the heterogeneity of the tumor biology and lack of curative treatment options. The most significant prognostic factor is detection at early stage and thus, surveillance strategies are of high importance. High-risk patients should undergo ultrasound and tumor marker tests at six-month interval in order to detect HCC at the earlier stage. However, in real-life practice, ultrasound has several limitations and the adherence to HCC surveillance is suboptimal due to various provider, patient, and health-care system factors. In this paper, we will address current methods of HCC surveillance and obstacles found in real-life practice.


hepatocellular carcinoma; surveillance; ultrasound; tumor markers; early detection


Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC Cancer Base no. 112012 6 September 2015. Available from:

Liu JH, Chen PW, Asch SM, et al. Surgery for hepatocellular carcinoma: does it improve survival? Annals Surg Oncol. 2004;11(3):298-303.

Facciuto ME, Koneru B, Rocca JP, et al. Surgical treatment of hepatocellular carcinoma beyond Milan criteria. Results of liver resection, salvage transplantation, and primary liver transplantation. Annals Surg Oncol. 2008;15(5):1383-91.

Shiina S, Tateishi R, Arano T, et al. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol. 2012;107(4):569-77.

El-Serag HB, Lau M, Eschbach K, et al. Epidemiology of hepatocellular carcinoma in Hispanics in the United States. Arch Int Med. 2007;167(18):1983-9.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: Cancer J Clinicians. 2005;55(2):74-108.

Zhu RX, Seto WK, Lai CL, Yuen MF. Epidemiology of hepatocellular carcinoma in the Asia-Pacific region. Gut Liver. 2016;10(3):332-9.

Tokushige K, Hashimoto E, Horie Y, et al. Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey. J Gastroenterol. 2011;46(10):1230-7.

McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma, present and future. Clin Liver Dis. 2011;15(2):223-x.

Llovet JM, Bustamante J, Castells A, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology (Baltimore, Md). 1999;29(1):62-7.

Loho IM, Hasan I, Lesmana CR, et al. Hepatocellular carcinoma in a tertiary referral hospital in Indonesia: Lack of improvement of one-year survival rates between 1998-1999 and 2013-2014. Asian Pacific J Cancer Prevention: APJCP. 2016;17(4):2165-70.

Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Current Opin Gastroenterol. 2013;29(3):285-92.

van Meer S, van Erpecum KJ, Sprengers D, et al. Hepatocellular carcinoma in cirrhotic versus noncirrhotic livers: results from a large cohort in the Netherlands. Eur J Gastroenterol Hepatol. 2016;28(3):352-9.

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

Gomaa AI, Khan SA, Toledano MB, et al. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol. 2008;14(27):4300-8.

Montalto G, Cervello M, Giannitrapani L, et al. Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Annals New York Acad Sci. 2002;963(1):13-20.

Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatol. 2011;53(3):1020-2.

EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56.

Kudo M, Izumi N, Kokudo N, et al. Management of hepatocellular carcinoma in Japan: Consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Digest Dis. 2011;29(3):339-64.

EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908-43.

Lok AS, Seeff LB, Morgan TR, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterol. 2009;136(1):138-48.

Kim SY, An J, Lim YS, et al. MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol. 2017;3(4):456-63.

Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med. 1996;101(4):422-34.

Arguedas MR, Chen VK, Eloubeidi MA, Fallon MB. Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis. Am J Gastroenterol. 2003;98(3):679-90.

Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Alimentary Pharmacol Therapeutics. 2009;30(1):37-47.

Sato T, Tateishi R, Yoshida H, et al. Ultrasound surveillance for early detection of hepatocellular carcinoma among patients with chronic hepatitis C. Hepatol Int. 2009;3(4):544-50.

Singal AG, Conjeevaram HS, Volk ML, et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012;21(5):793-9.

Marrero JA. Screening tests for hepatocellular carcinoma. Clin Liver Dis. 2005;9(2):235-51.

Tong MJ, Blatt LM, Kao VW. Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol. 2001;16(5):553-9.

Di Bisceglie AM, Sterling RK, Chung RT, et al. Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. J Hepatol. 2005;43(3):434-41.

Yamashita T, Forgues M, Wang W, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Research. 2008;68(5):1451-61.

Paul SB, Gulati MS, Sreenivas V, et al. Evaluating patients with cirrhosis for hepatocellular carcinoma: value of clinical symptomatology, imaging and alpha-fetoprotein. Oncology. 2007;72 Suppl 1:117-23.

Pote N, Cauchy F, Albuquerque M, et al. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol. 2015;62(4):848-54.

Park SJ, Jang JY, Jeong SW, et al. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine. 2017;96(11):e5811.

Lim TS, Kim DY, Han KH, et al. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients. Scandinavian J Gastroenterol. 2016;51(3):344-53.

Durazo FA, Blatt LM, Corey WG, et al. Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23(10):1541-8.

An C, Choi YA, Choi D, et al. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease. Clin Mol Hepatol. 2015;21(3):279-86.

Sheu JC, Sung JL, Chen DS, et al. Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterol. 1985;89(2):259-66.

Barbara L, Benzi G, Gaiani S, et al. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatol. 1992;16(1):132-7.

Trinchet JC, Chaffaut C, Bourcier V, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatol. 2011;54(6):1987-97.

Trevisani F, De Notariis S, Rapaccini G, et al. Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol. 2002;97(3):734-44.

Santi V, Trevisani F, Gramenzi A, et al. Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol. 2010;53(2):291-7.

Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362(9399):1907-17.

Kudo M, Matsui O, Izumi N, et al. JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014;3(3-4):458-68.

[National consensus on the management of hepatocellular carcinoma]. Jakarta: Indonesian Association for the Study of the Liver; 2017.

Van Beers BE, Pastor CM, Hussain HK. Primovist, Eovist: what to expect? J Hepatol. 2012;57(2):421-9.

Kudo M. Early hepatocellular carcinoma: definition and diagnosis. Liver Cancer. 2013;2(2):69-72.

Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130(7):417-22.

Chen JG, Parkin DM, Chen QG, et al. Screening for liver cancer: results of a randomised controlled trial in Qidong, China. J Med Screening. 2003;10(4):204-9.

Zoli M, Magalotti D, Bianchi G, et al. Efficacy of a surveillance program for early detection of hepatocellular carcinoma. Cancer. 1996;78(5):977-85.

McMahon BJ, Bulkow L, Harpster A, et al. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology. 2000;32(4 Pt 1):842-6.

Trevisani F, Santi V, Gramenzi A, et al. Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis? Am J Gastroenterol. 2007;102(11):2448-57; quiz 58.

Thompson Coon J, Rogers G, et al. Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis. Brit J Cancer. 2008;98(7):1166-75.

Singal AG, Yopp A, C SS, Packer M, et al. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J General Intern Med. 2012;27(7):861-7.

Singal AG, Nehra M, Adams-Huet B, et al. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol. 2013;108(3):425-32.

Dalton-Fitzgerald E, Tiro J, Kandunoori P, et al. Practice patterns and attitudes of primary care providers and barriers to surveillance of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13(4):791-8.e1.

Zapka JG, Taplin SH, Solberg LI, Manos MM. A framework for improving the quality of cancer care: the case of breast and cervical cancer screening. Cancer Epidemiol Biomarker Prevent. 2003;12(1):4-13.

Singal AG, Marrero JA, Yopp A. Screening process failures for hepatocellular carcinoma. Journal of the National Comprehensive Cancer Network: JNCCN. 2014;12(3):375-82.

Wong LL, Reyes RJ, Kwee SA, et al. Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in the real world? Clin Mol Hepatol. 2017;23(3):239-48.

Kudo M, Izumi N, Sakamoto M, et al. Improved survival in patients with hepatocellular carcinoma over 30 years in Japan: Analysis of nationwide prospective registry of 148,161 patients. J Clin Oncol. 2011;29:269.

Kudo M. Japan’s successful model of nationwide hepatocellular carcinoma surveillance highlighting the urgent need for global surveillance. Liver Cancer. 2012;1(3-4):141-3.

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