blot analysis of whole-liver homogenate and LCM-PCR of sinusoidal wall revealed overexpres-sions of apelin and APJ in Child's C-LC samples. Examination by IEM revealed immunogoldparticles, showing the presence of APJ, which had located particularly on hepatic stellatecells but which sparsely dispersed on sinusoidal endothelial cell (SEC)s in Child's C-LCtissue. Conclusions: Aberrant expression of Apelin in human cirrhotic liver indicates theproliferation of arterial capillaries directly connected to the sinusoids, increasing the sinus-oidal microvascular resistance. Enhanced expression of APJ on HSCs in cirrhosis inducessinusoidal microremodeling.

Mo1009

Modified Orientation-Log (MO-log) is an Objective Method to PredictOutcomes in Patients Admitted With Hepatic EncephalopathyMaher Salam, Imran S. Farooq, R. Todd Stravitz, Arun J. Sanyal, Douglas M. Heuman,Richard K. Sterling, Velimir A. Luketic, Michael Fuchs, Puneet Puri, Jasmohan S. Bajaj

Background and Aims: The subjectivity of the West-Haven criteria (WHC) is a majorchallenge in the evaluation of hepatic encephalopathy (HE). The orientation log is a validatedinstrument to assess mental status in traumatic brain injury (www.tbims.org/combi/olog/olog.pdf). This was modified to fit the situation in HE as Modified Orientation Log (MO-log) which has 8 simple questions and a score ranging from 0 through 24 (24 being normal).The aim was to validate the MO-log as a rapid quantitative measure of mental statusassessment for inpatients with HE. Methods: Patients admitted with HE between July 2009and November 2010 were administered the MO-log after house-staff had been trained onits administration. The following data was collected: demographics, cirrhosis severity, priorHE, HE therapy, precipitating factors, daily MO-logs, admission WHC grade (performed byanother examiner), sodium and ammonia at admission and discharge, time to reachmaximumMO-log score and length of stay (LOS). Outcomes analyzed were death and readmissionfor HE. The change in MO-log over the 1st 24 hours was evaluated as a predictor ofoutcomes. Results: Hospital course: 52 patients were included (age 54 yrs, 75% men, 42%HCV).69% of pts were admitted for their second HE episode (all on lactulose, 54% also onrifaximin). The median admission MELD was 20, mean ammonia 111±56 and sodium135±7mg/dl. Leading precipitating factors were non-adherence in 39%, infection in 21%and bleeding in 8%. The median admission WHC grade was 3 and mean MO-log score was11±8 (maximum possible is 24). The mean LOS was 8±5 days and 29% required ICU care.10% died during the admission. Discharge MO-log was ≥23 in 84% and the mean time toreach this level was 3.3±2.3 days. 40% required re-admission for HE a median of 3 weekspost-discharge. MO-log face validity: there was a significant negative correlation betweenadmission WHC grade and MO-log score (r=-0.4, p=0.012). MO-log predictive capability:within the 1st 24 hrs, MO-log improved in 71% of patients and improved by ≥5 pointsin 47% of patients. LOS was significantly shorter in patients with any improvement (6 vs11 days, p=0.037) or those with >5 point improvement (5 vs 9 days, p=0.016) in MO-login the 1st 24 hrs. Improvement within first 24 hrs also predicted in-hospital mortality; 80%of those who died did not improve within 24 hrs compared to only 27% who did not die(p=0.023). Discharge MO-log: MO-log on discharge was significantly lower in those whosubsequently returned for HE admission compared to those who remained HE-free (19 vs23, p=0.05).Conclusions: MO-log is an objective instrument to predict outcomes in patientsadmitted with HE.

Mo1010

Synergistic Roles of Hepatic Encephalopathy and Obstructive Sleep Apnea inDisturbance of Sleep Architecture in Patients With CirrhosisMatthew Kappus, Leonard C. Moses, Douglas M. Heuman, Jasmohan S. Bajaj

Background: Sleep disturbances in cirrhosis are often attributed to hepatic encephalopathy(HE). With the increasing prevalence of NASH, it is common to encounter cirrhotics withcomplications of obesity, including obstructive sleep apnea (OSA). Few previous studieshave attempted to distinguish between effects of OSA and HE on sleep architecture. Normalsleep has early (N1/N2), deep (N3/N4) and REM phases. N3/N4 stages determine therestfulness and have physically and mentally restorative functions. Aim: To evaluate theinteraction between OSA and HE on sleep architecture in cirrhosis. Methods: Cirrhoticswho underwent polysomnography between 2007 and 2010 were included. Records werereviewed for MELD score, HE (defined by use of lactulose/rifaximin), OSA, symptomsnecessitating the sleep study, details of the report including time spent in early stage (N1/N2), deep (N3/N4) and REM sleep and periodic limb movements (PLM) were recorded.HE patients were compared to non-HE patients. Results: 46 cirrhotics (58 yrs, 93% men,BMI 34±4, MELD 8, 50% HCV, 19% alcohol, Diabetes 43%, HTN 93%) were included. Allwere referred for the sleep study due to subjective sleeping difficulties (41% snored, 32%had daytime sleepiness). 89% had OSA and 21% had controlled HE (all HE pts also hadOSA). Sleep study results: Median sleep efficiency was 77% with 29 hypopneas, 5 apneas,67 arousals and 23 PLMs. The mean latency to sleep was 23 min; the mean % of sleep thatconsisted of N1(11%), N2 (57%), N3 (3%), N4(0.4%) and REM (11%); indicating a severedisruption. N3/N4 were absent in 67% of pts. HE, MELD score and sleep architecture:There was a significant correlation between MELD score and PLM (r=0.45,p=0.04) and with% in N1 sleep (r=0.33, p=0.037) but not with other sleep phases. Since the majority hadOSA, there was no significant difference in sleep efficiency (p=0.5), hypopneas(p=0.9),apneas (p=0.5) or arousal(p=0.7) in cirrhotics with or without HE. Compared to patientswith OSA alone, patients with HE+OSA spent a significantly higher % time in early (N1+N2)sleep (77% vs. 65%, p=0.007) but not in REM. 100% of pts with HE+OSA had no demon-strable N3/N4 sleep compared to only 29% of non-HE cirrhotics(p=0.021). Conclusions:In cirrhotics with OSA, the added presence of HE significantly shifts the sleep architecturetowards early, non-restorative sleep and impairs deep sleep.

S-953 AASLD Abstracts

Mo1011

Spontaneous Bacterial Peritonitis in Cirrhotic Patients Hospitalized in theTertiary Care HospitalArslan Kahloon, Rodjawan Supakul, Paul Y. Kwo, Raj Vuppalanchi, Marwan Ghabril,Rakesh Vinayek, Marco A. Lacerda, Hwan Y. Yoo, Naga P. Chalasani, SuthatLiangpunsakul

Background: Spontaneous bacterial peritonitis (SBP) is one of the most common complica-tions associated with cirrhosis and associated with high mortality. Empiric Intravenousantibiotics are recommended once the diagnosis of SBP is made on the basis of ascitic fluidcell count. Aim: To characterize the microorganisms seen on ascitic fluid culture, patternsof antibiotic use, and the outcome of hospitalized cirrhotic patients with culture-positiveSBP in a large tertiary care hospital. Methods: Retrospective chart review of all cirrhoticpatients who were hospitalized with a diagnosis SBP at Indiana University Hospital betweenJanuary 2005 and December 2009. Patient clinical, laboratory and microbiology data includ-ing organism identification and the use of antibiotics was collected and analyzed. Outcomesof interest were the trend towards gram positive organism and the choice of empiric antibioticused. Results: A total of 123 patients were hospitalized with the diagnosis of SBP. Of these,22(18%, age 55.4±7.7 yrs) had classical SBP, 97(79%, age 51.7 ± 10.6 yrs) had culturenegative neutrocytic ascites (CNNA) and remaining 4 (3%) had monobacter ascites orpolymicrobial ascites. 26 of 123 patients (21%) had positive ascitic fluid cultures on indexparacentesis. There were no differences in baseline admission laboratories, MELD scores,and the length of hospital stay between the groups. Only 13.6% of classical SBP patientshad a history of previous SBP and took prophylaxis with quinolones. Gram positive micro-organisms were found in 13 of 22 (61%) of classical SBP cases. Fifty percent of thesepatients(11/22) received a 3rd generation cephalosporin as the empiric antibiotic. Sixtypercent of patients started on empiric cephalosporins had clinical deterioration within 72hours requiring change to a broader spectrum antibiotic. Overall 64 %( 14/22) of classicalSBP patients required change of antibiotic after culture data became available. and thesepatients had a complication with renal failure or sepsis requiring higher level of care dueto ineffective empiric antibiotic use. In-hospital mortality in classical SBP and CNNA patientswas 9% and 22%, respectively (p < 0.05). Concomitant urinary tract infections were foundin 47% (in classical SBP group) and 33% (in CNNA group). Inpatient mortality was higherin those with gram positive microorganisms in the ascitic fluid (28.5% vs. 11.1%). Therewas no association between the use of SBP prophylaxis/rifaximin and the presence of grampositive ascitic fluid cultures. Conclusions: The majority of hospitalized cases with SBP wereCNNA. We found significantly higher prevalence of gram positive organisms in the asciticfluid cultures in those with classical SBP. This was associated with improper choice ofempiric antibiotic leading to higher complications and a trend towards higher mortality.

Mo1012

Hepatic Venous Outflow Tract Obstruction is Associated With Poor Outcomeof PregnancyAnupam Mahapatra, Akash Shukla, Anumeet Singh Grover, Shobna J. Bhatia

Introduction and Aim: There are limited data of effect of hepatic venous outflow tractobstruction (HVOTO) on fertility and none on fertility or pregnancy profile prior to onsetof symptoms. A retrospective study of pregnancy in sixteen women with HVOTO showedthat maternal and fetal outcome, beyond gestation week 20, are good [Rautou PE et al. JHepatol 2009;51:47-54]. We evaluated the fertility and outcome of pregnancy prior to onsetof symptoms and post intervention in women with HVOTO. Methods: Fifty-one consecutivemarried women (age 30.11 [5.6] years) with HVOTO, who were sexually active for at least2 years and not using any contraception, were prospectively included. Their detailed obstetrichistory was obtained. Results: Twenty-nine women had isolated hepatic vein (HV) throm-bosis, 6 had isolated inferior vena cava (IVC) obstruction and 11 had IVC + HV thrombosis.Portal vein was thrombosed in 4 patients. The median duration of symptoms was 3 months(range 0.5-48). Prothrombotic states were identified in 9 women (APLA-4, Factor V Leiden-1, PNH-1, FVL+APLA-1, FVL+MTHFR mutation-1, JAK2 [V617F] mutation-1). Six patientshad primary infertility. Forty-five women conceived 108 times - 29 patients had 52 livebirths, 19 had 28 first trimester abortions, 4 had 7 second trimester abortions and 6 hadseven still births; medical termination of pregnancy was done in 4 patients. None conceivedafter onset of symptoms. Presence of prothrombotic state was associated with increased riskof second trimester abortion (3/4 Vs 2/14, p=0.04, OR=18.0 [95% CI 1.2-271.5]), but notwith infertility, first trimester abortions or stillbirths. Women who had live births were olderat the time of diagnosis (33.1 [6.1] vs 28.2 [3.8] years; p=0.008, OR 5.5 [1.6-9.4]) andhad later onset of symptoms (32.4 [6.2] years vs 27.0 [3.9] years; p=0.023, OR 4.5 [1.2-17.1]), as compared to those who never had any live births. Treatment: Fourteen patientsunderwent a radiological procedure, and intervention was not feasible in 4 patients; 33 weretreated with anticoagulation alone. Post intervention 4 patients conceived 6 times, 1 had alive birth, 1 had a first trimester abortion, 2 had 3 second trimester abortions and medicaltermination of pregnancy was done in 1 patient. Pregnancy outcome and infertility did notcorrelate with duration of symptoms, anatomy of HV or IVC obstruction or intervention.Conclusion: Women with HVOTO have poor outcome of pregnancy even before the onsetof the symptoms.

Mo1013

Proinflammatory Cytokines Are Raised in Extrahepatic Portal VenousObstruction Patients With Minimal Hepatic EncephalopathyAnshu Srivastava, Santosh K. Yadav, Surender K. Yachha, Michael A. Thomas, Vivek A.Saraswat, Rakesh K. Gupta

Background and aims: Minimal hepatic encephalopathy and hyperammonemia is seen inextra-hepatic portal venous obstruction patients. Inflammation has been shown to play animportant role in pathogenesis of hepatic encephalopathy in cirrhotics. This study assessedthe serum proinflammatory cytokines and their correlation with hyperammonemia, 1Hmagnetic resonance spectroscopy (1H MRS) derived brain glutamine and diffusion tensor

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simaging derived metrics in extra-hepatic portal venous obstruction patients with and withoutminimal hepatic encephalopathy. Methods: Neuropsychological tests, diffusion tensorimaging, 1H magnetic resonance spectroscopy, estimation of blood ammonia and proinflam-matory cytokines (tumor necrosis factor alpha [TNF-α] and interleukin 6 [IL-6]) was donein 20 extra-hepatic portal venous obstruction patients and 8 healthy controls. Results:Proinflammatory cytokines (TNF-α and IL-6), blood ammonia, brain glutamine and meandiffusivity were increased in both patient groups as compared to controls. Patients withminimal hepatic encephalopathy (n-12) had significantly higher TNF-α, IL6, blood ammonia,brain glutamine and mean diffusivity signifying brain edema than controls. A significantpositive correlation was seen between TNF-α and IL-6 and between blood ammonia andTNF-α, IL-6 and brain glutamine. Significant positive correlations of TNF-α, IL-6 andblood ammonia with mean diffusivity values was seen in various brain regions includingspectroscopy voxel derived mean diffusivity. Conclusion: Extra-hepatic portal vein obstruc-tion patients have inflammation and hyperammonemia as evident by higher blood TNF-α,IL-6, ammonia and brain glutamine levels. Significant correlation between hyperammonemia,proinflammatory cytokines and cerebral edema on diffusion tensor imaging in various brainregions suggests that both these factors play a role in pathogenesis of minimal hepaticencephalopathy in these patients.

Mo1014

Reliability of Serum Creatinine in Assessing Renal Function is Reduced inPatients With Cirrhosis as Compared With Patients With Organic RenalDiseaseMatteo Garcovich, Emmanuel Tsochatzis, Dimosthenis Georgiadis, Giacomo Germani,Giuseppe Fede, Andrew K. Burroughs, Antonio Gasbarrini

Background/aims: Although serum creatinine is a well-recognized marker of prognosis incirrhosis, it is an inaccurate marker of renal function being affected by various extra-renalfactors. The measurement of glomerular filtration rate (GFR) by the plasma clearance Cr-EDTA is an acceptable substitute of the gold standard of inulin clearance. We assessed thecorrelations of serum creatinine with GFR measured by Cr-EDTA in patients with cirrhosisin comparison with patients with renal disease. Methods: We analysed data from 303consecutive patients who underwent GFR assessment by Cr-EDTA as part of their livertransplant work-up. We collected similar data on 320 consecutive non-cirrhotic patientswho attended the renal outpatient clinic. GFR was assessed by bolus infusion of Cr-EDTAand single or serial serum measurements after 2, 4, 6 and 24 hours. Spearman test wasused to correlate serum creatinine and GFR in renal and liver patients. The differences incorrelation coefficients were then compared by using the Fischer's z score through theMedCalc statistical software. Results: Serum creatinine significantly and inversely correlatedwith GFR in patients with cirrhosis (r=-0.720, P<0.001) and renal disease (r=-0.866,P<0.001), however the difference of the correlation was significant between patients withrenal disease and patients with cirrhosis (z=-4.8, P<0.001). When analysis was performedaccording to gender, the difference of the correlation was again significant among male andfemale patients with renal disease and cirrhosis, and particularly in male compared to femalepatients with cirrhosis (P<0.043). Therefore, for a given GFR, patients with cirrhosis hadlower serum creatinine values than patients with renal disease (Figure 1). Moreover, femalepatients with cirrhosis had lower serum creatinine values than male patients with the sameGFR. Conclusions: Serum creatinine underestimates renal function in patients with cirrhosiscompared to patients with renal disease. Serum creatinine cut-offs used to define renalfailure in the general population are not applicable to patients with cirrhosis and should bere-evaluated as they systematically underestimate renal function.

Mo1015

Implementing a Treatment Protocol Reduces Inpatient Cost of HepaticEncephalopathyWissam Bleibel, Beth Quatrara, Irene Melo, Linda Romeo, Carl L. Berg, Stephen H.Caldwell, Curtis K. Argo, Patrick G. Northup, Neeral L. Shah, Abdullah M. Al-Osaimi

Background: Chronic liver disease and cirrhosis affect millions in of people worldwide.Overt hepatic encephalopathy (HE) affects 30 to 45% of patients with cirrhosis. Treatmentof HE is directed at two levels: targeting the precipitating factor and reducing ammonia andother toxin levels with various medical therapies including oral and per rectal Lactulose.Management of HE is associated with significant morbidity and mortality in addition tohigh costs to the hospitals, medical system, and society with the highest percentage of thesecosts being spent on inpatient treatment. Aims: studying the effect of implementing HEalgorithmic treatment protocol on morbidity, mortality and cost of inpatient treatment ofHE. Patients and methods: This is a single center retrospective and prospective cohort study.The study enrolled all patients with primary or secondary diagnosis of HE that was evidentupon admission to the hospital or developed later in hospital over a 17 month period. The

S-954AASLD Abstracts

doses, frequency, and route of administration of Lactulose and/or Rifaximin were decidedaccording to a treatment algorithm. The outcomes of this group of patients were comparedto patients admitted in the 17 months preceding the study period. Results: In the 17 monthsof preimplementation period a total of 115 patients with HE were identified. This resultedin a total of 602 hospital days. 61 days (10.1%) of which were spent in the ICU. The averagelength of hospital stay (ALOS) was 5.2 days (ranging form 1 to 34 days). Two patients(1.7%) from this group died. The average cost of medical care during this hospitalizationwas 9,409$ per patient with a cumulative cost of 1,082,054$. During the 17 months ofpostimplementation period a total of 78 patients were admitted with primary or secondarydiagnosis of HE, thereby resulting in 318 hospital days of which 7 days (2.2%) were spentin the ICU. The average length of hospital stay (ALOS) was 4.1 days (ranging form 1 to 17days). One patient (1.3%) from this group died. The average cost was 6,765$ per patientand the cumulative cost for this group was 527,694$. Conclusions: The average length ofstay and the percentage of days spent in intensive care setting were significantly reduced.This difference was statistically significant with p<0.05. In addition, this resulted in savingmore than 90 days of hospitalization which translates to more than 220,000$ saving. Thus,implementation of inpatient treatment protocol for HE resulted in significant reduction inmorbidity, mortality, and healthcare cost.

This table compares the outcome of patients on the Digestive Health Service during the pre-implementation and post-implementations periods. ALOS: Average length of stay. ICU:Intensive care unit. SD: Standard deviation.

LOS: Length of hospital stay. ICU: intensive care unit.

Mo1016

Transjugular Intrahepatic Portosystemic Shunt is an Effective TreatmentModality in the Management of Refractory Hepatic Hydrothorax in PatientsWith Liver CirrhosisJustin E. Mitchell, Ashish Aggarwal, Ibrahim A. Hanouneh, Ashish Atreja, Nizar N. Zein

Introduction: Hepatic hydrothorax is one of the common complications of liver cirrhosis,occurring in approximately 5-12% of cirrhotic patients. Transjugular Intraheptic Portosys-temic Shunt (TIPS) has been used in the management of refractory hepatic hydrothorax insmall series of patients with variable outcomes. Aim: To examine the effectiveness andoutcomes of TIPS in cirrhotic patients with refractory hepatic hydrothorax. Methods: Weidentified all consecutive cirrhotic patients who underwent TIPS procedure for hepatichydrothorax at our institution from January 1, 2008 until April 30, 2010. Clinical responseof hepatic hydrothorax to TIPS was determined by the frequency of thoracentesis andradiological resolution of pleural effusion after procedure. Logistic regression analysis wasperformed to identify the factors associated with response of hepatic hydrothorax post TIPS.Results: Twenty one patients were included in the study. Mean age 61.7 + 8.2 years. PreTIPS mean MELD score was 14.3 + 4.4 and mean Child Pugh Score (CPS) was 9.0 + 1.5.The mean pre and post TIPS portosystemic gradients were 15.1 + 4.8 and 5.2 + 2.5 mmHg respectively. There was a mean follow-up time of 131.5 + 64.1 days. After TIPS, 15/21(71.4%) of the patients had favorable clinical response as determined by a decrease in pleuraleffusion on follow up imaging and/or decrease in frequency of thoracentesis. Of these 15subjects, 4 patients had complete resolution of hepatic hydrothorax as shown by chestimaging and no subsequent thoracentesis after TIPS. Post TIPS portosystemic gradient was3.5 + 1.9 mm Hg among the patients who had complete resolution of hepatic hydrothoraxcompared to 5.3 + 2.5 mm Hg for those with partial response (p=0.12). (Fig 1). Conclusion:TIPS is an effective treatment modality in the management of refractory hepatic hydrothoraxin patients with liver cirrhosis. Post TIPS gradient of less than 5 mmHgmay predict completeresolution of hepatic hydrothorax after TIPS.