Portal Area Of Liver Research Articles

ABOUT SURGICAL IMPORTANCE OF AVALABLITY OF COLLATERAL CONNECTION BETWEEN LIVER PORTAL AREAS (LOBE, SECTOR, SEGMENT) IN CASES OF NORMALITY AND LIVER CANCER

This work covers the problem of autonomy of liver portal areas [lobe, sector and segment] in cases of normality and liver cancer. Materials and methods of research correspond to and are enough for the purpose of the task. Based on research result it is established that gallbladder veins are connected only with portal system and there are supplementary portal veins found in 64.2% of cases: one vein is found in 39.51% of cases, two veins in 13.02%, three veins in 6.0%, four veins in 4.1% and five veins in 1.4%. Size of these veins fluctuated from 1 to 5 mm. These veins connect left and right lobular branches of portal vein with gallbladder veins, which allows us to assume that in case of partial or full blocking of portal vein due to cancer the supplementary portal veins and gallbladder veins have potentiality of certain degree compensation of portal blood flowing in the blocked part of liver. Restoration of collateral portal blood circulation promotes internal dissemination of the tumor process organ from one half of liver to another.

Anatomic pathology of cattle and goat liver collected from slaughterhouses in Mymensingh city of Bangladesh

The morphologic abnormality of cattle and goat livers (collected from slaughterhouses in Mymensinghcity of Bangladesh) were investigated in the present study. The livers of slaughtered cattle (n = 14) and goat (n = 20) were examined by gross visualization, palpation and incision as well as histopathology. The total liver lesion in cattle was 71.4% and in goat was 75%. Grossly, various pathological changes, mainly thickened, rough capsule which was whitish in color, necrotic foci, thickened bile ducts with matured flukes, fibrosis were seen. Histopathologically, necrosis, degenerative changes of hepatocytes, dilated sinusoids, inflammatory infiltrates, granuloma, bile duct hyperplasia, periportal and periductal fibrosis were found in cattle and goat livers. Extensive fibrosis was seen portal areas of liver by Goldner’s trichrome staining. Migratory tracts and immature flukes were seen in intrahepatic bile ducts. Most common cause of liver lesions found in the present study was Fascioliasis in both cattle and goat. It could be concluded that the major gross and microscopic alterationsin the livers of cattle and goat due to Fasciola giganticainfectionreflected tissue damage, which can lead to substantial financial losses in animals and great health problems in human. Therefore, special care and attention are required to ensure that seriously damaged livers of food animals are not passed on for human consumption, and extensive monitoring and epidemiological surveys are necessary to cope this adverse situation

Hematoxylin and Eosin (H&E) Stained Liver Portal Area Segmentation Using Multi-Scale Receptive Field Convolutional Neural Network

Portal area segmentation is an important step in the quantitative histological analysis process for hepatitis grading. However, portal areas often appear of different sizes and appearances due to the variations of surrounding components such as the ductule, bile duct, artery, and portal vein. The slim fibrosis expanding from the portal area further increases challenges of the portal area segmentation. A Multi-scale Receptive Field Convolutional Neural Network (MRF-CNN) for the segmentation of the liver portal areas in hematoxylin and eosin (H&E) stained whole slide images (WSIs) is proposed in this paper. The MRF-CNN adopts the atrous spatial pyramid pooling (ASPP) with multiple atrous rates and symmetric encoder-decoder with feature concatenation architecture. The atrous rates in ASPP are devised of receptive fields to extract features of meaningful tissue components in parallel in portal areas. Along with the MRF-CNN, a small object sensitive loss function is also proposed to have the network focus on small portal areas and slim fibrosis. The results show that the proposed model achieves Intersection over Union (IOU) of 0.87 and sensitivity of 0.92. Compared to recent segmentation researches such as Fully Convolutional Network (FCN), U-Net and SegNet, the proposed network achieves an overall the best IOU and sensitivity performance. Experimental results also show that the designed ASPP block benefits in feature extraction, and the ability of identifying small objects in proposed small object sensitive loss has a significant improvement of the segmentation result comparing to the original cross entropy loss.

Cytotoxic KLRG1 expressing lymphocytes invade portal tracts in primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease with an immunopathogenesis that includes highly differentiated cytotoxic T cell infiltration in portal areas. We have taken advantage of a large and well-defined cohort of patients with PBC, AIH, chronic hepatitis virus, and healthy controls to study for the presence of highly differentiated T cells which express the killer cell lectin-like receptor G1 (KLRG1). Such studies were performed using both liver and peripheral blood mononuclear cells. In particular, gene expression data (GSE79850) from 16 PBC patients stratified according to future risk of liver transplantation were analyzed for markers of highly differentiated cytotoxic T cells. Liver biopsy samples from 44 PBC patients were studied by immunohistochemistry and a separate cohort of PBC blood samples were studied by flow cytometry. Gene expression data demonstrated correlation of increased KLRG1 and cytotoxic lymphocyte molecules, such as granzyme B (GZMB) and perforin (PRF1), to disease severity as measured by future risk of liver transplantation. Immunohistochemistry demonstrated abundant infiltration of KLRG1+ cells into liver portal areas (mean of 45% of infiltrating cells, range 25–75%) positively correlated with hepatic inflammatory (r = 0.47, p = 0.001) and hepatic fibrosis (r = 0.34, p = 0.021) scores. KLRG1+ lymphocyte liver portal area infiltration was positively correlated with serum alkaline phosphatase (r = 0.45, p = 0.005) and GGT (r = 0.40, p = 0.014), and AST (r = 0.35, p = 0.033) levels. Mononuclear blood flow cytometry studies showed KLRG1+ lymphocytes had greater levels of cytotoxic molecules (granzyme B and perforin), inflammatory cytokines (IFN-γ and TNF-α) and inflammatory chemokine receptors (CCR5 and CX3CR1) than KLRG1-counterparts. However, clearly the most significant data was that found in liver with the intense portal infiltrates that are unique to PBC. Conclusion: Highly cytotoxic KLRG1+ lymphocytes have invaded PBC liver portal areas. Liver KLRG1 gene expression and the abundance of KLRG1+ lymphocytes are positively correlated with disease biomarkers used as clinical trial outcome measures (liver transplantation and serum alkaline phosphatase), suggesting the targeting of KLRG1+ lymphocytes as a rational approach for PBC therapeutic drug development.

Metabolomic study on the susceptible factors of idiosyncratic Traditional Chinese Medicine-induced liver injury: Exemplification of a <italic>Polygonum multiflorum</italic> preparation

The underlying mechanism(s) that govern idiosyncratic drug-induced liver injury (IDILI) have remained poorly defined. Several studies have shown that IDILI was caused by body diathesis, environment, metabolism, immunization, etc. However, the underlying mechanism(s) of IDILI was still ambiguous, which led to an unsolved issue in clinical toxicology. Understanding of such mechanisms is critical not only for the prevention of such DILI adverse effect as well as the clinical diagnosis, intervention or management of the affected individuals. In this study, we carried out a metabolomic study on mice treated with Runzao Zhiyang Capsule (RZZY), since Polygonum multiflorum , a key ingredient in this preparation, is known to cause DILI. Clinical case analysis showed that a small number of patients developed drug-induced liver injury (DILI) in a dose-independent manner. Meanwhile, the affected individuals often exhibited skin conditions associated with features of abnormal inflammatory responses. In normal mice, treatment with RZZY alone had no significant effects on biochemical indices of liver function, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. At the same time, it had no significant effects on liver histopathology either. Moreover, we used non-toxic dose of lipopolysaccharide (LPS) pretreatment to produce mild inflammatory stress mice model, which showed no significant liver injury phenotype, except for a small number of inflammatory immune cells infiltration in portal areas of liver. However, by metabolomics profiling, we found significant alterations of plasma metabolites in the LPS treated mice, including up-regulated histidine and alanine metabolic pathways ( P (P beta -alanine, l -histidine, cortexolone, cortisone, dihydrocortisol, melatonine and 18-hydroxycorticosterone, which may provide potential application value for recognition of susceptible individuals in clinical.

Development of a Fatty Liver Model by Restricted Feeding of Lactating Sheep

Background: As a frequent subclinical disease, fatty liver disease (FLD) is associated with a severe negative energy balance (NEB) during the early lactation period, and usually cause of economic loss to dairy farmers. Liver biopsy is the gold standard for the assessment of FLD. However, as an invasive procedure, liver biopsy has several limitations and such procedures are not readily available to dairy farmers. To further evaluate FLD in dairy cows, a FLD model of lactating sheep was developed by simulation of the state of negative energy balance (NEB).Materials, Methods & Results: Fourteen pregnancy thin-tail ewes were divided into control group (CG, n = 4), non-lamb restrained feeding group (NRG, n = 4) and single birth restrained feeding group (SRG, n = 6). After lambing, NRG and SRG ewe were received a feed restrained diet for 16 days. Liver biopsies and blood was collected on days 1, 4, 7, 10, 13, and 16, and biochemical parameters were analyzed. With restricted feeding and lactation administration, ewes in SRG showed increased liver fat concentrations (LFC) from days 4 post-administration and severe LFC was detected at day 13. Compared with CG, SRG sheep showed significant lower concentration of serum glucose (Glu) from days 7-13 and higher non-esterified fatty acid (NEFA) from days 4-16, β-hydroxybutyric acid (BHBA) from days 4-16, triglyceride from days 4-16, low-density lipoprotein cholesterol from days 4-16, lactate dehydrogenase (LDH) from days 13-16, aspartate aminotransferase (AST) at days 16. While, ewes in NRG showed normal LFC levels, and high concentration of serum Glu and insulin from days 4-16 were detected than CG and SRG ewes. With restricted feeding, ewes in NRG and SRG showed significant low level of revised quantitative insulin sensitivity check index from days 4-16 and high level of liver total cholesterol (TC) at day 16. Liver pathological characteristics showed LFC of NEB sheep was first detected around the liver portal area.Discussion: In this study, a model of FLD in lactating thin-tail sheep was developed by restricted feeding. Serum glucose concentrations were sharply decreased in SRG sheep，that was due to the large energy requirements for lactation and low energy provided by a restricted diet. While non-lactating NRG sheep demonstrated lower fat mobilization, which was considered to contribute to the high concentrations of serum glucose, as compared to SRG sheep. Meanwhile, in a state of NEB, oxaloacetic acid, which is generated by glycolysis and glycogenic amino acids, tends to be used for gluconeogenesis, that a generous amount of NEFA is incompletely oxidized to generate ketone body in SRG sheep, which is a major component of BHBA. Liver TC concentrations were significantly higher in NRG sheep than those in the SRG sheep, while liver triglyceride was significantly lower. The high level of liver TC in NRG sheep was considered to induce removal of triglyceride from the liver in the form of VLDL. Compared with CG sheep, although higher levels of liver TC were detected in SRG sheep on postpartum day 16, these levels were considered too low to induce significant depletion of triglycerides from the liver. In this study, the increase in serum AST and LDH was considered to cause by oxidative stress in mitochondria, and LDH concentrations was considered more sensitively than AST for LFC caused by NEB. Liver pathological characteristics showed that FLD caused by NEB had a major impact on reduced LFC, although no significant liver fibrosis was detected. While different from FLD caused by high-fat diet, TG was first accumulates around the hepatic lobules and LFC of NEB sheep was first detected around the liver portal area. It was considered that high concentrations of NEFA are prioritized for oxygenation in the liver portal area, which results in triglyceride accumulation.

Effects of Prescription Yiqi Huatan Quyu on oxidative stress level and pathological changes in chronic intermittent hypoxia rat liver

Objective: To investigate the effects of Yiqi Huatan Quyu prescription on oxidative stress and pathological changes in chronic intermittent hypoxia rats liver. Methods: A total of 24 male SD rats aged eight weeks were randomly divided into 3 groups by the random number table: normal control group (NC), chronic intermittent hypoxia group (CIH) and chronic intermittent hypoxia plus Yiqi Huatan Quyu prescription supplement group (Chinese medicine group, CM)(n=8 each). The CIH group and CIHN group were exposed to intermittent hypoxia every day for 8 consecutive weeks. In addition, the CIHN group received Yiqi Huatan Quyu prescription via gavage 30 min before the CIH. Eight weeks later, serums were collected to test alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. Meanwhile, rat livers were extracted to evaluate malondialdehyde (MDA), total superoxide dismutase (T-SOD), glutathione (GSH) and Nuclear factor κB (NF-κB) and observe the pathological changes of liver. Results: The levels of serum ALT and AST in the CIH group were significantly higher than those of NC group[(112.1±31.7) vs (41.3±6.6) U/L, (295.4±39.8) vs (104.5±12.3) U/L], the contents of the MDA and NF-κB in the CIH group were notably higher than those of NC group[(7.9±1.1) vs (3.6±0.7) nmol/mgprot, (16.2±3.3) vs (5.7±2.2) ng/L], the activities of T-SOD and GSH in the CIH group were significantly lower than those of control group[(181.6±28.6) vs (304.3±42.9) U/mgprot, (5.5±1.3) vs (14.9±2.4) mg/gprot](all P<0.001). The levels of the serum ALT and AST in CM group were significantly lower than those of CIH group[(52.2±8.6) vs (112.1±31.7) U/L, (148.1±20.4) vs (295.4±39.8) U/L], the contents of liver MDA in CM group was notably lower than those of CIH group[(4.5±0.7) vs (7.9±1.1) nmol/mgprot], the activities of liver T-SOD and GSH in CM group were significantly higher than those of CIH group[(226.9±38.9) vs (181.6±28.6) U/mgprot, (10.3±1.7) vs (5.5±1.3) mg/gprot](all P<0.05). Compared with CIH group, declining tendency was observed from contents of NF-κB in CM group, but there was no statistical difference[(15.8±2.1) vs (16.2±3.3) ng/L, P>0.05]. Pathology observation showed the CIH group had abundant inflammatory cells infiltration in the liver portal area and the inflammatory cells infiltration decreased following Chinese medicine treatments. Conclusion: Yiqi Huatan Quyu prescription has some protection to CIH rat liver, which might mediate by the reduction of oxidative stress and inflammatory mediator.

A chronic toxicity study of cyadox in Wistar rats

To investigate the chronic toxicity of cyadox, a growth promoting agent, five groups of Wistar rats (30 rats/group/sex) were fed with the diets containing cyadox (0, 100, 400 and 2000mg/kg) or olaquindox (400mg/kg) for 78weeks. There were significant decreases in body weights in both genders during most of the study period in 2000mg/kg cyadox and 400mg/kg olaquindox rats. Significant decreases in serum alkaline aminotransferase in the 2000mg/kg cyadox rats at weeks 26, 52 and 78 were observed. Relative weights of liver and kidney were significantly increased in 2000mg/kg cyadox and 400mg/kg olaquindox rats at weeks 26, 52 and 78. A significant increase in relative brain and heart weights in 2000mg/kg cyadox males was observed. The histopathological examinations revealed that 2000mg/kg cyadox diet or 400mg/kg olaquindox diet could induce proliferation of bile canaliculi in the portal area of liver and swelling and fatty degeneration of the proximal renal tubular epithelial cells in kidneys. In conclusion, the target organs of cyadox for rats were liver and kidney. The no-observed-adverse-effect level of cyadox in this study was estimated to be 400mg/kg diet.

Epstein–Barr virus-associated T-cell lymphoma in an adult patient: prominent infiltrates within the liver portal area revealed by autopsy

We herein report the case of a 67-year-old man who initially presented with fever and hepatosplenomegaly, and soon died of progressive liver failure. The bone marrow was infiltrated with tumor cells showing a variable morphology and macrophages phagocytosing blood cells. The tumor cells were CD2(+), CD3(+), CD4(-), CD8(+), CD25(+), CD56(+/-), and HLA-DR(+) and exhibited clonal cytogenetic abnormalities. Microscopic examination of the liver postmortem revealed, prominent cellular infiltrates that were confined within the portal area. The infiltrated cells were medium-sized with the CD3(+), CD4(-), CD8(+), CD56(+/-), and granzyme B(+) phenotype. In situ hybridization detected Epstein-Barr virus (EBV)-encoded RNA-positive cells in the liver and spleen as well as the bone marrow obtained before his death. These observations indicate that EBV-associated T-cell lymphoma expressing cytotoxic proteins was the underlying disorder. Prominent portal involvement was most likely responsible for the fatal clinical outcome of this patient.

Trafficking of recirculating lymphocytes in the rat liver: rapid transmigration into the portal area and then to the hepatic lymph

We have investigated how recirculating lymphocytes patrol the liver in a normal steady state. Thoracic duct lymphocytes of congeneic rats were intravenously transferred to host rats and donor cell trafficking in the liver and hepatic lymph was examined. Host hepatic lymph nodes (HLNs) were selectively removed, which allowed liver-derived donor cells to collect in the thoracic duct without transit in the intervening HLNs. The number of donor cells in the thoracic duct lymph significantly increased over the baseline 3, 5 and 11 h after transfer in the HLN-removed, non-pretreated, and HLN-ligated (in which a lymph efflux was blocked) groups, respectively. Histologically, donor cells appeared in the portal area from 0.5 h after transfer and frequently attached to the basal lamina of portal vein both externally and internally. Three hours after transfer, a few donor cells appeared in the subcapsular sinus of HLNs. The minimal transit time of rat recirculating lymphocytes is 3-4 h in the liver and 5-8 h in the hepatic LNs, in a normal steady state. Recirculating lymphocytes might transmigrate through the portal vein as well as the sinusoid in the periportal zone. This rapid transit might enable an efficient surveillance of the liver portal area by the recirculating lymphocytes.

Lymphoid Follicle Formation in Portal Areas of Liver With No Evidence of Liver Disease

Lymphoid Follicle Formation in Portal Areas of Liver With No Evidence of Liver Disease

The influence of cold preservation on the microcirculation of intrahepatic bile duct after liver transplantation

To discuss the influence of cold preservation on intrahepatic biliary microcirculation. Male Sprague Dawley (SD) rats were divided into 3 groups:cold preserve 1 h group (CP 1 h group), cold preserve 24 h group (CP 24 h group) and sham operation group (SO group). Five time points were determined as 0 h, 1 h, 6 h, 24 h and 72 h postoperation. Morphology was observed under light microscope. Dark microspheres were injected into hepatic artery and the number of microspheres in liver portal areas was measured under light microscope. The expressions of eNOS, ET-1 and ICAM-1 in microvascular endothelial cells of hepatic portal area were measured by immunofluorescence double staining technique and in situ hybridization histochemistry. The histological changes of intrahepatic bile duct were more severe in CP 24 h group than in CP 1 h group. The number of microspheres in implanted liver portal areas was increased significantly in CP 24 h group than in CP 1 h group at the same time point. Compared with CP 1 h group, the expression of eNOS in CP 24 h group significantly reduced after liver transplantation, while the expressions of ET-1 and ICAM-1 in CP 24 h group were significantly increased after liver transplantation. The changes of their mRNA expressions were the approximately same as well as their proteins expressions. Cold preservation brings obvious changes of intrahepatic biliary microcirculation and function of vascular endothelial cell after liver transplantation. The obstruction of microcirculation might play an important role in the reperfusion injury after cold preserve of intrahepatic biliary during liver transplantation.

Oligoclonal proliferation and local antigen-driven maturation of B cells in liver portal areas of patients with primary biliary cirrhosis: Takashi Sugimura, Satoshi Shiokawa, Junji Nishimura, Medical Institute of Bioregulation, Kyushu University, Beppu Japan

Oligoclonal proliferation and local antigen-driven maturation of B cells in liver portal areas of patients with primary biliary cirrhosis: Takashi Sugimura, Satoshi Shiokawa, Junji Nishimura, Medical Institute of Bioregulation, Kyushu University, Beppu Japan

Local antigen-driven oligoclonal expansion of B cells in the liver portal areas of patients with primary biliary cirrhosis.

The antigen-driven clonal proliferation of B cells within target tissue has been reported in some autoimmune diseases. The purpose of this study was to examine the clonal characteristics of B cells in the liver portal area of primary biliary cirrhosis (PBC). The liver portal area was microdissected from liver biopsy sections from two PBC patients. Genomic DNA was extracted and rearranged immunoglobulin heavy chain variable region (VH) genes were amplified and sequence analyzed. Sixteen VH sequences from portal area 1A of patient 1 had three different rearrangements. Nineteen VH sequences from portal area 1B of this patient had three different rearrangements. In three sequences from the portal area 1B, a stepwise accumulation of somatic mutations was observed. Between the sequences from the two portal areas, no common VH sequence was observed. In patient 2, 15 VH sequences from portal area 2A had three different rearrangements. Fourteen VH sequences from portal area 2B had two different rearrangements. One rearrangement was present both in the portal area 2A and portal area 2B. The oligoclonal B cell proliferation and stepwise accumulation of somatic mutations suggested that an antigen-driven B cell response had occurred in the portal area of PBC.

Apoptosis in organs of rats in early stage after polytrauma combined with shock.

Apoptosis in organs of rats in early stage after polytrauma combined with shock was researched. Sixty Sprague-Dawley rats were divided into six groups: normal control (A, n = 6), sham-operation (N, n = 6), single hemorrhagic shock (S, n = 6), two-site trauma/shock (B, n = 6), four-site trauma/shock (C, n = 6), and six-site trauma/shock (D, n = 30). Shock was kept 60 min by blood withdrawal. Polytrauma was performed by clamping different sites of limbs to make fractures according to different groups: B at both femurs; C at femurs and tibias; and D at femurs, tibias, and humeri. The animals of A were totally normal without any operation. The rats of N, S, B, and C were killed at 6 hours after resuscitation, and the rats of D were killed at 1, 3, 6, 12, and 24 hours, respectively. Then, DNA agarose gel electrophoresis, in situ end-labeling (ISEL), and light and electron microscopy were performed and the percentage of DNA fragmentation was detected to assess apoptosis. In B, C, and D, the special ladder patterns for apoptosis were seen in thymus, spleen, liver, lung, and intestine, but not in heart, kidney, and brain. However, positive responses were observed in all these eight organs by ISEL. At 6 hours after resuscitation, the percentages of DNA fragmentation in thymus, spleen, liver, lung, and intestine all increased together with the severity of trauma. In D, the percentages of DNA fragmentation in these five organs all increased significantly at 1 hour after resuscitation. At 3 hours, the percentages in spleen, liver, lung, and intestine reached peak, and declined gradually afterward, whereas those in thymus continued increasing after 3 hours and kept stable from 6 hours to 24 hours. It was shown by morphologic examination that the majority of apoptotic cells lay in cortex of thymus, in growth center of white pulp of spleen, in border area of hepatic lobule and portal area of liver, and at the base of crypts of intestine. In lung, multiple kinds of cells, including alveolar epithelial cells, vascular endothelial cells, and polymorphonuclear neutrophils, induced apoptosis. Apoptosis was induced in thymus, spleen, liver, lung, and intestine in early stage after polytrauma combined with shock, which may play partial roles in the development of multiple organ failure.