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

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 B1 (AFB1) 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 AFB1 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.

Field performance of HBsAg rapid diagnostic tests in rural Ethiopia.

Point-of-care rapid diagnostic tests (POC-RDTs) are widely used to screen and diagnose hepatitis B virus (HBV) infection and are often the only available diagnostic tools in resource-limited settings. The aim of this study was to evaluate the validity of three hepatitis B surface antigen (HBsAg) POC-RDTs (Healgen®, Advanced Quality™ and Determine™) in an area with high prevalence of HBV in eastern Ethiopia. Results were compared with a commercial enzyme linked immunosorbent assay (ELISA) as gold standard. Quantification of HBsAg was performed in false negative samples. A total of 511 subjects were screened, of whom 81 (15.9 %) were HBsAg-positive with the gold standard. All three POC-RDTs were positive in 65 of the 81 positive samples, yielding a sensitivity (95 % confidence interval) of 80.2 % (70.3-87.5) and a specificity of 99.8 % (98.7-100 for Healgen® and Determine™; 98.6-100 for Advanced Quality™). False negatives were observed in 16 patients associated with low levels of HBsAg (median 1.5 IU/mL). All three POC-RDTs had reasonably high sensitivity and excellent specificity, but false negative results were observed in patients with low titres of HBsAg. Thus, these POC-RDTs might be useful to identify patients in need of HBV treatment, but cannot be recommended as blood donor screening tests.

Unexplained chronic liver disease in Ethiopia: a cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation.

Khat chewing increases the risk for developing chronic liver disease: A hospital-based case-control study.

The chewing of the leaves of Catha edulis (khat) has been implicated in the development of liver disease, but no controlled observations have been undertaken. The objective of the present study was to determine whether khat chewing is associated with development of chronic liver disease (CLD). A case-control study was conducted at two public hospitals in Harar, Ethiopia, between April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees with CLD were included as cases, and 300 adult hospital attendees without clinical or laboratory evidence of CLD were included as controls. Khat consumption was quantified in "khat years"; 1 khat year was defined as daily use of 200 g of fresh khat for 1 year. A logistic regression model was used to control for confounders. There was a significant association between chewing khat and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval [CI], 1.56-4.58). In men, this risk, following adjustment for age, alcohol use, and chronic hepatitis B/C infection, increased with increasing khat exposure; thus, compared to never users the adjusted odds ratios were for low khat exposure 3.58 (95% CI 1.05-12.21), moderate khat exposure 5.90 (95% CI 1.79-19.44), and high khat exposure 13.03 (95% CI 3.61-47.02). The findings were robust in a post hoc sensitivity analysis in which individuals with identifiable risk factors for CLD were excluded. CONCLUSION: A significant association was observed between chewing khat and the risk for developing CLD, and in men the association was strong and dose-dependent, suggesting a causal relationship; as the prevalence of khat chewing is increasing worldwide, these findings have major public health implications. (Hepatology 2018;68:248-257).

High Seroprevalence of Autoantibodies Typical of Autoimmune Liver Disease in Eastern Ethiopia: Is Chewing of Khat (Catha edulis) a Triggering Factor?

Background: Recent studies have identified chewing of khat (Catha edulis) as an independent risk factor for liver injury; however, the pathogenetic mechanism remains poorly understood. Case series have found markers of autoimmune hepatitis in patients with khat-related liver disease, suggesting that khat chewing might trigger an autoimmune response. The aims of the present study were (i) to assess the prevalence of autoantibodies typical for autoimmune liver diseases in a healthy population in Ethiopia and (ii) to explore the hypothesis that khat usage triggers autoimmunity. Methods: Consenting adults (≥18 years) without known autoimmune disease or manifest liver disease were included. One-hundred-and-sixty-nine individuals with current khat use were compared to 104 individuals who never used khat. Seroprevalence of antinuclear (ANA), antismooth muscle (SMA), and antimitochondrial antibodies (AMA) were determined and compared between the groups using logistic regression models to adjust for age and sex. Results: Overall, 2.6% of the study subjects were positive for ANA, 15.4% for SMA, and 25.6% for AMA. When comparing khat users to nonusers, ANA was detected in 4.1% vs. 0% (p=0.047), SMA in 16.0% vs. 14.4% (p=0.730), and AMA in 24.9% vs. 26.9% (p=0.704). ANA was excluded from multivariable analysis since there was no seropositive in the reference group. After adjusting for sex and age, no significant association between khat use and SMA or AMA was found. Conclusions: No association between khat usage and the seropresence of SMA or AMA was found, weakening the hypothesis that khat-related liver injury is mediated through autoimmune mechanisms. However, the seroprevalences of AMA and SMA were strikingly high in this Ethiopian population compared to global estimates, suggesting that diagnostic algorithms for autoimmune liver diseases developed in Europe and North America might lead to misdiagnosis of patients on the African continent.