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

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 are 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). Additionally, it is not known whether recognized etiologic factors for cirrhosis constitute an exhaustive list or whether unidentified etiologic agents remain. HCC most commonly occurs in cirrhotic individuals (Chen et al. 2006; Takano et al. 1995). Risk factors for HCC have been extensively studied, and in addition to the etiologic factors for cirrhosis listed above, HCC is also associated with aflatoxin exposure [International Agency for Research on Cancer (IARC) 1993; Qian et al. 1994]. Although the biologic mechanisms that induce cirrhosis and carcinogenesis are different, the considerable overlap in causative factors between cirrhosis and HCC suggests that factors that have thus far only been linked to HCC may also predispose to cirrhosis. In this study, we investigated the diagnosis of liver cirrhosis via a noninvasive, validated ultrasound scoring system (Hung et al. 2003; Lin et al. 1993) among individuals with suspected liver disease in The Gambia, West Africa. Then, in a case–control study design, we examined environmental exposures for cirrhosis, including viral, dietary, and lifestyle risk factors in this population. Finally, we explored interactions between HBV and aflatoxin exposure to more precisely describe the etiology of this major public health problem in a sub-Saharan African population.