Mycotoxins--toxic substances produced by fungi or molds--are ubiquitous in the environment and are capable of damaging multiple biochemical mechanisms, resulting in a variety of human symptoms referred to collectively as "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with respect to their ultimate damage, but also in their routes of detoxification. This suggests potential therapeutic options for the challenging treatment of mycotoxicosis. In this brief review, the author examines the use of lipoic acid as an example of an inexpensive and available nutrient that has been shown to protect against, or reverse, the adverse health effects of mycotoxins.

Although gratifying progress has been made during the 20th century, much remains to be achieved. The principal objective must be prevention of HCC. Prevention of HBV-related tumors is already feasible, and prevention of HCV-related and aflatoxin-induced tumors should soon become possible. Not all HCCs are yet accounted for causatively, and the remaining risk factors need to be identified. Until primary prevention can be accomplished, attention must also be directed to obtaining a complete understanding of the pathogenesis of HCC so that strategies for secondary and tertiary prevention can be formulated and instituted. Finally, the search for effective anticancer treatment must continue.

This study investigated whether aflatoxin contamination of peanut products may contribute to the incidence of hepatocellular carcinoma (HCC) in Sudan. Thirty-seven peanut butter and peanut samples were collected from local markets. Aflatoxin concentrations were significantly higher in West Sudan [87.4 +/- 197.3 (SD) micrograms/kg], a high-risk area, than in Central Sudan (8.5 +/- 6.8 micrograms/kg), a low-risk area. In West Sudan, humid local storage conditions of peanut products were related to high aflatoxin concentrations. In a small case-control study of HCC patients (n = 24) and controls (n = 34), an odds ratio of 7.5 (95% confidence interval = 1.4-40.2) was observed for humid vs. dry local storage conditions. Development of an index of individual HCC exposure was less successful, probably because of year-to-year variability in aflatoxins in food. These preliminary findings justify further research into the role of aflatoxins and hepatitis in HCC incidence in Sudan.

The incidence of primary liver cancer in Chinese, Japanese, and Filipino migrants to the United States and their descendants is compared with that of United States-born Whites. Incident liver cancer cases were ascertained between 1973 and 1986 from population-based cancer registries serving the San Francisco/Oakland (CA) metropolitan area, 13 counties of western Washington, and Hawaii. The population of these three areas, with regard to age, race, and country of birth, was estimated from a special tabulation of the 1980 US census. Rates of primary liver cancer were higher for men born in Asia than Asian men born in the US, who, in turn, had higher rates than did US Whites (respective annual rates per 100,000: Chinese, 26.5 and 9.8; Japanese, 16.5 and 6.6; Filipinos, 11.4 and 6.5; US Whites, 3.4). Among Asian American women, the trends were not as consistent (respective annual rates per 100,000: Chinese, 2.2 and 3.7; Japanese, 1.9 and 1.4; Filipino, 2.6 and 0; US Whites, 1.1). In general, liver cancer incidence among Asian Americans was lower than among residents of Asia. These findings are compatible with substantial variation among Asians in the prevalence of one or more etiologic factors for liver cancer, such as hepatitis-B infection and aflatoxin consumption, in relation to residence and place of birth.

This review has focused on the unique role of radionuclide scintigraphy in characterization of hepatic mass lesions. Radionuclide scintigraphy, unlike most other imaging modalities, is based on specific physiological and biochemical properties of each pathological entity that affects the liver. Hepatic scintigraphy, with its widespread availability, noninvasive nature, and relatively low cost is a powerful adjunct to other imaging techniques in the investigation of hepatic mass lesions. We have reviewed clinical presentation and characteristic findings of most hepatic lesions and have described reported findings with all available imaging modalities with particular emphasis on hepatic scintigraphy (Table 1) as well as a suggested algorithm for workup of solid hepatic masses (Fig 6). Additionally, the role of newer, more specialized techniques including PET scanning, 123I-labeled VIP, and 111In-labeled DTPA-D-Phe-octreotide scanning are reviewed. Hepatic nuclear scintigraphy continues to play an important role in the management of patients with solid hepatic masses.

The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow-up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (chi 2 = 3.116, P < .05). Using the Kaplan-Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P = .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC cases.

Total hepatectomy plus liver transplantation was performed on 105 patients considered unsuitable for liver resection. Postoperative 5-year actuarial survivals correlated with the pathologic stage of the tumor: stage I 75%, stage II 68%, stage III 52.1%, and stage IVA 11%. The overall 5-year survival for all patients was 36%. Nodal disease, bilobar tumor, and macroscopic venous invasion were significant poor-prognosis features. In addition, 12 patients with pT4N1M0 lesions (also stage IVA) had hepatectomy plus more extensive en bloc regional resection (Whipple procedure or cluster resection) plus transplantation in an effort to prevent local recurrence. Only 2 of these 12 patients (16.7%) are alive and free of disease after 2 years. Seven patients (58%) have died from tumor recurrence usually originating from distant metastases an average of 10.6 months after transplantation. Successful transplantation for hepatoma depends on screening programs to identify early stage disease. Successful outcome of transplantation for late stage disease, which includes most of the patients in our series, awaits the development of neoadjuvant therapy to control distant microscopic metastases, which are almost certainly present though not apparent at the time of transplantation.

Male sex, age, cirrhosis, and HBsAg are the major risk factors for hepatocellular carcinoma (HCC). The geographic distribution of HCC is highly uneven, such that three distinct incidence areas are recognized. To clarify the reason(s) for this geographic variability of HCC, the risk factors in each incidence area were assessed. In parallel with the geographic distribution of HCC, HBsAg prevalence was highest in both HCC patients and in general population in Africa and Asia, where mothers of HCC patients are frequently HBsAg-positive, suggesting that hepatitis B virus hyperendemicity and perinatal infection account for the high HCC incidence in these areas. Cirrhosis, which is found on autopsy in 80% of the cases of HCC patients worldwide, is the most prevalent risk factor for HCC in areas where hepatitis B virus infection is less common. However, HBsAg carriage adds to the HCC risk carried by cirrhosis and explains the higher incidence of HCC in cirrhotics from Africa and Asia as well as elsewhere. Available data suggest that chronic HCV infection is a risk factor for cirrhosis and HCC. HBV vaccination should decrease HCC incidence rates worldwide; however, HCC prevention in regions where HBsAg carriage is infrequent may also require prevention of the other causes of cirrhosis in order for HCC rates to decline.

A sequence of events which appear to be common in the development of cancer in all mammalian species includes atrophy, hyperplasia, and neoplasia. Evidence to date suggests that cell death (necrosis) is an integral, perhaps essential, factor in the initiation and maintenance of the process but the extent to which necrosis is involved, and the nature of that participation is unclear. Choline deficient B6C3F1 mice have been used to accentuate and investigate necrosis and the development of liver neoplasia following exposure to aflatoxin B1. The binding of AFB1 to DNA correlates with the level of acute necrosis and the early appearance of foci of alteration and later, tumor development. Adducts of GSH-DNA varied as do other parameters including products of peroxidation, but the relation of these variables to necrosis and cancer are unclear at present. These parameters are currently under study.

For almost a century now numerous examples of acute and subacute hepatic injury from exposure to toxic agents in the occupational or non-occupational environment have been extensively studied and are well documented, but such events are comparatively rare. In contrast, epidemiological data associating exposure to environmental chemicals with chronic liver disease or primary hepatic malignancies in the human is scarce as compared with the vast body of literature concerning chronic pulmonary disease as a consequence of exposure at the workplace. Large-scale industrial production of many newly synthesized organic chemicals began during the period 1930-1940 but it was not until the 1960s that the output increased exponentially. Consequently, the spectrum of environmental influences is gaining increasing complexity since simultaneous or sequential exposure to a variety of pollutants is becoming the rule rather than the exception. Possible interaction or synergism of environmental agents--even of those which in themselves or for their low dosage level may be considered "harmless" - and particularly latency periods of more than one decade further complicate preventive strategies. The liver, as the central site for the biotransformation of xenobiotics, deserves special attention when new chemicals which are to be introduced into the environment are being tested for their potential toxicity, especially since many hepatotoxic agents have been shown to undergo bioactivation in the liver. Currently available information on hepatic injury due to environmental agents is briefly reviewed and comprises solvents and degreasing agents, pesticides, polyhalogenated biphenyls, dioxins and dibenzofuranes, epoxy resin hardeners, vinyl chloride, naturally occurring hepatotoxins in plants and fungi, herbal medicines and traditional remedies and a side-light on the Reye syndrome and the Spanish "toxic oil syndrome".