015 μM for G3, whereas alisporivir

IC50 for G1 was 0.139 ± 0.013 µM versus 0.044 ± 0.007 µM for G3). We tested telaprevir resistant viral isolates and identified changes in IC50. One patient with a poor clinical response to telaprevir Deforolimus ic50 and ‘wild type’ viral sequence showed reduced telaprevir sensitivity in our assay. We studied samples from a 2-week telaprevir monotherapy study in which 5/8 patients with G3 HCV did not respond whilst 3/8 patients did. The ‘capture-fusion’ assay correctly identified responders. Conclusion: The ‘capture-fusion’ model represents a promising new technique which may help identify appropriate treatment strategies for patients with chronic HCV infection. (Hepatology 2014;) “
“The aim of this study was to investigate the predictive factors for the response of ascites to a transjugular intrahepatic portosystemic shunt (TIPS) and the impact of improvement of ascites on the overall prognosis of patients with cirrhosis and refractory ascites. Forty-seven consecutive patients with liver cirrhosis who underwent TIPS for refractory ascites were studied retrospectively. The mean follow-up period was 615 ± 566 days. Thirty-six of the patients (77%) were responders at 4 weeks after TIPS (early responders) and 37 (79%) were responders at 8 weeks after TIPS. Of the 11 non-responders at 4 weeks, four showed an improvement of ascites at

8 weeks. Multivariate analysis showed that only the serum creatinine level before IBET762 TIPS was an independent predictor of an early response. The cumulative survival rate of early responders was significantly higher than that of non-responders. The survival of patients grouped according to creatinine level was better in patients with serum creatinine of 1.9 mg/dL or less than in those with serum creatinine of more than 1.9 mg/dL. A low serum creatinine level in patients with refractory ascites is associated with an early response to TIPS. An early response of ascites medchemexpress to TIPS provides better survival. A serum creatinine level below 1.9 mg/dL is required for a good response to TIPS. “
“The prevalence of relative adrenal insufficiency (RAI) in critically ill cirrhosis patients with severe sepsis is over 60% and associated

features include poor liver function, renal failure, refractory shock, and high mortality. RAI may also develop in noncritically ill cirrhosis patients but its relationship to the clinical course has not yet been assessed. The current study was performed in 143 noncritically ill cirrhosis patients admitted for acute decompensation. Within 24 hours after hospitalization adrenal function, plasma renin activity, plasma noradrenaline and vasopressin concentration, and serum levels of nitric oxide, interleukin-6 and tumor necrosis factor alpha were determined. RAI was defined as a serum total cortisol increase <9 μg/dL after 250 μg of intravenous corticotropin from basal values <35 μg/dL. Patients were followed for 3 months. RAI was detected in 26% of patients (n = 37).

015 μM for G3, whereas alisporivir

IC50 for G1 was 0.139 ± 0.013 µM versus 0.044 ± 0.007 µM for G3). We tested telaprevir resistant viral isolates and identified changes in IC50. One patient with a poor clinical response to telaprevir find more and ‘wild type’ viral sequence showed reduced telaprevir sensitivity in our assay. We studied samples from a 2-week telaprevir monotherapy study in which 5/8 patients with G3 HCV did not respond whilst 3/8 patients did. The ‘capture-fusion’ assay correctly identified responders. Conclusion: The ‘capture-fusion’ model represents a promising new technique which may help identify appropriate treatment strategies for patients with chronic HCV infection. (Hepatology 2014;) “
“The aim of this study was to investigate the predictive factors for the response of ascites to a transjugular intrahepatic portosystemic shunt (TIPS) and the impact of improvement of ascites on the overall prognosis of patients with cirrhosis and refractory ascites. Forty-seven consecutive patients with liver cirrhosis who underwent TIPS for refractory ascites were studied retrospectively. The mean follow-up period was 615 ± 566 days. Thirty-six of the patients (77%) were responders at 4 weeks after TIPS (early responders) and 37 (79%) were responders at 8 weeks after TIPS. Of the 11 non-responders at 4 weeks, four showed an improvement of ascites at

8 weeks. Multivariate analysis showed that only the serum creatinine level before CT99021 TIPS was an independent predictor of an early response. The cumulative survival rate of early responders was significantly higher than that of non-responders. The survival of patients grouped according to creatinine level was better in patients with serum creatinine of 1.9 mg/dL or less than in those with serum creatinine of more than 1.9 mg/dL. A low serum creatinine level in patients with refractory ascites is associated with an early response to TIPS. An early response of ascites 上海皓元 to TIPS provides better survival. A serum creatinine level below 1.9 mg/dL is required for a good response to TIPS. “
“The prevalence of relative adrenal insufficiency (RAI) in critically ill cirrhosis patients with severe sepsis is over 60% and associated

features include poor liver function, renal failure, refractory shock, and high mortality. RAI may also develop in noncritically ill cirrhosis patients but its relationship to the clinical course has not yet been assessed. The current study was performed in 143 noncritically ill cirrhosis patients admitted for acute decompensation. Within 24 hours after hospitalization adrenal function, plasma renin activity, plasma noradrenaline and vasopressin concentration, and serum levels of nitric oxide, interleukin-6 and tumor necrosis factor alpha were determined. RAI was defined as a serum total cortisol increase <9 μg/dL after 250 μg of intravenous corticotropin from basal values <35 μg/dL. Patients were followed for 3 months. RAI was detected in 26% of patients (n = 37).

05 level of significance. The characteristics of the 221 patients are shown in Table 1 according to assigned treatment regimen. Patients were comparable across both groups with regard to age, race, HBV genotype distribution, selleck chemicals llc baseline prevalence of cirrhosis, and ALT and HBV DNA levels. Overall, 43 (19%) patients had a response at week 78, and these patients were distributed

equally across the two study arms. Baseline mean serum HBsAg was 4.4 log IU/mL in both treatment groups. Serum HBsAg was positively correlated with HBV DNA (r = 0.66, P < 0.01) and inversely correlated with age (r = −0.16, P = 0.02) but did not correlate with ALT. Variation was observed in pretreatment HBsAg levels between genotypes, with the highest baseline levels in genotypes A and D (mean = 4.5 log IU/mL for both) and lower levels in genotypes B (mean = 4.3 log IU/mL) and C (mean = 3.8 IU/mL) (P < 0.001 for genotype C versus other genotypes with Bonferroni correction). Overall, HBsAg levels decreased significantly through 52 weeks of therapy (mean decline = 1.2 log IU/mL, P < 0.001), and the decrease was sustained after 26 weeks of follow-up (mean decline compared to baseline = 0.9 IU/mL, P < 0.001). Patterns of HBsAg decline for both treatment groups are depicted in Fig. 1. Declines

were similar in both treatment arms at weeks 4, 8, and 12, but slightly more pronounced in the combination (PEG-IFN + LAM) compared to the monotherapy group (PEG-IFN + placebo) at week 24 (mean decline = 1.0 log IU/mL versus 0.6 log IU/mL, P = 0.04) and at week 52 (mean decline = Gemcitabine cell line 1.46 and 0.87 log IU/mL for combination therapy and monotherapy, respectively, P = 0.04). This difference was not sustained through

posttreatment follow-up 上海皓元医药股份有限公司 (mean decline of 0.98 and 0.86 log IU/mL for combination and monotherapy at week 78, respectively, P = 0.63). Considering the equal response rates and HBsAg levels at week 78 in the two treatment groups, we analyzed the relationship between HBsAg decline and treatment response in all 221 patients. Baseline mean HBsAg levels were comparable in the 43 patients who achieved a response at week 78 and those who did not; 4.4 versus 4.3 log IU/mL in nonresponders and responders, respectively (P = 0.19). Mean HBsAg declines from baseline for responders and nonresponders at week 78 are shown in Fig. 2. Nonresponders showed a modest decline through 52 weeks of therapy (0.69 log IU/mL, P < 0.001), and relapsed during follow-up (decline from baseline at week 78 was 0.35 log IU/mL, P < 0.001 compared to week 52). Mean decline from baseline in responders was 3.3 log IU/mL at week 52 and 3.4 at week 78 (P < 0.001 for both when compared to baseline). Responders thus showed a more vigorous decline in HBsAg starting at week 4, and this difference increased through 52 weeks of therapy and was sustained during posttreatment follow-up (P < 0.005 for week 4 and P ≤ 0.001 for all other time points compared to nonresponders).

1977). Hence, protection is limited to the foliage surface where oil is applied (Simons et al. 1977). In several European countries, the use of mineral oil is prohibited for ecological reasons or due to phytotoxicity. Damage due to phytotoxicity may occur if mineral oil is mixed with fungicides

such as captafol (Bell 1980) or fluazinam (C. Corre, personal communication). In addition, when oils are sprayed under hot weather conditions, the oil heated by the sun in the sprayer pipes may burn potato leaves and stems (J.L. Rolot, personal communication). We describe three treatment strategies for the control of aphid populations and PVY spread in field, based respectively GSK458 ic50 on insecticide, oil and elicitor application on foliage. The first strategy involved re-investigating the effect of one insecticide, Karate Zeon® (lambda-cyhalothrin; Syngenta®, Basel, Switzerland). The quick-acting effect of this pyrethroid could neutralize the aphid before it has time to transmit.

Lambda-cyhalothrin has previously been found ineffective in preventing PVY spread when sprayed according to an aphid threshold (van Toor Smoothened Agonist et al. 2009). We adopted a different application modality, by spraying weekly, starting at plant emergence. This insecticide has been found ineffective by spraying weekly until 42 days after plant emergence (Hansen and Nielsen 2012); however, Basky and Almasi (2005) have shown that massive PVY infections can occur up to 45 days after plant emergence. Therefore, we decided to spray the plants until haulm killing. The second strategy involved testing one formulation of rapeseed oil, Telmion® (Omya AG AGRO®, Oftringen). The third strategy consisted of testing the effect of Bion® (acibenzolar-S-methyl; Syngenta®,

Basel), which has never previously been tested for PVY spread control. This benzothiadiazole is sold commercially as a fungicide. However, it has some insecticidal properties and also activates the general resistance mechanisms of the plant (Green 2009), medchemexpress and we here refer to it as an elicitor. A two-year field experiment was conducted in Switzerland in lowland conditions (425 to 720 m a.s.l.). Plots were planted according to a completely randomized block design, with five replications. Each plot was planted with four rows of 25 plants of the PVY-susceptible cv. Bintje (Schwaerzel et al. 2009) and surrounded by two rows of the same cultivar acting as a buffer zone. The rows were planted every 75 cm, and within a row, tubers were planted every 33 cm. Each plot presented 4% of secondary infected plants resulting from the planting of four tubers infected by PVYN605 isolate (Agroscope PVY collection). The experimental field was managed following standard cultural practices, and haulm killing was done 90 days after planting. The mixture volume sprayed on the plots was equivalent to 300 l/ha.

Controls were free from hepatic or neurological disorders at the time of death. Informed written selleck chemicals consent was given either by the patients or by their relatives or had been included in the body donor program of the Department of Anatomy, University of Düsseldorf, Germany. In addition to these brain samples from

European patients, brain samples from four Australian controls without cirrhosis, four Australian patients with cirrhosis who did not have HE, and five Australian patients with cirrhosis who had HE were analyzed. These brain samples were obtained from the Australian Brain Donor Programs New South Wales Tissue Resource Centre, which is supported by the University of Sydney, National Health and Medical Research Council of Australia, Schizophrenia Research Institute,

National Institute of Alcohol Abuse and Alcoholism, and New South Wales Department of Health. Details on Ibrutinib research buy the medical history of the European and Australian patients were published recently.9 Immunofluorescence analysis was performed as described recently6 and in the supplemental materials. Real-time polymerase chain reaction (PCR) was performed as described recently8 and in the Supporting Information. Western blot analysis was performed as described recently6 and in the Supporting Information. Reactive oxygen and nitrogen species were detected using the reactive oxygen species (ROS)-sensitive fluorescence dye CM-H2DCFDA and fluorescence microscopy as described in the Supporting Information. Cell migration was assessed using a commercial colorimetric cell migration medchemexpress assay (Chemicon QCM Colorimetric Cell Migration Assay) according to the manufacturer’s instructions. Phagocytosis of microglia was assessed by detection of latex beads using fluorescence microscopy. For further details, see the Supporting Information. For measuring cell diameter and filopodia length real-time differential interference contrast microscopy was performed as described in the Supporting Information. L-Glutamate in culture medium was measured as described.5 Concentrations of 6- keto-prostaglandin

F1α, which is a stable metabolite of prostaglandin I2, and prostaglandin E2 (PGE2) were determined in culture medium by using commercial enzyme immunoassay kits (Cayman Chemicals, Hamburg, Germany) according to the manufacturer’s protocol. Data processing was performed using Excel and Graph Pad Prism (4.0) for Windows. Data are presented as the mean ± SEM. Descriptive statistics were performed using a Student t test or one-way analysis of variance followed by Tukey’s or Dunnett’s multiple comparison post hoc test, where appropriate. P ≤ 0.05 was considered statistically significant. Microglia activation is associated with increased cell migration, which depends on a polarized cell morphology and local protrusion formation.

Rockey – Consulting: Ono; Grant/Research Support: Sucampo, Sucampo, Hyperion, Actelion William M. Lee – Consulting: Eli Lilly, Novartis; Grant/Research Support: Gilead, Roche, Vertex, BI, Anadys, BMS, merck; Speaking and Teaching: Merck The following people have nothing to disclose: Lafaine Grant, Jiezhun Gu, Saleh Alqahtani Background: Recently, cholangiocarcinoma cases have epidemically developed among offset color proof-printing workers NVP-BGJ398 research buy of a printing company in Japan. In this series, DNA damage of biliary epithelial cells due to inhalation of organic solvents including 1, 2-dichloropropane and/or dichloromethane (DCM) is supposed to be associated with the carcinogenic

process. The metabolism of DCM proceeds through two pathways; a cytochrome P450 (CYP) 2E1 dependent pathway and a Thetaclass glutathione S-transferase (GST) T1-1-catalyzed pathway, where the latter has been implicated in carcinogenicity. Aim: This study was performed to examine the carcinogenic process of cholangiocarcinoma cases developing among workers of the printing company. Methods: Immunostaining of GST T1-1, CYP2E1, and gamma-H2AX was performed using formalinfixed, paraffin-embedded tissue sections of the cholangiocarcinoma cases of the printing company (n = 5). For comparison, tissue sections of cholangiocarcinoma associated with hepatolithiasis (n =16) as well as

normal livers (n =10) were used. All cholangiocarcinoma cases were surgically resected, and were histologically associated with biliary intraepithelial neoplasia 上海皓元 (BilIN). Gamma-H2AX was used as a marker of DNA double strand break. Results: The immunohistochemical selleck expression of GST T1-1 was observed in biliary epithelial cells of normal biliary tract and hepatocytes. The expression

of GST T1-1 was also observed in the foci of BilIN and invasive adenocarcinoma for all cholangiocarcinoma cases used. The immunohistochemical expression of CYP2E1 was observed in hepatocytes of normal livers, while normal biliary epithelial cells as well as BilIN and cholangiocarcinoma were typically negative. Gamma-H2AX was detected in foci of invasive adenocarcinoma in 4 of 5 cholangiocarcinoma cases of the printing company, and 3 cases further showed occasional expression of gamma-H2AX in non-neoplastic biliary epithelial cells as well as BilIN. In the cases of cholangiocarcinoma associated with hepatolithiasis, 7 of 16 cases showed the expression of gamma-H2AX in the invasive foci, whereas non-neoplastic biliary epithelial cells and BilIN were typically negative. Conclusions: These results suggest that the inhalation of organic solvents may act as a carcinogen for biliary epithelial cells by causing DNA damage through the GST T1-1-catalyzed pathway, and provide evidence that supports the causal relation between organic solvent inhalation and cholangiocarcinoma development in the patients.

One expression study showed that G alleles of HLA-DP rs3077 and rs9277535 were

associated with decreased levels of messenger RNA expression of HLA-DPA1 and HLA-DPB1, respectively, in normal liver tissues.15 SNP rs3077 was also found to be associated with the methylation status of HLA-DPA1 and HLA-DPB1 in adult cerebellum samples.16 However, no phenotype data on the other two SNPs (rs2856718 and rs7453920) in HLA-DQ were reported. Both HLA-DP and HLA-DQ belong to HLA class II molecules, which are expressed as cell-surface glycoproteins that bind and present short peptide epitopes to cluster of differentiation Apoptosis Compound Library cell line (CD)4+ T cells.17 Although it remains elusive whether HBV-specific T-cell responses have crucial effects on the outcome of HBV infection, the weaker or undetectable HBV-specific CD4+ T-cell responses have been observed in patients with established chronic infection, but not in people with resolved infection.18 Moreover, CD4+ T cells significantly

Mitomycin C research buy increased in peripheral blood, tumor, and ascites of HCC patients.19 These evidences indicated that HBV-specific, HLA class II–restricted CD4+ T-cell responses may be related to both HBV infection recovery and HBV-related HCC development. Our study had a number of strengths. First of all, our HBV persistent carriers and subjects with nature HBV clearance came from a systematic screening of HBV and HCV markers in a large, population-based study conducted in Jiangsu Province and was well matched on age and sex, which may have reduced potential selection bias. Moreover, a relatively large sample size in this study provided enough statistical power, and it is the first study demonstrating that HLA-DP and HLA-DQ variants also influence HCC development. However, some associations could not survive multiple testing adjustments; therefore, the results should be treated with caution (like rs3077), and validations medchemexpress are warranted. Taken together, our study suggested that

HLA-DP and HLA-DQ loci are candidate susceptibility regions that have some marker SNPs for both HBV clearance and HBV-related HCC in Han Chinese. The authors thank Dr. Qingyi Wei of The University of Texas MD Anderson Cancer (Houston, TX) center for his scientific editing of the manuscript for this article. Additional Supporting Information may be found in the online version of this article. “
“The Wnt/β-catenin pathway has been known to play a role in induction of immune tolerance, but its role in the induction and maintenance of natural killer T (NKT) cell anergy is unknown. We found that activation of the Wnt pathways in the liver microenvironment is important for induction of NKT cell anergy. We identified a number of stimuli triggering Wnt/β-catenin pathway activation, including exogenous NKT cell activator, glycolipid α-GalCer, and endogenous prostaglandin E2 (PGE2).

4); however, there is a population of PD-1–positive cells. These PD-1–positive cells are also CD62L-low, indicating that they are recently activated CD8+ T cells. We have previously shown that activated CD8+ T cells are trapped in the liver in a TLR4-dependent manner.20 However, we cannot assume that the host liver PD-1 high cells were

trapped in this manner. To test the hypothesis that activation in the liver selleckchem up-regulates PD-1 on CD8+ T cells, we compared OT-1 cells activated by AAV-OVA in the liver and OT-1 cells activated in primary lymphoid tissues by SIINFEKL-pulsed DCs. Figure 5 shows that PD-1 expression is an indication of activation, because this molecule is expressed on OT-1 cells both in the liver of AAV-OVA–transduced mice, and in liver and lymphoid organs of DC-SIINFEKL–stimulated mice.

Furthermore, OT-1 cells activated by DC-SIINFEKL in all organs, and OT-1 cells activated by AAV-OVA in the liver, expressed a significantly higher level of PD-1 than did OT-1 cells taken from untreated mice. However, expression of PD-1 was significantly higher in OT-1 cells in the liver of mice stimulated with AAV-OVA, compared both with OT-1 cells from unstimulated mice and with those in any organ of mice stimulated with DC-SIINFEKL. This shows that whereas PD-1 expression follows HTS assay activation, the generation of PD-1hi cells is unique to cells primed in the liver. We can conclude that high PD-1 expression is not simply due to activated CD8+ T cells migrating to liver. Cross-presentation

depends on the transfer of antigen from an antigen-expressing cell to a distinct APC, and can lead either to cross-priming or to cross-tolerance.23-25 The APCs are generally MHC class I+ II+ bone marrow–derived cells such as macrophages or DCs. To test the participation of such cells in the OT-1 T cell response to AAV2-ova, we used bm8 mice. These mice harbor several mutations in the Kb MHC class I molecule, which prevent the presentation of the SIINFEKL peptide.26 We created 上海皓元医药股份有限公司 radiation bone marrow chimeras in which bm8 bone marrow was used to reconstitute lethally irradiated B6 mice or vice versa. Because a subset of bone marrow–derived Kupffer cells is resistant to depletion by radiation alone, mice were additionally treated with clodronate liposomes after the bone marrow transplant. This treatment effectively depletes both subsets of Kupffer cells.17 The response of OT-1 T cells to AAV2-ova in the liver in such chimeras is shown in Fig. 6. The negative controls were B6B6 chimeras transduced with antigen-negative AAV2-gfp vector, and the positive control was B6B6 mice given AAV2-ova. All mice received an intravenous adoptive transfer of CFSE-labeled OT-1 T cells. Flow cytometric measures of the T cell response are shown in Fig. 6A. In the negative controls, there was no dilution of CFSE, no down-regulation of CD62L, and no up-regulation of CD44.

We thank the members of our research groups and colleagues with the Colorectal Cancer Program. “
“Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in “normal” liver tissue, but these studies were compromised by small

sample size, limited age range, tissue derived from individuals with an increased risk of selleck products senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes. Following validation against the gold standard (Southern blotting), the technique was applied to normal archived paraffin-embedded liver tissue obtained following reperfusion of implanted donor liver. We studied 73 highly selected donors

Selleckchem GSK458 aged 5-79 years with a short medical illness preceding death and no history of liver disease, reperfusion injury, or steatosis and normal graft function 1-year posttransplantation. Cholangiocytes had significantly longer telomeres compared with all other intrahepatic lineages over a wide age range (P < 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e., Kupffer cells [P = 0.0054] and stellate cells [P = 0.0001]). Cholangiocytes and hepatocytes showed no age-related telomere shortening. Conclusion: In normal liver and over a broad age range, cholangiocytes have longer telomeres than all other intrahepatic lineages. Age-related telomere length decline is restricted to Kupffer cells and stellate cells. (HEPATOLOGY 2012) As the median MCE公司 age of populations increases worldwide, so too does that of patients presenting with liver disease. There are many structural and functional changes in all organs with increasing

age, including the liver.1, 2 Strong evidence links increased age with impaired liver regeneration and increased risk of fibrosis, hepatocellular carcinoma and death. Age is an important adverse factor in chronic liver disorders including chronic hepatitis C virus infection,3, 4 non–alcohol-related fatty liver disease,5 primary biliary cirrhosis, alcohol-related hepatitis and hemochromatosis.1 Donor age has an enormous impact on graft survival following liver transplantation.6 The risk of death with liver disease is substantially higher in older patients.7 Impaired liver regeneration with increasing age is demonstrated clinically in acute liver failure8 and acute hepatitis A virus infection9, 10 and rodent models of partial hepatectomy, where restoration of liver mass is slower in older animals.

Hence, separation of the pulmonary and systemic circulation is desirable. The Fontan operation allows systemic

venous return to the pulmonary arteries bypassing the right ventricle. The Fontan operation (Fig. 1) may be accomplished by either creating a direct cavopulmonary (sometimes in a staged manner) or atriopulmonary anastomosis. In the first stage (i.e., superior caval-pulmonary anastomosis or bidirectional Glenn procedure), the superior vena cava is connected to the pulmonary arteries. Eventually, the inferior vena cava is also connected to the pulmonary arteries completing the circulation (Fontan completion). In earlier iterations of the Fontan, an atriopulmonary anastomosis was created with the hope that a hypertrophied right atrium would serve as a functional pump. However, it was associated

with a risk PD98059 of atrial dysrhythmias and atrial thrombi.10 More commonly, a cavopulmonary anastomosis is achieved by the use of an intra-atrial tunnel or patch or by utilizing an extracardiac conduit to connect the vena cavae to the pulmonary arteries (Fig. 1). As a consequence of surgical palliation, significant liver disease can develop as a result of the interplay of central venous hypertension/passive congestion and hypoxia resulting from left ventricular http://www.selleckchem.com/products/ABT-263.html dysfunction. Development of significant hepatic injury after a Fontan procedure is multifactorial. The determinants of cardiac output are central venous pressure, pulmonary vascular resistance, and systemic ventricular MCE end-diastolic pressure. Over time, a “failure of Fontan physiology” is common. Failure of the Fontan circuit may result from elevated pulmonary vascular resistance, pulmonary thrombi, narrowing and scarring in the Fontan pathway or pulmonary arteries, and failure of the systemic ventricle, which results in elevated pressure in the pulmonary venous atrium. Chronic elevation of central venous pressure is common, and reduced cardiac output from the functioning single ventricle

is frequent, particularly as diastolic and systolic dysfunction ensues. The former results from the absence of a subpulmonic pump.11 There is impaired coupling between the ventricles and the arterial system with late ventricular dysfunction.12 Atrial arrhythmias may contribute to this decline with relative hypotension and desaturation. The development of pulmonary venovenous collaterals as pressure “pop-offs” are not uncommon in the adult population and further contribute to hypoxemia. Pulmonary arteriovenous malformations, most often observed after a classic Glenn procedure, also contribute to hypoxemia. Chronic hypoxia resulting from a depressed cardiac output, in addition to the aforementioned changes, may also lead to hepatic injury.