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      Drastic sex-dependent etiological distribution in severe liver diseases from Gabon

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          Abstract

          Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3–1.8). Ethanol consumption was highly prevalent in both disease types (65.0%–70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were also widespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50 mm and a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon.

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          Most cited references35

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Hepatocellular carcinoma

            Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.
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              Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability.

              Liver cancer is the second leading cause of global cancer mortality. The major risk factors for hepatocellular carcinoma (HCC) are being addressed with success by prevention efforts. Vaccination against hepatitis B virus has reduced incidence of HCC in Taiwan and is partly responsible for lower rates in China. New infections with hepatitis C virus are low in developed countries because of prevention of posttransfusion infections and reduced exposure to HCV by drug users. Aflatoxin exposure has been reduced by better grain storage and dietary changes. Obesity, metabolic syndrome, and diabetes are increasing in developed and developing countries and will lead to more cases of HCC.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1744768
                URI : https://loop.frontiersin.org/people/1899312
                URI : https://loop.frontiersin.org/people/1030960
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                15 September 2022
                2022
                : 12
                : 907554
                Affiliations
                [1] 1 Laboratoire de Biologie Moléculaire et Cellulaire (LABMC), Université des Sciences et Techniques de Masuku (USTM) , Franceville, Gabon
                [2] 2 Unité des Infections Rétrovirales et Pathologies Associées, Centre International de Recherches Médicales de Franceville (CIRMF) , Franceville, Gabon
                [3] 3 Service de Gastroentérologie, Centre Hospitalier Universitaire de Libreville (CHUL) , Libreville, Gabon
                [4] 4 Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et Service de Santeí Militaire (CIRMF-SSM) , Libreville, Gabon
                [5] 5 Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur , Paris, France
                Author notes

                Edited by: Prasanna K. Santhekadur, JSS Academy of Higher Education and Research, India

                Reviewed by: Khaled Farid, Mansoura University, Egypt; Eric Simon, Boehringer-Ingelheim Pharma GmbH&Co KG, Germany; Karan Kumar, Mahatma Gandhi University of Medical Sciences Technology, India

                *Correspondence: Pascal Pineau, pascal.pineau@ 123456pasteur.fr ; Pamela Moussavou-Boundzanga, pamelamoussavoub@ 123456gmail.com

                This article was submitted to Cancer Epidemiology and Prevention, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.907554
                9521596
                62431a08-b8a1-4586-b0a6-4fedc4b71ae2
                Copyright © 2022 Moussavou-Boundzanga, Itoudi Bignoumba, Mouinga-Ondeme, Iroungou, Bivigou-Mboumba, Marchio, Saibou, Moussavou Kombila and Pineau

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 March 2022
                : 22 August 2022
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 35, Pages: 11, Words: 4688
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                middle africa,gabon,liver cirrhosis,hepatocellular carcinoma,primary liver cancer (plc),hepatitis virus,alcohol,sex-difference

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