Hepatocellular Carcinoma: Challenges in Indian Scenario
Keywords:Hepatocellular carcinoma (HCC), risk factors, staging of HCC, liver transplantation, transarterial chemoembolisation (TACE), transareterial radioembolisation (TARE), targetted therapy, sorafenib.
Hepatocellular carcinoma (HCC), a leading solid organ malignancy is on the rise across the world, including India. Its incidence has almost tripled in the last 30 years and it is among the fastest growing malignancy in the USA. It is the third most frequent cause of death from cancer and the eighth most commonly occurring cancer in the world. A disease of multifactorial etiology, HCC poses many challenges. It demands multidisciplinary care involving diagnostic, medical and surgical inputs. A lot of research is ongoing in terms of attempts to improve its treatment and results thereof. Identification of some of the causative factors has resulted in efforts towards its primary prevention as well. Universal immunization against Hepatitis B virus is one such effort in this direction. Identification of role of various molecular pathways is leading to targeted drug developments offering personalized treatment to concerned patients. The authors have been involved in the diagnosis and management of this important liver cancer. This article summarizes the various challenges encountered in the diagnosis and management of HCC in India.
Keywords: Hepatocellular carcinoma (HCC), risk factors, staging of HCC, liver transplantation, transarterial chemoembolisation (TACE), transareterial radioembolisation (TARE), targetted therapy, sorafenib.
El-Serag HB and Rudolph KL (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132: 2557â€“2576.
Caldwell S and Park SH (2009). The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. J Gastroenterol 44(Suppl 19):96â€“101.
Newell P, Villanueva A and Llovet JM (2008). Molecular targeted therapies in hepatocellular carcinoma: from pre-clinical models to clinical trials. J Hepatol 49: 1â€“5.
Llovet JM, Ricci S, Mazzaferro V, et al. (2008). Sorafenib in advanced hepatocellular carcinoma. NEJM 359: 378â€“390.
Dhir V and Mohandas KM (1998). Epidemiology of digestive tract cancers in India III liver. Indian J Gastroenterol 17:100â€“103.
National Cancer Registry Program, ICMR http://ncpindia.org/.
Sarin SK, Thakur V, Guptan RC, et al. (2001). Profile of hepatocellular carcinoma in India : an insight into the possible etiologic associations. J Gastroenterol Hepatol 16:666â€“673.
Paul SB, Chalamalasetty B and Vishnubatla S (2009). Clinical profile, etiology and therapeutic outcome in 324 hepatocellular cancer in India. Oncology 77:162â€“ 171.
Coon JT, Rogers G and Hewson P (2007). Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis. Health Technol Assess 11:1â€“206.
Fattovitch G, Stroffolini T, Zagni I and Donato F (2004). Hepatocellular carcinoma in cirrhosis: incidence and risk factor (review). Gastroenterology 127(suppl I):S35â€“S50.
Paul SB, Sreenivas V, Gulati MS, et al. (2007). Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from tertiary care centre in northern India. Indian J Gastroenterol 26:274â€“278.
Sarin SKTV, Guptan RC, Saigal S, Malhotra V, Thyagarajan SP and Das BC (2001). Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations. J Gastroenterol Hepatol 16:666â€“673.
Kumar M, Kumar R, Hissar SS, et al. (2007). Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case control study of 213 hepatocellular carcinoma patients from India. J Gastroenterol Hepatol 22(7):1104â€“ 1111.
Feitelson M (1995). Hepatitis-B x-antigen in the pathogenesis of hepatocellular-carcinoma (review). Oncol Rep 2(2):193â€“202.
Paterlini P, Driss F, Pisi E, et al. (1993). Persistence of hepatitis B and C viral genomes in primary liver cancers from HBsAg negative patients: a study of a low endemic area. Hepatology 17:20â€“29.
Br Echot C, Minami M, De Mitri S and Paterlini P (1995). Hepatitis B and C viruses in hepatitis B surface antigen negative hepatocellular carcinoma patients. Princess Takamatsu Symp 25:199â€“209.
Tsukuma H, Hiyama T, Tanaka S, et al. (1993). Risk factors for hepatocellular carcinoma among patients with chronic liver disease.
Nalpas B, Martin S, Fontaine H, et al. (2001). Impact of medical recommendations on alcohol consumption in HCV positive patients. J Hepatol 35(2):312â€“313.
Huo TI, Wu JC, Lui WY, et al. (2003). Diabetes mellitus is a recurrence independent risk factor in patients with hepatitis B virus- related hepatocellular carcinoma undergoing resection. Eur J Gastroenterol Hepatol 15:1203â€“ 1208.
El-Serag HB (2004). Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127:S27â€“S34.
Groopman JD, Kensler TW and Wild CP (2008). Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health 29:187â€“203.
Bruix J, Sherman M, Llovet JM, et al. (2001). Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona- 2000 EASL Conference. J Hepatol 35: 421â€“430.
Sala M, FornerA,Varela Mand Bruix J (2005). Prognostic prediction in patients with hepatocellular carcinoma. Semin Liver Dis 25: 171â€“180.
Llovet JM, Bru C and Bruix J (1999). Prognosis of hepatocellular carcinoma: The BCLC staging classification. Semin Liver Dis 19:329-338.
The Cancer of the Liver Italian Program (CLIP) Investigators (1998). A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients. Hepatology 28:751-755.
Chevret S, Trinchet JC, Mathieu D, et al. (1999). A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe dâ€™Etude et de Traitement du Carcinome Hepatocellulaire. J Hepatol 31:133- 141.
Sobin LH (2003). TNM, sixth edition: New developments in general concepts and rules. Semin Surg Oncol 21:19-22.
Leung TW, Tang AM, Zee B, et al. (2002). Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: A study based on 926 patients. Cancer 94:1760-1769.
Kudo M, Chung H and Osaki Y (2003). Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol 38:207- 215.
Llovet JM, Di Bisceglie AM, Bruix J, et al. (2008). Panel of experts in HCC-design clinical trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100:698-711.
Balsells J, Charco R, Lazaro JL, et al. (1996). Resection of hepatocellular carcinoma in patients with cirrhosis. Br J Surg 83: 758â€“761.
Cho YK, Kim JK, Kim MY, et al. (2009). Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 49:453-459.
Mazzaferro V, Regalia E, Doci R, et al. (1996). Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. NEJM 334: 693â€“699.
Yao FY, Ferrell L, Bass NM, et al. (2001). Liver transplantation for hepatocellular carcinoma: Expansion of the tumor size limits does not adversely impact survival. Hepatology 33:1394-1403.
Lee SG, Hwang S, Moon DB, et al. (2008). Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume centre. Liver Transpl 14(7):935â€“945.
Zheng SS, Xu X, Wu J, et al. (2008). Liver transplantation for hepatocellular carcinoma : Hangzhou experiences. Transplantation 85(12):1726â€“1732.
Dâ€™Amico F, Schwartz M, Vitale A, et al. (2009). Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria. Liver Transpl 15(10):1278â€“1287.
Yao FY, Hirose R, LaBerge JM, et al. (2005). A prospective study on down staging of hepatocellular carcinoma prior to liver transplantation. Liver Transpl 11: 1505â€“1514.
Llovet JM, Real MI, Montana X, et al. (2002). Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359: 1734â€“1739.
Llovet JM and Bruix J (2003). Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37: 429â€“442.
Oliveri RS, Wetterslev J and Gluud C (2011). Transarterial (chemo) embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev CD004787.
Varela M, Real MI, Burrel M, et al. (2007). Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46: 474â€“481.
Malagari K, Chatzimichael K, Alexopoulou E, et al. (2008). Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: results of an open-label study of 62 patients. Cardiovasc Intervent Radiol 31: 269â€“280.
Kulik LM, Atassi B, van Holsbeek L, et al. (2006). Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol 94: 572â€“586.
Salem R, Lewandowski R, Roberts C, et al. (2004). Use of yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis. J Vasc Intervent Radiol 15: 335â€“345.
Thomas MB and Zhu AX (2005). Hepatocellular carcinoma: the need for progress. J Clin Oncol 23(13):2892-2899.
Simonetti RG, Liberati A, Angiolini C and Pagliaro L (1997). Treatment of hepatocellular carcinoma: a systemic review of randomized controlled trials. Ann Oncol 8(2): 117-136.
Thomas MB, Oâ€™ Beirne JP, Furuse J, et al. (2008). Systemic therapy for hepatocellular carcinoma: cytotoxic chemotherapy, targeted therapy and immunotherapy. Ann Surg Oncol 15:1008-1014.
Leung TW, Tang AM, Zee B, et al. (2002). Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon alpha, doxorubicin and 5-fluorouracil chemotherapy. Cancer 94(2):421- 427.
Cheng AL, Kang YK, Chen Z, et al. (2009). Efficacy and safety of Sorafenib in patients in the Asia Pacific region with advanced hepatocellular carcinoma: a phase III randomized, double-blind, placebo-controlled trial. Lancet Oncol 10:25-34.
Abou-Alfa GK, Schwartz L, Ricci S, et al. (2006). Phase II study of Sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293-4300.
Fairre S, Raymond E, Douillard J, et al. (2007). Assessment of safety and drug-induced tumor necrosis with Sunitinib in patients with unresectable hepatocellular carcinoma. J Clin Oncol 25:149s Abstract 3546.
Philip PA, Mahoney MR, Allmer C, et al. (2005). Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol 23(27): 6657-6663.
Zhu AX, Blaszkowsky LS, Ryan DP, et al. (2006). Phase II study of Gemcitabine and Oxaliplatin in combination with Bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol 24(12):1898-1903.
Cabrera R and Nelson DR (2010). Review article: the management of hepatocellular carcinoma. Aliment Pharmacol 31: 461-476.
Authors who publish with this journal agree to the following terms:
Copyright will be with Annals of the National Academy of Medical Sciences (India).
The work will be simultaneously licensed under Creative Commons Attribution Licence CC-BY 4.0Âhttp://creativecommons.org/licenses/by/4.0/