The role of hepatitis B and hepatitis C viral infections in the incidence of hepatocellular carcinoma in Sudan.

In Sudan, the incidence of hepatocellular carcinoma (HCC) is high and increasing. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. This study aims to assess the role of HBV and HCV infections in the incidence of HCC in 2 regions of Sudan. A case-control study was conducted in 1996-98 among 150 HCC patients and 205 controls from 2 regions in Sudan. Their demographic characteristics as well as food habits and chronic conditions have been investigated. In this study, 115 cases and 199 controls were tested for hepatitis B surface antigen (HBsAg) and for HCV antibodies. Strong positive associations were found between HBV or HCV, and HCC with odds ratios (ORs) 9.8 (95% CI 5.1-18.9) and 8.3 (95% CI 2.3-29.9), respectively. After adjustment for age, by logistic regression, the ORs for HBV and HCV were 16.1 (95% CI 7.4-34.9) and 4.5 (95% CI 1.1-18.6), respectively. Further adjustment for region, education level and job type did not appreciably affect the results. Given a prevalence of HBV and HCV of 7.0% and 1.5% among controls, about 57% of all HCC cases can be attributed to these viral infections. Hepatitis infections seem to be important risk factors for HCC in Sudan.

Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma.

Exposure to aflatoxins is a risk factor for hepatocellular carcinoma (HCC). Aflatoxins occur in peanut butter and are metabolized by genetically polymorphic enzymes such as glutathione-S-transferases encoded by glutathione-S-transferase mu 1 gene (GSTM1) and glutathione-S-transferase theta 1 gene (GSTT1) and microsomal epoxide hydrolase encoded by epoxide hydrolase gene (EPHX). The rate at which aflatoxins become activated or detoxified may depend on polymorphisms in the encoding genes. GSTM1 homozygous deletion was indeed found to modify the association between peanut butter consumption and HCC. In this study, we investigate possible roles of GSTT1 and EPHX polymorphisms in this relationship. From a Sudanese case-control study on HCC, we analyzed data of 112 incident cases and 194 controls. All participants were interviewed using a standardized questionnaire inquiring about social and demographic factors, peanut butter consumption, and other known HCC risk factors. Univariate analysis showed that GSTT1 polymorphism was not associated with HCC, whereas EPHX 113HH and 139HH genotypes increased the risk of HCC (Odds ratio, 3.10; 95% Confidence interval, 1.18-8.12). Adjustment for age and region of origin slightly attenuated this association (Odds ratio, 2.56; 95% Confidence interval, 0.83-7.95). Interestingly, unlike GSTM1, both GSTT1 and EPHX polymorphism did not modify the association between peanut butter consumption and HCC. In conclusion, these epidemiological findings do not suggest significant roles of GSTT1 and EPHX in aflatoxin metabolism, although EPHX polymorphism is possibly related to the increased risk of HCC. Further studies are needed to investigate mechanisms by which the EPHX polymorphism potentially modifies cancer risk.

Peanut butter intake, GSTM1 genotype and hepatocellular carcinoma: a case-control study in Sudan.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the major cancers in the world. In Sudan the incidence is thought to be high and increasing. This study aims to assess the association between peanut butter intake, as a source of aflatoxins, and the GSTM1 genotype in the etiology of HCC. METHOD: A case control study was conducted among 150 patients and 205 controls from two regions in Sudan. Food habits with special reference to peanut butter consumption, as well as peanut storage systems, have been investigated, as well as confounders such as hepatitis, drinking and smoking habits, and demographic characteristics. GSTM1 genotype was assessed in DNA extracted from blood samples (110 cases, 189 controls). RESULTS: A positive association was observed for highest vs. lowest quartile of peanut butter intake, humid storage system and HCC, with ORs (95% CI) being 3.0 (1.6-5.5) and 1.6 (1.1-2.5) respectively. The positive association with peanut butter intake was essentially limited to subjects with GSTM1 null genotype with OR for highest vs. lowest quartile 16.7 (2.7-105). CONCLUSION: Peanut butter consumption has been identified as a strong risk factor of HCC in a region with endemic aflatoxin contamination in Sudan and was essentially limited to subjects with the GSTM1 null genotype.

High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis.

Some patients develop post-kala-azar dermal leishmaniasis (PKDL) after they have been treated for the systemic infection kala-azar (visceral leishmaniasis). It has been an enigma why the parasites cause skin symptoms after the patients have been successfully treated for the systemic disease. We report here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL-10 is involved in the pathogenesis. Before treatment of visceral leishmaniasis, Leishmania parasites were present in skin which appeared normal on all patients. However, IL-10 was detected in the keratinocytes and/or sweat glands of all patients who later developed PKDL (group 1) and not in any of the patients who did not develop PKDL (group 2). Furthermore, the levels of IL-10 in plasma as well as in peripheral blood mononuclear cell culture supernatants were higher in group 1 than in group 2.

Aflatoxin and liver cancer in Sudan.

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 pathology of cutaneous leishmaniasis in the Sudan: a comparison with that in other geographical areas.

The pathology of cutaneous leishmaniasis (CL) caused by Leishmania major zymodeme LON 1 in the Sudan was compared with that caused by L. major zymodeme LON 4 in Saudi Arabia and with that already described for L. tropica infections in Iran and for localized CL in the New World. The lesions were classified according to Ridley's five histological types. Most of the lesions in the Sudan and Saudi Arabia were of types B and C, characterized, respectively, by diffuse macrophage necrosis and focalized necrosis. B was the most common type in Nicaragua and Guyana whereas responses of types A (in which there are heavily parasitized macrophages without necrosis) and D (reactive tuberculoid) were the most frequent in Iran. The type-E response, which is similar to D but with virtual absence of plasma cells, was uncommon in all areas. The type-D reaction is a chronic relapsing disease when associated with L. tropica but not when associated with L. major. The major differences in the pathology of CL in different geographical areas most probably relate to differences in the Leishmania species involved. Minor differences, however, not only occur between patients from the same area but may also occur, with time, in the same patient. Detailed comparison between areas is therefore difficult; lesions on one patient may heal asynchronously and show different histological types at any point in time and rebiopsy from the same lesion during healing reveals changes from one histological type to another.