Contribution of Aflatoxin B1 Exposure to Liver Cirrhosis in Eastern Ethiopia: A Case-Control Study

Mekuria, Abraham Nigussie; Xia, Lei; Ahmed, Tekabe Abdosh; Bishaw, Solomon; Teklemariam, Zelalem; Nedi, Teshome; Abula, Tefera; Engidawork, Ephrem; Gong, Yun

doi:10.2147/ijgm.s425992

Cited by 5 publications

(6 citation statements)

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“… 33–35 Indeed, in our recent study, HBV infection and AFB 1 exposure were the major culprits of liver cirrhosis in Eastern Ethiopia. 9 …”

Section: Discussionmentioning

confidence: 99%

“…This is a follow-up of a case–control study conducted from January 2020 – July 2021 to assess the risk factors associated with liver cirrhosis in the Internal Medicine Unit of Hiwot Fana Comprehensive Specialized University Hospital (HFCSUH), Harar, Eastern Ethiopia. 9 In brief, the study consisted of 127 confirmed cases of liver cirrhosis and 253 controls without any history or clinical evidence of liver diseases. Written consent from the participants was obtained after explaining aims of the study and a detailed questionnaire was filled out for each case and control by a trained interviewer.…”

Section: Methodsmentioning

confidence: 99%

“… 7 , 8 In our recent study, we found a strong association between AFB 1 exposure and liver cirrhosis. 9 AFB 1 is mainly metabolized by CYP3A4 into the reactive free radical AFB 1 -exo-8, 9-epoxide. 10 This intermediate metabolite is typically detoxified by conjugation with glutathione through the action of GST enzymes, mainly GSTM1 and GSTT1 encoded by the GSTM1 and GSTT1 gene, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia

Mekuria,

Seyoum,

Alemayehu

et al. 2023

TACG

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Background Polymorphisms in glutathione S-transferase M1 ( GSTM1 ) and T1 ( GSTT1 ) can cause an entire gene deletion. The current methodology can accurately identify GSTM1 and GSTT1 copy number variants (CNVs), which may shed light on the true contribution of each gene copy to the cellular detoxification process and disease risk. Because liver cirrhosis is becoming a critical worldwide health issue, this study determined the CNVs of GSTM1 and GSTT1 and their relationship to the risk of liver cirrhosis. Methods In this study, we compared 106 patients with liver cirrhosis to 104 healthy controls. Real-time PCR was used to identify the CNVs of GSTM1 and GSTT1 . Logistic and linear regression models were used to estimate the relationship between liver cirrhosis and clinical chemistry variables with the CNVs, respectively. Results In 3.3% of the study participants, >2 copies of the GSTM1 or GSTT1 genes were detected. GSTT1 carriers had a significantly lower risk of liver cirrhosis ( p <0.05) compared with individuals who had homozygous deletion (adjusted odds ratio (AOR) = 0.47; 95% CI: 0.25, 0.86). This risk reduction was significant ( p <0.05) in patients with a single copy of the GSTT1 gene (AOR = 0.48; 95% CI: 0.25, 0.91). Those with ≥2 copies of combined GSTM1 and GSTT1 also had a significantly ( p <0.05) lower risk of developing liver cirrhosis compared with double null genotypes (AOR = 0.38; 95% CI: 0.16, 0.91, p trend <0.001). Moreover, ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a substantial decrease in alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels, respectively. Conclusion A single copy number of GSTT1 , and ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a reduced risk of liver cirrhosis in Ethiopians. These findings underscore the importance of gene–environment interactions in the multifactorial development of liver cirrhosis.

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“… 33–35 Indeed, in our recent study, HBV infection and AFB 1 exposure were the major culprits of liver cirrhosis in Eastern Ethiopia. 9 …”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia

Mekuria,

Seyoum,

Alemayehu

et al. 2023

TACG

Self Cite

View full text Add to dashboard Cite

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“…This is part of a study conducted in a tertiary hospital in Harar, Eastern Ethiopia, to explore risk factors for liver cirrhosis from 1 January 2020 to 31 July 2021. 7 In short, the study included 253 controls who had no history of liver disease and 127 verified instances of hepatic cirrhosis. After explaining the study's objectives to the participants', written consent was obtained, and a professional interviewer completed a thorough questionnaire for each case and control.…”

Section: Study Setting and Subjectsmentioning

confidence: 99%

“…In this regard, our recent case-control study found aflatoxin B 1 (AFB 1 ) exposure as a potential missing etiologic factor of liver cirrhosis in Eastern Ethiopia, where significant cases of the disease were cryptogenic. 7 Thus, it is imperative to explore the potential predictive factors for the unknown etiology of liver cirrhosis to obtain clues for further missing etiologies and for potential sources of exposure to AFB 1 and its predictors. Hence, this study aimed to identify the possible sociodemographic, dietary, lifestyle, and clinical factors associated with the unknown etiology of liver cirrhosis in Eastern Ethiopia.…”

Section: Introductionmentioning

confidence: 99%

Liver Cirrhosis of Unknown Etiology and Its Predictors in Eastern Ethiopia

Mekuria,

Nedi,

Gong

et al. 2024

RMHP

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Background:The global burden of liver cirrhosis is increasing, with 2.1 million incident cases and nearly 1.5 million deaths in 2019. Despite the enormous progress in our understanding of the etiology of liver cirrhosis, significant cases of the disease have been reported in Eastern Ethiopia due to unidentified causes. Hence, this study aimed to identify predictors of liver cirrhosis of unknown etiology in Eastern Ethiopia. Methods: A score of 7 out of 11 possible points on the ultrasound-based cirrhosis scale was used as a diagnostic criterion to include 127 liver cirrhosis patients. The study participants' demographic, dietary, lifestyle, and clinical data were gathered using a structured questionnaire and standardized reporting forms. The associations between the outcome (known and unknown etiology) and independent variables were modeled using binary logistic regression analysis. Results: The etiology of liver cirrhosis was known in only 23% of patients and attributed to hepatitis B virus (21%), hepatitis C virus (0.8%), and alcohol abuse (0.8%). Sorghum consumption as a staple food (adjusted odds ratio (AOR) =3.8; 95% CI: 1.2, 12.5), splenomegaly (AOR = 4.0; 95% CI: 1.1, 14.4), and a family history of liver disease (AOR = 0.24; 95% CI: 0.06, 0.91) were significantly associated with liver cirrhosis of unknown etiology. Conclusion: Sorghum consumption was found to be the determinant factor of liver cirrhosis of unknown etiology, suggesting it as a possible source of exposure to aflatoxin B 1 .

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Establishing laboratory reference ranges for adults and children in Kilifi, Kenya

Downs,

Orindi,

Hamaluba

et al. 2024

Preprint

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Accurate laboratory reference ranges (RR) are essential for diagnosis and management of patients in routine clinical care and clinical trials. RRs vary between geographical location due to differences in population demographics and blood analysis equipment, so locally derived RRs are essential. Here we establish adult and paediatric RRs for a rural population in Kilifi, Kenya using clinical trial data from KEMRI-Wellcome Trust Research Programme (KWTRP). Data from healthy, non-pregnant participants from six clinical trials conducted between 2016 and 2020 were used. Coulter ACT 5 Diff and Ilab Aries were used for haematological and biochemical analysis respectively. Quality control was undertaken daily prior to sample analysis. Derived RRs were compared with RRs from other African countries and further afield. All analyses were performed using R version 3.6.1 (Reference Intervals package). 2338 adults and 2054 children were included, 52% of adults and 51% of children were male, median adult age was 32.5 years. Haemoglobin range was lower in women compared to men (9.5–14.2g/dL and 11.5–16.6g/dL respectively), platelet upper limit of normal (ULN) was higher in women compared to men (397 x 103/μL vs 358 x 103/ μL). Biochemistry values were higher in men (ALT ULN 57 U/L in men and 35 U/L in women, creatinine ULN 113umol/L in men and 91umol/L in women). Paediatric RRs showed differences in multiple parameters depending on the age of the child. In both adults and children, many parameters in 2023 Kilifi RRs differed from those in other countries. There was however little difference between 2023 and 2017 Kilifi paediatric RRs. This study provides RRs for adults and children in Kilifi, and the most extensive RRs available for much of East and Southern Africa. We show the need for locally derived reference ranges, highlighting differences between sex, age and geographical location.

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Contribution of Aflatoxin B1 Exposure to Liver Cirrhosis in Eastern Ethiopia: A Case-Control Study

Cited by 5 publications

References 57 publications

Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia

Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia

Liver Cirrhosis of Unknown Etiology and Its Predictors in Eastern Ethiopia

Establishing laboratory reference ranges for adults and children in Kilifi, Kenya

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