Endothelium Activation during Severe Yellow Fever Triggers an Intense Cytokine-Mediated Inflammatory Response in the Liver Parenchyma

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

Endothelium Activation during Severe Yellow Fever Triggers an Intense Cytokine-Mediated Inflammatory Response in the Liver Parenchyma

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist

For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.

IL28B-Gene Polymorphisms (rs12979860) in HCV Liver Parenchymal changes legitimize Screening for SNPs before DAAs Therapy

Background and objective: IL28B-gene polymorphisms show inconclusive relationships with CHCV DAAs-treatment outcomes on evaluation by serum-PCR. Solitary intra-PBMCs HCV-RNA antisense-strands are independently found in naïve and experienced cases regardless to viremia or hepatic-parenchymal changes. We correlated frequencies of IL28B-gene SNPs and alleles with HCV induced liver-changes during SVR evaluation by PBMCs-PCR after DAAs-therapy. Methods: Twelve weeks after completing DAAs-therapy, the impacts of IL28B-gene-SNPs were evaluated in three groups of patients: group-I (n=25) with negative serum and PBMCs HCV-PCR, group-II (n=52) had solitary intra-PBMCs HCV-RNA, and group-III (n=25) had positive serum HCV-RNA. All cases were subjected to IL28B-gene-SNP analyses and correlated with their ultrasonographic liver changes.Results: IL28B-genotyping in post-DAAs-treatment HCV-SVR and viral relapse revealed: a) dominant CC-genotype and C allele in normal hepatic parenchyma in group-I compared to group-II (P=0.0047, 0.0007) and group-III (P=0.0564, 0.000003) b) frequent CT-SNP and T-allele in bright hepatic parenchyma in group-II when compared with group-I (P=0.0077, 0.002 ) and group-III (P=0.0363, 0.0005) c) increased TT-SNP and T-allele frequencies in coarse liver in group-III compared to group-I (P=0.02256, 0.000130) and group-II (P=0.08647, 0.004308). Conclusions: Outcomes of HCV treatment with DAAs are dependent on host IL28B-gene polymorphisms and HCV induced liver changes. SVR is achieved when wild type-CC-genotype and C-allele are dominant in normal hepatic parenchyma; solitary intra-PBMCs-relapse occurs in increased frequency of CT-genotype when liver tissues are fibrotic; serologic-relapse is dominant when TT-genotype and T-allele are frequent in cirrhotic liver. IL28B-gene SNP analyses in relation to hepatic parenchymal changes are recommended before treating CHCV-infection with DAAs.

Role of Th17 Cytokines in Liver’s Immune Response during Fatal Yellow Fever:Triggering Cell Damage Mechanism

Yellow fever (YF) is an infectious disease whoseevolution and outcome arerelated to the host immune response pattern. We investigated the Th17 cytokine profile in the liver of humans with fatal YF. Liver tissue samples were collected from 26 patients, including 21 YF-positive and five flavivirus-negative patients with preserved hepatic parenchyma architecture who died of other causes. Samples underwent histopathological and immunohistochemical analysis to detect the Th17 profile (ROR-γ, STAT3, IL-6, TGF-β, IL-17,and IL-23). Substantial differences were found in the expression of markers between fatal YF cases and control samples with a predominance of Th17 cytokine markers in the midzonal region of the YF cases, the most affected area in the liver acinus. Histopathological changes in the hepatic parenchyma revealed cellular damage characterised mainly by the presence of inflammatory infiltrate, Councilman bodies (apoptotic cells), micro/macrovesicular steatosis, and lytic and coagulative necrosis.Th17 cytokines play a pivotal role during YF and contribute significantly to triggering the mechanisms of cell damage in the fatal outcome of severe cases.

Ultrastructure of the hemomicrocirculatory bed and parenchymatous-stromal elements of the pancreas and liver in a model of acute pancreatitis using different doses of L-arginin

Background. The development of acute pancreatitis is not limited to isolated damage to the pancreas. After creating models of acute pancreatitis using various substances that enhance the secretion of the gland, have a toxic or local activating effect, the researchers showed their dose-dependent effect. The question of the reaction of the hepatic microcirculation system during the development of acute pancreatitis, as well as their pathogenetic significance in the development of pathomorphological changes in the pancreas and liver in most aspects remains open. Objective. The purpose of the current study was to define the role of the hepatic mircocirculation in development of ultrastructural parenchymatous-stromal changes of the pancreas and liver in a model of acute pancreatitis using different doses of L-arginin. Methods. The variants of acute pancreatitis model were used with injection of L-arginin in dosage 3 g/kg; 4 g/kg and 5 g/kg. The morphological research of pancreas and liver were carried out in 1, 4, 8, 12, 24, 48 and 72 hours after initiation of inflammation. Results. The visible reaction of hepatic mircocirculation in the experimental model of acute pancreatitis was depended on character of pathomorphological changes in pancreas. This reaction demonstrated the phase character including: 1) activation of hepatic circulation, first of all in portal component, against a background of pancreatic enzyme toxemia; 2) development of inflammatory, dystrophic, destructive and necrotic changes in hepatic parenchyme together with mircocirculation disorders against a background of pancreatic necrotic toxemia; 3) recovery and adaptation or decompensation processes in mircocirculation system of liver and hepatic parenchyme depending on the degree of pancreatogenic toxemia|. Conclusion. Within 72 hours of the experiment, at the lowest and middling doses of L-arginin, in the context of reduction of acute pancreatitis, there is a gradual renovation of the structure of the microvessels and normalization of the microcirculation of the liver. In the maximum doses L-arginin cause degradation of the liver microvessels with the progression of hemorrhages, slit red blood cells and platelet aggregation, which causes blockage of the microcirculation and the development of necrotic changes in the hepatic parenchyma.

First Report and 3D Reconstruction of a Presumptive Microscopic Liver Lipoma in a Black Barbel (Barbus balcanicus) from the River Bregalnica in the Republic of North Macedonia

A lipoma is a benign tumour of mature adipocytes which may appear in various species, including marine and freshwater fish. It usually occurs in isolated locations, such as a superficial or deep mass, mainly in the skin and seldom in other organs. In non-mammalian vertebrates, there is no agreed minimal size for the mass to be considered a lipoma. This study histologically describes a case proposed to be a microlipoma in the liver of Barbus balcanicus. The structure was an oval-shaped mass of well-differentiated adipocytes, surrounded by hepatic parenchyma. The adipocyte cluster did not contact with major vascular or biliary tracts, the liver capsule, or the hilum. The cell mass reached a maximal linear length and width of ~0.5 mm and ~0.4 mm. A three-dimensional and software-assisted reconstruction of the adipocytic mass showed that it had the shape of a flattened prolate spheroid (~0.01 mm3). Given the histological criteria currently used in the literature, we consider the mass as a lipoma, or, better, a microlipoma because it was tiny. We interpret this structure as an early growing lipoma. This work is the second description of a liver lipoma in a fish to the best of our knowledge.

Laparoscopic Liver Resection Enhanced by an Intervention-Guided Fluorescence Imaging Technique Using Sodium Fluorescein

Background and Objectives: In laparoscopic liver resections, tumor localization is a critical aspect of ensuring clear resection margins and preserving the hepatic parenchyma. In this study, we designed a fluorescence imaging technique using a new fluorophore for tumor localization. Materials and Methods: Immediately before laparoscopic or transthoracic liver resection, microcatheter was inserted through the hepatic artery and used to engrave the segment containing the tumor in the intervention room. Under blue light, the fluorescence of the lesion was visually confirmed, and the location was determined through intraoperative sonography. After tumor localization, liver resection was performed. Results: From February 2017 to March 2020, 24 patients underwent laparoscopic liver resection (LLR) or video-assisted transthoracic liver resection (VTLR) using intervention-guided fluorescence imaging technique (IFIT). Conclusions: IFIT can provide some advantages in the field of LLR. In addition, in cases of VTLR for hepatocellular carcinoma in the superior posterior segment in patients with marginal liver function, IFIT is considered useful.

Cholelithiasis, choledocholithiasis and hepatolithiasis with secondary necrotizing hepatitis and cholangiohepatitis in a dairy cow

Biliary calculi are rare in cattle and occur usually in the gallbladder, without clinical signs. In humans, cholelithiasis is a common cause of hepatic abscess due calculi microbiota. Here is described a case of cholelithiasis, choledocholithiasis and hepatolithiasis in a 10-year-old female mixed breed dairy cow. The animal died during physical examination with signs as cachexia, icterus, and fever. At necropsy, a large number of green calculi were observed in the gallbladder, common duct lumen and in markedly distended biliary ducts. The liver was firm and decreased in volume with multiple abscess and multiple red foci measuring 0.5 cm in diameter in the hepatic parenchyma. Microscopically in the liver, marked ductal proliferation and abscedative cholangiohepatitis with abundant fibrosis and multiple foci of hepatocytes necrosis. In conclusion, choledocholithiasis and hepatolithiasis may occur in cattle and cause significant clinical signs and pathological alterations.

Effect of The Body Water and The Body Composition, Calculated by Bioelectrical Impedance Analysis, On Contrast-Enhanced Dynamic Computed Tomography Images of The Liver.

To improve its diagnosis on contrast-enhanced dynamic CT (CE-DCT) scans, contrast injection protocol must yield stable arterial contrast enhancement. To investigate how the body-water distribution and the body composition, calculated by bioelectrical impedance analysis (BIA), affect aortic and hepatic enhancement on CE-DCT scans. 236 patients with liver cirrhosis underwent CE-DCT before BIA. The CT number (in Hounsfield units, HU) of the abdominal aorta at the celiac artery level on unenhanced scans and during the hepatic arterial phase (HAP) scans was recorded. And, the mean CT number of the hepatic parenchyma of both hepatic lobes at the celiac artery level on unenhanced and portal venous phase (PVP) scans was recorded. We calculated changes in the iodine dose per contrast enhancement (mgI/HU) (IDCE) to evaluate the effect of the patient age and of various constituents of the body composition by performing BIA. The IDCE of the abdominal aorta during HAP was 121.5 ± 32.1 mgI/HU; it was 698.7 ± 211.1 mgI/HU in the hepatic parenchyma during the PVP. Among the parameters used in our BIA, the total body weight (TBW) was the most important factor affecting the IDCE of the liver abdominal aorta on CE-DCT scans acquired during the HAP (r = 0.83). The TBW and the skeletal muscle index most strongly affected the IDCE of the hepatic parenchyma on CE-DCT scans obtained during the PVP (r = 0.69). The TBW had the strongest effect on contrast enhancement. The skeletal muscle index exhibited the strongest correlation with hepatic parenchymal contrast enhancement during the PVP.