Portal Blood Supply Research Articles

Perfusion parameters of triphasic computed tomography hold preoperative prediction value for microvascular invasion in hepatocellular carcinoma

The purpose of this study was to evaluate perfusion parameters of triphasic computed tomography (CT) scans in predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). All patients were pathologically diagnosed as HCC and underwent triple-phase enhanced CT imaging, which was used to calculate the blood perfusion parameters of hepatic arterial supply perfusion (HAP), portal vein blood supply perfusion (PVP), hepatic artery perfusion Index (HPI), and arterial enhancement fraction (AEF). Receiver operating characteristic (ROC) curve was used to evaluate the performance. The mean values of PVP(Min), AEF(Min), the difference in PVP, HPI and AEF related parameters, the relative PVP(Min) and AEF(Min) in MVI negative group were significantly higher than those in MVI positive group, while for the difference in HPI(Max), the relative HPI(Max) and AEF(Max), the value of MVI positive group significantly higher than that of negative group. The combination of PVP, HPI and AEF had the highest diagnostic efficacy. The two parameters related to HPI had the highest sensitivity, while the combination of PVP related parameters had higher specificity. A combination of perfusion parameters in patients with HCC derived from traditional triphasic CT scans can be used as a preoperative biomarker for predicting MVI.

A Rare Case of Hepatic Visceral Larva Migrans

A systemic manifestation of nematode second-stage larvae migrating through the tissue of human viscera is termed visceral larva migrans (VLM). Although frequent, it is underdiagnosed in developing nations. Due to its portal venous blood supply, the liver is the organ that is affected the most frequently. The imaging results are subtle, making it challenging to distinguish them from granulomatous disorders, metastases, cystic mesenchymal hamartomas, and hepatocellular carcinoma (HCC). This case report includes clinical and laboratory information that aids in the diagnosis as well as imaging characteristics of hepatic lesions of VLM. It presents as coalescing and or conglomerated lesion(s) in the liver on imaging.

Identification of crucial lncRNAs and mRNAs in liver regeneration after portal vein ligation through weighted gene correlation network analysis

BackgroundPortal vein ligation (PVL)-induced liver hypertrophy increases future liver remnant (FLR) volume and improves resectability of large hepatic carcinoma. However, the molecular mechanism by which PVL facilitates liver hypertrophy remains poorly understood.MethodsTo gain mechanistic insight, we established a rat PVL model and carried out a comprehensive transcriptome analyses of hepatic lobes preserving portal blood supply at 0, 1, 7, and 14-day after PVL. The differentially expressed (DE) long-non coding RNAs (lncRNAs) and mRNAs were applied to conduct weighted gene co-expression network analysis (WGCNA). LncRNA-mRNA co-expression network was constructed in the most significant module. The modules and genes associated with PVL-induced liver hypertrophy were assessed through quantitative real-time PCR.ResultsA total of 4213 DElncRNAs and 6809 DEmRNAs probesets, identified by transcriptome analyses, were used to carry out WGCNA, by which 10 modules were generated. The largest and most significant module (marked in black_M6) was selected for further analysis. Gene Ontology (GO) analysis of the module exhibited several key biological processes associated with liver regeneration such as complement activation, IL-6 production, Wnt signaling pathway, autophagy, etc. Sixteen mRNAs (Notch1, Grb2, IL-4, Cops4, Stxbp1, Khdrbs2, Hdac2, Gnb3, Gng10, Tlr2, Sod1, Gosr2, Rbbp5, Map3k3, Golga2, and Rev3l) and ten lncRNAs (BC092620, AB190508, EF076772, BC088302, BC158675, BC100646, BC089934, L20987, BC091187, and M23890) were identified as hub genes in accordance with gene significance value, module membership value, protein–protein interaction (PPI) and lncRNA-mRNA co-expression network. Furthermore, the overexpression of 3 mRNAs (Notch1, Grb2 and IL-4) and 4 lncRNAs (BC089934, EF076772, BC092620, and BC088302) was validated in hypertrophic liver lobe tissues from PVL rats and patients undergoing hepatectomy after portal vein embolization (PVE).ConclusionsMicroarray and WGCNA analysis revealed that the 3 mRNAs (Notch1, Grb2 and IL-4) and the 4 lncRNAs (BC089934, EF076772, BC092620 and BC088302) may be promising targets for accelerating liver regeneration before extensive hepatectomy.

Pre-transplant portal vein thrombosis in non-alcoholic fatty liver disease patients-pathogenesis, risk factors, and implications on management.

Along with the worldwide increase in obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and its more severe subset, non-alcoholic steatohepatitis (NASH), are on path to become the leading cause of liver transplantation in the United States. NAFLD, as well as obesity, create an inflammatory milieu via the release of adipocytokines. In turn, the inflammatory environment can trigger an increase in prothrombotic factors. Independent of inflammation, the severity of NASH is associated with a graded increase in hypercoagulability such as an increase in factor VIII, increase in plasminogen activator inhibitor-1, and decrease in protein C. Ultimately, this environment creates an increase in thrombotic risk, leading to higher rates of pre-transplant portal vein thrombosis (PVT) in patients with NASH cirrhosis vesus other causes of cirrhosis. Many studies have shown worse outcomes in liver transplant recipients with PVT as it complicates anastomotic reconstruction which can negatively affect portal blood supply needed for adequate liver functioning. Management and treatment of PVT is not standardized, but from a pharmacologic standpoint, multiple classes of anticoagulants have shown to be successful in recanalization of the portal vein and preventing recurrence of clot with minimal bleeding complications. The increasing prevalence of NASH cirrhosis and subsequent increase in PVT require further research for improved outcomes.

Liver anatomy, intrahepatic vascular and biliary branching system of the mole rat (Spalax leucodon).

There are many studies on the morphology of the liver and its blood vessels in experimental animals, but such studies are lacking in the mole rat (Spalax leucodon). The aim of this paper was a detailed basic study on the topography, morphology, vascular and biliary branching systems of the liver in the mole rat. Coloured gelatine and mixture of coloured lead oxide and linseed oil were injection contrast masses used to obtain vascular and biliary branching pattern in the liver. It was revealed that the liver of the mole rat had five lobes (left, quadrate, right medial, right lateral and caudate lobes). The left, undivided lobe was the largest lobe of the liver. The quadrate lobe was divided into two components by a deep notch. The gallbladder, of cylindrical shape, was present and attached to the quadrate lobe. The common bile duct was formed by the union of the left and right hepatic ducts. The pancreatic duct joined the common bile duct before it entered the duodenum. In the present study, only the right medial lobe and quadrate lobe always showed a single lobar artery, portal and hepatic veins. The left lobe showed four lobar arteries, portal and hepatic veins. The caudate lobe with its two processes and the right lateral and medial lobes had different arterial and portal blood supply as well as hepatic and biliary drainage of these lobes. The intrahepatic branches of the proper hepatic artery ran parallel to the branches of the common portal vein in the same lobes of the liver. The results of this study are significant for comparative studies among different species of rodents and other experimental animals. Morphology, vasculature and biliary tract of the liver in the mole rat were similar to that of other experimental animals and identified differences may be related to the adaptation to the mode of life and diet of this rodent.

Value of perfusion parameters and histogram analysis of triphasic computed tomography in pre-operative prediction of histological grade of hepatocellular carcinoma.

Background:Pre-operative non-invasive histological evaluation of hepatocellular carcinoma (HCC) remains a challenge. Tumor perfusion is significantly associated with the development and aggressiveness of HCC. The purpose of the study was to evaluate the clinical value of quantitative liver perfusion parameters and corresponding histogram parameters derived from traditional triphasic enhanced computed tomography (CT) scans in predicting histological grade of HCC.Methods:Totally, 52 patients with HCC were enrolled in this retrospective study and underwent triple-phase enhanced CT imaging. The blood perfusion parameters were derived from triple-phase CT scans. The relationship of liver perfusion parameters and corresponding histogram parameters with the histological grade of HCC was analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal ability of the parameters to predict the tumor histological grade.Results:The variance of arterial enhancement fraction (AEF) was significantly higher in HCCs without poorly differentiated components (NP-HCCs) than in HCCs with poorly differentiated components (P-HCCs). The difference in hepatic blood flow (HF) between total tumor and total liver flow (ΔHF = HFtumor − HFliver) and relative flow (rHF = ΔHF/HFliver) were significantly higher in NP-HCCs than in P-HCCs. The difference in portal vein blood supply perfusion (PVP) between tumor and liver tissue (ΔPVP) and the ΔPVP/liver PVP ratio (rPVP) were significantly higher in patients with NP-HCCs than in patients with P-HCCs. The area under ROC (AUC) of ΔPVP and rPVP were both 0.697 with a high sensitivity of 84.2% and specificity of only 56.2%. The ΔHF and rHF had a higher specificity of 87.5% with an AUC of 0.681 and 0.673, respectively. The combination of rHF and rPVP showed the highest AUC of 0.732 with a sensitivity of 57.9% and specificity of 93.8%. The combined parameter of ΔHF and rPVP, rHF and rPVP had the highest positive predictive value of 0.903, and that of rPVP and ΔPVP had the highest negative predictive value of 0.781.Conclusion:Liver perfusion parameters and corresponding histogram parameters (including ΔHF, rHF, ΔPVP, rPVP, and AEFvariance) in patients with HCC derived from traditional triphasic CT scans may be helpful to non-invasively and pre-operatively predict the degree of the differentiation of HCC.

Insight into Bile Duct Reaction to Obstruction from a Three-dimensional Perspective Using ex Vivo Phase-Contrast CT.

Background Biliary obstruction leads to an increase in biliary pressure within the biliary system, which induces the morphologic adaptation of the biliary tree. Purpose To observe and to quantify the morphologic characteristics of the adaptation in a bile duct ligation rat model and verify it in patients with biliary atresia in a three-dimensional (3D) manner using x-ray phase-contrast CT. Materials and Methods A bile duct ligation model was induced in 40 male Sprague-Dawley rats, which were divided into five groups: the control group (no ligation) and groups 2, 4, 6, and 8 weeks after bile duct ligation (eight animals in each group). Liver tissue samples (approximately 1.8 cm in length and 1.3 cm in height) were imaged by using phase-contrast CT and compared with histologic analysis. With a combination of phase-contrast CT and 3D visualization technology, the entire biliary system and the intrahepatic vascular system were quantitatively analyzed according to downstream, midstream, and upstream domains based on bile duct volume, surface area, and other parameters. Additionally, liver explant tissues from 28 patients with biliary atresia were studied to determine the impact of biliary tract reconstruction. Results To offset the increased biliary pressure within the biliary system, the ductular reaction in the downstream, midstream, and upstream domains manifested as dilatation, spiderweb-like looping, and interconnected honeycomb-like patterns, respectively. The most severe ductular reaction occurred in the upstream domain, and the relative surface area (mean, 0.02 μm-1 ± 0.01, 0.04 μm-1 ± 0.01, 0.07 μm-1 ± 0.02, and 0.10 μm-1 ± 0.02 for the 2-8-week groups, respectively; P < .01 among the groups) and volume fraction of ductules (mean, 16.54% ± 4.62, 19.69% ± 6.41, 26.92% ± 5.82, and 38.34% ± 10.36 for the 2-8-week groups, respectively; P < .01 among the groups except between the 2- and 4-week groups [P = .062]) significantly increased over time. In patients with biliary atresia, it was observed that both fibrosis and proliferative ductules regressed after successful biliary tract reconstruction following Kasai portoenterostomy. Furthermore, ductular reaction was accompanied by a progressive increase in the arterial supply but a loss of portal blood supply. Conclusion X-ray phase-contrast CT with three-dimensional rendering of the biliary system in a bile duct ligation rat model provides key insights into ductular reaction or biliary self-adaptation triggered by increased biliary pressure. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vannier and Wang in this issue.

Early hemodynamics of hepatocellular carcinoma using contrast-enhanced ultrasound with Sonazoid: focus on the pure arterial and early portal phases.

To clarify the early hemodynamics of hepatocellular carcinoma (HCC), we defined the early portal phase of contrast-enhanced ultrasound (CEUS) and examined the reliability of this modality for determining HCC differentiation. Starting in 2007, we performed Sonazoid CEUS in 146 pathologically confirmed hepatic nodules; 118 HCC (8 poorly [Pd], 73 moderately [Md] and 37 well-differentiated [Wd]) and 28 benign nodules. We focused on the pure arterial and early portal phases up to 45 seconds after Sonazoid injection, and then the subsequent phase up to 30 minutes. We calculated covariance-adjusted sensitivities for nodule enhancement combinations of these three phases. Nodule enhancements were divided into hypo, iso and hyper. A positive predictive value of 100% was obtained for the following patterns: iso-iso-hypo, hypo-iso-iso, and hypo-hypo-hypo for Wd, hyper-iso-hypo and hyper-hypo-hypo for Md, hypo-hyper-hypo for Pd, and hyper-hyper-hyper for benign nodules. In Wd HCC (early HCC), there were seven enhancement patterns, thought to be characterized by various hemodynamic changes from early to advanced HCC. Two patterns allowing a diagnosis of Wd HCC were hypo in the pure arterial phase. Subsequent iso-enhancement in the early portal phase indicated a portal blood supply. Decreased enhancement in the early portal phase allows a diagnosis of Md HCC. However, gradual enhancement observed from the pure arterial to the early portal phase allows a diagnosis of Pd HCC. Therefore, even in the early portal phase, hemodynamic changes were visible not only in Wd but also in Md and Pd HCC. In conclusion, with division of the early phase hemodynamics into pure arterial and early portal phases, CEUS can provide information useful for determining the likely degree of HCC differentiation and for distinguishing early stage HCC from benign nodules.

Determination of portal vein tumor thrombus blood supply using in vivo cellular magnetic resonance imaging in a rabbit model.

Objective: This study aimed to investigate the anatomic configuration of the blood vessels that contribute to portal vein tumor thrombus (PVTT), a common complication of hepatocellular carcinoma, in VX2 rabbits.Materials and methods: Peripheral blood mononuclear cells (MNCs) were isolated and labeled using superparamagnetic iron oxide particles in vitro. Twenty-four rabbits were injected with the VX2 tumor via the portal vein to establish the PVTT model. The rabbits (n=6/treatment group) were randomly assigned into four groups. Rabbits of groups A, B and C received an infusion of iron-labeled MNCs via the hepatic artery, the portal vein or the auricular vein, respectively, whereas rabbits of group D received an injection of normal saline via the auricular vein 7 days after the injection of VX2 tumors. MRI was performed, and the signal intensity (SI) of the PVTTs was measured on T2-weighted images (T2WIs) 1 day after the transfusion of iron-labeled cells.Results: The SI of PVTTs, as measured on T2WIs, in rabbits of groups A, B, C and D was 241.400 (172.350, 364.825), 221.150 (203.775, 318.225), 590.200 (363.325, 728.875) and 568.050 (474.725, 705.150), respectively. Our data showed a significant decrease in the SI of PVTTs in rabbits of groups A and B compared with rabbits of groups C and D (group A vs group C, U=4.000, p=0.025; group A vs group D, U=2.000, p=0.010; group B vs group C, U=4.000, p=0.025; group B vs group D, U=1.000, p=0.006). There was no significant difference in the SI of PVTTs in rabbits of group A and B.Conclusion: Our results indicated that the portal vein and the hepatic artery supplied blood flow to the PVTT in rabbits.

An Efficient and Clinical-Oriented 3D Liver Segmentation Method

By segmenting, modeling, and visualizing computed tomography sequence data, surgeons can better understand the spatial relationship of the intrahepatic vein, portal vein, artery, and tumor. Accurate preoperative understanding of liver anatomy and volume of the corresponding liver segment are necessary for anatomical liver resection. This paper gives an efficient and semiautomatic method for segmenting the liver in clinical cases. This method is based on Couinaud’s theory and automatically divides the liver segment by portal vein branches. Considering the vascular variation of individual cases, the adjustment of the portal vein branches was provided on the basis of automatic segmentation, thus adaptability to various cases was implemented. For the final segmentation results, the portal vein blood supply of different liver segments can be confirmed by 3-D visualization, and the liver volume can be accurately estimated. Experiments show that this liver segmentation method has good clinical value.

Morphology and morphometry of the caudate lobe of the liver in two populations

The caudate lobe of the liver has portal blood supply and hepatic vein drainage independent of the remainder of the liver and may be differentially affected in liver pathologies. Ultrasonographic measurement of the caudate lobe can be used to generate hepatic indices that may indicate cirrhosis. This study investigated the relationship of metrics of the caudate lobe and other morphological features of human livers from a northwest Indian Punjabi population (n = 50) and a UK Caucasian population (n = 25), which may affect the calculation of hepatic indices. The width of the right lobe of the liver was significantly smaller, while the anteroposterior diameter of the caudate lobe and both Harbin’s Index and the Hess Index scores were significantly larger in NWI livers than in UKC livers. The Hess Index score, in particular, is much larger in the NWI population (265 %, p < 0.005). Two caudate lobe features were significantly different between the two populations—the shape of the caudate lobe and the development of the caudate process. This study shows significant population differences exist in several metrics and morphological features of the liver. These differences may affect the calculation of hepatic indices, resulting in a greater percentage of false positives of cirrhosis in the NWI population. Population-specific data are required to correctly determine normal ranges.

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Background/Aim: Liver size regulation is based on the balance between hepatic regeneration and atrophy. To achieve a better understanding of intrahepatic size regulation, we explored the size regulation of a portally deprived liver lobe on a liver subjected to concurrent portal vein ligation (PVL) and partial hepatectomy (PHx). Materials and Methods: Using a surgical rat model consisting of right PVL (rPVL) plus 70% PHx, we evaluated the size regulation of liver lobes 1, 2, 3, and 7 days after the operation in terms of liver weight and hepatocyte proliferation. Portal hyperperfusion was confirmed by measuring portal flow. The portal vascular tree was visualized by injection of a contrast agent followed by CT imaging of explanted livers. Control groups consisted of 70% PHx, rPVL, and sham operation. Results: The size of the ligated right lobe increased to 1.4-fold on postoperative day 7 when subjected to rPVL + 70% PHx. The right lobe increased to 3-fold when subjected to 70% PHx alone and decreased to 0.3-fold when subjected to rPVL only. The small but significant increase in liver weight after the combined procedure was accompanied by a low proliferative response. In contrast, hepatocyte proliferation was undetectable in the right lobe undergoing atrophy after PVL only. The caudate lobe in the rPVL + 70% PHx group increased to 4.6-fold, which is significantly more than in the other groups. This increase in liver weight was paralleled by persisting portal hyperperfusion and a prolonged proliferative phase of 3 days. Conclusions: A discontinued portal blood supply does not always result in atrophy of the ligated lobe. The concurrent regenerative stimulus induced by 70% PHx seemed to counteract the local atrophy after a simultaneously performed rPVL, leading to a low but prolonged regenerative response of the portally deprived liver lobe. This observation supports the conclusion that portal flow is not necessary for liver regeneration. The persisting portal hyperperfusion may be crucial for the specific kinetics of prolonged liver regeneration after rPVL + 70% PHx in the portally supplied caudate lobe. Both observations deserve more attention regarding the underlying mechanism in further studies.

Quantitative Measurements of Enhancement on Preprocedure Triphasic CT Can Predict Response of Colorectal Liver Metastases to Radioembolization.

Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization. We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4-8 weeks after treatment. A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate. Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT.

Diagnosis of the Different Aspects of Fat in the Liver

Liver fat infiltration usually appears as a diffuse abnormality that modifies the signal of the liver homogeneously. But this overload can be heterogeneous in different circumstances and in different ways: heterogeneous and focal steatosis and fatty focal sparing. It is important to know these aspects in order to not misdiagnose these abnormalities. The segmental repartition of the steatosis is easily explained by the different contribution to the portal flow that is both mesenteric or splenic. As portal flow is laminar and helicoidal, it could result in an incomplete mixing of splenic and mesenteric blood in the intraparen chymal liver vascularisation and therefore a preferential uptake of lipids coming from mesenteric blood flow in an area of the liver. Heterogeneous and focal fatty depositions are partially explained by vascular theories. An excess of insulin blood supply (due to an anatomical variant of pancreatic blood vessels) is the most accepted theory, but there are probably other explanations, such as ischemic mechanisms, that take a role in these abnormalities. These focal steatoses have typical semiology: Their signal drops on opposition phase T1 EG sequences. They are geographic margins; they produce no mass effect and vessels are not distorted inside the lesion. The enhancement is homogeneous, and the enhancement ratio between fatty and non-fatty liver is preserved on the different vascular phases. Finally, there is typical distribution in the liver (posterior part of the segment IV, gallbladder fosse, falciform ligament, and subcapsular region). The last type of focal steatosis is nodular steatosis, which is a rare entity, but it is really difficult to differentiate a tumour (benign or malign) from fatty content. In this situation, if there is oncologic context or in case of doubt, a biopsy should be performed. The second way of heterogeneous repartition of the steatosis is the heterogeneous and focal fatty sparing. This lesion is, at present, more frequent than focal steatosis. For this type of lesion, the explanation is quite clear. Anatomical vascular variants lead to a non-portal blood contribution. This is the theory of the third supply. In territory with systemic blood supply rather than portal blood supply, the uptake of lipids is low and there is no steatosis. In opposition phase T1 EG sequence, the signal of the liver is dropped except the signal of the sparing area. The semiology regarding homogeneity, vessels, and enhancement is similar to that of the focal steatosis. Preferential locations are also the same. Nodular fatty sparing is possible. In this situation, such as in the case of nodular steatosis, it is important to eliminate a real liver tumour in a fatty liver. Thus all sequences of the MRI should be carefully analysed to avoid a misdiagnosis, and in case of doubt, a biopsy should be performed. MRI is the key examination for the diagnosis of focal fatty liver or focal fatty sparing, but contrast enhanced ultrasound (CEUS) could be really useful. The enhancement of focal fatty liver or sparing is similar to the surrounding parenchyma. This is a strong argument to make a difference with real tumours. Focal fatty liver and, even more, focal fatty sparing are frequent lesions. They could be in the majority of cases easily diagnosed using CEUS and MRI. But in case of doubt, especially in case of nodular lesion, a biopsy should be performed.

Congenital Extrahepatic Portosystemic Shunts: Spectrum of Findings on Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

Congenital extrahepatic portosystemic shunt (CEPS) is a rare disorder characterised by partial or complete diversion of portomesenteric blood into systemic veins via congenital shunts. Type I is characterised by complete lack of intrahepatic portal venous blood flow due to an end to side fistula between main portal vein and the inferior vena cava. Type II on the other hand is characterised by partial preservation of portal blood supply to liver and side to side fistula between main portal vein or its branches and mesenteric, splenic, gastric, and systemic veins. The presentation of these patients is variable. Focal liver lesions, most commonly nodular regenerative hyperplasia, are an important clue to the underlying condition. This pictorial essay covers imaging characteristics in abdominopelvic region.

Vascular anatomy of canine hepatic venous system: a basis for liver surgery.

Detailed knowledge of the vascular anatomy is important for improving surgical approaches to the liver. Twelve canine livers were skeletonized to describe the anatomy of their portal and hepatic veins in details. Our data suggest that the liver can be divided into two sections, three divisions, seven lobes and two to four sub-lobes. This differs from the classic division into four lobes, four sub-lobes and two processes. The right section was perfused by the right portal branch and drained by independent hepatic veins, while most of the left section, perfused by the left portal branch, was drained by the main hepatic vein deriving from the middle and the left hepatic vein confluence. Part of the right medial lobe, and in some cases the papillary process of the caudate lobe, drained directly into the caudal vena cava. A proper right hepatic vein draining blood from more than one lobe was never observed. Portal connections between the quadrate and the left medial lobe were frequently recorded. Two sub-lobes with different portal blood supply and venous drainage could be identified in the right lateral (33.3% of cases) and the left lateral (100% of cases) lobes. From our results, the classic nomenclature of the liver lobes does not reflect their vascularization. Based on similarities between canine lobes and human segments, a new nomenclature is possible and may be less confounding in surgical settings.

Physiological hypoxia prevents bile salt-induced apoptosis in human and rat hepatocytes

Hydrophobic bile salts such as glycochenodeoxycholate (GCDC) accumulate in cholestatic liver disease and induce hepatocellular apoptosis, promoting profibrotic signalling. The tissue microenvironment is an integral player in cellular pathophysiology, but it is not routinely incorporated into laboratory studies. Tissue oxygen partial pressure (pO₂) may be an underestimated component of the microenvironment: in the liver, a pO₂ of 30-45 mmHg (approximately 6% O₂) is physiological, because of predominant portal blood supply. It was the aim of this project to investigate the impact of physiological hypoxia (i.e. 6% O₂) on hepatocellular function, namely, bile salt-induced apoptosis. Human hepatoma cells (HepG2-Ntcp) and primary rat hepatocytes were cultured at standard laboratory (hyperoxic) conditions (21% O₂) and at physiological hypoxia (6% O₂) in parallel for 1-8 days to study hepatocellular apoptosis and activation of signalling pathways. Standard laboratory analyses were applied for bile salt uptake, caspase-3/-7 activity, western blotting and gene-array analysis. Culturing at physiological hypoxia protected both human and rat hepatocytes against GCDC-induced apoptosis: caspase-3/-7 activation was diminished by 3.1 ± 0.5-fold in human HepG2-Ntcp and completely abolished in primary rat hepatocytes. Bile salt uptake was unaffected. Induction of hypoxia-inducible factor-1α indicated adaption to physiological hypoxia. The MEK/ERK cascade was activated and anti-apoptotic mediators were induced: N-Myc down-regulated gene, gelsolin and carbonic anhydrase IX were upregulated 12.4-, 6.5- and 5.2-fold respectively. We conclude from these data that (i) physiological hypoxia protects hepatocytes from bile salt-induced apoptosis, (ii) tissue pO₂ is a crucial, underestimated component of the microenvironment and should (iii) be considered when studying hepatocellular physiology in vitro.

Human and Rat ABC Transporter Efflux of Bisphenol A and Bisphenol A Glucuronide: Interspecies Comparison and Implications for Pharmacokinetic Assessment

Significant interspecies differences exist between human and rodent with respect to absorption, distribution, and excretion of bisphenol A (BPA) and its primary metabolite, BPA-glucuronide (BPA-G). ATP-Binding Cassette (ABC) transporter enzymes play important roles in these physiological processes, and their enzyme localization (apical vs. basolateral) in the plasma membrane allows for different cellular efflux pathways. In this study, we utilized an ATPase assay to evaluate BPA and BPA-G as potential substrates for the human and rat ABC transporters: P-glycoprotein (MDR1), multidrug resistance-associated proteins (MRPs), and breast cancer-resistant protein (BCRP). Based on high ATPase activity, BPA is likely a substrate for rat mdr1b but not for human MDR1 or rat mdr1a. Results indicate that BPA is a potential substrate for rat mrp2 and human MRP2, BCRP, and MRP3. The metabolite BPA-G demonstrated the highest apparent substrate binding affinity for rat mrp2 and human MRP3 but appeared to be a nonsubstrate or potential inhibitor for human MRP2, MDR1, and BCRP and for rat mdr1a, mdr1b, and bcrp. Analysis of ABC transporter amino acid sequences revealed key differences in putative binding site composition that may explain substrate specificity. Collectively, these results suggest that in both rat and human, apical transporters efflux BPA into the bile and/or intestinal lumen. BPA-G would follow a similar pathway in rat; however, in human, due to the basolateral location of MRP3, BPA-G would likely enter systemic and portal blood supplies. These differences between human and rodent ABC transporters may have significant implications for interspecies extrapolation used in risk assessment.

Idiopathic noncirrhotic portal hypertension is associated with poor survival: results of a long‐term cohort study

Idiopathic noncirrhotic portal hypertension (INCPH) is a rare disease in the Western world. As a result, little is known about the clinical characteristics and outcome of these patients. Survival in these patients is considered to be similar to that of the general population. To investigate the clinical manifestations, pathophysiology, outcome and determinants of survival in Western INCPH patients. Multicentre cohort study of INCPH patients. A total of 62 patients were followed for a median time of 90 months (range 24-310). Initial manifestations leading to the diagnosis of INCPH were related to portal hypertension in 82% of the patients. Histological signs of portal blood supply disturbances were present in nearly all patients. During follow-up, 12 of 62 patients developed liver decompensation, of which four were considered for liver transplantation. One patient died in the context of variceal bleeding. Hepatocellular carcinoma was not observed during follow-up. A total of 23 patients died during follow-up, only four of them due to liver related mortality. The Kaplan-Meier estimates for overall survival were 100% (95% CI 95-100%), 78% (95% CI 67-89%) and 56% (95% CI 40-72%) at 1, 5 and 10 years respectively. Survival for INCPH was significantly decreased (P < 0.001) compared to survival of the general population. Ascites was an independent predictor of poor outcome. In comparison to the general population, survival in INCPH patients is poor. Mortality is related to associated disorders and medical conditions occurring at older age. Patients rarely die due to liver related complications. Patients with ascites have a poor prognosis.

Liver functional magnetic resonance imaging analysis using a latent variables approach

The liver is a highly vascular organ with a dual blood supply, and it performs a remarkable number of vital functions. Here, we show, through measurement of blood oxygen level-dependent (BOLD) signal, that liver arterial and hepatic portal blood supplies can be modulated through hyperoxia exposure and by consumption of a standardized meal, respectively. As such, we suggest that hyperoxia modulates the hepatic arterial BOLD signal, whereas a controlled meal changes predominantly the hepatic portal BOLD signal. The hemodynamics of the dual liver blood supplies in response to the aforementioned challenges are complex and variable across subjects, making a general linear model-based analysis difficult. Therefore, we present the application of two local (at each voxel) hemodynamic response-independent techniques—principal component analysis and partial least squares—to observe the hypothesized reduction in BOLD contrast during cycles of hyperoxic breathing, when comparing preprandial versus postprandial states in a normally functioning liver. We illustrate the ability of our techniques to differentiate between healthy and diseased livers with an analysis of 17 subjects—11 with normal livers and 6 with liver disease (hepatitis or cirrhosis). Our local analysis can correctly classify all of the subjects. Copyright © 2012 John Wiley & Sons, Ltd.