Estimating the Risk of Hepatocellular Carcinoma in Developing Countries
		
                    
                                Deepika M*
Department of Pharmaceutical Sciences, JNTU Kakinada, Andhra Pradesh, India
  - Corresponding Author:
 
  -  Deepika M
    Department of Pharmaceutical Sciences
    Tel: 7032510554
    E-mail: deepika.mekala@gmail.com  
Received: 10/01/2015; Revised: 10/02/2015; Accepted: 18/02/2015
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                Abstract
        Hepatocellular Carcinoma is otherwise known as Liver Cancer is the third most affecting cancer in the world. According to the Statistics, the treatment is available in developed countries. Most of the parts of Asia and Africa are majorly affected due to this disease.The disease is heterogenous and more likely to spread rapidly in the body.Due to the disease, cells divide repeatedly and affects the metabolic and immune functions of the liver. The spread of Hepatitis B and C can be controlled by Vaccination and awareness programs.The present review focuses majorly on treatment options,prevention and future prospects of prevention of disease. The disease shows progressive effects due to poor medical facilities,Changes in life style, Improper dietary management and Alcoholism.
                Keywords
Hepatocellular       Carcinoma; Malignant;       Parenchymalcells; Liver       transplantation
Introduction
The cancer that affects liver is called Hepatocellular carcinoma.[1,2,3]. Hepatocellular carcinoma       otherwise known as Malignant hepatoma . It is the third leading cancer throughout the globe. It leads to       the damage of hepatocytes which leads to the death of the individual within 6-20 months. This type of       cancer is usually seen in men than in women.[2-7]. The occurrence of this cancer is more than 80% in       developing countries than in developed countries. More than 6,00,000 deaths occurring in Asia and       Africa annually due to this cancer. Although Liver cancer is the sixth most occurring cancer in the world,       due to its poor diagnosis it was detected as third [8,9].
Anatomy of Liver
Liver is the largest organ in the human body. It performs a wide variety of functions namely       metabolism, production of bile, carbohydrate synthesis, immune functions and urea formation [11-14]. The       microscopic anatomy of liver contains parenchymal and nonparenchymal cells [12,13]. Parenchymal cells or       hepatocytes comprise the bulk of the organ and carry out complex metabolic processes. Hepatocytes are       responsible for the major role in metabolism [11,12]. The liver also aids in the detoxification of drugs and       other foreign substances. Biliary passages begin as tiny bile canaliculi formed by hepatocytes [16-18].       These microvilli -lined structures progress into ductules, interlobular bile ducts, and larger hepatic ducts.
Causes of Liver Cancer
The major causes of this cancer are:
• Cirrhosis
• Hepatitis B and C infections [19,20]
• Other factors
Cirrhosis
The major and most common cause of Hepatocellular Carcinoma is Cirrhosis (Alcoholism). Most patients (90%)with this complication have underlying cirrhosis.The risk of developing hepatocellular carcinoma is 3-5 times more in alcoholic patients [19-21]. The most common causes of cirrhosis are alcoholism,fatty liver and Hepatitis C infection.
Hepatitis B and C Infections
Hepatitis B is mainly caused due to virus.The virus can be transmitted in unhygienic conditions.The causes of both Hepatitis B and C are more likely similar. In China, the development of Hepatocellular carcinoma is mainly due to Hepatitis B virus(HBV) [22,23]. In USA and Europe,both Hepatitis B and C equally contribute to the disease whereas in Japan, Hepatitis C is the major risk factor in the development of carcinoma.
Other factors
Diseases caused by abnormal liver function, such as hemochromatosis, a condition in which excessive iron is absorbed and deposited into the liver and other organs, and Wilson's disease, caused by the abnormal storage of copper in the liver.Prolonged exposure to environmental toxins and parasitic infections also causes Cirrhosis [23-25].
Pathophysiology
Body is composed of several cells. If there is an abnormal growth in the cells then it is termed as tumour.If there is abnormal growth in the cells of liver it is called hepatocellular carcinoma [26-29]. As the Hepatitis virus enters the liver cells,it multiplies more rapidly and inhibits the functioning of the liver.
As a result ,the liver loses its normal functioning and enlarges in its size at the initial stage. The chronic stage of hepatocellular carcinoma leads to complete liver failure [31-34].
The pathophysiology of hepatocellular carcinoma has not been definitively elucidated. In 1981, after Beasley linked HBV infection to hepatocellular carcinoma development, the cause of hepatocellular carcinoma was thought to have been identified [35]. However, subsequent studies failed to identify HBV infection as a major risk factor, and it became apparent that most cases of hepatocellular carcinoma developed in patients with underlying cirrhosis for HBV infection were found to have HBV DNA integrated in the hepatocyte genome [36-38].
Inflammation, necrosis, fibrosis, and ongoing regeneration characterize the cirrhotic liver and contribute to hepatocellular carcinoma development [39,40]. In patients with HBV, in whom hepatocellular carcinoma can develop in liver that are not cirrhotic, underlying fibrosis is usually present, with regeneration. By contrast, in patients with HCV, hepatocellular carcinoma invariably present in the setting of cirrhosis. This difference may relate to the fact that HBV is a DNA virus that integrates in the host genome and produces HBV X protein that may play a key regulatory role in hepatocellular carcinoma development.HCV is an RNA virus that replicates in the cytoplasm and does not integrate in the host DNA [41,42,43].
Symptoms of Hepatocellular Carcinoma
Early stages of liver cancer do not show any symptoms. As the tumour grows and spreads larger,several symptoms can be noticed. They are :
  Pain in the upper abdomen in the right side
  Nausea and Vomiting
  Weakness
  Yellow colour of skin
  Loss of apetite
  Weight loss
  Diagnosis of Liver Cancer:
  Different tests can be used to diagnose liver cancer.They are
  Physical Examination
  Blood tests
  Liver function tests
  CT and MRI scanning
  Ultrasound examination
  Liver Biopsy
Physical Examination
An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken [45-48].
Blood tests
The procedure in which a sample of blood is examined to measure the amounts of certain substances released into the blood by organs, tissues, or tumour cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the blood.[45,46] These are called tumor markers. An increased level of alpha-fetoprotein (AFP) in the blood may be a sign of liver cancer. Other cancers and certain noncancerous conditions, including cirrhosis and hepatitis, may also increase AFP levels. Sometimes the AFP level is normal even when there is liver cancer.
Liver function tests
A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by the liver. A higher than normal amount of a substance can be a sign of liver cancer [46,47].
CT and MRI scanning
A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the liver. This procedure is also called nuclear magnetic resonance imaging (NMRI [47-49].
Ultrasound imaging
A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram [50].
Liver Biopsy
Small cells or tissues are collected from the liver by means of a fine needle is called biopsy.It is the most accurate and final stage diagnosis of liver cancer [51].
Prevention of Hepatocellular Carcinoma
Liver Cancer can be prevented by vaccination.Hepatitis B is the major cause for liver cancer.Hence People in under developed and developing countries have to get awareness regarding the vaccination of Hepatitis B. Antiviral treatment helps in preventing cirrhosis in patients [52,53].
Treatment and Management
The treatment and Management of tumour depends on the size,number of tumours spread and the suitability of the patient for liver transplantation [54]. Some of the treatment options for patients affected with liver cancer are :
  Surgical resection
  Radiotherapy
  Chemotherapy
  Cisplatin gel injection
  Liver transplantation
Surgical Resection
Surgical resection is the most common treatment for noncirrhotic patients.In this method, if a part of liver is damaged,this can be surgically removed and liver can regrow the missed part.If it is totally damaged,then liver transplantation is the only option [55,56].
Radiotherapy
The tumour or cancer cells can be killed by passing radiation.Advanced techniques have been developed such as Stereotactic body radiation therapy through which the radiologists can easily target the tumour cells without destroying the healthy tissues [56-58].
Chemotherapy
Chemotherapy is the treatment of tumour with the help of drugs. It is usually given through IV administration [58].
Cisplatin gel injection
The technique in which the gel of cisplatin is inserted into the liver cells by means of a fine needle.The method has promising results in initial stages of treatment but the treatment at advanced stages has to be still assessed.This treatment option is under clinical trails [59,60].
Liver transplantation
Liver transplantation can be done to the patient only if the tumour is less than 6 cm in size.It can be transplanted to the patients .It is the best option for the patients with acute liver failure [61-63].
Conclusion
Liver Cancer is mostly affected to people in Africa,Asia and some of the developing countries. Lack of awareness,Lack of dietary management, Poor Medical facilities are the major causes of this disease. As the disease is heterogenous, genetic factors also play a key role for its occurrence [64]. Liver transplantation and Hepatic resection remain as the corner stones for curative therapy of Liver Cancer.However, the success rate of these therapies are 5 years [64,65].
Future Prospects
The advancement of Medicine has developed new techniques to identify the tumour at early stage.Researches being carried out on immunotherapy and gene therapy to identify and target on specific gene and increase the mortality [64,68].The major challenge is to develop a specific therapeutic modality for the patients with early diagnosis who could tolerate resection [66]. By developing these techniques, the treatment should be made available to the common people and should be cost effective [66,67].
References
  - http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm
 
  - http://emedicine.medscape.com/article/282814-overview
 
  - Mohamad RH, El-Said MGA, Zekry ZK,  Al-Bastawesy AM, Farag RM, et al. New Aspects of Therapy of Hepatocellular  Carcinoma Egyptian Patients. Biochem Physiol.2015; 4: s150.
 
  - Wong SY, Ren XD, Hann HW Development  of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Long After  Achieving Hbsag Seroconversion: A Need for an Improved Hepatitis B Virus DNA  Assay. Clin Microbial.2013; 2: 127.
 
  - Wu J  Prognostic Factors for Hepatocellular Carcinoma: Is it ready for  Primetime? J Liver.2013; 2: e104.
 
  - Wong SY, Hann HW Anti-Viral Therapy can Prevent Recurrent  Hepatocellular Carcinoma Associated with Hepatitis B: Recent Development. J  Antivir Antiretrovir.2015; 7: 022-025.
 
  - Sell S Prevention of Hepatocellular  Carcinoma: Vaccination and Dietary Changes Show Promise to Eliminate Most Cases  of Human Liver Cancer. J Carcinogene Mutagene.2012; 3: e108.
 
  - Lesmana CRA) Alcoholic Liver Disease  and Alcohol in Non-Alcoholic Liver Disease: Does it Matter?. J Metabolic  Synd.2014; 3: 147.
 
  - Huang W Influences of Gut Hormones on Hepatocellular  Carcinoma. Endocrinol Metab Synd.2015; 4: 155.
 
  - Jumpertz S, Bernhagen J, Schütz  AK Role of the COP9 Signalosome in  Gastrointestinal Cancers. J Carcinog Mutagen.2015; 6: 210.
 
  - Sonohara F, Nomoto S, Hayashi M,  Hishida M, Inokawa Y, et al. STEAP4 Inactivation Correlates Poor Prognosis and  might be a Possible Cause of steatotic Change in Hepatocellular Carcinoma,  Detected by Triple-Combination Array Analysis. J Carcinog Mutagen.2014; 5: 201.
 
  - Jeffs DB, Martin AC, Rosenvall ER,  Fillmore T, Barrett KE, et al. Cytotoxicity of Nutritional Supplement Galaxy®  against HepG2 Hepatocellular Carcinoma. Altern Integ Med.2014; 3: 175.
 
  - Otto W, Krol M, Maciaszczyk M,  Najnigier B, Sierdzinski J, et al. Levels and Values of Circulating  Hematopoietic and Endothelial Progenitor Cells in Patients with Hepatocellular  Carcinoma . J Liver.2014; 3: 167.
 
  - Sad LAA, Younis SG, Nagi HM Significance of Macrophage Migration  Inhibitory Factor (MIF) and Anti P 53 Antibodiesin Prognosis of Hepatocellular  Carcinoma. J Mol Biomark Diagn.2014; 5: 192.
 
  - Sell S Prevention of Hepatocellular Carcinoma:  Vaccination and Dietary Changes Show Promise to Eliminate Most Cases of Human  Liver Cancer. J Carcinogene Mutagene.2012; 3:e108.
 
  - Yildiran GS, Dizdar O, Oguz A,  Kucukoztas N, Rahatli S, et al. An Unusual Case: Gastric Metastasis of  Hepatocellular Carcinoma . Intern Med.2014; 4: 170.
 
  - Wen J, Wen X, Wang J, Shu Y, Qiu Z,  et al. Anti-cancer Effects of Glypican-3 on Huh-7 Hepatocellular Carcinoma  Cells. J Cell Sci Ther.2014; 5: 186.
 
  - Lewis M, Merched AJ Tumor-Associated  Macrophages, Inflammation and Pathogenesis of Hepatocellular Carcinoma. J Mol  Genet Med.2014; 8: 132.
 
  - Chen LY, Wang K, Chen Z Complete Response of Hepatocellular Carcinoma  to Sorafenib: A Case Report and Review of Literatures. J Liver.2014; 3: 164.
 
  - Sun CK, Chua MS, Wei W, So SK  Glypican-3-Mediates Autophagy and Promotes Self-Renewal and Tumor Initiation of  Hepatocellular Carcinoma Cells. J Stem Cell Res Ther.2014; 4:229.
 
  - Zakaria MK, Sankhyan A, Ali A, Fatima  K, Azhar E, et al. HBV/HCV Infection and Inflammation. J Genet Syndr Gene  Ther.2014; 5: 241.
 
  - Thakolwiboon S, Zhu J, Liang Q,  Welling TH, Zhang M, et al. Heterogeneity of The CD90+ Population in Different  Stages of Hepatocarcinogenesis. J Proteomics Bioinform.2014; 7: 296-302.
 
  - Kawabe N, Morise Z, Isetani M,  Arakawa S, Kawase J, et al. Is the  Indication of Liver Resection for Hepatocellular Carcinoma Expanding with the  Application of Laparoscopic Approach? J Gastroint Dig Syst.2014; 4: 214.
 
  - Chang PEJ, Purushotham S, Rumpel H,  Kee IHC, Ng RTH, et al. Novel Dual Magnetic Drug Targeting and Hyperthermia  Therapy in Hepatocellular Carcinoma with Thermosensitive Polymer-Coated  Nanoparticles. J Gastroint Dig Syst.2014; 4: 198.
 
  - Ma L  Pathology Features and Molecular Genetic Mechanisms of Hepatocellular  Carcinoma Development in Patients with Hepatitis C Associated Liver Cirrhosis.  Hereditary Genet .2014;3: e109.
 
  - Du L, Tang Z, Liu J, Tian J, Shao C  Therapeutic Effect Evaluation of 125I Seed Implantation for Treating Refractory  Hepatocellular Carcinoma. OMICS J Radiol.2014; 3: 165.
 
  - Hann HW, Li D, Yamada H, Satomura S,  Coben R, et al. Usefulness of Highly Sensitive AFP-L3 and DCP in Surveillance  for Hepatocellular Carcinoma in Patients with a Normal Alpha-Fetoprotein. J Med  Microb Diagn.2014; 3: 130.
 
  - Bertino G, Demma S, Bertino N, Ardiri  A Management of Hepatocellular Carcinoma: An Update at the Start of 2014. J  Gastroint Dig Syst.2014; 4: 178.
 
  - Abdelraouf A, Hamdy H, Ezzat H,  Hassan AMA, Elsebae MM Initial  Experience of Surgical Microwave Tissue Precoagulation in Liver Resection for  Hepatocellular Carcinoma in Cirrhotic Liver. J Liver.2014; 3: 150.
 
  - Zhang H, Xuan YC, Luo X, Cao J  Microwave Coagulation Therapy Combined with Laparoscopic Liver Resection for  Hepatocellular Carcinoma in Cirrhotic Patients. Journal of Vascular Medicine  & Surgery.2014; 2: 134.
 
  - Yamaguchi M The Regucalcin Gene is a Key in the Therapy  of Hepatocellular Carcinoma. J Cancer Sci Ther .2014;6: e132.
 
  - Kuo CJ, Wang SN, Liang SS, Chi SW, Yu  ZJ, et al. Shotgun Proteomics Analysis of Differentially Expressed Urinary  Proteins Involved in the Hepatocellular Carcinoma. J Proteomics Bioinform.2014;  7: 034-040.
 
  - Wu J, Ingham M Immunotherapy and Hepatocellular Carcinoma. J  Liver.2013; 2:e108.
 
  - Qasim A Role of Surveillance in Hepatocellular  Carcinoma. J Gastroint Dig Syst.2013; 3: 159.
 
  - Xie Y, Luo BW, Yuan XD, Tian PK, Ou  X, et al. Expression Characteristics of Surface Markers of Memory T cells,  CD45RO, CCR7 and CD62L, in Tumor-infiltrating Lymphocytes in Liver Cancer  Tissues of Patients with Hepatocellular Carcinomas. J Clin Cell Immunol  .2013;4: 181.
 
  - Vitale A, Salinas F, Zanus G,  Lombardi G, Senzolo M, et al. Could Sorafenib Disclose New Prospects as  Bridging Therapy to Liver Transplantation in Patients with Hepatocellular  Carcinoma? J Liver.2013; 2: 134.
 
  - Shabana MM, Salama MM, Ezzat SM,  Ismail LR. In Vitro and In Vivo Anticancer Activity of the Fruit Peels of  Solanum melongena L. against Hepatocellular Carcinoma. J Carcinogene  Mutagene.2013; 4: 149.
 
  - Cho W, Kim JM, Choi JY, Lee SH, Moon  HH, et al. Combination Therapy of Sirolimus and Sorafenibfor Recurrent  Hepatocellular Carcinoma after Liver Transplantation. Chemotherapy.2013; 2:  118.
 
  - Li W, Chen G, Yu X, Shi Y, Peng M, et  al. Accumulation of the Mutations in Basal Core Promoter of Hepatitis B Virus  Subgenotype C1 Increase the Risk of Hepatocellular Carcinoma in Southern China.  J Clin Exp Pathol.2013; 3: 141.
 
  - Kanda T, Yokosuka O, Omata M Androgen Receptor and Hepatocellular  Carcinoma. J Gastroint Dig Syst .2013;S12: 012.
 
  - Chen J, Yan G, Wang F, Yin X, Jin H,  et al. Quantitative Profiling of Histone H3 Methylation in Human Hepatocellular  Carcinoma. J Proteomics Bioinform.2013; S2: 003.
 
  - Fukui A, Ushijima K, Nishio S,  Fujiyoshi K, Kage M Long Survival in a Rare Case of Hepatocellular Carcinoma  that Metastasized to the Ovary: A Case Report. J Clin Case Rep.2013; 3:249.
 
  - Afzal M, Kazmi I, Khan R, Singh R,  Pravez M, et al. Pharmacological Evaluation of Gatifloxacin in Chemically  Induced Hepatocarcinogenesis: A New Tool for Hepatocellularcarcinoma Treatment.  J Cancer Sci Ther.2013; 5: 018-022.
 
  - Sell S Prevention of Hepatocellular Carcinoma:  Vaccination and Dietary Changes Show Promise to Eliminate Most Cases of Human  Liver Cancer. J Carcinogene Mutagene.2012; 3:e108.
 
  - de Almeida TMB, Cubero Leitão RM,  Yoshimoto M, Andrade JAD, Beçak W, et al. Detection of c-MYC Gene in  Micronucleated Hepatocytes from Regenerative Cirrhotic Nodules and  Hepatocellular Carcinoma of Hepatitis C Virus Infected Patients. J Carcinogene  Mutagene.2012; 3: 130.
 
  - Wang L, Wu H, Jiang M, Huang J, Lin  H, et al. Differential Differentiation- and Survival and Invasion-related  T-/H-cadherin (CDH13) Computational Downstream Network from No-Tumor  Hepatitis/Cirrhosis (HBV or HCV infection) to Human Hepatocellular Carcinoma  (HCC) Malignant Transformation. J Mol Biomark Diagn.2012; 2: 127.
 
  - Choi JH, Chung WJ, Jang BK, Hwang  JS Survival and Treatment Responses of  Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma. J  Cancer Sci Ther .2012;4: 292-298.
 
  - Qi L, Wang L, Jiang M, Huang J, Lin  HCytosolic Iron-Sulfur Protein Assembly 1 (CIAO1) Downstream Activation of  Phospholipase A2 and Hormone- Mediated Signaling-Induced Cell Death Network in  Human Hepatocellular Carcinoma (HCC) by Systems-Theoretical Analysis. Mol Biol.2012;  1: 105.
 
  - Chen W, Li M, Fang X, Fan Q, Yu  M Phase II Study of Bronchial Arterial  Infusion of P53 Gene in Treatment of Multiple Lung Metastases of Hepatocellular  Carcinoma. J Cancer Sci Ther.2012; 4: 124-126.
 
  - Wu J  Predictive Biomarkers to Therapy, do they Exist in Hepatocellular  Carcinoma? Chemotherapy.2012; 1:e104.
 
  - El Deen HSG, Sadaka EAE A Clinical  Phase II Study of Sorafenib in Advanced Hepatocellular Carcinoma. Anaplastology.2012;  1:101.
 
  - Hima Bindu A A New Era of Liver  Transplantation – Radioembolization, a Novel Therapy for Hepatocellular  Carcinoma. J Cancer Sci Ther .2011;S17
 
  - Naga Anusha P Risk  Factors in Hepatocellular Carcinoma. J Cancer Sci Ther.2011; S17.
 
  - Nguyen NTT, Harring TR, Guiteau JJ,  Cotton RT, de Armas IS, et al. Comparing Outcomes for Rare Primary Hepatic  Tumors after Liver Transplantation. J Transplant Technol Res.2011; 1:106.
 
  - Harring TR, Kuten DA, Nguyen NT, Goss  JA, O’Mahony CA Orthotopic Liver  Transplantation in Patients with Mixed Hepatocellular Carcinoma-  Cholangiocarcinoma. J Transplant Technol Res.2011; 1: 104.
 
  - Ettorre GM, Vennarecci G, Santoro R,  Miglioresi L, Lepiane P, et al. Experiences in Hepatic Surgery and  Transplantation after Radioembolization. J Nucl Med Radiat Ther.2011; 2:109.
 
  - Sangro B, Iñarrairaegui M Radioembolization for Hepatocellular  Carcinoma: Evidence-Based Answers to Frequently Asked Questions. J Nucl Med  Radiat Ther.2011; 2:110.
 
  - Schriefer P, Günes C, Wege H Rapid  Quantification of Telomerase Activity Employing an Improved Real-time Telomeric  Repeat Amplification Protocol in Clinical Tissue Samples Eliminates  Interference by PCR Inhibitors. J Cancer Sci Ther.2011; 3: 176-180.
 
  - Hao M, Lin H, Chen Q, Yu W, Zhou D, et  al. Efficacy of Transcatheter Arterial Infusion Alone or Combined with  Transcatheter Arterial Chemoembolization on Advanced Hepatocellular Carcinoma.  J Cancer Sci Ther.2011; 3: 130-133.
 
  - Yuan Y, Zhang YS, Qu XJ The Molecular Alterations Regarding Apoptosis  in Hepatocellular Carcinoma Cells at a Glance. J Carcinogene Mutagene.2011;  2:118.
 
  - Ishikawa T, Ishibashi J, Yamashita K,  Dalkhsuren SO, Sumida K, et al. Non-thermal Effects of Far-Infrared Ray (FIR) on Human Hepatocellular Carcinoma Cells HepG2 and their Tumors. J Cancer Sci  Ther .2009;1: 078-082.
 
  - Liu CY, Chang LC, Yang SW Metastatic Hepatocellular Carcinoma to the  Nasal Cavity: A Case Report and Review of the Literature. J Cancer Sci Ther.2011;  3: 081-083.
 
  - Koloukani SA, Cao A, Cao Q Radioembolization of Yttrium-90 Microspheres  for Clinical Treatment of Hepatic Malignancy. J Nucl Med Radiat Ther.2014; 5:  187.
 
  - Xie Y, Luo BW, Yuan XD, Tian PK, Ou  X, et al. Expression Characteristics of Surface Markers of Memory T cells,  CD45RO, CCR7 and CD62L, in Tumor-infiltrating Lymphocytes in Liver Cancer  Tissues of Patients with Hepatocellular Carcinomas. J Clin Cell Immunol .2013;4:  181.
 
  - Bei R Are Alpha-Fetoprotein  Based-Vaccines Potential Tools for Liver Cancer Therapy? J Liver .2013;2: e103.
 
  - Siddiqui A, Jeevani T, Naga Anusha P,  Hima Bindu A Stem Cell Therapy for Liver  Diseases. J Stem Cell Res The.2011; r 1: 111.