S1840 Refractory Spontaneous Bacterial Peritonitis: A Retrospective Study

according to MELD groups (20, respectively). Death rate in the high risk group was 50% for the MBT survival model compared with 41% for MELD. Conclusions: The 13C-MBT provides a rapid (15 min), non-invasive assessment of liver impairment in patients with chronic liver disease. 13C-MBT accurately predicts survival for a period of up to 2 years and may serve as a powerful tool for determining prognosis in this patient population.

review of patients with ascites admitted to the University of Chicago Medical Center between January 1, 2002 and July 31, 2007. Twenty-five demographics and clinical features were recorded, including peritoneal fluid characteristics, hepatic and renal function at time of diagnosis, time interval from initial paracentesis to receiving antibiotics and albumin, antibiotic choices, concomitant gastrointestinal bleeding, use of prophylactic antibiotics, HIV infection or immunocompromised status, severity of cirrhosis, and survival to the end of the hospitalization. SBP was defined by ascitic fluid PMN count >250 or a positive culture. Results: We identified 80 patients with SBP episodes. Of these, 20 patients did not show clearance of peritonitis within 48 hours and were labeled as refractory. Refractory SBP patients had a lower mean ascites albumin level 0.80 g/dL (95% CI 0.31, 1.29) and a higher SAAG 1.75 (1.28, 2.22) than non-refractory SBP patients 1.40 g/dL (1.11, 1.68), p = 0.04 and 1.08 (0.84, 1.32), p = 0.01. Refractory patients had a higher mean bilirubin 8.64 (4.48, 12.80) and a higher MELD score 25.11 (20.59, 29.63) than non-refractory patients 4.99 (3.37, 6.66), p = 0.03 and 20.29 (18.00, 22.58), p = 0.04. Additionally, refractory patients were more likely to have a positive fluid culture result than non-refractory patients [OR= 7.2, (2.3, 23.1), p < 0.001)]. Most importantly, in-hospital mortality in the refractory group was 40% compared to 18% in the non-refractory group [OR=3.0, (1.0, 9.2), p = 0.05]. Conclusions: Our institution's experience documents refractory cases of SBP in 25% of patients with increased odds of in-hospital mortality in the refractory group despite adherence to standard of care. To our knowledge, this study is the first to examine this cohort of patients and underscores the importance of further examination of this population in an effort to decrease the associated high mortality rate.

S1838 Usefulness of a Large Set of Tests for the Diagnosis of Hepatic Encephalopathy Andrzej Habior, Ewa Kraszewska, Agata Gos-Zajac, Marek Golebiowski, Joanna Szutkowska-Hoser, Krystyna Niedzielska, Maria Niewiadomska, Martyna PawluczykDyjecinska In patients with liver cirrhosis, minimal hepatic encephalopathy (MHE) is associated with a poor quality of life and difficulty in driving. It has also been suggested that MHE can precede the development of overt hepatic encephalopathy (OHE). No gold standard exists to detect MHE. Therefore the prevalence of this entity varies depending on the diagnostic methods used. Aims & Methods: To assess: a) the prevalence of MHE using standard (1) and nonstandard diagnostic methods, b) the usefulness of these tests for predicting of OHE, 51 patients with liver cirrhosis and portal hypertension (29 with primary biliary cirrhosis, 22 with HCV infection) were studied. In all patients we performed seven diagnostic tests: four psychometric tests (NTC-A, NTC-B, DST, BDT), EEG, spectral EEG, P300 auditory event related potential, critical flicker frequency (CFF), proton magnetic resonance spectroscopy of the brain (1HMRS) and serum concentration of astroglial protein S100β.Patients were followed up for a period of 4 years. Results: Based on the psychometric tests, 9 out of 51 patients (17.6%, 95% CI 7-28) were diagnosed to have MHE. If the results of EEG, P300 and spectral EEG were added, the prevalence of MHE raised to 16 of 51 patients (31.3%, 95% CI 18-44). Addition one nonstandard test (CFF, 1HMRS or S100β) raised the percentage of patients suspected of MHE to above 40%. During follow up OHE developed in 14 patients but MHE in this group was earlier diagnosed using psychometric tests in only 10 patients. Twelve of 14 patients with OHE had at least one abnormal result out of the seven tests. Multiple proportional hazard regression model showed a higher risk of OHE in patients with abnormal EEG (HR - 8.4, 95% CI 2.6 -27.3, p < 0.001). Other factors, including psychometric and standard and nonstandard tests, did not predict the OHE. Conclusions: 1. Diagnosis of minimal hepatic encephalopathy needs further standardization. 2. Among the seven different diagnostic methods, only EEG has a predicting value for overt hepatic encephalopathy in cirrhotic patients. Reference: 1.Ferenci P.et al: Hepatology.2002;35:716 Supported by grant MNiSzW 3PO5B03926

The Role of Small Intestinal Bacterial Overgrowth in Hepatic Encephalopathy (HE) Ilan S. Weisberg, Arun B. Jesudian, Katherine C. Barboza, Brian P. Bosworth, Thomas C. Liu, Samuel Sigal Background: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis characterized by reversible neurocognitive impairment. Bacterially derived toxins such as ammonia are produced in the gastrointestinal tract and are believed to play a central pathogenic role. Autonomic dysfunction is also common in cirrhosis and could contribute to the development of HE by impairing intestinal motility resulting in colonic inertia and small intestinal bacterial overgrowth (SIBO). Lactulose remains the mainstay of HE treatment, however nonabsorbable antibiotics, which decrease the bacterial burden, are also employed. This study aims to identify the prevalence of SIBO in cirrhotic patients and describe its association with HE severity. Methods: 34 consecutive patients with HCV cirrhosis were prospectively evaluated with neuropsychometeric testing to determine presence of HE. Lactulose breath testing (LBT) was performed by administering 10g of lactulose and collecting breath samples over a 180min period. Breath hydrogen (H2) and methane (CH4) were measured. LBT was considered positive for SIBO if: (a) fasting breath H2 of > 20 ppm, (b) increase in breath H2 in < 90 min, (c) dual H2 peaks (12 ppm increase over baseline with decrease of ≥ 5 ppm before second peak), or (d) fasting breath CH4 of > 1 ppm. Results: 29 (85%) patients had abnormal neuropsychometric testing and/or symptoms indicating HE, including 18 (53%) with mild and 10 (29%) with severe HE. 71% of 34 patients had abnormal LBT indicating SIBO. 50% (3/6) of patients without HE, 61% (11/18) of patients with mild HE, and 100% (10/10) patients with severe HE had abnormal LBT. SIBO was significantly associated with increasing prevalence and severity of HE (p = 0.046). Conclusions: SIBO is highly prevalent in HCV cirrhosis and is associated with the presence and increased severity of HE. These data further support the role of nonabsorbable antibiotics in the treatment of HE.

S1839 Pharmacokinetic (PK) and Safety Analyses of a Novel Ammonia-Reducing Agent in Healthy Adults and Patients with Cirrhosis Brendan M. McGuire, Sharron E. Gargosky, Bruce F. Scharschmidt, Vasyl Syplyviy, Igor A. Zupanets BACKGROUND: HPN-100 ((glyceryl tri-(4phenylbutyrate)) is an orally administered investigational product that is being developed for patients with urea cycle disorders. It is an organic liquid and pro-drug of phenylbutyrate which is metabolized in the liver to sodium phenylacetate (PAA). PAA conjugates with glutamine via acetylation to form phenylacetylglutamine (PAGN) and is excreted in the urine. Each molecule of HPN-100 has the potential to mobilize as many as six molecules of ammonia via PAGN. As a first step toward evaluating its potential utility for treatment of hepatic encephalopathy (HE), we have evaluated safety and PK in healthy adults and cirrhotic patients. STUDY DESIGN: This was an open-label PK study of HPN-100 in subjects with cirrhosis grouped according to Child-Pugh score (A, B, or C [n = 8 in each group]) and in age- and gender-matched healthy subjects with normal hepatic function (n = 8). Subjects received a single oral dose (100mg/kg/d) on day 1, two doses/day on days 8-14 (200mg/kg/d), and a single dose on day 15 (100mg/kg/d). RESULTS: HPN-100 was metabolized via the expected major pathway, from phenylbutyrate to PAA and PAA to PAGN. During BID dosing, steady-state plasma concentrations of PAA and PAGN where achieved within 3 days in all groups. Extent of plasma exposure to PAA significantly correlated with MELD score, increasing with worsening MELD score, but there was no significant relationship with GFR or Child-Pugh score. No consistent differences between cirrhotic subjects and healthy volunteers were seen for the plasma PK variables on days 1 or 15. There were no statistically significant differences in the PK characteristics when given after fasting (day 1) or with a meal (day 8). Excretion of the main metabolite PAGN, which is stoichiometrically related to ammonia excretion, was similar in all groups. CONCLUSION: The results indicate that hepatic impairment has little effect on the ability of HPN-100 to mobilize ammonia and that tolerability is satisfactory in cirrhotic and healthy control patients. In addition, excretion of PAGN following HPN-100 administration may offer an alternative to urea for ammonia excretion. The findings indicate that HPN-100 deserves further study for chronic management of HE.

S1842 Protein-Calorie Malnutrition As a Prognostic Indicator of Mortality Among Patients Hospitalized with Cirrhotic Portal Hypertension Justina J. Sam, Geoffrey C. Nguyen

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Background: Patients admitted with liver cirrhosis and sequelae of portal hypertension (PHTN) may be at increased risk for protein-calorie malnutrition (PCM) due to several factors, including inadequate nutritional intake and absorption, and the hypermetabolic state of cirrhosis. Our aims were to conduct a nationwide analysis of the prevalence of PCM in cirrhotics with portal hypertension and to assess its prognostic significance. Methods: We used the Nationwide Inpatient Sample (NIS), which is a stratified 20% sample of hospital discharges in the U.S., to identify admissions with cirrhotic PHTN between 1998 and 2005 using ICD-9-CM diagnostic codes. Prevalence of PCM in this group of cirrhotic patients was compared to that of general medical inpatients. We used multiple logistic regression to determine the independent effect of PCM on in-hospital mortality, while accounting for age, comorbidity, health insurance, income, alcoholic liver disease, and the presence of ascites and encephalopathy. Results: There were 114,703 admissions for cirrhotic PHTN in the NIS between 1998 and 2005. The prevalence of PCM was substantially higher among

Refractory Spontaneous Bacterial Peritonitis: A Retrospective Study Archita P. Desai, Nancy Reau, K. G. Reddy, Helen S. Te, Smruti R. Mohanty, Rohit S. Satoskar, Amanda K. DeVoss, Donald M. Jensen Background: Spontaneous bacterial peritonitis (SBP) occurs in 10-35% of patients admitted to the hospital with liver cirrhosis and ascites, and is associated with high in-hospital mortality rates. After treatment with empiric antibiotics, improvement in fluid polymorphonuclear cell (PMN) count within 48 hours is expected. Despite adherence to published guidelines, anecdotal evidence at our institution identifies cases unresponsive to standard treatment. Aim: With no published studies on these resistant cases, it was our aim to study patients with the refractory SBP with the hypothesis that predisposing characteristics increase their chance of developing a recalcitrant infection. Methods: We completed a retrospective chart

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AASLD Abstracts

AASLD Abstracts

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