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      Contribution of Aflatoxin B 1 Exposure to Liver Cirrhosis in Eastern Ethiopia: A Case-Control Study

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          Abstract

          Background

          Liver cirrhosis is a global health problem due to a large number of disability-associated life years and mortality. However, evidence is scarce on its causes in Eastern-Ethiopia, a place where there is a high prevalence of liver cirrhosis of unknown etiology. This study attempted to identify the risk factors related to liver cirrhosis in the area.

          Methods

          A case-control study was conducted at a tertiary care hospital from January 2020 to July 2021. Following diagnoses using an ultrasound-based cirrhosis scale, a total of 127 cases were identified and compared with 253 control patients. A structured questionnaire and data abstraction form were used to collect demographic, lifestyle, and clinical information. A blood sample was also taken from each participant for clinical chemistry, hepatitis B virus (HBV), and hepatitis C virus tests as well as for an aflatoxin B 1 (AFB 1) albumin adduct (AF-alb) assay. Binary logistic regression analysis was used to determine predictors of liver cirrhosis.

          Results

          AF-alb levels were detected in 75% of the cases and 64% of the controls, with a median (IQR) level of 11 pg/mg (5.5–25) and 7.0 pg/mg (4.3–20.5), respectively (p<0.05). Moreover, the number of subjects with high AF-alb levels (≥8.6 pg/mg) was greater in cases (45%, p<0.05)) than controls (28%). Age ≥55 years (adjusted odds ratio (AOR)=0.4; 95% CI: 0.2, 0.8), being a farmer (AOR= 3.0; 95% CI: 1.5, 6.0), family history of liver disease (AOR= 2.9; 95% CI: 1.1, 7.9), HBV seropositivity (AOR=4.0; 95% CI: 1.9, 8.8), and exposure to high levels of AF-alb (AOR=2.0; 95% CI: 1.1, 3.7) were significantly associated with liver cirrhosis.

          Conclusion

          This study found a strong link between AFB 1 exposure and liver cirrhosis. Mitigation of aflatoxin exposure and a better understanding of additional environmental risk factors like pesticides may be necessary to reduce the disease burden in Ethiopia.

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          Most cited references60

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          Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis

          Background Liver cirrhosis is a major yet largely preventable and underappreciated cause of global health loss. Variations in cirrhosis mortality at the country level reflect differences in prevalence of risk factors such as alcohol use and hepatitis B and C infection. We estimated annual age-specific mortality from liver cirrhosis in 187 countries between 1980 and 2010. Methods We systematically collected vital registration and verbal autopsy data on liver cirrhosis mortality for the period 1980 to 2010. We corrected for misclassification of deaths, which included deaths attributed to improbable or nonfatal causes. We used ensemble models to estimate liver cirrhosis mortality with uncertainty by age, sex, country and year. We used out-of-sample predictive validity to select the optimal model. Results Global liver cirrhosis deaths increased from around 676,000 (95% uncertainty interval: 452,863 to 1,004,530) in 1980 to over 1 million (1,029,042; 670,216 to 1,554,530) in 2010 (about 2% of the global total). Over the same period, the age-standardized cirrhosis mortality rate decreased by 22%. This was largely driven by decreasing cirrhosis mortality rates in China, the US and countries in Western Europe. In 2010, Egypt, followed by Moldova, had the highest age-standardized cirrhosis mortality rates, 72.7 and 71.2 deaths per 100,000, respectively, while Iceland had the lowest. In Egypt, almost one-fifth (18.1%) of all deaths in males 45- to 54-years old were due to liver cirrhosis. Liver cirrhosis mortality in Mexico is the highest in Latin America. In France and Italy, liver cirrhosis mortality fell by 50% to 60%; conversely, in the United Kingdom, mortality increased by about one-third. Mortality from liver cirrhosis was also comparatively high in Central Asia countries, particularly Mongolia, Uzbekistan and Kyrgyzstan, and in parts of sub-Saharan Africa, notably Gabon. Conclusions Liver cirrhosis is a significant cause of global health burden, with more than one million deaths in 2010. Our study identifies areas with high and/or rapidly increasing mortality where preventive measures to control and reduce liver cirrhosis risk factors should be urgently strengthened. Please see related commentary: http://www.biomedcentral.com/1741-7015/12/159/abstract. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0145-y) contains supplementary material, which is available to authorized users.
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            Aflatoxin B1 metabolism: regulation by phase I and II metabolizing enzymes and chemoprotective agents

            Aflatoxin B1 (AFB1) widely contaminates staple food and feed crops and is well-known as the most potent natural hepatocarcinogen in humans and domesticated animals. This review highlights significant advances in our understanding of the pivotal role of phase I and II metabolizing enzymes in the bioactivation and detoxification of AFB1 and its metabolites across species. In humans, cytochrome P450 (CYP) 1A2, CYP3A4, CYP3A5, and CYP3A7 in liver and CYP2A13 in lung are essential for the bioactivation of AFB1 to the extremely toxic exo-AFB1-8,9-epoxide (AFBO), whereas CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are important in the turkey and duck, CYP1A1 and CYP2A6 are important in the chicken and quail, CYP3A11 and CYP3A13 are important in mice, and CYP2A5 are important in the hamster. In contrast, glutathione-S-transferase (GST) M1 and GSTT1 are primary responsible for detoxification of the AFB1 by catalyzing the conjugation of GSH to AFBO in humans, whereas GSTM2 in a nonhuman primate, GSTA3 in mice, GSTA5 in rats, and GSTA1, GSTA2, GSTA3 and GSTA4 in the turkey are important. Additionally, microsomal epoxide hydrolase (mEH) and aflatoxin-aldehyde reductase (AFAR) have also been shown to play key roles in AFB1 detoxification in the human, rat, and pig. Moreover, an overview of the chemoprotective agents, including synthetic compounds and naturally occurring plant compounds, which can be used to reduce aflatoxicosis is provided based on their ability to regulate these key enzymes. Collectively, this review summarizes the pivotal enzymes in the metabolism of AFB1 among humans, experimental and farm animals, as well as the chemoprotective agents that can be used to minimize risk of aflatoxicosis.
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              The influence of age on the development of the hepatitis B carrier state.

              The relation between the age at infection with hepatitis B virus (HBV) and the development of the carrier state is examined by using data from a number of published and unpublished surveys. A remarkably consistent relation was found. Infants infected perinatally (within the first 6 months of life) were found to have a high probability of becoming carriers (0.885; 95% C.L. 0.84-0.93). Over the infant and early childhood age classes there was found to be a sharp decrease in the proportion of infections which lead to the carrier state. By adulthood (over 15 years) the probability of developing the carrier status was found to be about 0.1. A model was fitted to the data by using maximum likelihood, which provides a good empirical description of the observed data and can be used to predict the expected probability of developing the carrier state given the age at infection. It is postulated that, as a result of this rapid decline in the probability of becoming a carrier during early childhood, a mass childhood immunization campaign, which will tend to postpone the average age at infection in the unvaccinated community, will have a disproportionately large impact on the rate of generation of new carriers.
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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                ijgm
                International Journal of General Medicine
                Dove
                1178-7074
                16 August 2023
                2023
                : 16
                : 3543-3553
                Affiliations
                [1 ]Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University , Addis Ababa, Ethiopia
                [2 ]School of Food Science and Nutrition, University of Leeds , Leeds, UK
                [3 ]Department of Internal Medicine, School of Medicine, College of Health and Medical Sciences, Haramaya University , Harar, Ethiopia
                [4 ]Department of Radiology, School of Medicine, College of Health and Medical Sciences, Haramaya University , Harar, Ethiopia
                [5 ]School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University , Harar, Ethiopia
                Author notes
                Correspondence: Ephrem Engidawork; Yun Yun Gong, Email ephrem.engidawork@aau.edu.et; y.gong@leeds.ac.uk
                Author information
                http://orcid.org/0000-0003-0675-9862
                http://orcid.org/0000-0003-4567-7042
                http://orcid.org/0000-0002-9931-6421
                Article
                425992
                10.2147/IJGM.S425992
                10440104
                37605782
                71698b46-3c00-4906-ab28-f27da26db527
                © 2023 Mekuria et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 June 2023
                : 14 August 2023
                Page count
                Figures: 1, Tables: 4, References: 61, Pages: 11
                Categories
                Original Research

                Medicine
                liver cirrhosis,aflatoxin,hepatitis b virus,ethiopia
                Medicine
                liver cirrhosis, aflatoxin, hepatitis b virus, ethiopia

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