HEPATOCELLULAR CARCINOMA IN SUB-SAHARAN AFRICA

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Compared with HCC patients in other regions, Africa has the youngest mean age years at diagnosis 45 compared with Japan 69 , Europe 63 - 65 , North America 62 , Korea 57 and China 55 - 59 , which results in the greatest number of years of potential life lost. Potential causes of bias such as the younger population age distribution in Africa appear not to account entirely for the observed phenomenon.

Data from Asia suggests that particular HBV genotypes and sub-genotypes are associated with increased viral replication, which in turn is associated with an increased risk of HCC. The extent of the contribution of dietary Aflatoxin B1 exposure to the younger onset of HCC in Africa is also not clear. Increasingly, non-alcoholic fatty liver disease NAFLD is recognised as an important contributor to liver carcinogenesis.

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Survival of patients with HCC also varies between countries. Over 84 months of follow up, median survival was not reached in Taiwan and was 60 months in Japan, as compared to regions or countries with less effective programs such as North America 33 months , South Korea 31 months , Europe 24 months , and China 23 months.

The Right Drug for the Right Patient with Hepatocellular Carcinoma

Egypt had the longest median survival The molecular pathogenesis of HCC varies nearly as much as the epidemiology of this devastating disease. Fortunately, continual progress in genetic and molecular analyses is yielding rapidly increasing amounts of data on the genetic and molecular alterations associated with development and progression of HCC. HCCs contain, on average, 20 - mutations per genome, which is similar to the majority of solid tumours.


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In this section, we outline the most significant genetic and genomic aberrations. The inflammatory environment produces high levels of genotoxic reactive oxygen species ROS , which cause oncogenic mutations and mutational and epigenetic inactivation of tumor suppressors, contributing to the acquisition of the minimum complement of molecular alterations needed for the malignant phenotype.

Mutations associated with the tumour suppressor gene, TP53, are the second most common genetic alteration in HCC. The mutational spectrum of p53 in HCC also varies across geographical regions. Primary and secondary prevention of HCC. Primary and secondary prevention of HCC are particularly important in resource-limited countries, including most SSA countries, where imaging technology to identify early-stage disease and effective treatment options are both lacking.

In these countries, the main focus should be on primary prevention in order to decrease risk factors such as viral hepatitis and cirrhosis, and secondary prevention through identification of patients with established risk factors and enrolling them in surveillance programmes for HCC, which are more cost effective and require more basic measures. Community and patient education by national education campaigns and through primary care providers on the most common causes of HCC, including viral hepatitis, alcohol abuse, aflatoxin exposure and metabolic syndrome, is an important strategy for primary prevention.

Communities should be educated about routes of transmission and methods of protection against viral hepatitis, alcohol abuse screening and prevention, proper storage of grains and other harvested foods in hot, humid climates to prevent aflatoxin exposure, and obesity-associated liver disease. Given the strong association with viral hepatitis, prevention of new infections through applying universal precautions and avoiding unsafe medical procedures and injections, 38 HBV vaccination at birth and as part of the expanded programme of immunisation, postexposure prophylaxis and appropriate treatment of existing infections play key roles in the primary prevention of HCC.

Secondary prevention or screening tests are applied in a continuous programme of ongoing surveillance to enhance detection of cancer at early stages during which treatment is more likely to be curative. The decision to enroll a patient in a surveillance programme for HCC is dependent on the estimated risk for HCC and the likelihood of benefit from therapy if HCC is discovered at an early stage. High-risk patients include those with cirrhosis due to any aetiology excluding those with Child-Pugh stage C who are not on a transplant waiting list given the low anticipated survival for these patients and those with chronic viral HBV without cirrhosis if they were born in Africa or Asia and are over 20 years of age for Africans, over 40 years of age for Asian males, and over 50 years of age for Asian females.

Individuals with a family history of HCC or with chronic active hepatitis are at particularly increased risk. The use of alpha-fetoprotein AFP for HCC screening has been controversial Table 1 , given its low sensitivity for diagnosis of early-stage disease and difficulties with specificity in individuals with active liver inflammation and regeneration. However, since US is insensitive in patients with central obesity and for those with infiltrative HCCs that do not have a nodular component, there is increasing consensus that the use of AFP in addition to US is warranted.

The recommended surveillance interval is 6 months for suitable candidates. Challenges in SSA countries.

Epidemiology of hepatocellular carcinoma in sub-Saharan Africa. - PubMed - NCBI

Since HBV is the most common cause of HCC worldwide, a full appreciation of the current status and secular trends in rates of chronic HBV infection, the consequent development of cirrhosis, end-stage liver disease, and HCC, as well as the outcomes of these complications is important for the development of a sound global health policy. Several limitations present in SSA countries lead to inadequate primary prevention in these countries. The majority of chronic HBV infections in Africa are due to perinatal or early childhood transmission, which can be successfully prevented by HBV vaccination within 24 hours of birth followed by two additional doses, as recommended by WHO.

Consequently, a proportion of children who do not receive the birth dose will already be HBV-positive by the time they receive the first dose of pentavalent vaccine.

Despite the proven benefit for patients who are at risk of developing HCC, comprehensive surveillance programmes are lacking in SSA due to several challenges. Surveillance requires relatively expensive US machines and well-trained personnel. Lack of regional guidelines that take into consideration the limited resources in most SSA countries is another important challenge. Efforts should be spent to adapt the international guidelines Table 1 and make them more applicable to SSA countries.

Once HCC is diagnosed, there is also a critical need for local capability for the key curative and palliative treatments used for HCC, including surgical resection, local ablation, and locoregional chemoembolisation. There is a need to establish regional centers of excellence, to which patients with early and intermediate stage disease can be referred for treatment. There is also an urgent need for countries governments to approve treatments for advanced stage disease, and to negotiate lower costs for these often-expensive therapies.

The recent advances in the development of targeted anticancer therapies, including sorafenib, regorafenib, lenvatinib and the immune checkpoint inhibitor nivolumab can only be deployed to reduce the burden of morbidity and mortality from HCC in sub Saharan Africa if there are ardent efforts to ensure their availability at prices that are within the reach of patients in this region.

HCC incidence correlates closely with the incidence of viral hepatitis B and C, which are the most important risk factors for HCC worldwide. The pathogenic mechanisms underlying HCC development, progression and metastasis are being actively deciphered, and novel discoveries hold promise for the development of effective systemic therapies for patients with intermediate and advanced stage disease.

Finally, screening for HCC in high risk patients leads to detection of HCC at early curative stages, which in turn leads to improvement in overall survival. There is a critical need to build local capability in surgical resection, local ablation, and locoregional chemoembolisation, as well as a major need to address the cost of pharmaceutical treatments for patients with advanced stage disease. We gratefully acknowledge administrative support from Lisa M.

Author contributions. All authors contributed equally to the preparation of the manuscript for publication. Conflicts of interest. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, to A systematic analysis for the global burden of disease study. JAMA oncology ;3 4 Global and country underestimation of hepatocellular carcinoma HCC in and its implications. Cancer Epidemiol ;39 3 Problem of hepatocellular carcinoma in West Africa. World J Hep ;6 11 J Hepatol ;56 4 Int J Cancer ; 5 :E The global burden of viral hepatitis from to Findings from the Global Burden of Disease Study Lancet ; Kew MC.

Hepatocellular carcinoma: Epidemiology and risk factors.

Hepatitis C virus-induced hepatocellular carcinoma in sub-Saharan Africa

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Download: PPT. Table 1. Demographic and virological characteristics: HCC cases and age- and sex-matched control participants from the Johannesburg Cancer Case Control Study, to Table 2. Table 3.

Table 4.