A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage.

Malaria infection involves an obligatory, yet clinically silent liver stage1,2. Hepatocytes operate in repeating units termed lobules, exhibiting heterogeneous gene expression patterns along the lobule axis3, but the effects of hepatocyte zonation on parasite development at the molecular level remain unknown. Here we combine single-cell RNA sequencing4 and single-molecule transcript imaging5 to characterize the host and parasite temporal expression programmes in a zonally controlled manner for the rodent malaria parasite Plasmodium berghei ANKA. We identify differences in parasite gene expression in distinct zones, including potentially co-adaptive programmes related to iron and fatty acid metabolism. We find that parasites develop more rapidly in the pericentral lobule zones and identify a subpopulation of periportally biased hepatocytes that harbour abortive infections, reduced levels of Plasmodium transcripts and parasitophorous vacuole breakdown. These 'abortive hepatocytes', which appear predominantly with high parasite inoculum, upregulate immune recruitment and key signalling programmes. Our study provides a resource for understanding the liver stage of Plasmodium infection at high spatial resolution and highlights the heterogeneous behaviour of both the parasite and the host hepatocyte.

Core Hippo pathway components act as a brake on Yap and Taz in the development and maintenance of the biliary network.

The development of the biliary system is a complex yet poorly understood process, with relevance to multiple diseases, including biliary atresia, choledochal cysts and gallbladder agenesis. We present here a crucial role for Hippo-Yap/Taz signaling in this context. Analysis of sav1 mutant zebrafish revealed dysplastic morphology and expansion of both intrahepatic and extrahepatic biliary cells, and ultimately larval lethality. Biliary dysgenesis, but not larval lethality, is driven primarily by Yap signaling. Re-expression of Sav1 protein in sav1-/- hepatocytes is able to overcome these initial deficits and allows sav1-/- fish to survive, suggesting cell non-autonomous signaling from hepatocytes. Examination of sav1-/- rescued adults reveals loss of gallbladder and formation of dysplastic cell masses expressing biliary markers, suggesting roles for Hippo signaling in extrahepatic biliary carcinomas. Deletion of stk3 revealed that the phenotypes observed in sav1 mutant fish function primarily through canonical Hippo signaling and supports a role for phosphatase PP2A, but also suggests Sav1 has functions in addition to facilitating Stk3 activity. Overall, this study defines a role for Hippo-Yap signaling in the maintenance of both intra- and extrahepatic biliary ducts.

Comparative study on a novel lobule structure of the zebrafish liver and that of the mammalian liver.

The mammalian liver has a lobule structure with a portal triad consisting of the portal vein, hepatic artery, and bile duct, which exhibits zonal gene expression, whereas those of teleosts do not have a portal triad. It remains to be demonstrated what kind of the unit structures they have, including their gene expression patterns. The aims of the present study were to demonstrate the unit structure of the teleost liver and discuss it in terms of evolution and adaptation in vertebrates and the use of teleosts as an alternative model for human disease. The zebrafish liver was examined as a representative of teleosts with respect to its morphological architecture and gene expression. A novel, polygonal lobule structure was detected in the zebrafish liver. In it, portal veins and central veins were distributed at the periphery and center, respectively. Sinusoids connected both veins. Anxa4-positive preductules were incorporated into the tubular lumen of two rows of hepatocytes in sections. Intrahepatic bile ducts resided randomly in the liver lobule. Zebrafish livers did not have zonal gene expression for metabolic pathways examined. The lobules of the zebrafish liver with preductules located in the tubular lumina of hepatocytes may resemble the oval cell reaction of injured livers of mammals and might convey bile to the intestine more safely than mammalian livers. The gene expression pattern in liver lobules and our liver lobule model of the zebrafish may be important to discuss data obtained in experiments using this animal as an alternative model for human disease.

Discriminatory capacity of obesity indicators as predictors of high liver fat in US adolescents.

BACKGROUND: The aims of this study were to assess the potential of 16 anthropometric, body composition and endocrine indexes as predictors of high liver fat and determine the most appropriate cut-off points in US adolescents. METHODS: A cross-sectional study was conducted on a population of 816 adolescents aged 12-17 years. The FibroScan® 502V2 device was used to estimate the controlled attenuation parameter (CAP). Body fat percentage, fat mass, trunk fat percentage and trunk fat mass were measured by dual-energy X-ray absorptiometry. Anthropometric data and metabolic parameters were determined. Receiver operating characteristic curves were analysed to estimate the optimal cut-off points that best identify adolescents with high liver fat (CAP ≥90th percentile). RESULTS: In boys, triponderal mass index (TMI) had the highest area under curve (AUC) value (0.865) and the optimal cut-off score for TMI was 17.47 kg/m3 , which had 81.32 sensitivity and 82.99 specificity. In girls, trunk fat index (TFI) had the highest AUC value (0.826) and its optimal cut-off score in screening for high liver fat was 3.76 kg/m2 , which had 74.04 sensitivity and 88.03 specificity. Fat mass index (FMI) index had the second highest AUC values (0.863 in boys 0.812 in girls) in both sex; the cut-off point for the detection of high liver fat was <8.66 kg/m2 for girls and <7.45 kg/m2 for boys. CONCLUSION: Assessment of TMI in boys, TFI in girls, and FMI in both sexes are low-cost and easy-to-use parameters that may be useful as early screening tools for possible high liver fat in adolescents.

Triglyceride Paradox Is Related to Lipoprotein Size, Visceral Adiposity and Stearoyl-CoA Desaturase Activity in Black Versus White Women.

RATIONALE: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index. OBJECTIVE: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels. METHODS AND RESULTS: In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m2, we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P=0.001). Black women had smaller postprandial changes in large (P=0.005) and medium TRLPs (P=0.007). CONCLUSIONS: Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.

RLLB/Alb ratio: a promising noninvasive diagnostic marker in assessing esophageal varices in cirrhotic patients.

BACKGROUND: Endoscopy has long been widely used to screen for esophageal varices (EV) in cirrhotic patients. Recurrent endoscopy is a significant burden for the healthcare system of the endoscopic unit as well as uncomfortable and high costs for patients. This study intended to prognosticate Right Liver Lobe Diameter/Serum Albumin Ratio (RLLD/Alb) as a non-invasive approach in the early diagnosis of EV among chronic liver disease (CLD) Bangladeshi patients enrolled in a specific hospital. PARTICIPANTS AND METHODS: A total of 150 admitted patients with CLD were included in the study. Patients were subjected through a comprehensive biochemical checkup and upper digestive endoscopic or ultrasonographic inspection. The correlation was evaluated between the RLLD/Alb ratio and esophageal varices grades. RESULTS: The upper digestive endoscopy demonstration among 150 patients resulted in no EV in 18%, while 24% of patients was identified as EV grade I, 20% as grade II, 20% as grade III, and 18% patients as grade IV. The mean value of the RLLD/Alb ratio was 4.89 ± 1.49 (range from 2.30 to 8.45). The RLLD/Alb ratio diagnosed the EV employing the cut-off value of 4.01 with 85.3% sensitivity and 68.8% specificity. Furthermore, it was positively correlated with the grading of EV, when this ratio increased the grading of EV increases and vice versa (r = 0.630, p < 0.001). CONCLUSION: The RLLD/Alb ratio is a non-invasive parameter giving exact guidance relevant to the ascertainment of the existence of EV and their grading in chronic liver disease patients.

Anatomy of the vitelline vein remnant in human embryos and fetuses.

PURPOSE: To demonstrate the entire course of the human vitelline vein (VV) in specimens after degeneration of the yolk sac. METHODS: Sagittal and horizontal histological sections from 8 embryos and 19 fetuses (gestational age approximately 6-12 weeks; crown-rump length 11-61 mm) were examined. RESULTS: Two types of VV remnants were observed: a long VV on the right superior side of the mesentery of the jejunum (VV1) and a short VV on the left inferior side of the mesentery (VV2). The VV1, observed in 12 specimens, was 20-30 microns in diameter and ran dorsally between the right liver lobe and the jejunum, subsequently merging with an initial superior mesenteric vein on the pancreatic head immediately below the superior portion of the duodenum. The VV2, observed in four specimens, passed dorsally between loops of the ileum on the left side of the mesentery of the ileum and connected to the mesentery. Many of the VVs did not originate from the umbilical cord but suddenly started in the sack of physiological herniation. At 10-12 weeks, after herniation, the VVs originated from the umbilicus and were involved by the expanding greater omentum. CONCLUSIONS: The right-sided and left-sided VVs seemed to correspond to right and left VV remnants, respectively, and both took an upstream course outside the mesentery of the jejunum and ileum. The right VV upstream portion was likely to disappear later than the left one, but the timing of degeneration varied greatly among individuals, depending on the topographical relationship between the right liver lobe and the jejunum.

A comprehensive study and extensive review of morphological variations of liver with new insights.

PURPOSE: Liver is divided into four anatomical lobes presenting minor fissures and invisible major fissures. The prevalence of Accessory Fissures in liver ranges widely from 6 to 94%. The morphometric analysis of individual lobes is also scarce in literature. There have been instances where the surgeon has experienced some of these variations as a surprise during surgery as the existing data on the surface variations of liver is still contradictory. A sound knowledge of these variations would aid the surgeons and radiologists to circumvent the misdiagnosis and complications during surgeries. METHODS: The study was conducted in 93 cadaveric livers. Minor liver fissures, Accessory fissures and lobes were noted and measured. The livers were classified according to the Netter's classification. The morphology of caudate and quadrate lobes was studied. Any other variations in the appearance of groove for Inferior vena cava, gall bladder and its fossa were also studied. The results are tabulated. RESULTS: The study revealed several variations in the morphological features of liver. Accessory fissures were noted in 51.61% of livers, distributed on various liver surfaces. Accessory lobes were noted in 27.9%. Pons hepatis was present in 22.5%. Gall bladder variations that were noted include the Hartmann's pouch (n = 14; 15.05%) and the Phrygian cap (n = 2; 2.15%). 65.6% livers (n = 61) had the sulcus of the caudate process or fissure of Gans or Rouviere sulcus which is a normal fissure present in majority of normal healthy livers. CONCLUSION: The current study provides a complete understanding and a thorough knowledge of surface morphological variations in liver. We hope that this will be greatly helpful for surgeons and radiologists to avoid possible errors in interpretations, to plan appropriately and assist during liver surgeries and to do radiological interventions.

Gut-liver axis-mediated mechanism of liver cancer: A special focus on the role of gut microbiota.

Gut microbiota and the mammalian host share a symbiotic relationship, in which the host provides a suitable ecosystem for the gut bacteria to digest indigestible nutrients and produce useful metabolites. Although gut microbiota primarily reside in and influence the intestine, they also regulate liver function via absorption and subsequent transfer of microbial components and metabolites through the portal vein to the liver. Due to this transfer, the liver may be continuously exposed to gut-derived metabolites and components. For example, short-chain fatty acids (SCFA) produced by gut microbiota, through the fermentation of dietary fiber, can suppress inflammation via regulatory T cell induction through SCFA-induced epigenetic mechanisms. Additionally, secondary bile acids (BA), such as deoxycholic acid, produced by gut bacteria through the 7α-dehydroxylation of primary BAs, are thought to induce DNA damage and contribute to the remodeling of tumor microenvironments. Other substances that are also thought to influence liver function include lipopolysaccharides (components of the outer membrane of gram-negative bacteria) and lipoteichoic acid (cell wall component of Gram-positive bacteria), which are ligands of innate immune receptors, Toll-like receptor-4, and Toll-like receptor-2, respectively, through which inflammatory signaling is elicited. In this review, we focus on the role of gut microbiota in the liver microenvironment, describing the anatomy of the gut-liver axis, the role of gut microbial metabolites, and the relationships that exist between gut microbiota and liver diseases, including liver cancer.

Oncogenic KRAS-expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice.

Biliary tract cancer (BTC) arises from biliary epithelial cells (BECs) and includes intrahepatic cholangiocarcinoma (IHCC), gallbladder cancer (GC), and extrahepatic cholangiocarcinoma (EHCC). Although frequent KRAS mutations and epigenetic changes at the INK4A/ARF locus have been identified, the molecular pathogenesis of BTC is unclear and the development of corresponding anticancer agents remains inadequate. We isolated epithelial cell adhesion molecule (EpCAM)-positive BECs from the mouse intrahepatic bile duct, gallbladder, and extrahepatic bile duct, and established organoids derived from these cells. Introduction of activated KRAS and homozygous deletion of Ink4a/Arf in the cells of each organoid type conferred the ability to form lethal metastatic adenocarcinoma with differentiated components and a pronounced desmoplastic reaction on cell transplantation into syngeneic mice, indicating that the manipulated cells correspond to BTC-initiating cells. The syngeneic mouse models recapitulate the pathological features of human IHCC, GC, and EHCC, and they should therefore prove useful for the investigation of BTC carcinogenesis and the development of new therapeutic strategies. Tumor cells isolated from primary tumors formed organoids in three-dimensional culture, and serial syngeneic transplantation of these cells revealed that their cancer stem cell properties were supported by organoid culture, but not by adherent culture. Adherent culture thus attenuated tumorigenic activity as well as the expression of both epithelial and stem cell markers, whereas the expression of epithelial-mesenchymal transition (EMT)-related transcription factor genes and mesenchymal cell markers was induced. Our data show that organoid culture is important for maintenance of epithelial cell characteristics, stemness, and tumorigenic activity of BTC-initiating cells.

Experiences With Three-dimensional Printing in Complex Liver Surgery.

OBJECTIVE: We present a series of cases where we used 3D printing in planning of complex liver surgery. BACKGROUND: In liver surgery, three-dimensional reconstruction of the liver anatomy, in particular of vascular structures, has shown to be helpful in operation planning. So far, 3D printing has been used for medical applications only rarely. METHODS AND PATIENTS: From December 2017 to December 2019, in 10 cases where surgery was assumed to be challenging operation planning was performed using full size 3D prints in addition to standard 3 phase CT scans. Models included transparent parenchyma, hepatic veins, vena cava, portal vein, hepatic artery, (biliary tree if requested), and tumors. In 7/10 cases vascular reconstructions were needed during the procedure. Nonstructured feedback of the surgical team revealed that the major benefit was visualization of the critical areas of vascular reconstruction, the expected dimensions of tangential vascular infiltration and the planning of reconstruction. In the multifocal tumors, 3D prints were considered to be helpful for intraoperative orientation to detect metastases and to improve planning of the resection. CONCLUSIONS: In complex liver surgery with potential need for vascular reconstructions operation planning may be optimized using a 3D printed liver model. Prospective studies are needed to evaluate the clinical impact of 3D printing in liver surgery compared to other 3D visualizations.

The Risk of Going Small: Lowering GRWR and Overcoming Small-For-Size Syndrome in Adult Living Donor Liver Transplantation.

OBJECTIVE: The aim of this study was to determine the outcomes of living donor liver transplantation (LDLT) according to various graft-to-recipient weight ratio (GRWR). BACKGROUND: The standard GRWR in LDLT is >0.8%. Our center accepted predicted GRWR ≥0.6% in selected patients. METHODS: Data from patients who underwent LDLT from 2001 to 2017 were included. Patients were stratified according to actual GRWR (Group 1:GRWR ≤0.6%; Group 2: 0.6%0.8%). RESULTS: There were 545 LDLT (group 1 = 39; group 2 = 159; group 3 = 347) performed. Pretransplant predicted GRWR showed good correlation to actual GRWR (R2 = 0.834) and these figures differed within a ±â€Š10%margin (P = 0.034) using an equivalence test. There were more left lobe grafts in group 1 (33.3%) than group 2 (10.7%) and 3 (2.9%). Median donor age was <35 years and steatosis >10% was rare.There was no difference in postoperative complication, vascular and biliary complication rate between groups. Over one-fifth (20.5%) of group 1 patients required portal flow modulation (PFM) and was higher than group 2 (3.1%) and group 3 (4%) (P = 0.001). Twenty-six patients developed small-for-size syndrome (SFSS): 5 of 39 (12.8%) in group 1 and 21 of 159 (13.2%) in group 2 and none in group 3 (P < 0.001). There were 2 hospital mortalities; otherwise, the remaining patients [24/26 (92.3%)] survive with a functional liver graft. The 5-year graft survival rates were 85.4% versus 87.8% versus 84.7% for group 1, 2, and 3, respectively (P = 0.718). GRWR did not predict worse survivals in multivariable analysis. CONCLUSIONS: Graft size in LDLT can be lowered to 0.6% after careful recipient selection, with low incidence of SFSS and excellent outcomes. Accurate graft weight prediction, donor-recipient matching, meticulous surgical techniques, appropriate use of PFM, and vigilant perioperative care is important to the success of such approach.

PET Image Quality Improvement for Simultaneous PET/MRI with a Lightweight MRI Surface Coil.

Background During simultaneous PET/MRI, flexible MRI surface coils that lay on the patient are often omitted from PET attenuation correction processing, leading to quantification bias in PET images. Purpose To identify potential PET image quality improvement by using a recently developed lightweight MRI coil technology for the anterior array (AA) surface coil in both a phantom and in vivo study. Materials and Methods A phantom study and a prospective in vivo study were performed with a PET/CT scanner under three conditions: (a) no MRI surface coil (standard of reference), (b) traditional AA coil, and (c) lightweight AA coil. AA coils were not used in attenuation correction processing to emulate clinical PET/MRI. For the phantom study, PET images were reconstructed with and without time of flight (TOF) to assess quantification accuracy and uniformity. The in vivo study consisted of 10 participants (mean age, 66 years ± 10 [standard deviation]; six men) referred for a PET/CT oncologic examination who had undergone imaging between October 2019 and February 2020. Assessment of image quantification bias (defined as the standard error of the mean values) was conducted by comparing mean liver region of interest standardized uptake values with the no-coil standard of reference. A Wilcoxon signed-rank test was used to establish significance. Results For TOF and non-TOF, respectively, the phantom study revealed a mean PET quantification bias of -9.0% and -8.6% with the traditional AA coil and a mean PET quantification bias of -4.3% and -4.0% with the lightweight AA coil. The coefficients of variation reduced from 4.3% and 6.2% with the traditional AA coil to 2.1% and 2.7% with the lightweight AA coil, which demonstrated a homogeneity benefit from the lightweight coil that was greater with, versus without, TOF reconstruction. For the in vivo study, the mean liver standardized uptake value error was -5.9% with the traditional AA coil (P = .002 vs no coil) and -2.4% with the lightweight AA coil (P = .004 vs no coil). Conclusion The lightweight anterior array coil reduced PET image quantification bias by more than 50% compared with the traditional coil. Using the lightweight coil and performing time of flight-based reconstruction each reduced the variation of error. © RSNA, 2020 Online supplemental material is available for this article.

Hepatic Hilar Nerve Block for Hepatic Interventions: Anatomy, Technique, and Initial Clinical Experience in Thermal Ablation of Liver Tumors.

Background Image-guided procedures for treatment of liver diseases can be painful and require heavy sedation of the patient. Local-regional nerve blocks improve pain control and reduce oversedation risks, but there are no documented liver-specific nerve blocks. Purpose To develop a safe and technically simple liver-specific nerve block. Materials and Methods Between March 2017 and October 2019, three cadavers were dissected to evaluate the hepatic hilar anatomy. The hepatic hilar nerves were targeted with transhepatic placement of a needle adjacent to the main portal vein, under US guidance, and evaluated with use of an injection of methylene blue. A hepatic nerve block, using similar technique and 0.25% bupivacaine, was offered to patients undergoing liver tumoral ablation. In a prospective pilot study, 12 patients who received the nerve block were compared with a control group regarding complications, safety, pain scores, and intraoperative opioid requirement. Student t tests were used to compare the groups' characteristics, and Mann-Whitney U tests were used for the measured outcomes. Results Cadaver results confirmed that the hepatic nerves coursing in the hepatic hilum can be targeted with US for injection of anesthetic agents, with adequate spread of injected methylene blue around the nerves in the hepatic hilar perivascular space. The 12 participants (mean age ± standard deviation, 66 years ± 13; eight men) who received a hepatic hilar block before liver thermal ablations demonstrated reduced pain compared with a control group of 12 participants (mean age, 63 years ± 15; eight men) who received only intravenous sedation. Participants who received the nerve block had a lower mean visual analog scale score for pain than the control group (3.9 ± 2.4 vs 7.0 ± 2.8, respectively; P = .01) and decreased need for intraprocedural fentanyl (mean dose, 152 µg ± 78.0 vs 235.4 µg ± 58.2, respectively; P = .01). No major complications occurred in the hepatic hilar nerve block group. Conclusion A dedicated hepatic hilar nerve block with 0.25% bupivacaine can be safely performed to provide anesthesia during liver tumoral ablation. © RSNA, 2021.

Liver Fat and Cardiometabolic Risk Factors Among School-Age Children.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease is a major risk factor for cardiometabolic disease in adults. The burden of liver fat and associated cardiometabolic risk factors in healthy children is unknown. In a population-based prospective cohort study among 3,170 10-year-old children, we assessed whether both liver fat accumulation across the full range and nonalcoholic fatty liver disease are associated with cardiometabolic risk factors already in childhood. APPROACH AND RESULTS: Liver fat fraction was measured by magnetic resonance imaging, and nonalcoholic fatty liver disease was defined as liver fat fraction ≥5.0%. We measured body mass index, blood pressure, and insulin, glucose, lipids, and C-reactive protein concentrations. Cardiometabolic clustering was defined as having three or more risk factors out of high visceral fat mass, high blood pressure, low high-density-lipoprotein cholesterol or high triglycerides, and high insulin concentrations. Nonalcoholic fatty liver disease prevalences were 1.0%, 9.1%, and 25.0% among children who were normal weight, overweight, and obese, respectively. Both higher liver fat within the normal range (<5.0% liver fat) and nonalcoholic fatty liver disease were associated with higher blood pressure, insulin resistance, total cholesterol, triglycerides, and C-reactive protein concentrations (P values < 0.05). As compared with children with <2.0% liver fat, children with ≥5.0% liver fat had the highest odds of cardiometabolic clustering (odds ratio 24.43 [95% confidence interval 12.25, 48.60]). The associations remained similar after adjustment for body mass index and tended to be stronger in children who were overweight and obese. CONCLUSIONS: Higher liver fat is, across the full range and independently of body mass index, associated with an adverse cardiometabolic risk profile already in childhood. Future preventive strategies focused on improving cardiometabolic outcomes in later life may need to target liver fat development in childhood.

Spatial architecture of biliary tree in mammals: Fractal and Euclidean geometric features.

The study of the fractal architecture of various organs and structures expanded the possibilities for determining the ranges of their functioning and structural arrangement, which, as a result, was reflected in the development of new approaches to diagnostics and therapeutic impacts. The architecture of the excretory duct systems, similar to the hemo- and lymph- circulatory beds and the bronchial tree, is considered fractal. At the same time, information about hitherto unknown structures of the biliary tree continues to appear in the literature. We aimed to study the features of the spatial geometry of the biliary tree and assess the significance of both its fractal and Euclidean characteristics for the development of approaches that facilitate comprehensive description of intrahepatic biliary tract architecture. We investigated the architecture of the biliary trees of six men, seven male canines, and seven male Wistar rats using the corrosion casting method. Corrosion casts were prepared by injecting solidifying latexes into the bile ducts. The preparations were studied using a light stereomicroscope and a scanning electron microscope. Biliary tree branching is of various types. In addition, the correlation between variations in the caliber and length of the bile ducts and their order is not significant. Therefore, the biliary tree should not be considered as a classical fractal and it consists of the main modules, represented by the network of the bile canaliculi (first nonfractal module) and a biliary tree with a fractal branching (second module) that drains the bile canaliculi mesh and the additional modules represented by the mucosal biliary glands (in mammals with the gallbladder) or the periportal biliary plexus (in mammals without a gallbladder) and the aberrant biliary ducts. Such a configuration of the biliary bed should optimally ensure the smooth implementation of the physiological function of the liver, as well as its adaptation to different pathologies accompanied by biliary hypertension. It also might be considered in the diagnosis and assessment of ductular reaction, biliary regeneration, and/or carcinogenesis.

Resilience of three-dimensional sinusoidal networks in liver tissue.

Can three-dimensional, microvasculature networks still ensure blood supply if individual links fail? We address this question in the sinusoidal network, a plexus-like microvasculature network, which transports nutrient-rich blood to every hepatocyte in liver tissue, by building on recent advances in high-resolution imaging and digital reconstruction of adult mice liver tissue. We find that the topology of the three-dimensional sinusoidal network reflects its two design requirements of a space-filling network that connects all hepatocytes, while using shortest transport routes: sinusoidal networks are sub-graphs of the Delaunay graph of their set of branching points, and also contain the corresponding minimum spanning tree, both to good approximation. To overcome the spatial limitations of experimental samples and generate arbitrarily-sized networks, we developed a network generation algorithm that reproduces the statistical features of 0.3-mm-sized samples of sinusoidal networks, using multi-objective optimization for node degree and edge length distribution. Nematic order in these simulated networks implies anisotropic transport properties, characterized by an empirical linear relation between a nematic order parameter and the anisotropy of the permeability tensor. Under the assumption that all sinusoid tubes have a constant and equal flow resistance, we predict that the distribution of currents in the network is very inhomogeneous, with a small number of edges carrying a substantial part of the flow-a feature known for hierarchical networks, but unexpected for plexus-like networks. We quantify network resilience in terms of a permeability-at-risk, i.e., permeability as function of the fraction of removed edges. We find that sinusoidal networks are resilient to random removal of edges, but vulnerable to the removal of high-current edges. Our findings suggest the existence of a mechanism counteracting flow inhomogeneity to balance metabolic load on the liver.

Effects of dietary choline on liver lipid composition, liver histology and plasma biochemistry of juvenile yellowtail kingfish (Seriola lalandi).

Choline plays a crucial role in lipid metabolism for fish, and its deficiency in aquafeed has been linked to compromised health and growth performance. A 56-d experiment was conducted to examine the effects of dietary choline on lipid composition, histology and plasma biochemistry of yellowtail kingfish (Seriola lalandi; YTK; 156 g initial body weight). The dietary choline content ranged from 0·59 to 6·22 g/kg diet. 2-Amino-2-methyl-1-propanol (AMP) (3 g/kg) was added to diets, except for a control diet, to limit de novo choline synthesis. The results showed that the liver lipid content of YTK was similar among diets containing AMP and dominated by NEFA. In contrast, fish fed the control diet had significantly elevated liver TAG. Generally, the SFA, MUFA and PUFA content of liver lipid in fish fed diets containing AMP was not influenced by choline content. The SFA and MUFA content of liver lipid in fish fed the control diet was similar to other diets except for a decrease in PUFA. The linear relationship between lipid digestibility and plasma cholesterol was significant, otherwise most parameters were unaffected. When AMP is present, higher dietary choline reduced the severity of some hepatic lesions. The present study demonstrated that choline deficiency affects some plasma and liver histology parameters in juvenile YTK which might be useful fish health indicators. Importantly, the present study elucidated potential reasons for lower growth in choline-deficient YTK and increased the knowledge on choline metabolism in the fish.

Ginkgo biloba leaf extract improves growth, intestinal histomorphometry, immunity, antioxidant status and modulates transcription of cytokine genes in hapa-reared Oreochromis niloticus.

This study was designed to evaluate the impacts of dietary supplementation with Ginkgo biloba leaf extract (GBL) on the growth, intestinal histomorphometry, immunity, antioxidant status, and expression of cytokine genes in Nile tilapia reared in the hapas. A control diet was enriched with different GBL levels (0.0, 5.0, 7.0, and 9.0 g/kg) to form 4 experimental diets and were fed to Nile tilapia for 8 weeks. The findings illustrated that dietary GBL significantly enhanced the growth and feed utilization indices compared to those reared in the control group. A dose-dependent increase of hepatic catalase, superoxide dismutase, and glutathione peroxidase activities alongside a decline of hepatic malondialdehyde levels were recorded in GBL groups compared with the control. Serum lysozyme activity, complement C3, and immunoglobulin M levels were significantly increased in GBL groups compared with the control group. Moreover, dietary GBL maintained the normal intestinal and hepatopancreatic histological structures with a significant increase of some histomorphometric measurements of proximal, middle, and distal intestinal parts of the treated fish. Interestingly, dietary GBL supplementation significantly increased the mRNA expression of interleukin-1 beta (IL-1ß), IL-6, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) genes in the splenic tissues of treated fish over the control group. To conclude, it could be recommended to use GBL as a functional phytogenic feed additive to improve the growth, hepatic and intestinal health status, hepatic antioxidant status, and immunity of treated Nile tilapia. Besides, the second order polynomial regression revealed that 7.50 g GBL/kg diet is the optimal inclusion level to improve growth with no negative impacts on the overall health condition of treated Nile tilapia.

Large for size in pediatrics liver transplant using left lateral segment grafts: A single center experience.

BACKGROUND: There are still controversies in using the large left lateral segment in pediatrics LT, with the possibility of the problem of LFS grafts, and the use of monosegmental or reduced liver grafts in small infants. This study aimed to evaluate our experience with LFSG in pediatrics LT. METHODS: A cohort retrospective analysis was conducted including pediatric recipients who underwent LT between January 2011 and October 2019. We compared recipients with GRWR ≥ 4% (LFS) vs GRWR < 4% as an average for size grafts. RESULTS: There were 331 pediatric LT, 74 patients with GRWR ≥ 4%, and 257 patients with GRWR < 4%. In the group of LFS grafts, temporary abdominal closure by silicon patch was done in 39 patients (52.7%), 2 patients (2.7%) had postoperative HAT, 3 patients (4.1%) early PVT, 1 patient (1.3%) bile leak, and 3 patients (4.1%) had wound infection, with no significant difference in these complications between the 2 groups. In patients with LFS- grafts, the 1-, 3-, 5-, and 7-year patients survival rates were 94.6%, 91.7%, 91.7%, and 91.7%, respectively, while the survival rates in patients of the other group were 96.1%, 92.6%, 91.9%, and 91.9%, respectively, with no significant difference (p = .85). CONCLUSION: Using LFS graft by left lateral segment in pediatric LT with potential delayed abdominal closure is a safe and feasible option with good outcomes and unnecessary need for graft reduction if performed by an experienced multidisciplinary team.