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Purpose: The aim of this study was to determine the elastic modulus values of normal liver tissue in school-age children by shear wave elastography (SWE) and to study the factors that influence these stiffness measurements.Methods: Six hundred and four school-age children (295 girls and 309 boys) who were recruited at a hospital and had normal results of specific laboratory tests and imaging studies underwent SWE examinations. The elastic modulus values were obtained in segment V and VI for each subject and comparisons were made between age groups.Results: The mean elastic modulus values for school-age children were 6.3 ± 1.1 kPa for segment V and 6.2 ± 1.1 kPa for segment VI. A positive linear trend in liver stiffness was found for the 6 to 9-year-old age group in segments V and VI (R2 = 0.076 vs R2 = 0.085, respectively, P < .05). No statistically significant difference in liver stiffness was found between genders and between segment groups (P > .05).Conclusion: SWE is a feasible method to measure liver stiffness in the school-age population. We established a normal range of liver elastic modulus values in school-age children, which will provide a basis for evaluating the changes in liver stiffness caused by various diseases. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) on normal liver is very rare. The goal of this study was to determine the clinical manifestations and the role of ultrasonography (US) in the diagnosis of HCC arising in normal liver.Methods: The clinical data and US findings in 12 cases of surgically resected HCC in normal liver were retrospectively analyzed.Results: The patients were asymptomatic, had no hepatocarcinogenic factor, and hepatic function tests were almost normal in most cases. HCCs were large, encapsulated, and solitary, and there were predominantly well-differentiated or moderately differentiated in most cases. US showed a hypoechoic rim and lateral shadowing, suggestive of peritumoral capsule formation, and on contrast-enhanced US (CEUS), the tumor was hyperenhanced in arterial phase and washed out in postvascular phase, revealing typical HCC findings.Conclusions: US raises suspicion of HCC by showing lateral shadowing on grayscale ultrasound and hypervascularity on CEUS of the lesion. [ABSTRACT FROM AUTHOR]

Aim Past hepatitis B virus (HBV) infection is considered a risk factor for hepatocarcinogenesis, but the clinicopathological characteristics of non-B non-C hepatocellular carcinoma (NBNC-HCC) excluding past HBV infection have not been investigated. This study aimed to clarify the clinicopathological features of strictly defined NBNC-HCC. Methods Among HCC patients who underwent surgical resection at our affiliated hospitals in Nagano prefecture, Japan, between 1996 and 2012, 77 were negative for serum anti-HBV core/surface antibodies in addition to HBV surface antigen and anti-hepatitis C virus antibody without signs of autoimmune liver disease, Wilson disease, or hemochromatosis. These patients were divided into the alcohol intake-positive group (ethanol intake >20 g/day, n = 31), non-alcoholic fatty liver group (steatosis >5% and ethanol intake <20 g/day, n = 30), and cryptogenic group (no ethanol intake or steatosis, n = 16). Preoperative clinical parameters, tumor and background liver pathology, and prognosis were analyzed. Results Advanced fibrosis and steatosis were detected in 64% and 60% of all patients, respectively. Approximately 85% of the alcohol intake-positive patients had advanced fibrosis. Non-alcoholic fatty liver HCC subjects had the highest body mass index and prevalence of diabetes, but 30-40% had none to mild fibrosis. The cryptogenic group of HCC patients had the lowest incidence of accompanying hepatic inflammation/fibrosis but the largest tumor size. Recurrence/survival rates were comparable among the groups. Conclusions Liver fibrosis and steatosis are risk factors of HCC regardless of past HBV infection and ethanol consumption. The present results also indicate the possibility of hepatocarcinogenesis independent of hepatic steatosis, inflammation and fibrosis, ethanol intake, and past HBV infection. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2010; 40 (7): 575–584 Background/aims Conflicting observations exist concerning the role of nuclear factor kappa B (NFκB) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll-like receptors (TLRs) expressions in conjunction with NFκB activation in non-active end-stage human ALD compared with normal livers and hepatitis C virus (HCV) related end-stage disease. Methods mRNA and protein expression were examined by quantitative PCR and Western blotting, DNA-binding by electrophoretic mobility shift assays and NFκB sub-cellular localization by immunofluorescent staining of livers. Results NFκB mRNA and protein expression as well as strong DNA-binding were preserved in ALD but significantly down-regulated in HCV compared with normal livers. P50 immunofluorescence was found in hepatocytes and bile ducts in ALD and normal livers, whereas a shift was observed in p65 staining from non-parenchymal cells in normal livers to hepatocytes in ALD. NFκB responsive genes mRNA levels IkBα and interleukin 6 were significantly higher in ALD compared with HCV. Tumour necrosis factor alpha (TNFα), TLRs 3 and 7 mRNA were up-regulated in ALD and HCV compared with normal liver with TNFα and TLR7 being the highest in HCV. Strong induction of interferon beta was found in HCV but not in ALD or normal liver tissue. Conclusions Persistent NFκB activation together with high pro-inflammatory cytokine expression and upregulation of TLR3 and TLR7 is associated with end-stage ALD in humans and could contribute to disease progression even in absence of alcohol intake. [ABSTRACT FROM AUTHOR]

ABSTRACT- Aims/Background: The anatomic structure of the liver suggests that it is a place of intense trafficking between intra-hepatic and peripheral blood compartment leukocytes. Furthermore, the liver contains a large number of passenger leukocytes that may play a role in the appearance of donor-type microchimerism after transplantation. In this study, we aimed to define the principal lymphocyte sub-populations contained in donor peripheral blood and liver grafts and in normal liver removed during minimally invasive surgery. Methods: Liver biopsies were taken at the time of vascular clampage during liver extraction from donors in a brain dead state (GI: n=14). Normal liver biopsies were removed during minimaly invasive surgery (GII: n=10). Results: We observed evidence of the presence of lymphocytic activation associated with the two major CD8+ lymphocyte and natural killer (NK) cell populations in the two groups, with a significant increase in TCR γδ-bearing lymphocyte receptors between normal liver and the liver graft. Conclusions: The presence of activated leukocytes in the graft could have a fundamental role in induction of peripheral tolerance. This activation could be the result of a basic immunological response linked to the interaction of T cells and NK cells, and of secondary activation due to stress and the conditions necessary for organ removal from donors in a brain dead state. [ABSTRACT FROM AUTHOR]

The expression of proliferating cell nuclear antigen (PCNA) was examined in normal human and rat liver fixed in either formaldehyde or methanol, and was compared with the incorporation of bromo-deoxyuridine (BrdU) in S-phase cells. Codistribution of PCNA and BrdU was assessed in rat liver by double immunohistochemical staining using PC10 and anti-BrdU monoclonal antibodies to identify labelled nuclei of parenchymal and sinusoidal cells. In formaldehyde-fixed human biopsies (n = 13) PCNA-labelling index (PCNA LI) was 0.43 ± 0.24% (mean ± SEM) for hepatocytes and 0.09 ± 0.03% for sinusoidal cells. A great inter-specimen variability was observed and a preferential lobular distribution was not evident. In methanol-fixed human liver (n = 8) the immunostaining was strong. PCNA LI was 0.05 ± 0.01%) for hepatocytes and 0.14 ± 0.01% for sinusoidal cells. 75% of labelled hepatocytes and 60% of labelled sinusoidal cells were found in acinar zone 1. In formaldehyde-fixed rat liver (n = 10) a weak nuclear staining and a great interspecimen variability were evident. LI was 0.13 ± 0.07%) for hepatocytes and 0.40 ± 0.21% for sinusoidal cells without preferential acinar distribution. In methanol-fixed rat liver (n = 10), PCNA LI was 0.14 ± 0.02% for hepatocytes and 0.40 ± 0.04% for sinusoidal cells. 64% of labelled hepatocytes and 50% of labelled sinusoidal cells were found in zone 1. Only on methanol-fixed material did double immunohistochemistry show an almost complete overlap of BrdU and PCNA labelling. The PCNA LIs and the zonal distribution of labelled nuclei as obtained in methanol-fixed material are in keeping with previous reports using 3H-thymidine (3H-Thy) incorporation, suggesting that PCNA immunostaining represents a valid alternative to 3H-Thy. In addition, the present data support the hypothesis that S-phase associated PCNA is more selectively retained in methanol-fixed liver tissue. [ABSTRACT FROM AUTHOR]

ABSTRACT- A model of pressure profile along the sinusoids in the liver is presented. The major prerequisite is a converging sinusoidal flow pattern through a network of tubes with almost equal diameter. In this case the main hemodynamic resistance is located downstream at the outlet. Different geometric configurations (sphere, cylinder, and sections of these) are considered, and it is concluded that the precise shape of the microcirculatory unit is not crucial. The applicability in cirrhosis is considered in relation to a decreased diameter and number of the sinusoids in this condition. Estimated pressure profiles along the sinusoids indicate a steep downstream pressure fall in cirrhosis, implying that the spatial average of sinusoidal pressure is close to that of the inlet, i.e. portal pressure. Another prediction is an increased blood flow rate (flow rate per vessel) in the region near the outlet of the sinusoids. [ABSTRACT FROM AUTHOR]