Aflatoxin B1 residues in human livers and their relationship with markers of hepatic carcinogenesis in São Paulo, Brazil.

In this study, hepatic biopsies from autopsy cases in São Paulo, Brazil, showing hepatocellular carcinoma (HCC, n = 8), cirrhosis associated with viral hepatitis (VC, n = 20), cirrhosis associated with alcoholism (AC, n = 20), and normal livers (NL or controls, n = 10) were subjected to determination of aflatoxin B1 (AFB1) and its main metabolites, and of markers of hepatic carcinogenesis Only non-metabolized AFB1 was detected in 13 samples (27.1%, N = 48) of liver disorders (HCC, VC and AC), at levels between 10.0 and 418.0 pg/g (mean: 76.6 ± 107.7 pg/g). Immuno-labeling of p53, cyclin D1, p21, ß-catenin, and Prohibitin (PB) increased mainly in HCC patients, in relation to the controls. AFB1+ samples of HCC presented higher expressions of p53, cyclin D1, p21, and ß-catenin compared with AFB1-livers. In contrast, p27, p16, and Rb immuno-labeling decreased in HCC, VC, and AC samples, compared with NL, with lowest values in AFB1+ samples for all liver disorders. Compared with NL, gene expression of cyclin D1 and PB in AFB1+ samples of HCC and AC were also higher, along with higher gene expression of p21 in VC and AC AFB1+ livers. Results indicated that patients with liver disorders were exposed to dietary aflatoxins, and that residual AFB1 in liver negatively affected the p53 and protein Rb pathways in HCC. Moreover, the presence of AFB1 in cirrhotic livers warrants concern about the potential contribution of dietary aflatoxin to disease progression during VC and AC.

Liver HLA-E Expression Is Associated with Severity of Liver Disease in Chronic Hepatitis C.

Hepatitis C virus (HCV) can escape from innate and adaptive immunity, making the immune response ineffective. Human leukocyte antigen E (HLA-E) might regulate the antiviral function of immune response and contribute to the persistence of HCV and the severity of liver disease. This study aimed to evaluate the expression of HLA-E in the liver and its association with the severity of liver disease in HCV patients. We performed a retrospective analysis of liver biopsies from 125 HCV patients and from 20 control subjects without liver disease. Liver biopsies were reviewed and classified according to severity of fibrosis and inflammatory activity. The pathologist assessed the magnitude of HLA-E expression in a semiquantitative way, attributing scores from 0 to 3. Immunohistochemistry showed positive for HLA-E in hepatocyte and Kupffer cells. The rate of HLA-E positivity in hepatocytes and Kupffer cells was significantly higher in HCV patients compared to controls. The liver samples classified as severe fibrosis and necroinflammatory activity presented greater expression of HLA-E on Kupffer cells and hepatocytes, with a significant linear association. It indicates that HLA-E expression may have an immunomodulatory effect and a possible role in the severity of liver disease in chronic hepatitis C.

Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA.