Published: 2018-11-26

Trends of etiology and treatment in hepatocellular carcinoma over the years

Sezgin Vatansever, Zehra B. Pakoz


Background: HCC has been the fastest-growing cause of cancer-related deaths. The aim of this study was to investigate the change trends in the etiology, treatment and mortality of HCC over the last 12 years.

Methods: The study included 523 patients who were admitted to our clinic with the diagnosis of primary malignancy of the liver between 2006-2018. Demographic data, HCC etiologies, alpha feto-protein (AFP) values and imaging characteristics were recorded. The patients were divided into two groups as diagnosed before 2013 and 2013 and later. Because the number of patients with alcohol and HBV was high, it was evaluated as a separate etiology group. HCC was accepted related to NASH in the patients with obesity and diabetes mellitus (DM) after exclusion of HBV, HCV, and autoimmune hepatitis. The patients without obesity and DM were accepted as cryptogenic HCC and added to other etiologies group.

Results: When the patients were evaluated, there was a significant increase in the rate of patients who were in compensated cirrhosis stage and in UCSF criteria in and 2013 and later (p = 0.0001, p = 0.037, respectively). A significant increase was observed in the ratio of NASH-related HCC 2013 and later (p = 0.032). Transplantation, resection and RFA / PEI rates were 14.9% before 2013 and 22.2% 2013 and later (p = 0.047).

Conclusions: The rates of NAFLD related HCC due to diabetes and obesity are increasing. Knowing the change of HCC causes over the years is necessary for the effective treatment for these reasons in the future.


Hepatocellular carcinoma, Hepatitis B, Hepatitis C, Mortality, Non-alcoholic steatohepatitis

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Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, et al. World gastroenterology organisation global guideline. Hepatocellular carcinoma (hcc): A global perspective. J gastrointestin liver dis. 2010 Sep 1;19(3):311-7.

El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterol. 2012 May 1;142(6):1264-73.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86.

Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clinical Oncol. 2009 Mar 20;27(9):1485.

Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat database: incidence-SEER 9 Regs research data, Nov 2009 Sub (1973-2007). Bethesda, MD: National Cancer Institute, April 2010.

Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatol. 2011 Mar 1;53(3):1020-2.

Myers RP, Krajden M, Bilodeau M, Kaita K, Marotta P, Peltekian K, et al. Burden of disease and cost of chronic hepatitis C infection in Canada. Can J Gastroenterol Hepatol. 2014 May;28(5):243-50.

Can A, Dogan E, Bayoglu IV, Tatli AM, Besiroglu M, Kocer M, et al. Multicenter epidemiologic study on hepatocellular carcinoma in Turkey. Asian Pac J Cancer Prev. 2014;15(6):2923-7.

Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328:1797-801.

Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterol. 2004 Nov 1;127(5):1372-80.

Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013. Gastroenterol. 2015 Nov 1;149(6):1471-82.

Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis C virus infection as the leading indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2018 Aug 1;16(8):1356-8.

Hashimoto E, Tokushige K. Hepatocellular carcinoma in non‐alcoholic steatohepatitis: Growing evidence of an epidemic?. Hepatol Res. 2012 Jan;42(1):1-4.

Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterol. 2011 Oct 1;141(4):1249-53.

Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013. Gastroenterol. 2015 Nov 1;149(6):1471-82.

Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Internal Med. 2006 Sep 25;166(17):1871-7.

Turati F, Talamini R, Pelucchi C, Polesel J, Franceschi S, Crispo A, et al. Metabolic syndrome and hepatocellular carcinoma risk. Br J Cancer. 2013 Jan;108(1):222.

White DL, Kanwal F, El–Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012 Dec 1;10(12):1342-59.

El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118-27.

World Health Organization. 2016. Hepatitis B fact sheet. Available at: Accessed March 10, 2017.

Tosun S, Aygün O, Özdemir HÖ, Korkmaz E, Özdemir D. The impact of economic and social factors on the prevalence of hepatitis B in Turkey. BMC Public Health. 2018 Dec;18(1):649.

Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression. Gastroenterol. 2003 Dec 1;125(6):1695-704.

Hallager S, Brehm Christensen P, Ladelund S, Rye Clausen M, Lund Laursen A, Moller A, et al. Mortality rates in patients with chronic hepatitis C and cirrhosis compared with the general population: a Danish cohort study. J Infect Dis. 2017;215:192-201.

Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004 Apr 1;39(4):1147-71.

Pradat P, Virlogeux V, Trépo E. Epidemiology and elimination of HCV-related liver disease. Viruses. 2018 Oct 6;10(10):545.

Goldberg D, Ditah IC, Saeian K, Lalehzari M, Aronsohn A, Gorospe EC, et al. Changes in the Prevalence of hepatitis C virus infection, non-alcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterol. 2017;152(5):1090-9.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta‐analytic assessment of prevalence, incidence, and outcomes. Hepatol. 2016 Jul 1;64(1):73-84.

Singal AG, El-Serag HB. Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice. Clin Gastroenterol Hepatol. 2015 Nov 1;13(12):2140-51.

Tateishi R, Okanoue T, Fujiwara N, Okita K, Kiyosawa K, Omata M, et al. Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol. 2015 Mar 1;50(3):350-60.

Ioannou GN, Green P, Lowy E, Mun EJ, Berry K. Differences in hepatocellular carcinoma risk, predictors and trends over time according to etiology of cirrhosis. PLoS One. 2018 27;13(9):e0204412.

Yuan JM, Govindarajan S, Arakawa K, Mimi CY. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US. Cancer. 2004 Sep 1;101(5):1009-17.

Hashimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, Tokushige K, et al. Hepatocellular carcinomain patients with nonalcoholic steatohepatitis. J Gastroenterol. 2009;44 Suppl 19:89-95.

Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Medicine. 2014 Apr 1;11(4):e1001624.

Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence‐based management of hepatocellular carcinoma–an updated analysis of randomized controlled trials. Alimentary Pharmacol Therapeutics. 2006 Jun;23(11):1535-47.

Kim D, Li AA, Perumpail BJ, Gadiparthi C, Kim W, Cholankeril G, Glenn JS, et al. Changing Trends in Etiology‐and ethnicity‐based annual mortality rates of cirrhosis and hepatocellular carcinoma in the United States. Hepatol. 2018 Jul 16.

Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49(s5):S28-34.