Risk factors and seroprevalence of hepatitis E evaluated in frozen-serum samples (2002-2003) of pregnant women compared with female blood donors in a Southern region of Brazil.

Hepatitis E has always been related to morbidity in pregnant women. Its epidemiology is not well understood in Brazil. Therefore, we tested sera from 209 pregnant women and 199 female blood donors, collected at a single center in Curitiba, Brazil. The Wantai assay was used for testing the anti-hepatitis E virus (anti-HEV), immunoglobulin G (IgG), and an in-house polymerase chain reaction process for testing HEV RNA. Anti-HEV was detected in 22.5% of the total group, 19% in the pregnant women group, and 26% in the blood donor group (P = 0.11), a much higher prevalence when compared with other studies in Brazil. Demographical analysis showed that 92.4% were born in the South Region of Brazil, 4.9% in the Southeast, and 2.7% were distributed over other regions of the country. With respect to their origin, 99% were from the South, 0.7% from the Southeast, and 0.2% from the Central-West regions. Income, education, race, number of pregnancies, and abortion did differ significantly when comparing both the groups (P < 0.001). Age >30 (P = 0.012) and the number (>3) of pregnancies (P = 0.008) were related to anti-HEV positivity. All anti-HEV IgG-positive females were HEV RNA negative. In conclusion, HEV positivity was found in one out of five young women, which showed an urgent need for further epidemiological studies in Brazil.

Coexistence of primary sclerosing cholangitis in a patient with myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disease that compromises the postsynaptic membrane of the neuromuscular junction. Primary sclerosing cholangitis (PSC) is considered an immune-mediated cholestatic liver disease. Both MG and PSC include an autoimmune pathogenesis, so there is some evidence that patients with MG or PSC have a higher risk of developing autoantibodies and other immune disorders than normal controls, but the coexistence of these two disorders has never been documented. We report a 40-year-old woman who presented with MG when she was 20 years old and developed PSC 20 years after a thymectomy. Liver biochemistry revealed cholestasis. Magnetic resonance imaging showed multifocal strictures and beads involving the intrahepatic bile ducts. A liver biopsy confirmed sclerosing cholangitis. Serological analysis demonstrated positive autoantibodies (Anti-nuclear antibodies, anti-smooth muscle antibodies). Repetitive stimulation had a decremental response, and antibodies to acetylcholine receptors were detectable. To our knowledge, this is the first case of PSC in a patient with MG. The main characteristics of both MG and PSC combination are discussed.

Clinical evaluation of serum tissue inhibitor of metalloproteinases-1 levels in patients with liver diseases.

Serum levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1) were measured in 268 patients with liver diseases by means of a one-step sandwich enzyme immunoassay. In the cases of acute hepatitis, chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), the levels of TIMP-1 were higher than those of the control group. Tissue inhibitor of metalloproteinases-1 levels correlated with type III procollagen peptide and with type IV collagen, indicating TIMP-1 as a useful marker for hepatic fibrosis. Levels of TIMP-1 also correlated with aspartate aminotransferase and alanine aminotransferase levels and showed the highest levels in acute hepatitis. Thus, TIMP-1 might also reflect hepatic inflammation. Serum levels of alpha-fetoprotein and TIMP-1 had a significant positive correlation in patients with HCC. A cut-off level of TIMP-1 between LC and HCC was set at 440 ng/mL, having a low sensitivity and a high specificity. These results suggest the usefulness of TIMP-1 as a tumour marker in cases of HCC where alpha-fetoprotein levels are not elevated.

Ultrastructural cytochemistry of eosinophilic inclusions in the cells of hyperplastic nodules and hepatomas in mouse liver.

Intracisternal inclusions in the cells of 48 hyperplastic nodules and hepatomas in mouse liver were examined by electron microscopy to determine the precise compositions of the inclusions in relation to their ultrastructure, and some preliminary attempts at isolation and chemical analysis of the inclusions were performed. We classified the inclusions into two types. One was mainly of larger size, consisting of a single electron-lucent core and a granular cortical zone of high electron density. The other type was smaller, with a number of tiny, electron-lucent areas crowded into the central area instead of a single core. The cortical material of the inclusions was digested by pepsin treatment of thin sections, whereas the core and the electron-lucent areas within the cortical zone were not extracted. On the other hand, in materials treated with ethanol before post-osmication, only the core and electron-lucent areas within the cortical zone were partially extracted. The ultrastructure of the isolated inclusions was very similar to that of inclusions in situ. The chemical composition of the isolated fractions was estimated to be 60% protein and 35% lipid. Electrophoretically, the protein of this fraction showed a single band. We conclude that the cortical substance is proteinaceous in nature, probably consisting of a single protein or a group of proteins with identical electrophoretic mobility, whereas the core is composed of lipid. The possibility that the inclusions are due to an impairment in the mechanism of intracellular lipoprotein transport is discussed.

Alcoholic hepatitis with hyperleukocytosis.

We report a fatal case of alcoholic hepatitis with hyperleukocytosis mainly consisting of mature granulocytes in a 43-year-old woman. White blood cell count was increased in parallel with clinical deterioration to 54,800/mm3 with no immature neutrophils on a differential count. The bone marrow aspirate revealed normal maturation and no evidence of hematological malignancy. It has been postulated that severe leukocytosis accompanied by alcoholic hepatitis may be provoked by release of high levels of colony stimulating factor from damaged hepatic cells. However, the present patient showed a normal level of serum granulocyte colony stimulating factor, and could not prove the above assumption.