The mechanisms responsible for CCA invasiveness are unclear. S100A4, a member of the S100 family of small Ca2+-binding proteins, is expressed in mesenchymal cells, regulates cell motility in several cell types, and is expressed FK506 molecular weight in some epithelial cancers. Thus, we aimed to study the role of S100A4 in CCA invasiveness and metastasization. The expression of S100A4 was studied by immunohistochemistry in 93 human liver samples of CCA

patients undergoing surgical resection and correlated with metastases development (67 cases) and patient survival following surgery using log rank tests and multivariate analysis. S100A4 expression was studied in EGI-1 and TFK-1, human CCA cell lines with and check details without nuclear S100A4 expression, respectively. Metastatic properties of CCA cells were assessed by xenotransplantation in severe combined immunodeficiency (SCID) mice after transduction with lentiviral vectors encoding firefly luciferase gene. Proliferation, motility (wound healing), invasiveness (Boyden chamber), and metalloproteinases (MMPs) secretion were studied in CCA cells, with or without lentiviral

silencing of S100A4. Nuclear expression of S100A4 by neoplastic ducts was a strong predictor of metastasization and reduced survival after resection (P < 0.01). EGI-1 CCA cells showed stronger metastatic properties than TFK-1 when xenotransplanted in SCID mice. S100A4-silenced EGI-1 cells showed significantly reduced motility, invasiveness, and MMP-9 secretion in vitro, without changes in cell proliferation. Conclusion: Nuclear S100A4 identifies

a subset of CCA patients with a poor prognosis after surgical resection. Nuclear expression of S100A4 increases CCA cells invasiveness and metastasization, indicating that S100A4 may also represent a potential therapeutic target. (HEPATOLOGY 2011; 54:890–899) Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver; the incidence of intrahepatic Erlotinib in vitro CCA in Western countries has been steadily growing in the last two decades.1 In spite of the rising incidence, treatment options for CCA remain unsatisfactory,1, 2 particularly because of the strong and early invasiveness of the tumor. In many patients, lymphnodal or distant metastasis or micrometastasis are present already at the time of the diagnosis, limiting and worsening the prognosis in patients otherwise eligible for surgical resection. However, a subset of patients with less aggressive CCA may even undergo liver transplantation after neoadjuvant radiochemotherapy and have excellent survival. Biomarkers able to predict tumor invasiveness and prognosis would be an important decision-making tool. Unfortunately, mechanisms that determine CCA invasiveness are largely unknown. Cancer invasiveness and metastasization requires tightly adherent epithelial cells to convert to a more motile phenotype expressing several mesenchymal features.

However, these results are not sufficient to indicate that TRIM35 can be considered a candidate biomarker for HCC. HEY1 encodes a nuclear protein belonging Quizartinib in vivo to the hairy

and enhancer of split-related (HESR) family, which plays important roles in blood vessel formation and is involved in proliferation, migration, and network formation in endothelial cells.36 However, the roles of HEY1 in HCC have not been reported previously. Here, HEY1 was identified as a significant target gene in the 8q21.13 amplificon and the resulting up-regulation of HEY1 was obviously observed in HCC. Functional experiments showed that enhanced expression of HEY1 could significantly promote in vitro and in vivo proliferation of HCC cells. Additionally, SNRPE appears to function in RNA metabolism and has been shown to interact with DDX20.37 It was previously reported that SNRPE was amplified and up-regulated in malignant gliomas and oral squamous cell carcinomas.24, 38 In the present study we identified it as a new oncogene candidate for HCC, as it was widely amplified and Selleckchem MK2206 up-regulated in HCC and was capable of significantly enhancing HCC cell proliferation and

tumorigenicity. In conclusion, we produced a comprehensive copy number profile and found 1,241 somatic CNAs in HCC genomes using whole-genome SNP 6.0 arrays. By integrating genomic, transcriptional, and functional data we further identified one novel tumor suppressor candidate and

two novel potential oncogenes for HCC, which will facilitate better understanding of the molecular mechanisms of hepatocarcinogenesis. We thank Bin Cai from CapitalBio Ltd., Co. (Beijing, China) for help with SNP array analysis and data processes. We also thank Qi Li from the Invitrogen part of LifeTech for helping with data analysis, and Lin Li, Feng Su, Rui Li, and Amy Ai from Genminix Informatics Ltd., Co. for technical assistance. We thank Dr. T. Didier for gifts of the pWPXL, psPAX2, and pMD2.G lenti-virus plasmids. Additional Prostatic acid phosphatase Supporting Information may be found in the online version of this article. “
“Histologically, poorly differentiated hepatocellular carcinomas (HCC) are considered highly malignant. Here, we aimed to evaluate the relative efficacy and safety of hepatic resection or radiofrequency ablation (RFA) for treating this malignancy. Between April 2004 and May 2011, we enrolled 48 patients who had poorly differentiated HCC that had been diagnosed postoperatively by pathological assessment. All the tumors had a maximum diameter of 3 cm and all patients had three or less tumors. Fifteen of these patients underwent hepatic resection (HR group) and 33 patients underwent RFA (RF group). The patient background, tumor characteristics, overall survival rate and recurrence-free survival rate were assessed in both groups. The mean maximum tumor diameter was 2.5 and 2.0 cm in the HR and RF groups, respectively.

Food-intake and weight loss after stent placement were recorded as well. Results: All 30 rabbits were anesthetized and received stent placement and 22 rabbits survived to the sacrificed time. The average tumor volume was 7.00 ± 4.30 cm3 in SEMS group and 0.94 ± 1.51 cm3 in PEMS group,

respectively (P < 0.05). The area of the esophageal wall defect was 0.70 ± 0.63 cm2 in SEMS group and 0.17 ± 0.16 cm2 in PEMS group, respectively (P < 0.05). Tumor area 2 weeks after stent placement under EUS was Ensartinib chemical structure 4.40 ± 1.47 cm2 in SEMS group and 1.30 ± 1.06 cm2 in PEMS group, respectively (P < 0.05). Other indices were not significantly different among these two groups. Conclusion: A PEMS can be an alternative tool for advanced esophageal cancer which may inhibit tumor growth by serving a drug sustained-release platform. Clinical trails of this stent are needed in the near future. Key Word(s): 1. complete defect closure with purse-string sutures in gastric submucosal tumors Presenting Author: KAZUTOSHI FUKASE Additional Authors: Na Corresponding Author: KAZUTOSHI FUKASE Affiliations: Na Objective: From January 2002 to December

2012, 611 cases (662 lesions) of early gastric cancers (EGCs) NVP-BGJ398 ic50 were treated by endoscopic submucosal dissection (ESD) at Yamagata Prefectural Central Hospital. Out of 611 cases of EGCs treated by ESD, lymphatic vessel infiltrations were pathologically diagnosed in 3.3%. All cases underwent additional gastrectomy and lymph node metastases were pathologically diagnosed in 25%.

This result means that 75% of cases were over-treated by surgery. We need to research more diagnostic factors of lymphatic vessel infiltration patterns which indicate the risk factor for lymph node metastases. Methods: [Patients] From January 2005 to June 2012, specimens by ESD undertaken in 19 EGC patients were reassessed for lymphatic vessel infiltration(ly). [Methods] Sections of specimens were stained with hematoxylin-eosin (HE) and immunostained for D2-40 expression. They were evaluated by counting the number of infiltrating lymphatic vessels and measuring the maximum extent of infiltration (or determining the number of slides from the same specimen showing lymphatic vessel infiltration). Results: Five of 19 patients (26.3%) with ly(+) ESD PIK-5 specimens and none of 14 patients with ly(−) ESD specimens had metastatic lymph nodes. The 5 patients with metastatic lymph nodes had ESD specimens with 5 or more infiltrating vessels and a maximum distance of infiltration greater than 2 mm. Eight patients with ly(+) specimens having less than 5 infiltrating vessels or a maximum distance of infiltration less than 2 mm had no metastatic lymph nodes. Conclusion: These findings suggest that the criteria for additional gastrectomy after ESD might exclude ly(+) patients with less than 5 infiltrating vessels or a maximum distance of infiltration less than 2 mm.

In addition, on analysis of liver biopsies from HCV-infected individuals, they found increasing numbers of IL-17 positive cells with increasing HAI scores; the correlation with serum ALT but not HCV RNA was again observed.25 While this result is very interesting, its implications are not entirely clear. In particular, as the proportion of the total infiltrate comprised by IL-17 positive cells

was not characterized, it remains to be determined whether the apparent increase is a true enrichment of IL-17-producing cells associated with increasing levels of intrahepatic inflammation, or simply a function of the increased total number of cells associated with higher inflammatory scores. In addition, it should be borne in mind that a number of cell types other than GSI-IX clinical trial Th17 lymphocytes can produce IL-17, including neutrophils, NK cells, NKT cells, and γδ T cells. Thus, the nature of the IL-17 producing cells

in the livers of HCV infected individuals is not yet clear; further selleck investigation is required before the contribution of Th17 cells to the pathogenesis of chronic hepatitis C can be established. Nevertheless, despite these caveats, these data provide tantalizing additional indications of a link between Th17 responses and liver injury in HCV infection. The positioning of Th17 responses at the interface between the adaptive and innate immune responses, with the ability of these cells to induce tissue injuring inflammatory responses, will likely motivate much further research into the role of this arm of the helper T cell response in HCV immunopathogenesis. Despite TCL the advent of direct acting antiviral

agents in HCV treatment, it is likely that other avenues of treatment for HCV infected individuals will still be required in the foreseeable future. Treatments that interfere with Th17 responses, such as anti-IL-12/Il-23 p40 antibodies are already available, and given the intense interest in this pathway, further agents are likely to be developed. As discussed above, and summarized in Table 1, a range of data indicate that Th17 responses are involved in the pathogenesis of viral hepatitis. However, a range of outstanding questions will require answering before therapeutic interventions manipulating the Th17 response are attempted in HCV. In particular, interactions between Th17 cells and other aspects of the adaptive immune response, including regulatory T cells and Th1 responses require further exploration. In addition, while there is growing evidence of correlations between active inflammation and Th17 responses in chronic HCV infection, it is unclear whether the magnitude of Th17 responses correlate with advancing fibrosis in the non-immunosuppressed state, as has long been demonstrated for Th1 responses.

5±0. 2 vs 0. 7±0. 3, p<0. 5) and pDC exhibited a lower HLA-DR (MFI: 1673±525 vs 1523±531, p<0. 3) and a higher IL-T4 (MFI: 2303±632 vs 2743±718, p<0. 4), CD39 (MFI: 69. 4±7. 6 vs 74. 0±10. 6, p<0. 5; %: 16. 2±8. 7 vs 22. 1 ±9. 4, p<0. 5) and HLAG (MFI: 26. 2±8. 1 vs 36. 1 ±8. 6, p<0. 4) expression as compared with the baseline. No correlation

was found between these markers and HCV viral load. In addition, after Sil treatment mDC show a higher ICOSL (MFI: 29. 5±12. 6 vs 36. 2±7. 2, p<0. 4) expression that was inversely correlated to viral load. No changes were detected in Treg frequency and PD-1 expression. Conclusions: this is the first study in liver transplant patients with HCV recurrence showing Selleck RG 7204 the impact of Sil on DC and Treg. Findings show changes, not correlated with viral load, in circulating pDC that have previously been associated with tolerogenic conditions, providing new insight into how Sil might regulate allo-immunity. Additional in vitro functional studies are warranted to further explore the tolerogenic potential of Sil. Disclosures: Antonino Castellaneta – Grant/Research Support: Rottapharm Nadia Brambilla – Employment: Rottapharm Giampaolo Giacovelli – Employment: Rottapharm Lucio Rovati – Employment: SAHA HDAC solubility dmso Rottapharm S. p. A. Massimo D’Amato – Employment: Rottapharm The following people have nothing to disclose:

Antonio Massaro, Maria Rendina, Nicola Maurizio Castellaneta, Marianna Zappimbulso, Francesca Derrico, Alfredo Di Leo In the United States, less than a third of the 30, 000 patients with liver failure will receive a transplant this year. Machine perfusion is an investigational tool that can expand the donor pool by improving and quantifying liver viability, essential for the safe recovery of discarded livers. We have demonstrated that perfusate biochemical markers and liver biopsies provide highly sensitive indicators of viability; however, they only reflect an average overview of organ performance or focal information, respectively. To test whether greater measurement specificity can be achieved Astemizole across the entire organ,

we introduced dynamic contrast-enhanced ultrasound (DCEUS) for real-time, non-invasive, non-ionizing visualization of liver anatomy and perfusion. Here we use DCEUS to describe trends in perfusion as a function of ischemic severity, perfusion time, and treatment choice. A bolus of contrast passing through either the portal vein or hepatic artery was quantified with parameters such as wash-in time, time to peak intensity, and mean transit time. We observed that as exposure to warm ischemia in nonheparinized porcine livers (a model of uncontrolled cardiac death) increased from 30-60-90 minutes, the measured parameters differed significantly between groups and tended towards normal (0 minutes warm ischemia) at a dose-dependent rate.

Whereas the solitary silvery mole-rat Heliophobius argenteocinereus occurs there in the afromontane

grasslands, the social Whyte’s mole-rat Fukomys whytei is bound to the Miombo woodlands. The habitat of F. whytei was characterized by a lower food supply and harder soil. We suppose that the niche segregation of the two species in the Nyika Plateau is due to the inability of the solitary species to survive under the harsh ecological conditions. Absence of F. whytei in higher altitudes may be due to its less effective thermoregulation, competitive exclusion by H. argenteocinereus, or other unknown factors. Analysis of available data on food supply and precipitation from different mole-rat localities revealed that there is no clear separation of the localities inhabited by solitary, social and so-called eusocial species. “
“Monitoring learn more programmes and studies selleck inhibitor focused on secondary sexual characters (SSCs) depend on the accuracy of measurements. However, methods of measurements of SSC, such as horns of ungulates, vary throughout the literature.

Thus, the accuracy of horn growth measurements as proxies of true horn growth and the comparability of results inferred from different horn growth measurements may be questionable. We used the horns of Iberian ibex Capra pyrenaica to compare horn growth measurements and to analyse reliability with true horn growth. Our results reveal that measurements used in previous studies differed substantially from true horn growth and volume estimated as a barrel appeared as the best proxy of annular segments of horns in the Iberian ibex. Horn growth measurements are not necessarily mutually comparable, just as classical measurements are not necessarily representative of true horn growth. We discuss the wider implications of these results and suggest that biological processes linked to horns of ungulates should be reappraised using

improved and accurate measurements because horn growth pattern medroxyprogesterone is a key factor in sustainable management and conservation plans of ungulate species around the world. “
“Avoidance of roads has been demonstrated for many animal species, but little is known about the relationship between anthropogenic disturbance levels and the degree of avoidance by animals. We investigated the hypothesis that the strength of road-avoidance behaviour increases with the intensity of the disturbance for a large, disturbance-sensitive herbivore: the forest-dwelling caribou Rangifer tarandus caribou. We assessed the behaviour of 53 global positioning system-collared caribou monitored during the gradual modification of a highway over a 7-year period, while controlling for potentially confounding factors. We studied caribou movements, resource selection and distribution before, during and after road modifications at multiple scales.

Some studies have Histone Methyltransferase inhibitor reported that PPAR δ agonists play a role in regulating glucose metabolism, lipid metabolism and insulin resistance in type 2 diabetes, metabolic syndrome and coronary atherosclerosis .However there is few report of the effect of PPAR δ agonists on NAFLD.

The aim of this study is to determine the effect of PPARδ agonist (GW501516) on liver function, insulin resistance and lipid metabolism in high-fat diet rats. Methods: Male Sprague-Dawley (SD) rats were randomly divided into three groups: normal diet group (NC group, n = 10), high-fat diet group (HF group, n = 10), high-fat + GW501516 (GW group, n = 10). The rats in GW group were treated with GW501516 (10 mg/kg/d, intragastric PD0325901 order administration once daily) after 8 weeks with high-fat diet. After 4 weeks of the treatment, all rats were sacrificed. Histopathological and biochemical analyses were carried out. Real-time-PCR was used to detect the mRNA expression of lipid metabolism-related genes in the liver. Results: The body weight, liver wet weight, liver index and BMI in GW group were lower

than HF group and higher than NC group. Fasting blood glucose, serum ALT and AST level, blood lipids, fasting insulin and insulin resistance index were increased in HF group and were reduced by GW501516 treatment. GW501516 significantly attenuated high-fat diet induced liver fat deposition. Moreover, as compared with the HF group, the mRNA expression of DGAT1, CPT-1,

ACOX1 and ACOX3 was reduced in GW group. Conclusion: PPARδ agonist (GW501516) can improve liver function, insulin resistance and liver pathological change induced by high-fat diet and regulation (-)-p-Bromotetramisole Oxalate of lipid metabolism related genes may be one of the mechanisms. Key Word(s): 1. PPARδ agonist; 2. High-fat diet; 3. Insulin resistance; 4. Lipid metabolism; Presenting Author: AYASKANTA SINGH Additional Authors: SHIVARAMPRASAD SINGH, MANASKUMAR PANIGRAHI, GIRISHKUMAR PATI, BIJAY MISRA, SANJIBKUMAR KAR, DEBASIS MISRA Corresponding Author: AYASKANTA SINGH Affiliations: S.C.B Medical college; S.C.B Medical college; S.C.B Medical college; S.C.B Medical college; S.C.B Medical college Objective: NAFLD encompasses a spectrum. of liver disorders ranging from simple steatosis through steatohepatitis to cirrhosis.Although obesity is a known risk factor for NAFLD, many recent studies have indicated that visceral fat accumulation may be a more important risk factor for metabolic syndrome and NAFLD than overall obesity.Waist circumference is a well-known surrogate marker of abdominal fat accumulation, may underestimate.

Furthermore,

in vivo RBP4 infusion induced SREBP-1c activation and consequently accelerated hepatic lipogenesis and plasma TAG in C57BL/6J mice, a phenomenon not observed in Ppargc1b knockout mice. Conclusion: These findings reveal a novel mechanism by which EX 527 solubility dmso RBP4 achieves its effects on hepatic lipid metabolism. (HEPATOLOGY 2013;8:564-575) Retinol binding protein 4 (RBP4), a protein that belongs to the lipocalin family, was initially known as a specific carrier for the delivery of retinol (vitamin A) in the circulation.[1, 2] It is encoded by the RBP4 gene, localized in chromosome 10q23-q24.[3] Hepatocytes are regarded as the major source of RBP4 secretion under normal conditions[4]; however, adipose tissue expresses a considerable amount of RBP4[5] and could make a substantial contribution to elevated serum RBP4 levels in insulin-resistant states.[6] RBP4 is identified as a new adipokine suggested to link obesity with its comorbidities, especially insulin resistance, type 2 diabetes (T2D), and certain components of the metabolic syndrome. Serum RBP4 concentrations are elevated in subjects with impaired glucose tolerance, T2D, and correlate inversely with insulin sensitivity in nondiabetic subjects with a family history of T2D.[7] Circulating see more RBP4 levels correlate with the degree of insulin resistance in these subjects and the relationship

is independent of obesity.[8] Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice induced until insulin resistance.[10] Conversely, heterozygous or homozygous RBP4 knockout mice had improved insulin sensitivity.[10] Increased serum RBP4 decreased glucose transporter type 4 (Glut4)

expression in adipocytes and induced expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) in hepatocytes, thus contributing to the impairment of systemic insulin resistance.[10] Recently, a high circulating level of RBP4 was demonstrated to associate with elevated liver fat accumulation in human studies.[11] Blocking RBP4 expression in the liver was sufficient to reduce lipid droplets and ameliorate high fat diet-induced hepatic steatosis in C57BL/6 mice, which confirmed the potential role of RBP4 in the regulation of lipid metabolism in liver.[14] However, the pathophysiological roles of RBP4 involved in the regulation of hepatic lipid metabolism and the underlying molecular mechanism has not yet been fully characterized. Sterol regulatory element binding protein (SREBP) is known as a key lipogenic transcription factor controlling the biosynthesis of cholesterol, fatty acids, and triglyceride (TAG).[15, 16] Mammalian genomes have two separate SREBP genes (SREBF1 and SREBF2). SREBP-1 expression produces two different isoforms, SREBP-1a and -1c.

Similarly, leptin incubation alone also resulted in a significant decrease in gel surface area compared with a gel treated with buffer alone. Furthermore, the concomitant administration of leptin with ETAR antagonist (BQ123) reversed the leptin-induced decrease in gel surface area. In contrast, simultaneous administration of ETBR antagonist (BQ788) with leptin did not modify the

leptin-induced contraction of gel. It should be noted that leptin incubation resulted in an up-regulated in the expression of ETAR and OBRb protein as well as higher levels of activator protein-1 mRNA in the HSC-T6 and primary HSC supernatant (Fig. 6C-E; Supporting Fig. 2C-E). In the current study, we successfully created a NASH cirrhotic model that was characterized by insulin and leptin resistance, hyperleptinemia, increased IHR, and portal check details hypertension in obese Zucker rats by feeding the rats an HF/MCD diet and in lean rats by feeding them the HF/MCD diet in addition to chronic exogenous leptin administration.5, 6, 22 Microcirculatory dysfunction in the NASH liver is characterized by increased adherence of leukocytes to the sinusoidal lining (sticky leukocytes) and impaired sinusoidal perfusion.7 Consistent with previous reports, in the present study we observed the typical microcirculatory dysfunction associated with cirrhosis and portal hypertension in HF/MCD-Zucker

and HF/MCD+leptin-lean rats.7, 8 Both leptin and osteopontin are profibrogenic extracellular matrix proteins that can be activated in the NASH liver.1, 2, 5 In our HF/MCD-Zucker rats with hyperleptinemia, up-regulated hepatic TGF-β1, leptin and osteopontin expression were associated with severe hepatic steatosis, inflammation, fibrogenesis and cirrhosis compared with normal-Zucker rats. In our HF/MCD+leptin-lean rats, concomitant exogenous leptin administration and an HF/MCD diet creates liver cirrhosis that is similar to that which occurs in HF/MCD-Zucker rats. Increased hepatic endocannabinoids also participate in the mechanisms that result in hepatic fibrogenesis and increased IHR in cirrhosis.15

Endocannabinoids are mainly released by Vorinostat nmr activated leukocytes through the TNF-α/MAPK pathway.17 Our current study showed that the increased IHR and liver cirrhosis in the HF/MCD-Zucker rats was associated with an increase in hepatic endocannabinoid level and an up-regulation of the TNF-α/p38MAPK and CB1 receptors. In parallel, we found a positive correlation between hepatic endocannabinoid levels and increased sticky leukocyte numbers in the HF/MCD-Zucker and HF/MCD+leptin-lean rats with NASH cirrhotic livers. It has been reported that hyperleptinemia may cause leukocyte activation in obese rats.23 We observed a positive correlation among plasma leptin levels and the numbers of sticky leukocytes in our Zucker rats. It has also been reported that leptin enhances TNF-α production by way of the p38MAPK pathway in Kupffer cells.

96, 97 In selected patients with INCPH (e.g., abdominal discomfort or hypersplenism patients), these interventions can be regarded as effective therapeutic modalities. Based on the high prevalence of thrombophilia and incidence of portal vein thrombosis in INCPH patients, several investigators

have incriminated thrombosis of small intrahepatic portal veins as an important etiological factor in the development of this disorder.6, 30 Additionally, a trend toward poor prognosis has been reported in patients with INCPH who develop portal vein thrombosis.6 As a result, anticoagulation therapy has been proposed by Sirolimus research buy several investigators to prevent disease progression and to maintain portal vein patency.6, 32, 98 However, considering the fact that gastrointestinal Selleckchem ABT 263 bleeding is the main complication of INCPH and the uncertain role of thrombophilia in the pathogenesis, this treatment is still a matter of debate and cannot be generally implicated until more solid data are present. Nonetheless, we believe that anticoagulation therapy must be considered in patients

with underlying prothrombotic conditions and in patients who develop portal vein thrombosis. Generally, patients with isolated INCPH have a normal liver function and the complications of portal hypertension can be managed successfully with endoscopic therapy and shunting. However, several reports describing liver transplantation in patients with INCPH have been published. The reported indications requiring liver transplantation in these patients were medical unmanageable portal hypertension, hepatopulmonary syndrome, hepatic encephalopathy, and progressive find more hepatic failure.49, 63, 78 Recently, Karsinskas et al. described a small cohort of INCPH patients treated with liver transplantation.63 The main indication for liver transplantation was medically unmanageable severe portal hypertension; a minority was listed because of hepatic encephalopathy. Notwithstanding the fact that resistant bleeding in INCPH patients should be treated with portosystemic shunting before considering the option of

liver transplantation, only two patients underwent pretransplantation portosystemic shunting procedures (e.g., TIPS and mesocaval shunt). Presumably, the high frequency of cirrhosis misdiagnoses in these patients led to early referral for liver transplantation. To prevent unnecessary liver transplantation in these patients, early discrimination between cirrhosis and INCPH is extremely important. Based on small-sized cohorts (with limited follow-up), post-transplantation outcome in these patients is good and INCPH tends not to recur.63, 99, 100 Data on the etiology and management of INCPH are scarce, and currently applied diagnostic and therapeutic algorithms are based on personal experience or data from limited numbers of patients.