Academic journal article Environmental Health Perspectives

Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in the Gambia, West Africa

Academic journal article Environmental Health Perspectives

Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in the Gambia, West Africa

Article excerpt

BACKGROUND: Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region.

OBJECTIVES: We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia.

METHODS: Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and die aflatoxin-associated [249.sup.ser] TP53 mutation.

RESULTS: HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (CI), 4.4-14.7] as was the presence of HBeAg (OR = 10.3; 95% CI 2.0-53.9) and HCV infection (OR = 3.3; 95% CI, 1.2-9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the [249.sup.ser] TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1-7.7 and OR = 3.8; 95% CI, 1.5-9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant. CONCLUSIONS: Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis.

Key WORDS: aflatoxin, Africa, hepatitis B virus, liver cirrhosis, p53, The Gambia, ultrasound. Environ Health Perspect 116:1553-1557 (2008). doi:10.1289/ehp.11661 available via http://dx.doi.org/ [Online 10 July 2008]

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide [World Health Organization (WHO) 2003], and a heavy burden of HCC has been documented in sub-Saharan Africa (Bah et al. 2001; Bosch et al. 2005). Chronic infection with hepatitis B virus (HBV) is endemic in sub-Saharan Africa, and hepatitis C virus (HCV) infection is also present (McMahon 2005; The Global Burden of Hepatitis C Working Group 2004). Dietary exposure to aflatoxin, primarily through ingestion of contaminated maize and groundnuts (peanuts), is also widespread (Turner et al. 2005; Wild et al. 1993). Largely because of the lack of clinical and research infrastructure, rigorous investigation into the etiology and characteristics of chronic liver disease in sub-Saharan Africa has been limited. Studies on HCC ate relatively rare, and controlled studies on the etiology of cirrhosis have been reported even less frequently (Lesi et al. 2002).

Worldwide, cirrhosis of the liver is the 16th leading cause of death, responsible for hundreds of thousands of deaths each year (WHO 2003). Cirrhosis onset is often asymptomatic or associated with mild clinical symptoms, and individuals with subclinical cirrhosis can lead relatively normal lives for many years. Cirrhotic persons, however, are at high risk for liver decompensation and, irrespective of etiology, have a high risk for development of HCC. Diagnosis of cirrhosis, generally requiring histopathologic review of a liver biopsy specimen, is infrequently performed in many resource-constrained settings. In developed countries, cirrhosis is associated with chronic infection with HBV and HCV viruses (Corrao et al. 1998; Tsai et al. 1994, 2003), excessive use of alcohol (Corrao et al. 1998; Tsai et al. 2003), hereditary factors (Gershwin et al. 2005), obesity (Poonawala et al. 2000), smoking (Tsai et al. 2003), and occupational exposure to vinyl chloride (Mastrangelo et al. 2004), but evaluation of potential interactions between these risk factors are only beginning to be conducted (Corrao et al. 1998; Mastrangelo et al. 2004). …

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