Download PDF
Semin Liver Dis 2020; 40(02): 111-123
DOI: 10.1055/s-0039-3399566
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Epidemiology of Liver Cancer in Africa: Current and Future Trends

Edith Okeke
1   Department of Internal Medicine, University of Jos, Jos, Plateau, Nigeria
,
Pantong Mark Davwar
1   Department of Internal Medicine, University of Jos, Jos, Plateau, Nigeria
,
Lewis Roberts
2   Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
,
Kurt Sartorius
3   Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, South Africa
,
Wendy Spearman
4   Division of Hepatology, Department of Medicine, University of Cape Town, Rondebosch, Western Cape, South Africa
,
Abraham Malu
1   Department of Internal Medicine, University of Jos, Jos, Plateau, Nigeria
,
Mary Duguru
1   Department of Internal Medicine, University of Jos, Jos, Plateau, Nigeria
› Author Affiliations
Further Information

Publication History

Publication Date:
14 November 2019 (online)

   Permissions and Reprints

Abstract

Hepatocellular carcinoma (HCC) is a disease of global public health significance with mortality on the rise, despite the preventable nature of its risk factors especially in Africa. It is now the sixth most common cancer worldwide, fifth in males, and ninth in females. HCC incidence and mortality are predicted to increase in African countries constrained by limited resources to combat endemic levels of viral infection and synergistic environmental risk factors. The changing nature of HCC etiology is particularly illustrated here with the traditional risk factors like viral hepatitis coexisting alongside high human immunodeficiency virus (HIV) prevalence and rapidly increasing urbanization that have promoted a sharp increase in additional risk factors like coinfection, type 2 diabetes mellitus, and obesity. Although there are some differences in etiology between North Africa and sub-Saharan Africa, risk factors like chronic viral hepatitis B and C, aflatoxin exposure, and iron overload predominate. Aggressive hepatitis B genotypes, combined with hepatitis B virus/hepatitis C virus/HIV coinfections and aflatoxin exposure, promote a more aggressive molecular phenotype. In parallel to a better understanding of the molecular etiology of HCC, policy and planning initiatives to address the burden of HCC must be anchored within the reality of the limited resources available. Establishment and coordination of cancer registries across Africa is needed to improve the quality of data necessary to galvanize action. Preventive measures including hepatitis B vaccination programs, measures to prevent maternal-to-child and child-to-child transmission, delivery of universally accessible antiretroviral and antiviral treatments, and reduction of dietary aflatoxin exposure can contribute markedly to reduce HCC incidence. Finally, the development of biomarkers and new therapeutic interventions will need a better understanding of the unique genetic and epigenetic characteristics of HCC on the continent. We present a narrative review of HCC in Africa, discussing present and future trends.

Keywords

hepatocellular carcinoma - epidemiology - Africa - HBV/HCV/HIV/ aflatoxin coinfections - iron overload
 

  • References

  • 1 New Global Cancer Data. GLOBOCAN 2018 | UICC. Available at: https://www.uicc.org/new-global-cancer-data-globocan-2018 . Accessed April 18, 2019
    PubMed
  • 2 Lemoine M, Thursz MR. Battlefield against hepatitis B infection and HCC in Africa. J Hepatol 2017; 66 (03) 645-654
    CrossrefPubMedGoogle Scholar
  • 3 Msyamboza KP, Manda G, Tembo B. , et al. Cancer survival in Malawi: a retrospective cohort study. Pan Afr Med J 2014; 19: 234
    PubMedGoogle Scholar
  • 4 Yang JD, Mohamed EA, Aziz AOA. , et al; Africa Network for Gastrointestinal and Liver Diseases. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium. Lancet Gastroenterol Hepatol 2017; 2 (02) 103-111
    PubMedGoogle Scholar
  • 5 Ng J, Wu J. Hepatitis B- and hepatitis C-related hepatocellular carcinomas in the United States: similarities and differences. Hepat Mon 2012; 12 (10 HCC): e7635
    PubMedGoogle Scholar
  • 6 Sukocheva OA. Estrogen, estrogen receptors, and hepatocellular carcinoma: are we there yet?. World J Gastroenterol 2018; 24 (01) 1-4
    CrossrefPubMedGoogle Scholar
  • 7 Iyer JK, Kalra M, Kaul A, Payton ME, Kaul R. Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis. World J Gastroenterol 2017; 23 (37) 6802-6816
    CrossrefPubMedGoogle Scholar
  • 8 Parkin DM, Bray F, Ferlay J, Jemal A. Cancer in Africa 2012. Cancer Epidemiol Biomarkers Prev 2014; 23 (06) 953-966
    CrossrefPubMedGoogle Scholar
  • 9 Bahri O, Ezzikouri S, Alaya-Bouafif NB. , et al. First multicenter study for risk factors for hepatocellular carcinoma development in North Africa. World J Hepatol 2011; 3 (01) 24-30
    CrossrefPubMedGoogle Scholar
  • 10 Wiredu EK, Armah HB. Cancer mortality patterns in Ghana: a 10-year review of autopsies and hospital mortality. BMC Public Health 2006; 6: 159
    CrossrefPubMedGoogle Scholar
  • 11 Tognarelli J, Ladep NG, Crossey MME. , et al. Reasons why West Africa continues to be a hotbed for hepatocellular carcinoma. Niger Med J 2015; 56 (04) 231-235
    CrossrefPubMedGoogle Scholar
  • 12 Liver cancer statistics. World Cancer Research Fund. Published August 22, 2018 . Available at: https://www.wcrf.org/dietandcancer/cancer-trends/liver-cancer-statistics . Accessed May 5, 2019
    PubMed
  • 13 WHO. | World Health Organization Assesses the World's Health Systems. WHO. Available at: https://www.who.int/whr/2000/media_centre/press_release/en/ . Accessed May 12, 2019
    PubMedGoogle Scholar
  • 14 Spearman CW, Afihene M, Ally R. , et al; Gastroenterology and Hepatology Association of sub-Saharan Africa (GHASSA). Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets. Lancet Gastroenterol Hepatol 2017; 2 (12) 900-909
    PubMedGoogle Scholar
  • 15 Sartorius K, Sartorius B, Aldous C, Govender PS, Madiba TE. Global and country underestimation of hepatocellular carcinoma (HCC) in 2012 and its implications. Cancer Epidemiol 2015; 39 (03) 284-290
    CrossrefPubMedGoogle Scholar
  • 16 Ofosu A, Ramai D, Reddy M. Non-alcoholic fatty liver disease: controlling an emerging epidemic, challenges, and future directions. Ann Gastroenterol 2018; 31 (03) 288-295
    PubMedGoogle Scholar
  • 17 Kew MC. Hepatocellular carcinoma in African Blacks: recent progress in etiology and pathogenesis. World J Hepatol 2010; 2 (02) 65-73
    CrossrefPubMedGoogle Scholar
  • 18 Yang X, Gao JY, Wang J, Cheng J. The impact of anti-HBV treatment on the occurrence and recurrence of hepatocellular carcinoma: focus on Asian studies. Discov Med 2015; 19 (103) 89-99
    PubMedGoogle Scholar
  • 19 World Health Organization, World Health Organization, Global Hepatitis Programme. Global Hepatitis Report, 2017. 2017. Available at: http://apps.who.int/iris/bitstream/10665/255016/1/9789241565455-eng.pdf?ua=1 . Accessed August 6, 2019
    PubMed
  • 20 Stanaway JD, Flaxman AD, Naghavi M. , et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet 2016; 388 (10049): 1081-1088
    CrossrefPubMedGoogle Scholar
  • 21 WHO. There's a reason viral hepatitis has been dubbed the “silent killer.” WHO. Available at: http://www.who.int/mediacentre/commentaries/viral-hepatitis/en/ . Accessed May 5, 2019
    PubMed
  • 22 WHO. _CDS_CSR_LYO_2002.2_HEPATITIS_B.pdf. Available at: https://apps.who.int/iris/bitstream/handle/10665/67746/WHO_CDS_CSR_LYO_2002.2_HEPATITIS_B.pdf;jsessionid=66B632636661BB9BDADC50C3C593CF89?sequence=1 . Accessed August 19, 2019
    PubMed
  • 23 Ladep NG, Lesi OA, Mark P. , et al. Problem of hepatocellular carcinoma in West Africa. World J Hepatol 2014; 6 (11) 783-792
    CrossrefPubMedGoogle Scholar
  • 24 Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn) 2018; 22 (03) 141-150
    PubMedGoogle Scholar
  • 25 Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118 (12) 3030-3044
    CrossrefPubMedGoogle Scholar
  • 26 Tamandjou C, Mufenda J, Landuleni W. Mother-to-child transmission of hepatitis B virus in Windhoek, Namibia: transmission dynamics and prevention [abstract 13]. Conference on Liver Disease in Africa. Nairobi, Kenya
    PubMed
  • 27 Tamandjou CR, Maponga TG, Chotun N, Preiser W, Andersson MI. Is hepatitis B birth dose vaccine needed in Africa?. Pan Afr Med J 2017; 27 (Suppl. 03) 18
    PubMedGoogle Scholar
  • 28 Yang JD, Altekruse S, Nguyen MH, Gores GJ, Roberts LR. Impact of Country of Birth on the Age of Diagnosis of Hepatocellular Carcinoma in the United States. Cancer 2017; 123 (01) 81-89
    CrossrefPubMedGoogle Scholar
  • 29 Yang JD, Roberts LR. Epidemiology and management of hepatocellular carcinoma. Infect Dis Clin North Am 2010; 24 (04) 899-919 , viii
    CrossrefPubMedGoogle Scholar
  • 30 Hepatitis C - Annual Epidemiological Report 2016 [2014 data]. European Centre for Disease Prevention and Control. Published May 23, 2016 . Available at: http://ecdc.europa.eu/en/publications-data/hepatitis-c-annual-epidemiological-report-2016-2014-data . Accessed August 6, 2019
    PubMed
  • 31 Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018; 391 (10127): 1301-1314
    CrossrefPubMedGoogle Scholar
  • 32 Yang JD, Altekruse SF, Nguyen MH, Gores GJ, Roberts LR. Impact of country of birth on age at the time of diagnosis of hepatocellular carcinoma in the United States. Cancer 2017; 123 (01) 81-89
    CrossrefPubMedGoogle Scholar
  • 33 Forbi JC, Ben-Ayed Y, Xia GL. , et al. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. J Clin Virol 2013; 58 (01) 59-66
    CrossrefPubMedGoogle Scholar
  • 34 Rajoriya N, Combet C, Zoulim F, Janssen HLA. How viral genetic variants and genotypes influence disease and treatment outcome of chronic hepatitis B. Time for an individualised approach?. J Hepatol 2017; 67 (06) 1281-1297
    CrossrefPubMedGoogle Scholar
  • 35 Kramvis A. Genotypes and genetic variability of hepatitis B virus. Intervirology 2014; 57 (3-4): 141-150
    CrossrefPubMedGoogle Scholar
  • 36 Kramvis A. Molecular characteristics and clinical relevance of African genotypes and subgenotypes of hepatitis B virus. S Afr Med J 2018; 108 (8b): 17-21
    CrossrefPubMedGoogle Scholar
  • 37 Brah S, Moussa S, Inoua A. , et al. Molecular characterization of hepatitis B virus from chronically-infected patients in Niamey, Niger. Int J Infect Dis 2016; 45: 18-23
    PubMedGoogle Scholar
  • 38 Ahmad AE, Bakari AG, Musa BOP. , et al. Pattern of prevalent hepatitis B virus genotypes in Zaria, Nigeria. Niger Postgrad Med J 2019; 26 (02) 80-86
    CrossrefPubMedGoogle Scholar
  • 39 Abd-Elsalam S, Elwan N, Soliman H. , et al. Epidemiology of liver cancer in Nile delta over a decade: a single-center study. South Asian J Cancer 2018; 7 (01) 24-26
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Ocama P, Opio KC, Kagimu M, Seremba E, Wabinga H, Colebunders R. Hepatitis B virus and HIV infection among patients with primary hepatocellular carcinoma in Kampala, Uganda. Afr Health Sci 2011; 11 (3, Suppl 1): S20-S23
    PubMedGoogle Scholar
  • 41 Andoulo FA, Kowo M, Talla P. , et al. Epidemiology of hepatitis B-associated hepatocellular carcinoma in Cameroon. Health Sci Dis 2013; 14 (01) 16-19
    PubMedGoogle Scholar
  • 42 Duduyemi BM, Asante D, Titiloye N, Afihene M. Abstract 5044: molecular analysis of HBV in histologically confirmed hepatocellular carcinoma in a tertiary hospital in Ghana. Cancer Res 2018; 78 (13, Supplement): 5044-5044
    PubMedGoogle Scholar
  • 43 Ndububa DA, Ojo OS, Adeodu OO. , et al. Primary hepatocellular carcinoma in Ile-Ife, Nigeria: a prospective study of 154 cases. Niger J Med 2001; 10 (02) 59-63
    PubMedGoogle Scholar
  • 44 Otedo A, Simbiri KO, Were V, Ongati O, Estambale BA. Risk factors for liver Cancer in HIV endemic areas of Western Kenya. Infect Agent Cancer 2018; 13 (01) 41
    CrossrefPubMedGoogle Scholar
  • 45 Mak D, Babb de Villiers C, Chasela C, Urban MI, Kramvis A. Analysis of risk factors associated with hepatocellular carcinoma in black South Africans: 2000-2012. PLoS One 2018; 13 (05) e0196057
    CrossrefPubMedGoogle Scholar
  • 46 Stockdale AJ, Mitambo C, Everett D, Geretti AM, Gordon MA. Epidemiology of hepatitis B, C and D in Malawi: systematic review. BMC Infect Dis 2018; 18 (01) 516
    CrossrefPubMedGoogle Scholar
  • 47 Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2017; 2 (03) 161-176
    PubMedGoogle Scholar
  • 48 Riou J, Aït Ahmed M, Blake A. , et al; HCV epidemiology in Africa group. Hepatitis C virus seroprevalence in adults in Africa: a systematic review and meta-analysis. J Viral Hepat 2016; 23 (04) 244-255
    CrossrefPubMedGoogle Scholar
  • 49 Epidemiology of Hepatitis C-Related Hepatocellular Carcinoma. Medscape. Available at: http://www.medscape.org/viewarticle/560012 . Accessed May 8, 2019
    PubMed
  • 50 Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014; 61 (1, Suppl): S58-S68
    CrossrefPubMedGoogle Scholar
  • 51 Ziada DH, El Sadany S, Soliman H. , et al. Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: a single center study. J Egypt Natl Canc Inst 2016; 28 (04) 257-262
    Google Scholar
  • 52 Raad II, Chaftari A-M, Torres HA. , et al. Challenge of hepatitis C in Egypt and hepatitis B in Mauritania. World J Hepatol 2018; 10 (09) 549-557
    CrossrefPubMedGoogle Scholar
  • 53 Reig M, Mariño Z, Perelló C. , et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016; 65 (04) 719-726
    CrossrefPubMedGoogle Scholar
  • 54 El Kassas M, Funk AL, Salaheldin M. , et al. Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: a comparative analysis. J Viral Hepat 2018; 25 (06) 623-630
    CrossrefPubMedGoogle Scholar
  • 55 Waziry R, Hajarizadeh B, Grebely J. , et al. Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: a systematic review, meta-analyses, and meta-regression. J Hepatol 2017; 67 (06) 1204-1212
    CrossrefPubMedGoogle Scholar
  • 56 Carrat F, Fontaine H, Dorival C. , et al; French ANRS CO22 Hepather cohort. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet 2019; 393 (10179): 1453-1464
    CrossrefPubMedGoogle Scholar
  • 57 Mariño Z, Darnell A, Lens S. , et al. Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: relevance of non-characterized nodules. J Hepatol 2019; 70 (05) 874-884
    CrossrefPubMedGoogle Scholar
  • 58 Na SK, Song B-C. Development and surveillance of hepatocellular carcinoma in patients with sustained virologic response after antiviral therapy for chronic hepatitis C. Clin Mol Hepatol 2019; 25 (03) 234-244
    CrossrefPubMedGoogle Scholar
  • 59 Ide T, Koga H, Nakano M. , et al. Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study. Hepatol Int 2019; 13 (03) 293-301
    CrossrefPubMedGoogle Scholar
  • 60 List of classifications, Volumes 1–123–IARC. Available at: https://monographs.iarc.fr/list-of-classifications-volumes/ . Accessed May 9, 2019
    PubMed
  • 61 Hamid AS, Tesfamariam IG, Zhang Y, Zhang ZG. Aflatoxin B1-induced hepatocellular carcinoma in developing countries: geographical distribution, mechanism of action and prevention. Oncol Lett 2013; 5 (04) 1087-1092
    CrossrefPubMedGoogle Scholar
  • 62 Ross RK, Yuan JM, Yu MC. , et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992; 339 (8799): 943-946
    CrossrefPubMedGoogle Scholar
  • 63 Bannasch P, Khoshkhou NI, Hacker HJ. , et al. Synergistic hepatocarcinogenic effect of hepadnaviral infection and dietary aflatoxin B1 in woodchucks. Cancer Res 1995; 55 (15) 3318-3330
    PubMedGoogle Scholar
  • 64 Selim MI, Popendorf W, Ibrahim MS, el Sharkawy S, el Kashory ES. Aflatoxin B1 in common Egyptian foods. J AOAC Int 1996; 79 (05) 1124-1129
    CrossrefPubMedGoogle Scholar
  • 65 Atawodi SE, Atiku AA, Lamorde AG. Aflatoxin contamination of Nigerian foods and feeding stuffs. Food Chem Toxicol 1994; 32 (01) 61-63
    CrossrefPubMedGoogle Scholar
  • 66 Korley Kortei N, Akomeah Agyekum A, Akuamoa F, Baffour VK, Wiisibie Alidu H. Risk assessment and exposure to levels of naturally occurring aflatoxins in some packaged cereals and cereal based foods consumed in Accra, Ghana. Toxicol Rep 2018; 6: 34-41
    PubMedGoogle Scholar
  • 67 Tchana AN, Moundipa PF, Tchouanguep FM. Aflatoxin contamination in food and body fluids in relation to malnutrition and cancer status in Cameroon. Int J Environ Res Public Health 2010; 7 (01) 178-188
    CrossrefPubMedGoogle Scholar
  • 68 Obade MI, Andang'o P, Obonyo C, Lusweti F. Sources of aflatoxin exposure in Kisumu County, Kenya. Food Nutr Current Res 2018; 1 (02) 42-50
    PubMedGoogle Scholar
  • 69 Kachapulula PW, Akello J, Bandyopadhyay R, Cotty PJ. Aflatoxin contamination of groundnut and maize in Zambia: observed and potential concentrations. J Appl Microbiol 2017; 122 (06) 1471-1482
    CrossrefPubMedGoogle Scholar
  • 70 Aflatoxin contamination in unrecorded beers from Kenya – A health risk beyond ethanol | Scinapse | Academic search engine for paper. Scinapse. Available at: https://scinapse.io/papers/2604990539 . Accessed May 9, 2019
    PubMed
  • 71 Kang'ethe EK, Korhonen H, Marimba KA. , et al. Management and mitigation of health risks associated with the occurrence of mycotoxins along the maize value chain in two counties in Kenya. Food Qual Safe 2017; 1 (04) 268-274
    PubMedGoogle Scholar
  • 72 Nigussie A, Bekele T, Gemede HF, Woldegiorgis AZ. Level of aflatoxins in industrially brewed local and imported beers collected from Ethiopia market. Cogent Food Agric 2018; 4 (01) 1453317
    PubMedGoogle Scholar
  • 73 Anwar WA, Khaled HM, Amra HA, El-Nezami H, Loffredo CA. Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res 2008; 659 (1-2): 176-184
    PubMedGoogle Scholar
  • 74 Kew MC. Synergistic interaction between aflatoxin B1 and hepatitis B virus in hepatocarcinogenesis. Liver Int 2003; 23 (06) 405-409
    CrossrefPubMedGoogle Scholar
  • 75 Molina-Sánchez P, Lujambio A. Iron overload and liver cancer. J Exp Med 2019; 216 (04) 723-724
    CrossrefPubMedGoogle Scholar
  • 76 Kew MC. Hepatic iron overload and hepatocellular carcinoma. Liver Cancer 2014; 3 (01) 31-40
    CrossrefPubMedGoogle Scholar
  • 77 Moyo VM, Mandishona E, Hasstedt SJ. , et al. Evidence of genetic transmission in African iron overload. Blood 1998; 91 (03) 1076-1082
    PubMedGoogle Scholar
  • 78 WHO. | Controlling the global obesity epidemic. WHO. Available at: https://www.who.int/nutrition/topics/obesity/en/ . Accessed June 13, 2019
    PubMed
  • 79 Afolabi WAO, Addo AA, Sonibare MA. Activity pattern, energy intake and obesity among Nigerian urban market women. Int J Food Sci Nutr 2004; 55 (02) 85-90
    CrossrefPubMedGoogle Scholar
  • 80 Misra A, Khurana L. Obesity and the metabolic syndrome in developing countries. J Clin Endocrinol Metab 2008; 93 (11, Suppl 1): S9-S30
    CrossrefPubMedGoogle Scholar
  • 81 Fezeu LK, Assah FK, Balkau B. , et al. Ten-year changes in central obesity and BMI in rural and urban Cameroon. Obesity (Silver Spring) 2008; 16 (05) 1144-1147
    CrossrefPubMedGoogle Scholar
  • 82 Ford ND, Patel SA, Narayan KMV. Obesity in low- and middle-income countries: burden, drivers, and emerging challenges. Annu Rev Public Health 2017; 38 (01) 145-164
    CrossrefPubMedGoogle Scholar
  • 83 Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol 2017; 23 (47) 8263-8276
    CrossrefPubMedGoogle Scholar
  • 84 Tuei VC, Maiyoh GK, Ha C-E. Type 2 diabetes mellitus and obesity in sub-Saharan Africa. Diabetes Metab Res Rev 2010; 26 (06) 433-445
    CrossrefPubMedGoogle Scholar
  • 85 Hall V, Thomsen RW, Henriksen O, Lohse N. Diabetes in sub Saharan Africa 1999-2011: epidemiology and public health implications. A systematic review. BMC Public Health 2011; 11: 564
    CrossrefPubMedGoogle Scholar
  • 86 Kengne AP, Bentham J, Zhou B. , et al; NCD Risk Factor Collaboration (NCD-RisC) – Africa Working Group. Trends in obesity and diabetes across Africa from 1980 to 2014: an analysis of pooled population-based studies. Int J Epidemiol 2017; 46 (05) 1421-1432
    CrossrefPubMedGoogle Scholar
  • 87 Wong CR, Nguyen MH, Lim JK. Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease. World J Gastroenterol 2016; 22 (37) 8294-8303
    CrossrefPubMedGoogle Scholar
  • 88 Ascha MS, Hanouneh IA, Lopez R, Tamimi TA-R, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010; 51 (06) 1972-1978
    CrossrefPubMedGoogle Scholar
  • 89 Said A, Ghufran A. Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma. World J Clin Oncol 2017; 8 (06) 429-436
    CrossrefPubMedGoogle Scholar
  • 90 Lurie MN, Rosenthal S. The concurrency hypothesis in sub-Saharan Africa: convincing empirical evidence is still lacking. Response to Mah and Halperin, Epstein, and Morris. AIDS Behav 2010; 14 (01) 34
    CrossrefPubMedGoogle Scholar
  • 91 Hoffmann CJ, Thio CL. Clinical implications of HIV and hepatitis B co-infection in Asia and Africa. Lancet Infect Dis 2007; 7 (06) 402-409
    CrossrefPubMedGoogle Scholar
  • 92 Thio CL, Seaberg EC, Skolasky Jr R. , et al; Multicenter AIDS Cohort Study. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002; 360 (9349): 1921-1926 1
    CrossrefPubMedGoogle Scholar
  • 93 Price JC, Thio CL. Liver disease in the HIV-infected individual. Clin Gastroenterol Hepatol 2010; 8 (12) 1002-1012
    CrossrefPubMedGoogle Scholar
  • 94 Kaspar MB, Sterling RK. Mechanisms of liver disease in patients infected with HIV. BMJ Open Gastroenterol 2017; 4 (01) e000166
    CrossrefPubMedGoogle Scholar
  • 95 Chang JJ, Sirivichayakul S, Avihingsanon A. , et al. Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection. J Virol 2009; 83 (15) 7649-7658
    CrossrefPubMedGoogle Scholar
  • 96 Mastroianni CM, Lichtner M, Mascia C, Zuccalà P, Vullo V. Molecular mechanisms of liver fibrosis in HIV/HCV coinfection. Int J Mol Sci 2014; 15 (06) 9184-9208
    CrossrefPubMedGoogle Scholar
  • 97 Dixon LJ, Barnes M, Tang H, Pritchard MT, Nagy LE. Kupffer cells in the liver. Compr Physiol 2013; 3 (02) 785-797
    PubMedGoogle Scholar
  • 98 Sacchi P, Cima S, Corbella M. , et al. Liver fibrosis, microbial translocation and immune activation markers in HIV and HCV infections and in HIV/HCV co-infection. Dig Liver Dis 2015; 47 (03) 218-225
    CrossrefPubMedGoogle Scholar
  • 99 Dika IE, Harding JJ, Abou-Alfa GK. Hepatocellular carcinoma in patients with HIV. Curr Opin HIV AIDS 2017; 12 (01) 20-25
    CrossrefPubMedGoogle Scholar
  • 100 Ladep NG, Agbaji OO, Agaba PA. , et al. Hepatitis B co-infection is associated with poorer survival of HIV-infected patients on highly active antiretroviral therapy in West Africa. J AIDS Clin Res 2013; (Suppl. 03) 006
    PubMedGoogle Scholar
  • 101 Cainelli F, Vento S. Liver disease in patients with HIV in sub-Saharan Africa. Lancet HIV 2015; 2 (10) e412-e413
    CrossrefPubMedGoogle Scholar
  • 102 Auerbach BJ, Reynolds SJ, Lamorde M. , et al; Rakai Health Sciences Program. Traditional herbal medicine use associated with liver fibrosis in rural Rakai, Uganda. PLoS One 2012; 7 (11) e41737
    CrossrefPubMedGoogle Scholar
  • 103 Debes JD, Bohjanen PR, Boonstra A. Mechanisms of accelerated liver fibrosis progression during HIV infection. J Clin Transl Hepatol 2016; 4 (04) 328-335
    PubMedGoogle Scholar
  • 104 Conference Programme AIDS 2018 . Available at: http://programme.aids2018.org/Abstract/Index . Accessed May 9, 2019
    PubMed
  • 105 HIV viremia and low cd4+ increase HCC risk in those without advanced liver fibrosis | CROI Conference. Available at: http://www.croiconference.org/sessions/hiv-viremia-and-low-cd4-increase-hcc-risk-those-without-advanced-liver-fibrosis . Accessed May 4, 2019
    PubMed
  • 106 Matsuzaki K, Murata M, Yoshida K. , et al. Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology 2007; 46 (01) 48-57
    CrossrefPubMedGoogle Scholar
  • 107 Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006; 6 (09) 674-687
    CrossrefPubMedGoogle Scholar
  • 108 Molecular mechanism of hepatocellular carcinoma. Available at: https://hrjournal.net/article/view/2730 . Accessed June 2, 2019
    PubMed
  • 109 Balakrishnan L, Milavetz B. Epigenetic regulation of viral biological processes. Viruses 2017; 9 (11) E346
    CrossrefPubMedGoogle Scholar
  • 110 Dizdaroglu M. Oxidatively induced DNA damage: mechanisms, repair and disease. Cancer Lett 2012; 327 (1-2): 26-47
    CrossrefPubMedGoogle Scholar
  • 111 Machida K, Cheng KT-N, Sung VM-H. , et al. Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci U S A 2004; 101 (12) 4262-4267
    CrossrefPubMedGoogle Scholar
  • 112 Ho DW-H, Lo RC-L, Chan L-K, Ng IO-L. Molecular pathogenesis of hepatocellular carcinoma. Liver Cancer 2016; 5 (04) 290-302
    CrossrefPubMedGoogle Scholar
  • 113 Schulze K, Nault J-C, Villanueva A. Genetic profiling of hepatocellular carcinoma using next-generation sequencing. J Hepatol 2016; 65 (05) 1031-1042
    CrossrefPubMedGoogle Scholar
  • 114 Ferreira RG, Cardoso MV, de Souza Furtado KM, Espíndola KMM, Amorim RP, Monteiro MC. Epigenetic alterations caused by aflatoxin b1: a public health risk in the induction of hepatocellular carcinoma. Transl Res 2019; 204: 51-71
    CrossrefPubMedGoogle Scholar
  • 115 Vhriterhire RA. Aflatoxin contribution to liver cancer burden in Nigeria: a mini review. Jos J Med 2016; 10 (02) 29-32 –32
    PubMedGoogle Scholar
  • 116 Qian GS, Ross RK, Yu MC. , et al. A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People's Republic of China. Cancer Epidemiol Prev Biomark 1994; 3 (01) 3-10
    PubMedGoogle Scholar
  • 117 Kutlu O, Kaleli HN, Ozer E. Molecular pathogenesis of nonalcoholic steatohepatitis- (NASH-) related hepatocellular carcinoma. Can J Gastroenterol Hepatol 2018; 2018: 8543763
    PubMedGoogle Scholar
  • 118 Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol 2013; 10 (11) 656-665
    PubMedGoogle Scholar
  • 119 Wei J, Feng L, Li Z, Xu G, Fan X. MicroRNA-21 activates hepatic stellate cells via PTEN/Akt signaling. Biomed Pharmacother 2013; 67 (05) 387-392
    CrossrefPubMedGoogle Scholar
  • 120 Spearman CWN, Sonderup MW. Preventing hepatitis B and hepatocellular carcinoma in South Africa: The case for a birth-dose vaccine. S Afr Med J 2014; 104 (09) 610-612
    CrossrefPubMedGoogle Scholar
  • 121 Cooke GS, Andrieux-Meyer I, Applegate TL. , et al; Lancet Gastroenterology & Hepatology Commissioners. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol 2019; 4 (02) 135-184
    CrossrefPubMedGoogle Scholar
  • 122 Mendy M, Peterson I, Hossin S. , et al. Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: no need for a booster dose. PLoS One 2013; 8 (03) e58029
    CrossrefPubMedGoogle Scholar
  • 123 Abozeid M, Alsebaey A, Abdelsameea E. , et al. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018; 75: 109-114
    CrossrefPubMedGoogle Scholar
  • 124 Gupta N, Mbituyumuremyi A, Kabahizi J. , et al. Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial. Lancet Gastroenterol Hepatol 2019; 4 (02) 119-126
    PubMedGoogle Scholar
  • 125 Liew W-P-P, Mohd-Redzwan S. Mycotoxin: its impact on gut health and microbiota. Front Cell Infect Microbiol 2018; 8: 60
    CrossrefPubMedGoogle Scholar
  • 126 Wang J, Tang L, Glenn TC, Wang J-S. Aflatoxin B1 induced compositional changes in gut microbial communities of male F344 rats. Toxicol Sci 2016; 150 (01) 54-63
    CrossrefPubMedGoogle Scholar
  • 127 El-Nezami HS, Polychronaki NN, Ma J. , et al. Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China. Am J Clin Nutr 2006; 83 (05) 1199-1203
    CrossrefPubMedGoogle Scholar
  • 128 WHO. . | Global Status Report on Alcohol and Health 2014 . WHO. Available at: http://www.who.int/substance_abuse/publications/alcohol_2014/en/ . Accessed May 9, 2019
    PubMed
  • 129 Akinyemiju T, Abera S, Ahmed M. , et al; Global Burden of Disease Liver Cancer Collaboration. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncol 2017; 3 (12) 1683-1691
    CrossrefPubMedGoogle Scholar
  • 130 Ferreira-Borges C, Esser MB, Dias S, Babor T, Parry CDH. Alcohol control policies in 46 African countries: opportunities for improvement. Alcohol Alcohol 2015; 50 (04) 470-476
    CrossrefPubMedGoogle Scholar
  • 131 Aflasafe - Aflasafe. Available at: https://aflasafe.com/aflasafe/ . Accessed May 11, 2019
    PubMed
  • 132 Atehnkeng J, Ojiambo PS, Cotty PJ, Bandyopadhyay R. Field efficacy of a mixture of atoxigenic Aspergillus flavus Link:Fr vegetative compatibility groups in preventing aflatoxin contamination in maize (Zea mays L.). Biol Control 2014; 72: 62-70
    CrossrefPubMedGoogle Scholar
  • 133 Latest on Economic Impacts of Aflatoxins in Africa and PACA Efforts to Catalyze Mitigation of the Problem. Published April 2, 2018 . Available at: https://www.agrilinks.org/post/latest-economic-impacts-aflatoxins-africa-and-paca-efforts-catalyze-mitigation-problem . Accessed March 14, 2019
    PubMed
  • 134 Jemal A, Bray F, Forman D. , et al. Cancer burden in Africa and opportunities for prevention. Cancer 2012; 118 (18) 4372-4384
    CrossrefPubMedGoogle Scholar
  • 135 Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999; 49 (01) 33-64 , 1
    CrossrefPubMedGoogle Scholar
  • 136 Kirk GD, Lesi OA, Mendy M. , et al. The Gambia Liver Cancer Study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa. Hepatology 2004; 39 (01) 211-219
    CrossrefPubMedGoogle Scholar
  • 137 Just 12 countries worldwide on track to eliminate hepatitis C infection by 2030, with United Kingdom, Italy and Spain among those joining the list – CDA Foundation. Available at: https://cdafound.org/just-12-countries-worldwide-on-track-to-eliminate-hepatitis-c-infection-by-2030-with-united-kingdom-italy-and-spain-among-those-joining-the-list/ . Accessed May 11, 2019
    PubMed
  • 138 Nde H, Robbins S, Razavi-Shearer-Spink D, Brandon S, Gamkrelidze I, Razavi H. Achieving World Health Organization targets for hepatitis B by 2030: results from 17 WHO AFRO countries. J Hepatol 2018; 68: S153-S154
    PubMedGoogle Scholar
  • 139 Ladep NG, Dona AC, Lewis MR. , et al. Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans. Hepatology 2014; 60 (04) 1291-1301
    CrossrefPubMedGoogle Scholar
  • 140 Inc MG. Towards Elucidating a Universal Panel of Diagnostic Biomarkers for... by Abellona U. Available at: https://livertree.easl.eu/easl/2018/international.liver.congress/206977/abellona.u.towards.elucidating.a.universal.panel.of.diagnostic.biomarkers.for.html . Accessed June 14, 2019
    PubMedGoogle Scholar
  • 141 Zekri A-RN, Alam El-Din HM, Bahnassy AA. , et al. Serum levels of soluble Fas, soluble tumor necrosis factor-receptor II, interleukin-2 receptor and interleukin-8 as early predictors of hepatocellular carcinoma in Egyptian patients with hepatitis C virus genotype-4. Comp Hepatol 2010; 9 (01) 1
    CrossrefPubMedGoogle Scholar
  • 142 Xu X, Tao Y, Shan L. , et al. The role of microRNAs in hepatocellular carcinoma. J Cancer 2018; 9 (19) 3557-3569
    CrossrefPubMedGoogle Scholar
  • 143 Qu C, Wang Y, Wang P. , et al. Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy. Proc Natl Acad Sci U S A 2019; 116 (13) 6308-6312
    CrossrefPubMedGoogle Scholar
  • 144 Bruix J, Raoul J-L, Sherman M. , et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 2012; 57 (04) 821-829
    CrossrefPubMedGoogle Scholar
  • 145 Nada Y, Rashad N, Eissa M. , et al. Outcomes of treatment with sorafenib in Egyptian patients with hepatocellular carcinoma: a retrospective cohort study. Expert Rev Gastroenterol Hepatol 2018; 12 (01) 99-107
    CrossrefPubMedGoogle Scholar
  • 146 Finkelmeier F, Waidmann O, Trojan J. Nivolumab for the treatment of hepatocellular carcinoma. Expert Rev Anticancer Ther 2018; 18 (12) 1169-1175
    CrossrefPubMedGoogle Scholar
  • 147 Pembrolizumab in Sorafenib-Pretreated Hepatocellular Carcinoma - The ASCO Post. Available at: https://www.ascopost.com/issues/december-25-2018/pembrolizumab-in-sorafenib-pretreated-hepatocellular-carcinoma/ . Accessed July 1, 2019
    PubMed