• Source
    • "Volume fraction determination [29] and proliferative activity of CCF were evaluated in representative sections, randomly selected from 88 cases containing CCF. The degree of steatosis, steatohepatitis and fibrosis was determined for all liver specimens [30]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Activation of the AKT/mTOR and Ras/MAPK pathways and the lipogenic phenotype are evident both in human hepatocellular carcinoma and in the rat model of insulin-induced hepatocarcinogenesis in the earliest preneoplastic lesions, i.e. clear cell foci (CCF) of altered hepatocytes. These CCFs have also been described in the human liver but characterization of molecular and metabolic changes are still pending. In this study, human sporadic CCFs were investigated in a collection of human non-cirrhotic liver specimens using histology, histochemistry, immunohistochemistry, electron microscopy and molecular pathological analysis. Human CCFs occurred in approximately 33 % of non-cirrhotic livers and stored masses of glycogen in the cytoplasm, largely due to reduced activity of glucose-6-phosphatase. Hepatocytes revealed an upregulation of the AKT/mTOR and the Ras/MAPK pathways, the insulin receptor, glucose transporters and enzymes of glycolysis and de novo lipogenesis. Proliferative activity was 2-fold higher than in extrafocal tissue. The CCFs of altered hepatocytes are metabolically and proliferatively active lesions even in humans. They resemble the well-known preneoplastic lesions from experimental models in terms of morphology, glycogen storage, overexpression of protooncogenic signaling pathways and activation of the lipogenic phenotype, which are also known in human hepatocellular carcinoma. This suggests that hepatic CCFs also represent very early lesions of hepatocarcinogenesis in humans.
    Der Pathologe 10/2015; DOI:10.1007/s00292-015-0089-9 · 0.39 Impact Factor
    • "The minimum biopsy size was 1.7 cm and the number of portal areas 10. Liver biopsies were scored the severity of fibrosis according to Ishak for CHC patients [34] and NAFLD clinical research network activity score for NAFLD patients [35]. Severe fibrosis was defined as Ishak fibrosis score F4–F6 for CHC patients or NAFLD fibrosis stage F3–F4 for NAFLD patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Increased levels of adiponectin, a major adipokine with insulin sensitizing properties showing a strong sexual dimorphism, have been reported in individuals with chronic HCV infection (CHC), but data are limited by small samples and lack of control for the genetic background and hepatic fibrosis. The aim of this study was to compare adiponectin levels between CHC patients and accurately matched controls. We considered 184 CHC patients, matched (1:1) for age, gender, body mass index, and Adiponectin genotype (ADIPOQ) with healthy individuals. To control for the severity of liver disease, a second control group consisting of 95 patients with histological nonalcoholic fatty liver disease (NAFLD) further matched (1:1) for severe fibrosis was exploited. ADIPOQ genotype was evaluated by Taqman assays, serum adiponectin measured by ELISA. Serum adiponectin was higher in CHC patients than in healthy individuals (9.0±5.0μg/ml vs. 7.3±4.0μg/ml; p=0.001; adjusted estimate +1.8, 1.7-2.9; p=0.001), and than in NAFLD patients (8.3±4.5μg/ml vs. 6.0±4.2μg/ml; p<0.001; adjusted estimate +0.8, 0.2-1.4, p=0.006). After stratification for sex, serum adiponectin was higher in males with CHC than in healthy individuals and NAFLD patients (p<0.005 for both), whereas the difference was not significant in females. CHC is associated with increased serum adiponectin independently of age, body mass, diabetes, ADIPOQ genotype, and of severe liver fibrosis, particularly in men. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
    European Journal of Internal Medicine 08/2015; 26(8). DOI:10.1016/j.ejim.2015.08.001 · 2.89 Impact Factor
    • "Study group, anti-HCV (+) HCV-RNA (−) individuals; SVR, sustained virological responders; CHC, patients with chronic HCV infection; ALT, alanine aminotransferase; NA, not applicable. a Histological activity index and fibrosis scores of liver biopsies were determined as described by Ishak et al [18]. Fig. 2. (A) HCV-and (B) influenza-specific lymphocyte response. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV) status cannot be reliably predicted in anti-HCV positive/HCV-RNA negative individuals who may either have recovered spontaneously or have a false-positive test due to antibody cross-reaction. Investigating T lymphocyte responses in individuals with different HCV status may help understand the cellular immune mechanisms underlying spontaneous recovery, treatment response, and chronicity. We aimed to determine whether anti-HCV positive, HCV-RNA negative individuals are truly spontaneous recoverers from acute HCV infection. We used enzyme-linked immunosorbent spot (ELISPOT) assay to compare HCV-specific lymphocyte response among anti-HCV positive/HCV-RNA negative individuals, patients with sustained virological response to interferon-γ/ribavirin treatment, and patients with chronic HCV infection. We found that 83% of anti-HCV positive/HCV-RNA negative individuals without a past medical history of acute icteric hepatitis had an HCV-specific T lymphocyte response in peripheral blood. Lymphocyte responses in these individuals were similar in magnitude to treatment responders unlike patients with chronic HCV whose virus-directed immunity was significantly suppressed. Detection of HCV-specific T lymphocyte responses using ELISPOT is a feasible method to ascertain past asymptomatic acute HCV infection. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 04/2015; 67. DOI:10.1016/j.jcv.2015.04.014 · 3.02 Impact Factor
Show more

Similar Publications