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Background: The pathogenesis of portal vein thrombosis (PVT) in cirrhosis is multifactorial, with altered hemodynamics being proposed as a possible contributor. The present systematic review was conducted to study the role of assessment of portal hemodynamics for the prediction of PVT in patients with cirrhosis., Methods: Three databases (Medline, Embase, and Scopus) were searched from inception to February 2023 for studies comparing portal venous system parameters in patients with cirrhosis developing PVT with those not. Results were presented as mean difference (MD) or odds ratio (OR) with their 95% confidence intervals (CIs)., Results: A total of 31 studies (patients with cirrhosis: 19 studies, patients with cirrhosis undergoing splenectomy: 12 studies) were included. On pooling the data from multivariable analyses of the included studies, a larger portal vein diameter was a significant predictor of PVT in patients with cirrhosis without or with splenectomy with OR 1.74 (1.12-2.69) and OR 1.55 (1.26-1.92), respectively. On the other hand, a lower portal vein velocity (PVV) was a significant predictor of PVT in cirrhotics without or with splenectomy with OR 0.93 (0.91-0.96) and OR 0.71 (0.61-0.83), respectively. A PVV of <15 cm/s was the most commonly used cut-off for the prediction of PVT. Patients developing PVT also had a significantly higher splenic length, thickness, and splenic vein velocity., Conclusion: The assessment of portal hemodynamic parameters at baseline evaluation in patients with cirrhosis may predict the development of PVT. Further studies are required to determine the optimal cut-offs for various parameters., (© 2023 Wiley Periodicals LLC.)

The dynamics of morphological changes developed in liver and bile ducts in biliary obstruction are well studied in the animal models of biliary obstruction, however,the data on the morphology of the portal tracts are scarce. The aim of the research was to study the structure of the portal tracts and interrelationship of their structural components in experimental biliary obstruction. The investigation was conducted on albino Wistar rats weighing 200-250 g, undergone biliary obstruction by common bile duct ligation (CBDL). The histological, histochemical and immunohistochemical investigation of the liver tissue stained with Hematoxylin& Eosin, Masson's trichrome and marked with CK8antibody were performed on the 3rd, 6th and 12th days after CBDL. The CBDL-induced biliary obstruction triggers a systemic reaction of the bile ducts and a complex of accompanying reactions that is heterogeneous, depending on the caliber of both the bile ducts themselves and the portal tracts containing them.CBDL causes dilation of the large bile ducts, their pressure on the portal veins with the deformation of their lumens, changes in the architectonics of the portal tracts, and expansion of the portal areas accompanied by increasing portal fibrosis and ductular reaction. The small bile ducts are less prone to dilation under CBDL conditions but actively proliferate and penetrate widely into the parenchyma of the liver lobules. Based on this ductal reaction, fibrosis of increasing intensity develops, which connects the adjacent portal tracts as well as the portal tracts and the connective tissue sheaths of the thin tributaries of hepatic veins. In the conditions of such fibrosis, it is difficult to identify the individual portal tracts of small caliber and, moreover, to clarify the relationship between their elements.

Nonalcoholic fatty liver disease often progresses to cirrhosis and causes liver cancer, but mechanisms of its progression are yet to be elucidated. Although nonalcoholic fatty liver disease is often associated with abnormal portal circulation, there have not been any experimental studies to test its pathogenic role. Here, whether decreased portal circulation affected the pathology of nonalcoholic steatohepatitis (NASH) was examined using congenital portosystemic shunt (PSS) in C57BL/6J mice. Whereas PSS significantly attenuated free radical-mediated carbon tetrachloride injury, it augmented pericellular fibrosis in the centrilobular area induced by a 0.1% methionine choline-deficient l-amino acid-defined high-fat diet (CDAHFD). PSS aggravated ductular reaction and increased the expression of connective tissue growth factor. Pimonidazole immunohistochemistry of the liver revealed that the centrilobular area of PSS-harboring mice was more hypoxic than that of control mice. Although tissue hypoxia was observed in the fibrotic area in CDAHFD-induced NASH in both control and PSS-harboring mice, it was more profound in the latter, which was associated with higher carbonic anhydrase 9 and vascular endothelial growth factor expression and neovascularization in the fibrotic area. Furthermore, partial ligation of the portal vein also augmented pericellular fibrosis and ductular reaction induced by a CDAHFD. These results demonstrate that decreased portal circulation, which induces hypoxia due to disrupted intralobular perfusion, is an important aggravating factor of liver fibrosis in NASH., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Histopathology is essential for the diagnosis and evaluation of disease activity of autoimmune hepatitis (AIH). We aimed to elucidate the characteristics of AIH from the localization of inflammation. We re-evaluated a nationwide survey that was performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017. A total of 303 patients were enrolled, and the clinical and treatment characteristics were compared between the patients with predominantly portal inflammation (230 patients) or lobular inflammation (73 patients). AIH patients with lobular inflammation had a higher probability of being diagnosed with acute hepatitis than those with portal inflammation. Liver enzyme levels were higher in patients with lobular inflammation, whereas immunoglobulin G levels were higher in patients with portal inflammation. The prevalence of an alanine aminotransferase level < 30 U/L after 6 months of treatment was significantly higher in patients with lobular inflammation than in those with portal inflammation (81.7% vs. 67.3%, P = 0.046). The localization of inflammation may be useful for evaluating the onset of AIH.

Background: Liver biopsy remains essential for the diagnostic work-up of patients with liver disease., Aims: To evaluate aspiration vs. core-biopsy needles for transjugular liver biopsy (TJLB) in patients undergoing hepatic venous pressure gradient (HVPG) measurements., Methods: 84 patients undergoing TJLB between 06/2017 and 12/2018 were prospectively included. Liver biopsy specimens were systematically evaluated for quantitative and qualitative criteria such as number of portal tracts, sample length and fragmentation., Results: In direct comparison of paired TJLB specimens (n=35), core-biopsy samples were significantly longer (median 12 vs. 9mm, p=0.012), tended to contain more portal tracts (median 8 vs. 6, p=0.064) and were less fragmented (p<0.001), which resulted in better confidence for liver fibrosis assessment (p=0.035). However, a superior quality in terms of less fragmentation of core-biopsy specimens (p<0.05) was only confirmed in patients with HVPG ≥10mmHg or liver stiffness measurement >40kPa. In contrast, the aspiration needle provided significantly longer samples in patients with HVPG <10mmHg (median 21 vs. 12mm, p=0.007) or with liver stiffness measurement <20kPa (median 21 vs. 11mm, p=0.025)., Conclusion: In patients with HVPG ≥10mmHg, we recommend to performed TJLB using core-biopsy needles, while the aspiration needle provides high quality liver biopsy specimens in patients with HVPG <10mmHg., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose regarding the work under consideration for publication. The following authors disclose conflicts of interests outside the submitted work: J.S. received grant support from Eli Lilly and Company, and Gilead. B.Si. received travel support from AbbVie. B.Sch. received travel support from AbbVie and Gilead. P.S. received travel support from Boehringer Ingelheim and Gilead as well as speaker fees from Boehringer Ingelheim. M.P. received travel support from Bayer and served as advisory board member for Bayer, Bristol-Myers Squibb, and Eisai. M.T. received travel support from AbbVie, Falk, Gilead and Intercept, grant support from Albireo, Cymabay, Falk, Gilead, Intercept, MSD, and Takeda, honoraria for consulting from AbbVie, BiomX, Boehringer Ingelheim, Falk, Gilead, Genfit, Intercept, MSD, Novartis, Phenex and Regulus, as well as speaker fees from Falk, Gilead, Intercept and MSD. M.M. received travel support from AbbVie, Bristol-Myers Squibb, and Gilead, and served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead, and W. L. Gore & Associates. T.R. received travel support from Boehringer Ingelheim, Gilead, and Roche, served as a speaker and/or consultant and/or advisory board member for AbbVie, Bayer, Boehringer Ingelheim, Gilead, Intercept, MSD, Roche, Siemens, and W. L. Gore & Associates, and received grants/research support from AbbVie, Boehringer Ingelheim, Gilead, MSD, Philips, and W. L. Gore & Associates. G.S., K.W., R.P., A.F.S., T.M. and A.B. have nothing to disclose., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The association between nonalcoholic fatty liver disease (NAFLD) and renal function changes remains inconclusive. We explored whether the histological severity of NAFLD is associated with early deterioration of renal function., Methods: Patients with biopsy-proven NAFLD were prospectively followed for renal function monitoring. A renal outcome was defined as a ≥ 50% increase in serum creatinine, a < 30% decrease in the estimated glomerular filtration rate (eGFR) or an eGFR < 45 mL/min/1.73 m 2 ., Results: Among 455 NAFLD patients, 221 (48.6%) had nonalcoholic steatohepatitis (NASH), and no difference in baseline eGFR was found between NASH and NAFL patients. During a median follow-up of 32 months, a renal outcome occurred in 15 patients; the incidence rate was 12.3 per 1,000 person-years. Compared with NAFL, NASH did not increase the risk of renal outcomes. Among the histological components of NAFLD, lobular inflammation (≥ 2), fibrosis (≥ F3), and portal inflammation (≥ 3) significantly increased the risk of renal outcomes in the crude analysis (HR 3.35, 95% CI 1.10-9.11; HR 3.25, 95% CI 1.12-8.84; and HR 7.73, 95% CI 2.86-22.22). After adjustment for risk factors for renal dysfunction, including sex, age, diabetes, hypertension, and chronic kidney disease, only portal inflammation significantly increased the risk of renal outcomes (HR 5.88, 95% CI 1.87-18.42, p = 0.002)., Conclusions: Portal inflammation predicts early deterioration of renal function in patients with biopsy-proven NAFLD. Individualized monitoring of renal function based on the histological severity of NAFLD may be helpful for early identification of long-term renal outcomes.

Background and Aims: It has become clear that vein resection and reconstruction for pancreatic ductal adenocarcinoma (PDAC) is the standard of care as supported by multiple guidelines. However, resection of large peri-pancreatic arteries remains debatable., Materials and Methods: This review examines the current state of vascular resection with curative intent for PDAC in the last 5 years. Herein, we consider venous (superior mesenteric vein, portal vein), as well as arterial (superior mesenteric artery, celiac trunk, hepatic artery) resection or both with or without reconstruction., Results: Improvement of multidrug chemotherapy has revolutionized care for PDAC that should shift traditional surgical thinking from an anatomical classification of resectability to a prognostic and biological classification., Conclusion: The present review gives an overview on the results of pancreatectomy associated with vascular resection, with consideration of new perspectives offered by the availability of better systemic therapies.

Prolonged and persistent hypermetabolism and excessive inflammatory response after severe trauma is detrimental and associated with poor outcome. The predisposing pathology or signals mediating this complex response are essentially unknown. As the liver is the central organ mediating the systemic metabolic responses and considering that adult hepatic stem cells are on top of the hierarchy of cell differentiation and may pass epigenetic information to their progeny, we asked whether liver progenitor cells are activated, signal hypermetabolism upon post-traumatic cellular stress responses, and pass this to differentiated progeny. We generated Sox9CreER T2 : ROSA26 EYFP mice to lineage-trace the periportal ductal progenitor cells (PDPCs) and verify the fate of these cells post-burn. We observed increased proliferation of PDPCs and their progeny peaking around two weeks post-burn, concomitant with the hepatomegaly and the cellular stress responses. We then sorted out PDPCs, PDPC-derived hepatocytes and mature hepatocytes, compared their transcriptome and showed that PDPCs and their progeny present a significant up-regulation in signalling pathways associated with inflammation and metabolic activation, contributing to persistent hypermetabolic and hyper-inflammatory state. Furthermore, concomitant down-regulation of LXR signalling in PDPCs and their progeny implicates the therapeutic potential of early and short-term administration of LXR agonists in ameliorating such persistent hypermetabolism., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The renin-angiotensin-aldosterone system (RAAS) is activated in humans with portal hypertension (PH) associated with liver disease. However, involvement of RAAS in dogs with intrahepatic PH is not clear., Objective: To measure plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in dogs with PH (chronic hepatitis [CH] and primary hypoplasia of the portal vein [PHPV]), dogs with extrahepatic congenital portosystemic shunt (EH-CPSS), and healthy dogs and to determine whether the RAAS is activated in dogs with PH., Animals: Twenty-seven dogs with acquired portosystemic collaterals (APSCs; 15 dogs with CH, 12 dogs with PHPV), 9 dogs with EH-CPSS, and 10 healthy dogs., Methods: Retrospective study. Plasma renin activity and PAC were measured by radioimmunoassay., Results: Plasma renin activity was significantly higher in the CH group (median, 4.4 ng/mL/h) than in the EH-CPSS (median, 1.0 ng/mL/h; P < .01) and the healthy (median, 1.1 ng/mL/h; P < .01) groups. No significant differences were found between the PHPV group (median, 2.2 ng/mL/h) and other groups. Plasma aldosterone concentration was significantly higher in the CH (median, 111.0 pg/mL) and PHPV (median, 89.5 pg/mL) groups than in the EH-CPSS (median, 1.0 pg/mL; P < .001, P < .01, respectively) and healthy (median, 14.5 pg/mL; P < .001, P < .05, respectively) groups., Conclusions and Clinical Importance: Activation of the RAAS contributes to the pathophysiology of intrahepatic PH in dogs, suggesting that spironolactone may not only be effective for the treatment of ascites but also for the suppression of intrahepatic PH., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background/aims: Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking., Methods: A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models., Results: The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson's capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities., Conclusions: These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.

Introduction and Objectives: Liver cirrhosis is characterized by increased intrahepatic resistance, splanchnic vasodilation/angiogenesis, and formation of portosystemic collateral vessels. Collaterals can cause lethal complications such as gastroesophageal variceal hemorrhage. Homocysteine is linked to vascular dysfunction and angiogenesis and higher levels have been reported in cirrhotic patients. It is also known that folic acid supplementation reverses the effects of homocysteine. However, the treatment effect in cirrhosis has yet to be investigated., Material and Methods: Liver cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (CBDL). The CBDL rats randomly received (1) vehicle; (2) dl-homocysteine thiolactone (1g/kg/day); (3) dl-homocysteine thiolactone plus folic acid (100mg/kg/day); or (4) folic acid. On the 29th day, hemodynamic parameters, liver and renal biochemistry, protein expressions of proangiogenic factors, mesenteric vascular density and portosystemic shunting were evaluated., Results: In the cirrhotic rats, homocysteine increased mesenteric vascular density and the severity of shunting. It also up-regulated the protein expressions of mesenteric vascular endothelial growth factor (VEGF) and phosphorylated-endothelial nitric oxide synthase (p-eNOS). These effects were reversed by folic acid treatment (P<0.05)., Conclusion: Folic acid ameliorated the adverse effects of homocysteine in the cirrhotic rats, which may be related to down-regulation of the VEGF-NO signaling pathway., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

This is a case with associated radiologic images for a pediatric patient who developed portomesenteric and splenic vein thrombosis (PMSVT) after Roux-en-Y gastric bypass with subsequent development of portal cavernoma and gallbladder varices (GBV). This case highlights both the importance of post-operative prophylactic anti-coagulation after gastric bypass and detailed imaging following a diagnosis of PMSVT. This case is relevant for pediatric surgeons as they are performing this operation more frequently with the increase in pediatric obesity., (Published by Elsevier Inc.)

Background/objectives: To demonstrate the utility of portal encasement as a criterion for early diagnosis of local recurrence (LR) after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC)., Methods: A total of 61 patients who underwent PD for PDAC were included in this retrospective study. Portal stenosis was evaluated by sequential postoperative computed tomography (CT) scans and correlated with disease recurrence. In addition to the conventional LR diagnostic criterion of a growing soft tissue mass, LR was evaluated using portal encasement as an additional diagnostic criterion. Portal encasement was defined as progressive stenosis of the portal system accompanied by a soft tissue mass, notwithstanding the enlargement of the mass., Results: Benign portal stenosis was found on the first postoperative CT imaging in 16 patients. However, stenosis resolved a median of 81 days later in all but one patient whose stenosis was due to portal reconstruction during PD. Portal encasement could be distinguished from benign portal stenosis based on the timing of emergence of the portal stenosis. Portal encasement developed in 13 of the 19 patients with LR, including 6 patients in whom the finding of portal encasement led to the diagnosis of LR a median of 147 days earlier with our diagnostic criterion compared with the conventional diagnostic criteria., Conclusions: Portal encasement should be considered as a promising diagnostic criterion for earlier diagnosis of LR after PD for PDAC., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The ileum was morphologically examined in 45 sexually mature white male rats, which were divided into 3 groups: I group included 15 intact animals, II - 15 rats, in which 31.5% of the liver parenchyma was removed, III - 15 animals after resection 58,1% of liver parenchyma. Euthanasia of rats was performed by bloodletting under the conditions of thiopental anesthesia 1 month after the beginning of the experiment. Histological micropreparations were made from the ileum, which were studied morphometrically. Quantitative indicators were processed statistically. It was revealed that after resection of 31.5% of the parenchyma of the liver, the morphometric parameters studied were insignificantly altered. Resection of 58.1% of the liver parenchyma lead to postresectional portal hypertension, which was characterized by venous full-blood in the veins of the portal hepatic vein system and morphological changes in the ileum. Venous thrombosis, edema, dystrophic, necrotic, infiltrative, sclerotic and atrophic processes were observed in the investigated organ. The relative volume of the damaged epitheliocytes of the mucous membrane of the ileum reached 64.50±0.72%, and myocytes in the muscular membrane - 41.10±0.54%. The pronounced changes in nuclear-cytoplasmic relations in epitheliocytes and stromal-myocytic muscle tissue testified to violations of tissue and cellular structural homeostasis. Thus, the removal of large volumes of liver parenchyma leads to postresectional portal hypertension expressed by remodeling of the structures of the ileum, which is characterized by uneven disproportional changes in the spatial characteristics of the organ structures, disturbances between them, vascular disorders, edema, dystrophic, necrobiotic changes in epitheliocytes, endothelial cells, myocytes, stromal elements, infiltrative, sclerotic and atrophic processes.

Portal myofibroblasts (PMF) form a sub-population of highly proliferative and proangiogenic liver myofibroblasts that derive from portal mesenchymal progenitors. Endoplasmic reticulum (ER) stress was previously shown to modulate fibrogenesis, notably in the liver. Our aim was to determine if ER stress occurred in PMF and affected their functions. PMF were obtained after their expansion in vivo from bile duct-ligated (BDL) rats and referred to as BDL PMF. Compared to standard PMF obtained from normal rats, BDL PMF were more myofibroblastic, as assessed by higher alpha-smooth muscle actin expression and collagen 1 production. Their proangiogenic properties were also higher, whereas their proliferative and migratory capacities were lower. CHOP expression was detected in the liver of BDL rats, at the leading edge of portal fibrosis where PMF accumulate. BDL PMF displayed ER dilatation and an overexpression of the PERK pathway downstream targets, Chop, Gadd34 and Trb3, in comparison with standard PMF. In vitro, the induction of ER stress by tunicamycin in standard PMF, caused a decrease in their proliferative and migratory activity, and an increase in their proangiogenic activity, without affecting their myofibroblastic differentiation. Conversely, the treatment of BDL PMF with the PERK inhibitor GSK2656157 reduced ER stress, which caused a decrease in their angiogenic properties, and restored their proliferative and migratory capacity. In conclusion, PMF develop ER stress as they expand with the progression of fibrosis, which further increases their proangiogenic activity, but also inhibits their proliferation and migration. This phenotypic switch may restrict PMF expansion while they support angiogenesis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to clarify the correlation between image classification and the pathological degree of portal system invasion (PSI) and to evaluate the prognostic impact of PSI in pancreatic cancer (PC)., Methods: Pancreatic cancer patients with surgical resections (head, n = 244; body and tail, n = 80) were enrolled in this study., Results: Based on imaging findings, portal vein (PV) invasion was classified as type A (absent), B (unilateral narrowing), C (bilateral narrowing), or D (stenosis or obstruction with collaterals). Splenic vein (SPV) invasion was classified as type α (absent), β (stenosis), or γ (obstruction). The pathological grade of venous invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima). In PV and SPV invasions, image classification and pathological grade showed significant correlation (PV: ρ = 0.696; SPV: ρ = 0.681). Patients with PV invasion deeper than type B exhibited significantly poorer survival than type A (P < 0.0001). In contrast, there was no difference in survival among types α, β, and γ., Conclusions: Image classification was correlated with the pathological grade of PSI in PC. Although not applicable for SPV invasion, image classification of PV invasion is a robust indicator for PC prognosis.

Aim: To investigate the incidence and risk factors of portosplenomesenteric vein thrombosis (PSMVT) in the early stage of severe acute pancreatitis (SAP)., Methods: Patients with SAP in a tertiary care setting from January 2014 to December 2016 were retrospectively reviewed. All contrast-enhanced computed tomography (CT) studies were reassessed and reviewed. Clinical outcome measures were compared between SAP patients with and without PSMVT in the early stage of the disease. Univariate and multivariate logistic regression analyses were sequentially performed to assess potential risk factors for the development of PSMVT in SAP patients. A receiver operating characteristic (ROC) curve was generated for the qualifying independent risk factors., Results: Twenty-five of the one hundred and forty (17.86%) SAP patients developed PSMVT 6.19 ± 2.43 d after acute pancreatitis (AP) onset. PSMVT was confirmed by contrast-enhanced CT. Multivariate stepwise logistic regression analyses showed that Balthazar's CT severity index (CTSI) scores [odds ratio (OR): 2.742; 95% confidence interval (CI): 1.664-4.519; P = 0.000], hypoalbuminemia (serum albumin level < 25 g/L) (OR: 32.573; 95%CI: 2.711-391.353; P = 0.006) and gastrointestinal wall thickening (OR: 4.367, 95%CI: 1.218-15.658; P = 0.024) were independent risk factors for PSMVT developed in patients with SAP. The area under the ROC curve for Balthazar's CTSI scores was 0.777 ( P = 0.000), the sensitivity was 52%, and the specificity was 93% at a cut-off value of 5.5., Conclusion: High Balthazar's CTSI scores, hypoalbuminemia and gastrointestinal wall thickening are independent risk factors for PSMVT developed in the early stage of SAP., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension (PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The PubMed database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: "liver cirrhosis", "portal hypertension", "pathogenesis", "angiogenesis", and "antiangiogenic therapy". Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studied only in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications., Competing Interests: Conflict-of-interest statement: Dr. Arefyev reports a grant from RFBR (Russian Foundation for Basic Research), during the conduct of the study. The information included in this manuscript is not related to the interests of RFBR. Prof. Garbuzenko and Prof. Kazachkov have nothing to disclose.

Purpose: The aim of the study was to compare safety and efficacy of transjugular liver biopsy (TJLB) and percutaneous liver biopsy (PLB) with tract embolization in pediatric patients with liver disease., Materials and Methods: TJLB and PLB between December 2009 and October 2015 were retrospectively reviewed. Primary endpoints were adequate sampling and complication rate. Patient age, weight, coagulation factors, ascites, blood transfusions, adequacy of biopsy sample, number of biopsy samples, and complications were compared., Results: There were 39 TJLB (average age 10.6 years) and 120 PLB (average age 7.1 years) (P value <0.05). Average weight was 40.2 kg for TJLB and 26.8 kg for PLB (P value <0.05). Average platelets were 155 for TJLB and 252 for PLB (P value <0.05). Average international normalized ratio was 1.7 for TJLB and 1.3 for PLB (P value <0.05). Mean postbiopsy hematocrit decrease was 0.8 and 0.9, for TJLB and PLB, respectively. Mean postbiopsy hemoglobin decrease was 0.3 in both groups. Number of core biopsy samples was 4.5 and 4.3, for TJLB and PLB, respectively. There was 1 biopsy yielding insufficient sample in each group. TJLB had 1 (2.6%) complication of supraventricular tachycardia. PLB had 4 (3.3%) complications, with 1 hemoperitoneum, 1 hypotension, 1 patient with decreased hemoglobin, and 1 patient with bilious drainage from the biopsy site., Conclusions: TJLB and PLB with gelatin sponge pledget tract embolization are both safe and effective for the diagnosis of hepatic disease in pediatric patients. To avoid radiation, PLB may be considered as first-line approach in the pediatric population, even in the setting of coagulopathy.

Background: Pregnancy with massive splenomegaly is a rare entity and is associated with increased risk to both mother and foetus. There is paucity of studies in the literature to guide clinicians for the management of this condition., Methods: We reviewed the course of pregnancy, maternal and foetal outcomes of 5 pregnant women with massive splenomegaly who were managed in our unit during 2015-16., Results: All 5 women had anaemia and thrombocytopenia, and had different causes for splenomegaly. One patient had chronic malaria, 2 had portal hypertension with cirrhosis and the remaining 2 had non-cirrhotic portal hypertension. Life-threatening complications were present in 2 patients; one of them had severe pre-eclampsia complicated by pulmonary oedema, cardiac arrest and the other patient developed spontaneous bacterial peritonitis. Intrauterine growth restriction and meconium-stained liquor were the most common perinatal complications. Two patients had vaginal delivery and 3 required emergency caesarean section. Postpartum haemorrhage was present in 2, and the hospital stay was prolonged in all the patients. All mothers and babies were discharged in a satisfactory condition., Conclusion: Pregnancy with massive splenomegaly poses a challenge because of diverse aetiology and potentially adverse outcomes. Multidisciplinary care in a tertiary centre can help optimize the outcome., Competing Interests: None

Competing Interests: None

Background/purpose: The pattern of tumor cell spread via the portal system has not been fully clarified in patients with hepatocellular carcinoma (HCC). This study aimed to evaluate the intrahepatic distribution of cancer cells derived from the main tumor by assessing histological portal invasion and/or intrahepatic metastasis (vp/im)., Methods: In 14 patients who underwent anatomical resection of primary solitary HCC ≤ 50 mm in diameter, vp/im were examined pathologically, and the sites of the lesions were reproduced on preoperative 3D-CT images. The number of vp/im and the distance of each lesion from the tumor margin were also determined., Results: The tumor diameter was <30 mm in seven patients (smaller HCCs) and 30-50 mm in seven patients (larger HCCs). 3D mapping revealed that almost all vp/im were localized to the peritumoral area within one cm of the tumor margin in smaller HCCs, whereas vp/im seemed to spread extensively to the feeding 3rd level portal branches in larger HCCs. The number of vp/im was greater in patients with larger HCCs than in those with smaller HCCs., Conclusions: 3D mapping suggested tumor cells of HCC spread via the portal vein extensively in several cases., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Congenital or acquired obstruction of the inferior vena cava may lead to the development of collateral pathways with tributary vein to portal system. We present a patient with intrahepatic cavoportal collateral pathway due to hepatic hydatid cyst.

The etiopathogenesis of primary sclerosing cholangitis is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome-wide association studies as risk factors for primary sclerosing cholangitis. We investigated the role of Fut2 in murine liver pathophysiology by studying Fut2 -/- mice. Fut2 -/- mice were viable and fertile, had lower body weight than wild-type (wt) littermates and gray fur. Half of the Fut2 -/- mice showed serum bile salt levels 40 times higher than wt (Fut2 -/- high ), whereas the remainder were normocholanemic (Fut2 -/- low ). Fut2 -/- mice showed normal serum liver tests, bile flow, biliary bile salt secretion, fecal bile salt loss, and expression of major hepatocellular bile salt transporters and cytochrome P450 7a1, the key regulator of bile salt synthesis, indicating that elevated serum bile salts in Fut2 -/- high mice were not explained by cholestasis. Fut2 -/- high mice, but not Fut2 -/- low mice, were sensitive to hydrophobic bile salt feeding (0.3% glycochenodeoxycholate); they rapidly lost weight and showed elevation of serum liver tests (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase) and areas of liver parenchymal necrosis. Histomorphological evaluation revealed the presence of paraportal shunting vessels, increased numbers of portal vascular structures, wall thickening of some portal arteries, and periductal fibrosis in Fut2 -/- high mice more than Fut2 -/- low mice and not wt mice. Unconjugated bilirubin and ammonia were or tended to be elevated in Fut2 -/- high mice only. Portosystemic shunting was demonstrated by portal angiography, which disclosed virtually complete portosystemic shunting in Fut2 -/- high mice, discrete portosystemic shunting in Fut2 -/- low mice, and no shunting in wt littermates., Conclusion: Liver pathology in Fut2 -/- mice is dominated by consequences of portosystemic shunting resulting in microcirculatory disturbances, mild (secondary) periductal fibrosis, and sensitivity toward human bile salt toxicity. (Hepatology 2017;66:542-554)., (© 2017 by the American Association for the Study of Liver Diseases.)

Objectives: Noncirrhotic portal fibrosis (NCPF) has been classically described as a disease of young to middle age with limited literature regarding its occurrence, onset, or clinical presentation in children. We hereby present a series of 19 patients diagnosed and managed as NCPF in pediatric age group., Methods: A retrospective review of all the patients presenting to the pediatric hepatology department (age <18 years) and diagnosed as NCPF was done and data were evaluated., Results: A total of 19 patients were diagnosed as NCPF with median age at onset of symptoms and diagnosis as 10 years and 13.8 years respectively. Majority presented with left upper quadrant discomfort or mass. Laboratory parameters showed hypersplenism in majority with preserved liver synthetic functions. Median values for hepatic venous pressure gradient and liver stiffness measurement were 13.5 mmHg and 10.6 kPa, respectively. Classical hepatic histopathological features seen were maintained lobular architecture, atretic portal tracts, approximation of portal-portal and portal-central areas, and aberrant peripheral portal channels. During follow-up, majority of the patients did not show disease progression., Conclusions: NCPF is not an uncommon entity in pediatric population with age of onset in early second decade. Hepatic histopathology must be used to exclude cirrhosis and to confirm the diagnosis. Hepatic venous pressure gradient and liver stiffness measurement values, in some cases, may overlap with those in patients with cirrhosis and may not be diagnostic in isolation. Any patient presenting with evidence of portal hypertension with preserved hepatic functions, irrespective of the age, should be evaluated for possible NCPF.

The liver has a complex vascular supply, which involves the inflow of oxygenated blood through the hepatic artery (systemic circulation) and deoxygenated blood through the portal vein (portal circulation), as well as the outflow of deoxygenated blood through the hepatic veins to the inferior vena cava. A spectrum of vascular variants can involve the liver. Some of these variants may result in areas of enhancement that can mimic more serious pathologic conditions. In this article, the authors discuss a spectrum of variants and pathologic conditions that may involve the liver vasculature. These include variants, anomalies, and diseases involving the portal vein, such as rudimentary portal vein, thrombosis, cavernous transformation, thrombotic angiitis, thrombophlebitis, transient hepatic attenuation difference or transient hepatic intensity difference, portal venous aneurysm, and portal vein gas. The hepatic artery can be involved by various diseases, including thrombosis, stenosis, and aneurysm or pseudoaneurysm. Unusual "third inflow" sources of venous inflow are also discussed, including aberrant right gastric vein, aberrant left gastric vein, epigastric-paraumbilical veins, and cholecystic vein. A spectrum of variants and diseases involving the inferior vena cava and hepatic veins, including thrombosis, Budd-Chiari syndrome, veno-occlusive disease, stenosis, torsion, congestive hepatopathy, and peliosis hepatis, are discussed. Vascular shunts are illustrated, including portosystemic shunts (intra- and extrahepatic), arterioportal shunt, shunts of hereditary hemorrhagic telangiectasia, and acquired arteriovenous fistula. Familiarity with the pathogenesis and imaging features of these vascular entities can aid radiologic diagnoses and guide appropriate patient management. © RSNA, 2017.

Objective: To describe the morphology of porto-azygos shunts in a large series of dogs using computed tomography (CT) angiography., Study Design: Retrospective study., Animals: Dogs (n=36) with porto-azygos shunts., Methods: CT angiography was performed in dogs subsequently proven to have a porto-azygos shunt. The origin and insertion of the shunts were assessed on native images. The diameter of the porto-azygos shunt and the portal vein, cranial and caudal to the shunt origin, were measured. The porto-azygos shunt anatomy was studied on three-dimensional images., Results: All porto-azygos shunts originated either in the left gastric vein (33 left gastro-azygos shunts) or the right gastric vein (3 right gastro-azygos shunts). Two left gastro-azygos shunts had concurrent caval-azygos continuation and 2 right gastro-azygos shunts had a caudal splenic loop. All shunts crossed the diaphragm through the esophageal hiatus. The majority of porto-azygos shunts (32) followed a straight pathway after traversing the diaphragm, although 4 shunts followed a tortuous route. All shunts terminated in the thoracic part of the azygos vein, perpendicular to the aorta. The shunt diameter at insertion was only 3 mm on average. The insertion site was consistently the narrowest part of the shunt., Conclusion: CT angiography was well suited to provide anatomic details of porto-azygos shunts and comprehensively documented that all porto-azygos shunts had a thoracic terminus, after crossing the diaphragm through the esophageal hiatus. Different shunt types existed with minor variations., (© Copyright 2016 by The American College of Veterinary Surgeons.)

Objective: To describe the surgical technique and document the application of a transdiaphragmatic approach to attenuate porto-azygos shunts inserting in the thoracic section of the azygos vein., Study Design: Cadaveric study and prospective case series., Animals: Canine cadavers (n=6) and client-owned dogs with porto-azygos shunts inserting in the thoracic section of the azygos vein (n=9)., Methods: In the cadavers, the azygos vein was filled with aqueous latex. Landmarks were established for creating a safe transdiaphragmatic approach to the caudal intrathoracic portion of the azygos vein. In the clinical cases, porto-azygos communication was diagnosed by trans-splenic portal scintigraphy. All shunts were attenuated close to their insertion site via ventral midline celiotomy and a transdiaphragmatic approach to the shunt. Perioperative complications were recorded., Results: A 3-5 cm incision, 0.5-1 cm ventral and lateral to the level of the aortic hiatus, was made in the pars lumbalis part of the diaphragm. Stay sutures at both sides of the diaphragmatic incision were placed to open up the incision and a retractor was used to push the esophagus away from the aorta. Intrathoracic insertion of the shunt was confirmed intraoperative. Exposure of the shunt insertion site at the azygos vein was excellent in all clinical cases. No intraoperative or postoperative complications were encountered., Conclusion: If thoracic attenuation of a porto-azygos shunt is considered, a transdiaphragmatic approach exposes the insertion site for shunt attenuation. This approach is straightforward, without unnecessary abdominal organ manipulation, and since attenuates at the insertion, avoids missing additional contributing branches., (© Copyright 2016 by The American College of Veterinary Surgeons.)

Purpose: To describe ultrasonography (US) findings of Fontan-associated liver disease (FALD) and to determine whether screening US examinations can identify FALD before biochemical hepatic dysfunction., Methods: This retrospective study included 55 patients who underwent Fontan procedure over a 20-year period. Hepatobiliary US findings (n=55), CT or MRI findings (n=19), biochemical hepatic function tests (n=49), and histopathological results (n=4) were analyzed. Images were reviewed focusing on the hepatic parenchymal changes, presence of focal lesions, and signs of portal hypertension., Results: Hepatic parenchymal changes (either heterogeneous echotexture or surface nodularity) evident on US were present in 67% (37/55) and showed positive correlation with the Fontan duration. Hyper-echoic lesions were noted in 35% (19/55) and showed a predilection for multiplicity, small size, right lobe location, and irregular margin on high-frequency transducer. These lesions were not demonstrated by CT or MRI or by low-frequency transducer. Histopathological results of targeted biopsy for hyper-echoic lesions revealed lesser degree of patchy sinusoidal and portal fibrosis than seen in cases with surface nodularity. Abnormal parenchymal enhancement was commonly seen with CT or MRI in 63% (12/19) and hypervascular nodules in 21% (4/19). Most patients (82%, 40/49) showed normal biochemical hepatic function tests, despite the presence of hepatic parenchymal changes on imaging., Conclusion: The common US findings of FALD included heterogeneous parenchymal echotexture, surface nodularity, and hyper-echoic lesions. We suggest that hyper-echoic lesions without surface nodularity detected by high-frequency transducer may represent the early stage of fibrosis. US examination may be useful for identifying the progression of FALD before biochemical hepatic dysfunction., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Two children developed hepatoblastoma concurrent with congenital portosystemic shunts (PSSs) (Abernethy malformations). Both underwent operative ligation of their PSSs. One received concurrent tumor resection, whereas the other was deemed initially unresectable and underwent biopsy followed by neoadjuvant chemotherapy. Although benign hepatic masses, such as focal nodular hyperplasia and nodular regenerative hyperplasia, are common in patients with Abernethy malformations, malignant tumors have also been documented and should always be considered in the differential diagnosis of a patient with a congenital PSS and a hepatic mass.

In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis are the morphological aspects of the necroinflammatory process best correlated to the occurrence and development of fibrosis.

There remain significant obstacles in developing biologics to treat primary biliary cholangitis (PBC). Although a number of agents have been studied both in murine models and human patients, the results have been relatively disappointing. IL-22 is a member of the IL-10 family and has multiple theoretical reasons for predicting successful usage in PBC. We have taken advantage of an IL-22 expressing adeno-associated virus (AAV-IL-22) to address the potential role of IL-22 in not only protecting mice from autoimmune cholangitis, but also in treating animals with established portal inflammation. Using our established mouse model of 2-OA-OVA immunization, including α-galactosylceramide (α-GalCer) stimulation, we treated mice both before and after the onset of clinical disease with AAV-IL-22. Firstly, AAV-IL-22 treatment given prior to 2-OA-OVA and α-GalCer exposure, i.e. before the onset of disease, significantly reduces the portal inflammatory response, production of Th1 cytokines and appearance of liver fibrosis. It also reduced the liver lymphotropic chemokines CCL5, CCL19, CXCL9, and CXCL10. Secondly, and more importantly, therapeutic use of AAV-IL-22, administered after the onset of disease, achieved a greater hurdle and significantly improved portal pathology. Further the improvements in inflammation were negatively correlated with levels of CCL5 and CXCL10 and positively correlated with levels of IL-22. In conclusion, we submit that the clinical use of IL-22 has a potential role in modulating the inflammatory portal process in patients with PBC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: We investigated whether portal tract inflammation observed in non-alcoholic fatty liver disease (NAFLD) is associated with hepatic progenitor cell compartment activation, as thoroughly evaluated with different markers of the staminal lineage., Methods: Fifty-two patients with NAFLD were studied. NAFLD activity score, fibrosis and portal inflammation were histologically evaluated. Putative hepatic progenitor cells, intermediate hepatobiliary cells and bile ductules/interlobular bile ducts were evaluated by immunohistochemistry for cytokeratin (CK)-7, CK-19 and epithelial cell adhesion molecule (EpCAM), and a hepatic progenitor cell compartment score was derived. Hepatic stellate cell and myofibroblast activity was determined by immunohistochemistry for α-smooth muscle actin., Results: Portal inflammation was absent in a minority of patients, mild in 40% of cases and more than mild in about half of patients, showing a strong correlation with fibrosis (r=0.76, p<0.001). Portal inflammation correlated with CK-7-counted putative hepatic progenitor cells (r=0.48, p<0.001), intermediate hepatobiliary cells (r=0.6, p<0.001) and bile ductules/interlobular bile ducts (r=0.6, p<0.001), and with the activity of myofibroblasts (r=0.5, p<0.001). Correlations were confirmed when elements were counted by immunostaining for CK-19 and EpCAM. Lobular inflammation, ballooning, myofibroblast activity and hepatic progenitor cell compartment activation were associated with portal inflammation by univariate analysis. In the multivariate model, the only variable independently associated with portal inflammation was hepatic progenitor cell compartment activation (OR 3.7, 95% CI 1.1 to 12.6)., Conclusions: Portal inflammation is frequent during NAFLD and strongly associated with activation of putative hepatic progenitor cells since the first steps of their differentiation, portal myofibroblast activity and fibrosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To describe the anatomy of congenital portosystemic shunts involving the right gastric vein in dogs., Materials and Methods: Retrospective review of a consecutive series of dogs managed for congenital portosystemic shunt., Results: Twenty-two dogs met the inclusion criteria of a congenital portosystemic shunt involving the right gastric vein with recorded intraoperative mesenteric portovenography or computed tomography angiography and gross observations at the time of surgery. Of these, 20 (91%) had a shunt that entered the pre-hepatic caudal vena cava at the level of the epiploic foramen and two (9%) had a shunt that entered the post-hepatic caudal vena cava at the level of the diaphragm. Shunts entering the pre-hepatic caudal vena cava could be further classified into three consistent subdivisions., Clinical Significance: The morphology of each shunt type described appeared to be a result of an abnormal communication between the left gastric vein and the caudal vena cava, the presence or absence of an abnormal communication between the splenic, left gastric and portal veins and the subsequent development of preferential blood flow through essentially normal portal vessels within the portal venous system. The abnormal communication (shunt) was through the left gastric vein and not the right gastric vein, as might have been expected. This information may help with surgical planning in cases undergoing shunt closure surgery., (© 2015 British Small Animal Veterinary Association.)

Background and Objective: To determine associations of patterns of portosystemic collaterals and diameters of portal venous system in cirrhotic patients with hepatitis B on magnetic resonance (MR) imaging with Child-Pugh classification., Materials and Methods: Eighty-eight consecutive patients with cirrhosis resulting from chronic hepatitis B graded by Child-Pugh classifications were recruited and undergone MR portography. Patterns of the collaterals (presented as no collateral, isolated esophageal varices, and esophageal varices combined with other shunts), and diameters of portal venous system including portal vein (PV), left portal vein (LPV), right portal vein (RPV), splenic vein (SV) and superior mesenteric vein (SMV) were assessed statistically to determine associations of patterns of collaterals and diameters of the portal veins with Child-Pugh classification., Results: From no collateral, to isolated esophageal varices, and to the varices combined with other shunts, the Child-Pugh classifications tended to increase (r=0.516, P<0.001). Diameters of PV, LPV, RPV, SV and SMV tended to increase from Child-Pugh A to B but decrease from B to C. Differences in diameter of LPV and SV were significant between Child-Pugh A-B and C (all P<0.05) while no differences in diameters of other portal veins were found (all P>0.05). For discriminating Child-Pugh A-B from C, either a cut-off LPV diameter of 8.98mm or SV diameter of 9.10mm achieved a sensitivity of 67%-70%, specificity of 51%-53%., Conclusion: Patterns of portosystemic collaterals and diameters of LPV and SV tend to be associated with Child-Pugh classifications of cirrhosis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Investigations were conducted in 37 patients, suffering complicated pancreatic pseudocysts. In accordance to data of ultrasound Doppler flowmetry for the blood flow along portal vein, a. hepatis communis, a. mesenterica superior in complicated pancreatic pseudocysts compensatory--adaptive reactions on level of hepatic--spanchnic blood flow are directed towards restriction of the blood inflow through the portal vein system. This is accompanied by the common peripheral vascular resistence raising in basin of a. mesenterica superior, which have depended upon the patients' state severity, caused by reduction of the volume blood flow in a certan vascular collector. The oxygen debt of the liver in these patients is compensated by the volume blood flow enhancement along a. hepatis communis.

Objective: To evaluate the relationship between hepatic steatosis and increase in liver size and resolution of shunting after surgical attenuation of congenital extrahepatic portosystemic shunts in dogs., Study Design: Prospective study., Animals: Dogs (n = 20) with congenital extrahepatic portosystemic shunts., Methods: Shunts were attenuated using ameroid ring constrictors. Portal blood flow and liver volume were evaluated using computed tomography before and ≥8 weeks after surgery. Hepatic steatosis was quantified by stereological point counting of lipid droplets and lipogranulomas (LG) in liver biopsies stained with Oil-red-O. Associations between steatosis and preoperative liver volume, liver growth after surgery, and development of acquired shunts were evaluated., Results: Acquired shunts developed in 2 dogs (10%). Dogs with larger preoperative liver volumes relative to bodyweight had fewer lipid droplets per tissue point (P = .019). LG per tissue point were significantly associated with age: 0.019 ± 0.06 for dogs <12 months versus 0.25 ± 0.49 for dogs >12 months (P = .007). There was a significant positive association between liver growth after surgery and the number of LG/month of age in dogs >12 months (P = .003). There was no association between steatosis, presence of macrosteatosis, the number of LG or development of acquired shunts., Conclusions: This preliminary study suggests that the presence of hepatic lipidosis and LG has no demonstrable effect on development of acquired shunts or the magnitude of increase in liver volume after attenuation of congenital extrahepatic portosystemic shunts in dogs., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Objective: To investigate differences in clinical variables among dogs with extrahepatic portosystemic shunts (EHPSSs) of various morphologies., Design: Retrospective case series., Animals: 53 dogs with EHPSSs., Procedures: Medical records of dogs undergoing preoperative CT angiography of an EHPSS over a 3-year period were reviewed. Analysis was performed to investigate relationships of clinical variables with shunt morphology. Morphologies were analyzed individually as well as in several groups., Results: Shunt morphologies included 10 splenocaval, 9 splenophrenic, 11 splenoazygos, 10 right gastric-caval, 12 right gastric-caval with a caudal loop, and 1 right gastric-azygos with a caudal loop. Several biochemical variables associated with EHPSS were lowest in dogs with splenocaval shunts. Preoperative clinical signs were more common in dogs that had shunts with vena caval than right azygos vein insertion (36/41 [88%] vs 7/12 [58%]) and insertion caudal to the liver than diaphragmatic insertion (29/32 [91%] vs 14/21 [67%]). Neurologic signs were more common when shunts inserted into the vena cava caudal to the liver than in other locations (21/32 [66%] vs 6/21 [29%]) and were most frequent with splenocaval shunts. Urinary tract signs were more common when shunts had right gastric vein origin than gastrosplenic vein origin (14/23 [61%] vs 10/30 [33%])., Conclusions and Clinical Relevance: Splenocaval shunts caused more clinical abnormalities than did other shunt morphologies. Results suggested that dogs with shunt insertion in the caudal vena cava, especially caudal to the liver, were most likely to have clinical signs.

The purpose of this study was to elucidate the micro CT findings of tumoral vessels supplied by portal circulation during establishment of hepatic metastasis of colorectal cancer in a mouse model. Hepatic metastases were induced in 15 BALB/c mice through the injection of murine colonic adenocarcinoma tumor cells into the mesenteric vein. Micro-CT imaging of the tumoral vessels was obtained to clarify the microvascular architecture. We evaluated the sinusoidal structure, diameter of the tumoral vessels (DTV) and blood vessel density (BVD) according to tumor sizes ranging from 201 to 3,000 µm in diameter. A total of 116 tumors were observed on day 15 after cell injection. The mean diameter of a normal hepatic sinusoid was 11.7 ± 2.0 µm on micro CT. The DTV supplied by the portal vein of tumors measuring 1,001-1,500 µm in diameter was greater than that of tumors 200-1,000 µm in diameter. The mean BVD from the portal vein gradually decrease according to size of tumor from 201 to 3,000 µm in diameter (r(2)  = -0.584, P < 0.01). The characteristics of tumoral vessels supplied by portal circulation during establishment of hepatic colorectal metastases were well visualized with micro-CT imaging., (© 2014 Wiley Periodicals, Inc.)

Unlabelled: Although nonalcoholic fatty liver disease (NAFLD) is conventionally assessed histologically for lobular features of inflammation, development of portal fibrosis appears to be associated with disease progression. We investigated the composition of the portal inflammatory infiltrate and its relationship to the ductular reaction (DR), a second portal phenomenon implicated in fibrogenesis. The portal inflammatory infiltrate may contribute directly to fibrogenesis as well as influence the fate of the DR hepatic progenitor cells (HPCs), regulating the balance between liver repair and fibrosis. The presence of portal inflammation in NAFLD was strongly correlated with disease severity (fibrosis stage) and the DR. The portal infiltrate was characterized by immunostaining NAFLD liver biopsy sections (n = 33) for broad leukocyte subset markers (CD68, CD3, CD8, CD4, CD20, and neutrophil elastase) and selected inflammatory markers (matrix metalloproteinase 9 and interleukin [IL]-17). Cells expressing all markers examined were identified throughout the liver lobules and in portal tracts, although portal tracts were more densely populated (P < 0.01), and dominated by CD68(+) macrophages and CD8(+) lymphocytes, at all stages of disease. An increase in portal macrophages in NAFLD patients with steatosis alone (P < 0.01) was the earliest change detected, even before elevated expression of the proinflammatory cytokines, IL1B and TNF, in patients with early NASH (P < 0.05). Portal and periductal accumulation of all other cell types examined occurred in progressed NASH (all P < 0.05)., Conclusion: Knowledge of the complex cellular composition of the portal inflammatory infiltrate and HPC/DR niche in NAFLD will shape future functional studies to elucidate the contribution of portal inflammation to HPC differentiation and NAFLD pathogenesis., (© 2014 by the American Association for the Study of Liver Diseases.)

Canine extrahepatic congenital portosystemic shunts (EH-cPSS) are classified into several anatomical types, depending on the origin and termination of the shunt vessel. The aim of this retrospective study was to determine the proportion and clinical features of each anatomical shunt type in a population of dogs presented to a veterinary teaching hospital in Japan. Dogs diagnosed with EH-cPSS using computed tomographic (CT) portography were included (n=172) and shunts were classified based on previous reports. Clinical data were collected from case records and analysed statistically. The most common anatomical type was the spleno-phrenic shunt (n=64), followed by the spleno-azygos (n=38), right gastric-caval (n=29), spleno-caval (n=21), right gastric-caval with caudal loop (n=9), right gastric-phrenic (n=6), colono-caval (n=3), spleno-phrenic and azygos (n=1), and porto-caval (n=1) shunts. Spleno-phrenic and spleno-azygos shunts were diagnosed more frequently in older dogs than right gastric-caval and spleno-caval shunts (P<0.05). The portal vein/aortic (PV/Ao) ratio was significantly larger in dogs with spleno-phrenic shunts than in dogs with spleno-azygos, right gastric-caval or spleno-caval shunts (P<0.05). The PV/Ao ratio was significantly larger in dogs with spleno-azygos shunts than in dogs with right gastric-caval shunts. Dogs with spleno-phrenic shunts had significantly lower serum alkaline phosphatase activities than those with right gastric-caval or spleno-caval shunts. Dogs with spleno-phrenic shunts had significantly lower fasting ammonia concentrations than those with spleno-caval shunts., (Copyright © 2014. Published by Elsevier Ltd.)

Objective: To report long-term clinical outcome in dogs treated for single congenital extrahepatic portosystemic shunt (CEHPSS) with a ameroid ring constrictor (ARC) and to identify perioperative variables associated with outcome., Study Design: Retrospective, multi-institutional study., Animals: Dogs (n = 206) with CEHPSS., Methods: Medical records of dogs with CEHPSS treated by ARC were reviewed for perioperative and short-term (<1 month) data. Long-term follow-up information was obtained by telephone interview with referring veterinarians and/or owners. Kaplan-Meier analysis was used to estimate median survival time. Factors associated with short-term survival, outcome grade, and total survival time were identified., Results: Fifteen dogs died <1 month after ARC placement. Follow-up data were obtained for 112 of 191 dogs that survived >1 month; median follow was 54 months (range, 1-175 months) and 103 (92%) dogs had no clinical signs. Estimated median survival time was 152 months. Variables significantly associated with short-term survival included being intact and a low total white blood cell (WBC) count. Variables significantly associated with a successful outcome included having surgery later in the study period and negative postoperative nuclear scintigraphy. In the long-term survival analyses, intact dogs and those with higher WBC counts and occlusion pressures and lower bile acid concentrations were more likely to survive., Conclusions: Dogs with CEHPSS treated by ARC generally have a good prognosis and prolonged postoperative survival., (© Copyright 2013 by The American College of Veterinary Surgeons.)

Purpose: To describe the vascular and tissue histopathological changes in seven sequential experimental liver transplantations in pigs., Methods: Fourteen female pigs, Sus domesticus species, with body mass between 5 and 8 kg were utilized. After the end of all anastomoses of the graft implantation in the receptor, the animal was monitored for 30 minutes, and at its end one of the biopsies was collected for histological analysis. The histological criteria utilized were: lytic hepatocyte necrosis, density of septal and portal inflammatory infiltrated, sinusoidal congestion and hemorrhage. The analysis was performed separately for the portal region in zone 1, 2 and 3., Results: Among the structural changes undergone by the graft, those with greater frequency and intensity were vascular congestion and steatosis, which stood out in transplantations 5, 6 and 7., Conclusions: The technique demonstrated vascular alterations represented by vasocongestion, edema and minimum inflammatory reaction. In relation to the parenchyma, was observed macrovacuolar pan-acinar steatosis, focal lytic and occasional hemorrhages, beyond the accumulation of hemosiderin in Kuppfer's cells.