Sa1603 Endoscopic Cyanoacrylate Glue Injection in Management of Gastric Variceal Hemorrhage; US Tertiary Care Center Experience

Sa1603 Endoscopic Cyanoacrylate Glue Injection in Management of Gastric Variceal Hemorrhage; US Tertiary Care Center Experience

a high risk for the development of diabetes. We aim to determine the frequency of NODAT in liver Mexican transplant patients. Materials and Methods. T...

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a high risk for the development of diabetes. We aim to determine the frequency of NODAT in liver Mexican transplant patients. Materials and Methods. This is a retrospective study that included all liver transplant patients from January 2010 to June 2015. Patients who had a diagnosis of type 2 diabetes mellitus before the surgery were excluded. Demographic, clinical and laboratory data were collected. The diagnosis was made if an HbA1c >6.5% after the third month of Liver transplantation (LT) was reported. The highest glucose during the first month after the surgical procedure, the utilization of insulin infusion in the immediate pos-surgical period and the use of hypoglucemic medication were analyzed. Data was analyzed by descriptive statistic and a p <0.05 with statistical significance. Results. One hundred and forty one patients were evaluated and 105 (74%) patients were included. Mean age of patients were 48 ± 13.2 years, with 55.2% males. The main cause for LT was Hepatitis C virus (HCV) with 31.4%. Up to 40% of patients had vitamin D insufficiency and 21.9% had deficiency, with a level of 9 ± 8.8. In our cohort, 93% (n=98) of the patients had hypomagnesemia during follow up, with a value of 1.5 (IQR 0.3 - 2.2). The first month after LT, 51.4% of patients had a serum magnesion level < 1.8 mg/dL. At that moment 51.4% (n=55), did not use Protein Pump Inhibitor (PPI), and 51.4% (n=54) did not have magnesium supplementation. Median glucose pre LT was 90 ± 16.4, of these, 5 patients had a fasting glucose level >126mg/dL,but with normal HBA1c before LT. In the first month after LT a glucose level of 234 ± 91.09 mg/dL was seen and 50.5% of patients did not receive an insulin infusion. For the final analysis, results from 75 patients were available. Of these, 17 (22.6%) had an HbA1c diagnostic for NODAT. From the 77.3% (n=58) who did not meet the criteria, 32.7% (n = 19) had HbA1c between 5.5 and 6.5%. In the NODAT patients 47% (n = 8) were using antidiabetic medications and 53% (n=9) required insulin. Most of the patients 99%, used tacrolimus. When risk factors for NODAT development were analysed, age >40 years-old and male gender were significant (15.2%, p=0.008 and 64,7%, p=0.05) respectively. Conclusion. The prevalence of NODAT in our cohort of Mexican patients is 22.3%, higher than previous reports, especially in males older than 40 years-old. Clinicians must be aware of this complication of LT, so an appropriate diagnosis and an early management can be implemented for improvement of graft survival.

Acute Kidney Injury Is Common in Cirrhosis With Worse Survival and Increased Use of Hospital Resources Sivani B. Reddy, Syed J. Shah, Yousaf B. Hadi, Steven Young, Ashwani K. Singal Introduction: Acute Kidney Injury (AKI) is common in patients with cirrhosis. We performed this meta-analysis to determine the prevalence of AKI and its impact on mortality and hospital resource utilization. Methods: We searched PUBMED and EMBASE through August 2015 to select prospective and retrospective studies describing prevalence of AKI defined based on acute kidney injury network criteria. MeSH words "acute kidney injury" and "cirrhosis" were used for search. Pooled data were reported as odds ratios (OR) with 95% confidence intervals (95% CI), using the random effects model of the comprehensive metaanalysis software. I2 index and Eger's regression tests were used to determine heterogeneity and publication bias respectively. P value <0.05 was considered significant. Results: A total of 19 studies were selected for analysis. Among 17 studies on 12,177 patients, AKI was present in 2,287 patients with pooled prevalence of 27.8% (95% CI: 19.5-37.9%). Prevalence was higher in ICU patients (2 studies) compared to patients on the floor (15 studies): 54.3% (45.2-63.1%) vs. 24.8% (17.6-33.7%). In hospital mortality was higher in the presence of AKI: 62% (447/726) vs. 26% (324/1256), with over 6 fold higher risk of dying in the presence of AKI (Figure), P<0.0001. Data were heterogeneous (I2=75, P<0.0001) without any publication bias (Egger's P=0.31). Variations in sample size, study design, and inclusion / exclusion criteria probably explain the heterogeneity. Need for intensive care and cardiovascular support was also higher in the presence of AKI: 217 out of 350 (62%) vs. 110 out of 299 (37%); with about 4 fold higher need in AKI patients, 3.9 (2.4-6.2, P<0.0001). These data were homogeneous and publication bias could not be assessed with only 2 studies in this analysis. Conclusion: AKI occurs in about 28% of patients with cirrhosis and twice more common in ICU patients as compared to patients on the floor. AKI is associated with higher in-hospital mortality and need for hospital resources. Prospective studies are needed as basis for developing strategies to reduce the incidence of AKI among patients with cirrhosis and improve their outcomes.

Sa1602 Prospective Validation of the AST-to-Platelet Ratio Index (APRI) Score As a Predictor of Variceal Etiology of Acute Upper Gastrointestinal Bleeding Jesse Civan, Christopher Henry, Colin Smith, Steven Krawitz, Haroon Shahid, Tripti Chopade, Steven Herrine Background: Variceal hemorrhage is associated with significant mortality, which can be mitigated by adherence to published management guidelines, including use of vasoactive medical therapy and antibiotic prophylaxis against spontaneous bacterial peritonitis. Physical exam findings of otherwise compensated cirrhosis are unreliable, so an objective measure of risk for variceal etiology could reduce mortality in patients with acute upper GI bleed (UGIB), by guiding early management pending endoscopy. We previously demonstrated in a retrospective study that the AST-to-Platelet Ratio Index (APRI) score with a cutoff value of 0.4 can identify UGIB patients at high risk for variceal etiology. We aimed in this study to prospectively validate the APRI score as an objective screening tool to identify those patients with acute UGIB at highest risk for variceal etiology. Methods: This was a singlecenter, IRB-approved, prospective study. Over a 52 week period, we identified all patients undergoing inpatient upper endoscopy, who had been admitted through the emergency department with acute overt UGIB. Prospectively, we queried the GI consultant whether a variceal etiology of UGIB was suspected prior to EGD. We also prospectively queried the endoscopist whether a variceal UGIB was confirmed on EGD. APRI scores were calculated as previously described in the literature, using first available lab parameters from the emergency department. An APRI value of >0.4 was defined as predicting variceal etiology of UGIB. Results: 51 patients met criteria for inclusion, 11 (21%) of which had variceal hemorrhage. The APRI score with cutoff value 0.4 had sensitivity 100%, specificity 68%, PPV 46%, and NPV 100% in predicting a variceal etiology of UGIB. In contrast, the GI consultant's preendoscopy impression had sensitivity 82%, specificity 95%, PPV 82%, and NPV 95%. In two cases, the APRI score correctly predicted a variceal bleed while the GI consultant incorrectly predicted a non-variceal etiology of bleeding. Conclusion: Although less specific than expert opinion of a consulting gastroenterologist, the APRI score had a higher sensitivity for early prediction of variceal etiology of acute UGIB. If a decision rule to medically manage patients with acute UGIB as presumed variceal bleed for APRI >0.4 was implemented, then the number needed to treat would be 2.2. Further study is needed to determine if overall patient outcomes could be improved by such a strategy, given the high mortality associated with variceal hemorrhage, and the low risk of a short course of vasoactive therapy & antibiotics.

Forrest plot on the impact of AKI on in-hospital mortality in patients with cirrhosis.

Sa1600 Treatment of Uncontrollable Acute Variceal Bleeding With Self-Expanding Metal Stent: A Single Center Experience Pavel Drastich, Jan Brezina, Jan Sperl, Sona Frankova, Marek Benes, Julius Spicak Background: Acute variceal bleeding is a severe complication of portal hypertension associated with high risk of mortality reaching up to 20% in six week. Despite intensive vasoactive and endoscopic therapy 10-20% of patients are not adequately controlled. The Baveno V consensus conference recommended "early" TIPS in patients at high risk of treatment failure. The use of self-expanding metal stents (SEMS) represents an alternative therapeutical approach especially if TIPS is not available. Aims: A retrospective analysis of patients who underwent the therapy with SEMS to arrest uncontrollable acute variceal bleeding in a single center. Patients and Methods: A total of 14 patients (7 men, 7 women, mean age 52.9 years, range 27-80) who underwent esophageal stent implantation in IKEM (Czech Republic) between June 2011 and November 2014 were included into the retrospective analysis. All patients failed to previous intensive endoscopic and vasoactive therapy. Esophageal varices were the source of bleeding in 11 patients and deep bleeding ulcers after banding ligation (EVL) in three subjects. In all patients a removable covered self-expanding metal stent (SXELLA stent Danis, ELLA-CS, Hradec Kralove, Czech Republic) was used. Results: Immediate bleeding control was achieved in 11/14 patients (78.2%), while in all 3 patients with post EVL ulcers the bleeding was ceased. The stent was successfully places in all except two patients, in one patient due to technical failure and in second one due to stent migration. Ten-day, 30 day and 6 month mortality was 14.3%, 21.4% and 50% respectively. Stent dislocation occurred in 2 out of 13 patients (15.4%). SEMS was successfully extracted without immediate complications in 10 patients after median of 9.5 days (range 7-26). In 2 patients SEMS was not extracted until death (1 and 11 days after stent placement). Conclusions: The implantation of SEMS in patients with uncontrolled bleeding from esophageal varices is effective and safe. Bleeding was controlled in all patients with post EVL ulcers. Mortality is still very high and SEMS should serve as a bridging intervention to definitive therapy including liver transplantation.

Sa1603 Endoscopic Cyanoacrylate Glue Injection in Management of Gastric Variceal Hemorrhage; US Tertiary Care Center Experience Subhash Chandra, Adrian Holm, Rami El Abiad, Henning Gerke Background and Objectives: Gastric variceal hemorrhage has a high mortality. Endoscopic cyanoacrylate glue injection (ECGI) is successfully used in other countries; however there is limited experience with this method in the US because it is not currently approved by the Food and Drug Administration. Here we report our 10-year experience of ECGI treatment for gastric variceal hemorrhage. Patients and Methods: We performed a retrospective chart review of patients undergoing ECGI for gastric variceal hemorrhage at a US tertiary care center between 6/2005 and 5/2015. Assessed outcomes were primary hemostasis, early rebleeding during hospitalization, recurrent bleeding during follow-up, eradication of gastric varices and complications. Results: Fifty-eight patients were treated for gastric variceal bleeding over a period of 10 years. ECGI was the primary treatment in all but one patient who underwent ECGI for bleeding despite patent TIPS. Patient demographics and procedural details are described in table 1. Primary hemostasis was achieved in all the patients with ECGI (figure 1). One (n = 7) or more (n=8) additional ECGI sessions were performed in 15 patients. Early rebleeding from gastric varices during hospitalization occurred in 3 patients (5%), bleeding stopped spontaneously in one patient with mild oozing from injection site.

Sa1601 In Search for New-Onset Diabetes After Liver Transplantation in Mexican Patients Ariadna I. Ramírez Polo, Liz N. Toapanta-Yanchapaxi, Alberto Palacios Ávila, Alan G. Contreras, Mario Vilatobá, Ignacio Garcia, Sergio Gabriel Muñoz Martínez Background and aims. The prevalence of type 2 diabetes mellitus worldwide has estimated in 9.8% in men and 9.2% in women (2008). In epidemiological studies in Mexico a prevalence of 14.4% (2006) was reported. For liver transplant patients a prevalence of 9 - 21% has been established. Alimentation type, obesity and genetics confer to the Mexican population

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Permanent hemostasis could not be achieved in two patients. Retrograde balloon obliteration in one patient and repeat ECGI and failed TIPS attempt in another one, and these patients died. Immediate complications of ECGI included ischemic stroke in 3 patients without residual deficit on follow up, asymptomatic portal vein cyanoacrylate emboli in one patient (2%) and asymptomatic pulmonary emboli in 3 patients. Follow-up beyond initial hospitalization was available in 41 patients (median 12 months; IQR 3-53 months). Gastric varices were eradicated in 32 patients (78%). Recurrent bleeding occurred in 10 patients (20%). Bleeding was attributed to gastric varices in 7, glue ulcer in 1 and esophageal varices in 2. The 7 patients with recurrent gastric varices hemorrhage were treated with repeat ECGI in 4, ECGI and TIPS in 1, TIPS alone in 1 and splenic artery embolization followed by splenectomy in one patient. One patient died of a combination of hemorrhagic shock and sepsis despite achieving hemostasis with repeat ECGI. Conclusion: Endoscopic cyanoacrylate glue injection is effective in achieving hemostasis of bleeding gastric varices and their eradication. Serious adverse events, albeit infrequent, are most often related to glue emboli. Future studies are warranted to determine if the risk of embolization can be reduced through technical modifications such as coil insertion. Table 1: Demographics of patients underwent endoscopic cyanoacrylate glue injection for gastric variceal hemorrhage and procedural details.

Sa1605 Outcomes Related to Intravenous Fluid Selection for Patients Admitted With Hyponatremia and Decompensated Cirrhosis Nicole T. Shen, Anika K. Anam, Parimal Patel, Yecheskel Schneider, Arun Jesudian Background: Currently, there is no standard of care regarding intravenous fluid selection for patients admitted with decompensated cirrhosis and hyponatremia (Na £130 mEq/L). Given the total body volume overload and intravascular depletion in decompensated cirrhosis, albumin infusion and subsequent increased plasma oncotic pressure might be more effective at correcting hyponatremia than crystalloid solutions. Methods: We conducted a single center retrospective chart review of patients hospitalized between 1/2011 and 12/2014 with admission serum sodium £130 and ICD-9 diagnosis codes for cirrhosis, portal hypertension, ascites, or hepatic encephalopathy. Patient characteristics, the quantity and type of fluid administered, changes in serum sodium, weight, and 6-month mortality were recorded. Results: Of 785 hospitalizations that met inclusion criteria, 639 were excluded: 151 readmissions, 455 lacked evidence of cirrhosis, 25 were fluid restricted, and 8 were on dialysis. Of the 146 subjects included, the crystalloid cohort (91 subjects) received only crystalloid or crystalloid and <500 cc of albumin, and the albumin cohort (55 subjects) received only albumin or crystalloid and >500 cc of albumin. Baseline admission characteristics were remarkable for history of refractory ascites in >50% of the albumin cohort vs. <30% of the crystalloid cohort (p<0.001) and diuretic use, present in >75% of the albumin cohort vs. 56% of the crystalloid cohort (p=0.03). Patient characteristics were otherwise similar between the cohorts. While mean admission Na was not significantly different (126-127, p=0.72), there was significant difference for mean creatinine range, 1.3-2.31 in the crystalloid cohort, compared to 1.55-1.81 in the albumin cohort (p=0.006), and mean MELD, 17-24 in the crystalloid cohort, compared to 22-27 in the albumin cohort (p<0.001). Serum sodium and creatinine, weight, and days hospitalized were not significantly different between groups with p values of 0.14, 0.32, 0.55, and 0.18, respectively. There was a trend toward significance for change in MELD (p=0.09) and six-month mortality (p=0.05) favoring the crystalloid cohort, but this was thought to be due to the higher baseline MELD and associated complications, such as spontaneous bacterial peritonitis and variceal bleeding, in the albumin cohort that dictate albumin therapy as standard of care. (p=0.02 and p=0.003, respectively). Conclusion: Though we did not find that fluid selection had a significant effect on serum sodium correction, we observed significant trends toward changes in MELD score and mortality favoring the crystalloid cohort. Further sensitivity analyses and prospective studies need to be done to see if this is truly associated with fluid selection or a reflection of the higher baseline MELD with mortality associated complications making up the albumin cohort.

Sa1606 Effect of Liver Progenitor Cells on Hepatic Stellate Cells Iris Chen, Varinder S. Athwal, Ana Blas-Garcia, Youngmin A. Lee, Scott L. Friedman Sa1604 Background: Chronic and severe acute liver injury is associated with an expansion of hepatobiliary cells known as ductular reaction (DR). Although functionally not well understood, DR has been postulated as a reservoir of liver progenitor cells (LPCs). Intriguingly, the extent of DR is positively correlated with the severity of hepatic fibrosis, which results from extracellular matrix (ECM) deposition by activated hepatic stellate cells (HSCs), the main fibrogenic cell within the liver. During liver injury, LPCs and HSCs localize adjacent to each other within regions of fibrogenesis. The functional significance of this interaction remains elusive. Understanding the behavior of DR/LPCs during liver fibrosis and regeneration, and in particular their interaction with HSCs, is important to uncovering the pathobiology of liver injury and repair. Hypothesis: LPCs stimulate HSC activation and fibrogenesis leading to increased collagen production. Study design/methods: HSCs were cultured with and without LPCs on a semi-porous insert membrane (porosity 3.0µm). After 48 hours, cells were harvested at >60% confluence. Cell lines used included TWNT4 (immortalized human HSC cell line) and PIL2 (immortalized murine LPC cell line). Primary murine stellate cells (mHSCs) and primary murine liver progenitor cells (mLPCs) were isolated from wildtype and Atg7 KO mice using standard methods for HSC isolation and magnetic bead cell separation protocol for LPCs with an EpCAM antibody. HSCs, in dual-culture experiments with and without LPCs, were analyzed by quantitative polymerase chain reaction for fibrogenic mRNA expression and by immunoblotting for protein expression. Results: TWNT4 cells expressed less COL1 mRNA (p=0.009) and more TIMP1 (p=0.01) mRNA (normalized to GAPDH) when in dual-culture with PIL2 cells compared to controls. Primary mHSCs expressed less Col1 (p=0.0009) and Asma (p=0.04) mRNA (normalized to Gapdh) when in dual-culture with mLPCs compared to controls. By immunoblotting, TWNT4 cells expressed less COL1 (p=0.001) and more TIMP1 (p=0.02) protein (normalized to GAPDH and TUB, respectively) when in dual-culture with PIL2 cells compared to controls. Conclusions / Significance: These data demonstrate potential paracrine cross-talk of LPCs with HSCs, resulting in alteration of key fibrogenic factors. The findings, if replicated in vivo, could begin to clarify cellular interaction between these two cell types and shed light on the role of DR in liver regeneration and fibrosis.

Muscle Cramps in Patients With Liver Cirrhosis: Systematic Evaluation of 1224 Cases With Meta-Analysis Nirmal S. Mann, Anthony Albanese, Virmeet Singh Background:Muscle cramps(MC) associated with liver Cirrhosis(LC) represent a significant complication of LC and are known to adversely affect quality of life(QOL).We evaluated the world literature of MC in LC and performed Qualitative Meta-Analysis(QMA) on these cases.Methods:A PubMed search without time or language barrier using the terms muscle cramps and liver cirrhosis was performed. Additional papers were manually added from the reference lists of key articles.QMA was performed using the well-established methods of Qualitative Research viz Diagramming,Theme Repetition Without Serious Contradiction,Theme Saturation and Investigator Reflexivity(Eval Rev 1985:9:627-643,Lancet 2001;358:483-488).Quantitative data can be used to perform QMA.To facilitate QMA,Summary Sheets of all the papers were created.Papers dealing with pediatric cases and animal research were excluded from evaluation.The clinical definition of MC is an involuntary,visible or palpable asymmetric painful contraction that is abrupt,often nocturnal and usually occurs at rest.Results:The search yielded 1224 cases of MC in LC patients.The information about gender was available in 1152/1224(94.2 %).There were 688/1152(59.7 %) Men and 464/ 1152(40.3 %) Women. Information about age was available in 1162/1224(95 %) The mean age was 60 (Range 17--91 ) years.The mean incidence of MC in LC was 58 % (Range 31-88 %).The mechanism of MC in LC is not completely established. Abnormality of energy metabolism mediated by decreased ATP concentration in muscles,decreased taurine concentration and altered branched chain/aminos acid(BCCA/AA) ratio may be responsible.Another possible mechanism is demyelinization of nerves,axonal loss, oxidative stress all leading to decreased threshold potential for spasm.The third possible mechanism is decrease in plasma volume resulting in decrease nerve perfusion and possible electrolyte loss. Zinc,Vit D and E deficiency and low albumin may also play a role.The MC are often nocturnal but may occur any time of the day. MC can occur in any muscle groups but are more frequent in the lower legs and feet.MC can be quite painful and significantly impair the QOL. Based on possible pathogenetic mechanisms mentioned the treatment of MC includes volume and electrolyte correction,Vit D E and Zinc and albumin administration. BCAA especiallyt taurine and also L-Carnitine have been effective In some cses; especially in leg cramps quinine, quinidine or Beclofen were found to be useful.Antispasmodic Esperisone hydrochloride were successfully used in some cases.Chinese herbal medications such as Nuiche-shen-quiwan,Arofuto and Sairei-to have shown beneficial effects.Conclusions:Painful MC occur in 58 % cases of LC.They can significantly affect QOL in LC patiernts.There is slight male predominence. Possible pathogenetic mechanisms and therapeutic interventions are discussed.

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Sa1607 Clinical, Biochemical and Histopathological Profile of Subjects With Glycogenic Hepatopathy and Comparison With Type 1 Diabetes Patients Saurabh S. Mukewar, Ayush Sharma, Felicity Enders, Kandace Lackore, Patrick Kamath, Lewis Roberts, Yogish C. Kudva Background and aims: Glycogenic hepatopathy is a syndrome of elevated transaminases and liver enlargement in type-1 diabetes (T1D) patients. Since its description, there have been mostly case reports discussing this condition. We conducted a retrospective study to describe the clinical, biochemical and histo-pathologic profile of these patients. In addition, we conducted a matched case-control study to determine whether T1D with glycogenic hepatopathy had more frequent diabetic ketoacidosis (DKA) episodes compared to those without. Methods: Electronic medical records at Mayo Clinic, Rochester from January 1, 1998 to January 1, 2014 were searched using the terms "Mauriac syndrome" and "Glycogenic

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