Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion

seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. “adaptive cytoprotection”). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective,

that is, a key element in the complex pathophysiologic response during MAPK Inhibitor Library mouse acute gastroprotection. Over the years, “gastroprotection” was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth find more factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence “gastric cytoprotection” research is still relevant. It’s not widely known that gastroprotective drugs (e.g. sofalcone, sucralfate) which prevent and/or accelerate healing of gastric ulcers, without inhibiting acid secretion, were first introduced in Japan, before or around Andre Robert’s historic article on “gastric cytoprotection” in 1979.[1, 2] Furthermore,

some poorly defined and locally acting “protective” drugs (e.g. carbenoxolone and bismuth salts) were empirically used in Europe and North America, but their mechanisms of action were not widely investigated.[3] Since medchemexpress Robert’s studies were solely focused on prostaglandins (PG), they became the center of gastrointestinal (GI) research for more than 30 years, preceding the popularity of Helicobacter pylori investigations. As endogenous products, PG were implicated in mediating the gastroprotective effect of other drugs such as sofalcone and sucralfate[4, 5] despite that the cyclooxygenase inhibitor indomethacin diminished but never abolished gastroprotection by other drugs. Another group of endogenous substances, that is, sulfhydryls (SH), investigated in parallel with PG, also seem to play a mechanistic role in gastroprotection, especially since SH alkylators like N-ethylmaleimide (NEM) counteract virtually any form of gastroprotection.

22 Adenosine acts via A2a receptor and the cAMP/PKA pathway and inhibits the intracellular calcium wave induced by HGF, which in turn inhibits Rac1

activation, actin polymerization, and cell migration. In addition to inhibiting MSC chemotaxis, adenosine also may provide a differentiation GDC0068 signal to MSCs that have stopped migrating in areas of high levels of adenosine. Adenosine receptor activation can induce the expression of several endodermal and hepatocyte-specific genes in mouse or human MSC, including EpCAM. GSC and Sox 17 are critical genes for the development of definitive endoderm and hepatocytes during embryogenesis.29 These genes are up-regulated in human MSCs by the effect of NECA. We also demonstrated that NECA induces the expression of a variety of genes in MSC. In murine MSCs, there was up-regulation of Foxa1, Foxa2, and GSC. In human MSCs, there was up-regulation of GSC, Sox 17, EpCAM, albumin, and TAT. The major pathways SCH727965 ic50 by which MSCs are thought to contribute to the hepatic response to injury are by stimulation of endogenous hepatocyte replication through paracrine action, secretion

of anti-inflammatory cytokines and chemokines, differentiation into hepatocytes, and differentiation into myofibroblasts, resulting in matrix remodeling. The up-regulation of genes important in mesodermal and endodermal patterning provides support for MSC differentiation but does not exclude paracrine effects of MSCs on hepatocytes. We have identified an important role for adenosine in the localization of MSCs to sites of tissue injury, and subsequent differentiation through activation of the A2a receptor. The development of adenosine receptor agonists and antagonists medchemexpress is an active area of drug development, allowing for therapeutic manipulation of our findings.35 The full differentiation of MSCs clearly requires multiple signals, and the manipulation of A2a receptor activation will form a part of this complex process. One application may be in

cases of cirrhosis without ongoing injury, for example, with alcoholic cirrhosis in which the patient has stopped drinking. By using liver-specific A2a antagonists, one may be able to enhance localization of MSC to the liver. Although adenosine was able to induce the expression of some important endodermal or hepatocyte-specific genes in MSCs, some other important genes (such as AFP) could not be induced by adenosine. We propose that adenosine helps to localize MSCs at sites of tissue injury and promotes differentiation of MSCs; however, hepatocytic differentiation in vivo is a complex process that likely requires other factors not yet identified. In conclusion, adenosine inhibits MSC chemotaxis, which may help localize MSCs and may provide differentiation signals for MSCs at sites of injury. “
“To compare the clinical outcome of patients undergoing liver resection under ischemic preconditioning (IP) versus intermittent clamping (IC).

22 Adenosine acts via A2a receptor and the cAMP/PKA pathway and inhibits the intracellular calcium wave induced by HGF, which in turn inhibits Rac1

activation, actin polymerization, and cell migration. In addition to inhibiting MSC chemotaxis, adenosine also may provide a differentiation PLX4032 signal to MSCs that have stopped migrating in areas of high levels of adenosine. Adenosine receptor activation can induce the expression of several endodermal and hepatocyte-specific genes in mouse or human MSC, including EpCAM. GSC and Sox 17 are critical genes for the development of definitive endoderm and hepatocytes during embryogenesis.29 These genes are up-regulated in human MSCs by the effect of NECA. We also demonstrated that NECA induces the expression of a variety of genes in MSC. In murine MSCs, there was up-regulation of Foxa1, Foxa2, and GSC. In human MSCs, there was up-regulation of GSC, Sox 17, EpCAM, albumin, and TAT. The major pathways Epigenetics inhibitor by which MSCs are thought to contribute to the hepatic response to injury are by stimulation of endogenous hepatocyte replication through paracrine action, secretion

of anti-inflammatory cytokines and chemokines, differentiation into hepatocytes, and differentiation into myofibroblasts, resulting in matrix remodeling. The up-regulation of genes important in mesodermal and endodermal patterning provides support for MSC differentiation but does not exclude paracrine effects of MSCs on hepatocytes. We have identified an important role for adenosine in the localization of MSCs to sites of tissue injury, and subsequent differentiation through activation of the A2a receptor. The development of adenosine receptor agonists and antagonists MCE is an active area of drug development, allowing for therapeutic manipulation of our findings.35 The full differentiation of MSCs clearly requires multiple signals, and the manipulation of A2a receptor activation will form a part of this complex process. One application may be in

cases of cirrhosis without ongoing injury, for example, with alcoholic cirrhosis in which the patient has stopped drinking. By using liver-specific A2a antagonists, one may be able to enhance localization of MSC to the liver. Although adenosine was able to induce the expression of some important endodermal or hepatocyte-specific genes in MSCs, some other important genes (such as AFP) could not be induced by adenosine. We propose that adenosine helps to localize MSCs at sites of tissue injury and promotes differentiation of MSCs; however, hepatocytic differentiation in vivo is a complex process that likely requires other factors not yet identified. In conclusion, adenosine inhibits MSC chemotaxis, which may help localize MSCs and may provide differentiation signals for MSCs at sites of injury. “
“To compare the clinical outcome of patients undergoing liver resection under ischemic preconditioning (IP) versus intermittent clamping (IC).

Accordingly, curative treatments, like orthotopic liver transplantation (OLT), resection, or radiofrequency ablation (RFA) are reserved for patients with early stage HCC (BCLC stage 0/A). Unfortunately, HCC is commonly diagnosed at intermediate (BCLC stage B) or advanced (BCLC stage C) tumor stages6, 7 where only palliative treatment options can be offered, resulting in a limited overall survival (OS) of 11-20 months. Transarterial chemoembolization (TACE) is the recommended treatment modality I-BET-762 concentration for asymptomatic, large, or multifocal HCC without macrovascular

invasion or extrahepatic metastasis (intermediate HCC, BCLC stage B). As most patients with HCC also suffer from liver cirrhosis, not only tumor characteristics but also the degree of liver dysfunction are of prognostic importance for patients undergoing TACE. Several studies showed8 that baseline tumor characteristics like tumor size or extent, alpha-fetoprotein (AFP) values, as well as baseline Child-Pugh score, presence of ascites, and several baseline lab values, e.g., AST9 are associated with OS of HCC patients. Furthermore, tumor-related

dynamics after TACE are important for patient prognosis, as radiologic and biochemical (AFP) tumor responses have been associated with improved patient outcome.10-12 Finally, deterioration this website of liver function after TACE may negatively impact the patient prognosis and liver function may further worsen after repeated TACE sessions or even MCE obviate any consequent antitumor treatment. The aim of this study was to establish a clinically usable point score to guide the decision for retreatment with TACE in patients with HCC. Using a stepwise multivariate regression model we developed a novel point score predicting patient outcome with respect to patient characteristics prior to the second TACE as well as the dynamic of tumor and liver-function related parameters after the first TACE session. All patients, >18 years old at the time of the first TACE cycle, diagnosed with HCC by histology or dynamic imaging (computed

tomography [CT] / magnetic resonance imaging [MRI] scans) according to the European Association for the Study of the Liver (EASL) diagnostic criteria4 who were treated with conventional TACE (cTACE), transarterial embolization (TAE), or TACE with drug-eluting beads (DEB-TACE) (hereafter summarized and referred to as TACE) at the Department of Gastroenterology and Hepatology of the Medical University of Vienna between January 1999 and December 2009 (n = 231) were screened for eligibility (Fig. 1). Patients with HCC at BCLC stage A or B and preserved liver function (Child-Pugh stage A or B) who received at least two TACE sessions within 3 months (≤90 days) were included and formed the training cohort for all further analysis.

021) was significantly associated with preS/S mutant infection. Of note, infection with the preS/S HBV mutants was positively correlated with cirrhosis (r = 0.386; P = 0.014), and this correlation persisted ACP-196 ic50 after adjustment for age, viral loads, HBeAg status, and presence of basal core promoter mutations. Sequencing of the basal core promoter (BCP)/precore (PC) region of the HBV isolates obtained from the 40 patients revealed the presence of the G1896A mutation (PC mutation) combined with the

A1762T and/or G1764A mutations (BCP mutations) in nine patients, the presence of BCP mutations alone in three patients, and of PC mutation alone in 18 patients. In 10 patients, the HBV DNA sequence was WT at both BCP and PC sites. Statistical analysis applied to all variants revealed that BCP/PC mutations—either in combination or alone—were not associated with preS/S mutations and, when present, BCP/PC mutations had no impact on HBsAg production and replication capacity of preS/S HBV mutants (data not shown). Three different HBV full-length genomes were cloned and functionally tested by three independent transient X-396 in vitro transfection experiments of HepG2 cells. pHBV-mtpreS1, which was isolated from patient 14 (HBV DNA, 2 × 107 IU/mL; HBsAg, 1.6 × 103 IU/mL) showed an in-frame deletion of 183 nucleotides in the preS1

region (a 61-aa deletion [Δ47-108 aa] within the L protein). pHBV-mtpreS2, which was isolated from patient 4 (HBV DNA, 5.7 × 107 IU/mL; HBsAg, 1.9 × 103 IU/mL) showed the deletion of the preS2 start codon. pHBV-mtS, which was isolated from patient 8 (HBV DNA, 2.4 × 108 IU/mL; HBsAg, 9 × 102 IU/mL) showed a G1035A mutation introducing a stop signal at codon 182 within the S gene (sW182*) (Fig. 1A). As a note, pHBV-mtpreS1 and pHBV-mtpreS2 cloned genomes carried

the nucleotide mutation G1896A, introducing a stop signal at codon 28 within the 上海皓元医药股份有限公司 precore region and preventing HBeAg synthesis. A plasmid-free HBV transfection cell–based replication assay relying on the generation of transcriptionally active nuclear cccDNA to replicate HBV was used.28, 29, 30 Because the three mtHBV genomes were genotype D, a standard WT HBV genome of the same genotype was used as a control. Two days after transfection, HBV DNA from intracellular replicative intermediates and extracellular viral particles were analyzed by way of Southern blotting. As shown in Figs. 3A and 3B, all three HBV genomes were replication-competent and were able to release viral particles into the cell culture medium. However, whereas the levels of intracellular replicative intermediates were comparable between cells transfected with mutated HBV genomes and cells replicating WT HBV, the HBV DNA level in the supernatant of cells transfected with mutant viruses was 30%-50% lower than in cells transfected with WT virus.

6C). The same specimens were subjected to an in situ apoptosis TUNEL assay. Fewer apoptotic nuclei were noted in the tumor specimens from mice injected with Huh7 and HepG2 cells transfected with pcDNA3-CypB/WT than in those from mice injected with Ivacaftor supplier Huh7 and HepG2 cells transfected with Mock after cisplatin treatment (Fig. 6D). Collectively, these data indicate that CypB has a crucial role in HCC cell survival and chemoresistance to cisplatin in vivo. To explore the clinical relevance of CypB, we evaluated its expression levels in human HCC and colon cancer tissues by using IHC analysis. Pathologically confirmed HCC, colon cancer, and corresponding noncancerous tissues were also obtained. HCC and colon

cancer tissues showed intense CypB staining, compared with the corresponding ABT-199 cost noncancerous normal tissues (Fig. 7A,B). We also confirmed CypB upregulation in 7 and 9 of 10 HCC and colon cancer samples, respectively, by western blotting analysis (Fig. 7C,D). Furthermore, in 61 (78%) of the 78 HCC samples and 112 (91%) of the 123 colon cancer samples, strong immunopositivity of CypB was clearly observed (Table 1). The specimens exhibiting ++ immunoreactivity were considered positive. Interestingly, the level of CypB expression was not associated with tumor grade or developmental stage. To investigate the association between CypB expression

level and 5-year survival, we evaluated HCC and colon cancer patients using the Kaplan-Meier method. We examined survival information of 40 cases of HCC among 78 cases and 123 cases of colon cancer. Unfortunately, we lost survival information for 38 HCC cases, because we got the specimen of HCC patients from multiple hospitals. The Kaplan-Meier survival curve, with a follow-up period of 60 months, demonstrated that patients with lower expression of CypB (CypB [−]) survive significantly longer than those with higher expression of CypB

(CypB [+]) in both cancer patients (Fig. 7E,F). Currently, the only available treatment for HCC is either surgical resection or liver transplantation. However, as many HCCs involve scattered tumors, they cannot be removed surgically. Therefore, most patients with HCC receive only palliative treatments, including transarterial chemoembolization (TACE), anticancer drugs, and antiangiogenic agents. medchemexpress However, TACE eventually results in hypoxia, leading to HIF-1α activation and thus chemoresistance and radioresistance in HCC. Furthermore, anticancer and antiangiogenic agents are ineffective in patients with HCC because of multidrug resistance, resulting from the induction of diverse factors such as multidrug resistance-associated protein, glutathione, and glutathione S-transferase as well as apoptosis-related genes, including bcl-2, c-myc, p53, and protein kinase C.27-29 Therefore, the development of a more effective treatment would clearly have a tremendous benefit.

6C). The same specimens were subjected to an in situ apoptosis TUNEL assay. Fewer apoptotic nuclei were noted in the tumor specimens from mice injected with Huh7 and HepG2 cells transfected with pcDNA3-CypB/WT than in those from mice injected with SB525334 Huh7 and HepG2 cells transfected with Mock after cisplatin treatment (Fig. 6D). Collectively, these data indicate that CypB has a crucial role in HCC cell survival and chemoresistance to cisplatin in vivo. To explore the clinical relevance of CypB, we evaluated its expression levels in human HCC and colon cancer tissues by using IHC analysis. Pathologically confirmed HCC, colon cancer, and corresponding noncancerous tissues were also obtained. HCC and colon

cancer tissues showed intense CypB staining, compared with the corresponding Dabrafenib noncancerous normal tissues (Fig. 7A,B). We also confirmed CypB upregulation in 7 and 9 of 10 HCC and colon cancer samples, respectively, by western blotting analysis (Fig. 7C,D). Furthermore, in 61 (78%) of the 78 HCC samples and 112 (91%) of the 123 colon cancer samples, strong immunopositivity of CypB was clearly observed (Table 1). The specimens exhibiting ++ immunoreactivity were considered positive. Interestingly, the level of CypB expression was not associated with tumor grade or developmental stage. To investigate the association between CypB expression

level and 5-year survival, we evaluated HCC and colon cancer patients using the Kaplan-Meier method. We examined survival information of 40 cases of HCC among 78 cases and 123 cases of colon cancer. Unfortunately, we lost survival information for 38 HCC cases, because we got the specimen of HCC patients from multiple hospitals. The Kaplan-Meier survival curve, with a follow-up period of 60 months, demonstrated that patients with lower expression of CypB (CypB [−]) survive significantly longer than those with higher expression of CypB

(CypB [+]) in both cancer patients (Fig. 7E,F). Currently, the only available treatment for HCC is either surgical resection or liver transplantation. However, as many HCCs involve scattered tumors, they cannot be removed surgically. Therefore, most patients with HCC receive only palliative treatments, including transarterial chemoembolization (TACE), anticancer drugs, and antiangiogenic agents. medchemexpress However, TACE eventually results in hypoxia, leading to HIF-1α activation and thus chemoresistance and radioresistance in HCC. Furthermore, anticancer and antiangiogenic agents are ineffective in patients with HCC because of multidrug resistance, resulting from the induction of diverse factors such as multidrug resistance-associated protein, glutathione, and glutathione S-transferase as well as apoptosis-related genes, including bcl-2, c-myc, p53, and protein kinase C.27-29 Therefore, the development of a more effective treatment would clearly have a tremendous benefit.

6C). The same specimens were subjected to an in situ apoptosis TUNEL assay. Fewer apoptotic nuclei were noted in the tumor specimens from mice injected with Huh7 and HepG2 cells transfected with pcDNA3-CypB/WT than in those from mice injected with Autophagy Compound Library cost Huh7 and HepG2 cells transfected with Mock after cisplatin treatment (Fig. 6D). Collectively, these data indicate that CypB has a crucial role in HCC cell survival and chemoresistance to cisplatin in vivo. To explore the clinical relevance of CypB, we evaluated its expression levels in human HCC and colon cancer tissues by using IHC analysis. Pathologically confirmed HCC, colon cancer, and corresponding noncancerous tissues were also obtained. HCC and colon

cancer tissues showed intense CypB staining, compared with the corresponding Sirolimus noncancerous normal tissues (Fig. 7A,B). We also confirmed CypB upregulation in 7 and 9 of 10 HCC and colon cancer samples, respectively, by western blotting analysis (Fig. 7C,D). Furthermore, in 61 (78%) of the 78 HCC samples and 112 (91%) of the 123 colon cancer samples, strong immunopositivity of CypB was clearly observed (Table 1). The specimens exhibiting ++ immunoreactivity were considered positive. Interestingly, the level of CypB expression was not associated with tumor grade or developmental stage. To investigate the association between CypB expression

level and 5-year survival, we evaluated HCC and colon cancer patients using the Kaplan-Meier method. We examined survival information of 40 cases of HCC among 78 cases and 123 cases of colon cancer. Unfortunately, we lost survival information for 38 HCC cases, because we got the specimen of HCC patients from multiple hospitals. The Kaplan-Meier survival curve, with a follow-up period of 60 months, demonstrated that patients with lower expression of CypB (CypB [−]) survive significantly longer than those with higher expression of CypB

(CypB [+]) in both cancer patients (Fig. 7E,F). Currently, the only available treatment for HCC is either surgical resection or liver transplantation. However, as many HCCs involve scattered tumors, they cannot be removed surgically. Therefore, most patients with HCC receive only palliative treatments, including transarterial chemoembolization (TACE), anticancer drugs, and antiangiogenic agents. medchemexpress However, TACE eventually results in hypoxia, leading to HIF-1α activation and thus chemoresistance and radioresistance in HCC. Furthermore, anticancer and antiangiogenic agents are ineffective in patients with HCC because of multidrug resistance, resulting from the induction of diverse factors such as multidrug resistance-associated protein, glutathione, and glutathione S-transferase as well as apoptosis-related genes, including bcl-2, c-myc, p53, and protein kinase C.27-29 Therefore, the development of a more effective treatment would clearly have a tremendous benefit.

000,

respectively) for patients with reduced serum zinc levels. Serum zinc levels remained an independent risk factor for development of hepatic encephalopathy (OR = .82 ; 95% CI: .73-.92; p = .001) and hepatorenal syndrome (OR = .79 ; 95% CI: .68-.91; p = .001) when subjected to multivariate analysis. Furthermore, actuarial survival free of liver transplantation was reduced for patients with low serum zinc levels (low zinc: 22.2 months; 95% CI: 17.4–27.0 vs. normal zinc: 30.1 months; 95% CI: 25.5–35.0; p = .003). FDA-approved Drug Library in vivo Patients with primary sclerosing cholangitis (PSC) are particularly affected by reduced zinc levels (low zinc: 12.5 months ± 2.4; 95% CI: 7.7–17.2 vs. normal zinc: 39.1 months ± 4.7; 95% CI: 29.8–48.5) resulting in impaired survival (p =.001) while this was not the case for patients with viral liver disease (p =.294), alcoholic liver diseaes (p =.545) or patients classified with other learn more hepatic disorder (p =.087). In PSC patients, serum zinc levels remained an independent predictor of survival when subjected to multivariate analysis (OR = .80; 95% CI: .64-.98; p = .038). Conclusions: We were able to identify serum zinc levels as a predictor

of reduced survival in ESLD patients, particularly in PSC patients. Whether zinc supplementation might be beneficial for patients on liver transplantation list needs to be further addressed. Disclosures: The following people have nothing to disclose: Kilian Friedrich, Christian Rupp, Andreas Wannhoff, Wolfgang Stremmel, Daniel Gotthardt

Background: Patients are prioritized for liver transplantation (LT) by their anticipated 90-day wait list mortality using the MELD score, but MCE the MELD underestimates wait list mortality when hyponatremia is present. A revised MELD that incorporates the added mortality due to hyponatremia, the MELD-Na, was shown to reduce wait list mortality in hyponatremic patients in a modeling study. In UNOS Region 6, regional agreement has resulted in prioritization of cirrhotic patients with hyponatremia for LT using a MELD-Na exception since 2008. Aims: (1) Determine if patients granted a MELD-Na exception in Region 6 have similar waitlist mortality compared to patients with similar MELD scores without hyponatremia. (2) Determine if patients granted a MELD-Na exception in Region 6 have similar post-transplant survival compared to patients with similar MELD scores without hyponatremia. Methods: In the UNOS registry, we selected all patients listed for LT in Region 6 from Jan 2008 to Mar 2014 who received a MELD-Na prioritization exception based on regional agreement. We compared their wait list mortality to a MELD-matched group listed for LT without hyponatremia using multiple Cox regression. We then compared post-LT mortality of MELD-Na prioritized patients who received LT with a MELD-matched group without hyponatremia who received LT using multiple Cox regression.

000,

respectively) for patients with reduced serum zinc levels. Serum zinc levels remained an independent risk factor for development of hepatic encephalopathy (OR = .82 ; 95% CI: .73-.92; p = .001) and hepatorenal syndrome (OR = .79 ; 95% CI: .68-.91; p = .001) when subjected to multivariate analysis. Furthermore, actuarial survival free of liver transplantation was reduced for patients with low serum zinc levels (low zinc: 22.2 months; 95% CI: 17.4–27.0 vs. normal zinc: 30.1 months; 95% CI: 25.5–35.0; p = .003). INK 128 price Patients with primary sclerosing cholangitis (PSC) are particularly affected by reduced zinc levels (low zinc: 12.5 months ± 2.4; 95% CI: 7.7–17.2 vs. normal zinc: 39.1 months ± 4.7; 95% CI: 29.8–48.5) resulting in impaired survival (p =.001) while this was not the case for patients with viral liver disease (p =.294), alcoholic liver diseaes (p =.545) or patients classified with other find more hepatic disorder (p =.087). In PSC patients, serum zinc levels remained an independent predictor of survival when subjected to multivariate analysis (OR = .80; 95% CI: .64-.98; p = .038). Conclusions: We were able to identify serum zinc levels as a predictor

of reduced survival in ESLD patients, particularly in PSC patients. Whether zinc supplementation might be beneficial for patients on liver transplantation list needs to be further addressed. Disclosures: The following people have nothing to disclose: Kilian Friedrich, Christian Rupp, Andreas Wannhoff, Wolfgang Stremmel, Daniel Gotthardt

Background: Patients are prioritized for liver transplantation (LT) by their anticipated 90-day wait list mortality using the MELD score, but MCE公司 the MELD underestimates wait list mortality when hyponatremia is present. A revised MELD that incorporates the added mortality due to hyponatremia, the MELD-Na, was shown to reduce wait list mortality in hyponatremic patients in a modeling study. In UNOS Region 6, regional agreement has resulted in prioritization of cirrhotic patients with hyponatremia for LT using a MELD-Na exception since 2008. Aims: (1) Determine if patients granted a MELD-Na exception in Region 6 have similar waitlist mortality compared to patients with similar MELD scores without hyponatremia. (2) Determine if patients granted a MELD-Na exception in Region 6 have similar post-transplant survival compared to patients with similar MELD scores without hyponatremia. Methods: In the UNOS registry, we selected all patients listed for LT in Region 6 from Jan 2008 to Mar 2014 who received a MELD-Na prioritization exception based on regional agreement. We compared their wait list mortality to a MELD-matched group listed for LT without hyponatremia using multiple Cox regression. We then compared post-LT mortality of MELD-Na prioritized patients who received LT with a MELD-matched group without hyponatremia who received LT using multiple Cox regression.