Mo1022 Proton Pump Inhibitors Independently Increase Mortality in Cirrhotic Patients With Spontaneous Bacterial Peritonitis

AASLD Abstracts

Mo1018

Mo1021

Validation of 4 Noninvasive Scoring Systems to Identify Patients With Advanced Fibrosis in the Thai NAFLD Population Tanassanee Soontornmanokul, Panida Piyachaturawat, Sith Siramolpiwat, Naruemon Wisedopas, Pisit Tangkijvanich, Varocha Mahachai, Pinit Kullavanijaya, Sombat Treeprasertsuk

Decreased Liver Stiffness Measured by Acoustic Radiation Force Impulse Imaging Is Associated With Metabolic Syndrome in University-Aged Youths Yuko Nishise, Hitoshi Togashi, Tomohiro Katsumi, Kyoko Tomita, Chikako Sato, Rika Ishii, Hiroaki Haga, Kazuo Okumoto, Hisayoshi Watanabe, Takafumi Saito, Yoshiyuki Ueno

BACKGROUND: The evaluation of liver fibrosis in patients with non alcoholic fatty liver disease (NAFLD) is important in predicting to predict the outcome of disease. Liver biopsy is the gold standard whereas the noninvasive scoring systems for liver fibrosis assessment in NAFLD patients have been studied and showed promising results. We aimed to validate the utility of these noninvasive scoring systems to identify patients with advanced fibrosis (.F3) in the Thai NAFLD population METHODS: This is a cross sectional study to collect 115 liver biopsy-proven NAFLD patients during Jan 2009-Dec 2011 at the King Chulalongkorn Memorial Hospital (KCMH) and Ramathibodi Hospital, Bangkok, Thailand. Four noninvasive scoring systems including AST/ALT ratio, BARD score, FIB-4 and NAFLD Fibrosis Score (NFS) were used to identify patients with advanced fibrosis. RESULTS: One hundred and fifteen liver biopsy proven NAFLD patients were included with mean age of 50.5+/- 12.4 years and 49.6% of them were male. Eighty patients (69.6%) had impaired fasting glucose or diabetes. 15 patients (13%) showed advanced fibrosis by liver histology. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of these 4 tools were shown in Table 1. BARD score .2 is the best tool with highest sensitivity to screen patients with advanced fibrosis, followed by NFS with cut-off .-1.455, FIB-4 with cut off .1.45 and AST/ALT ratio .0.8, respectively. By using these 4 noninvasive scoring systems, liver biopsy could potentially be avoided in 60% of patients with NFS, 62% with BARD score, 74% with FIB-4, and 84% with AST/ALT ratio (Table 1). CONCLUSIONS: With the prevalence of advanced liver fibrosis of 13% in Thai NAFLD population, these 4 non invasive scoring systems can be used to identify patients with advanced fibrosis with the acceptable sensitivity and high NPV so that liver biopsy could potentially be avoided in about two-thirds of patients. Table 1. Comparison of four non-invasive scoring systems for the diagnosis of advanced fibrosis in 115 Thai patients with NAFLD

Background: The prevalence of non-alcoholic fatty liver disease is increasing in Japan. The aim of this study was to determine whether the degree of liver stiffness, measured by acoustic radiation force impulse (ARFI) imaging, is associated with the elements of metabolic syndrome in non-obese Japanese youths. Methods: We conducted abdominal ultrasound examinations in 160 men and 101 women (median age, 20 years; range, 18-31 years). All subjects were students at Yamagata University. ARFI sonoelastography was performed during ultrasound examination. Fatty liver was diagnosed by observation of the criteria for steatosis: 1) a hyperechoic liver with fine, tightly packed echoes compared with normal, and 3) contrast between the average optical density of the liver and that of the right kidney. We also performed biochemical tests of liver and metabolic functioning. We then assessed the associations among liver stiffness and factors related to metabolic syndrome using a multivariate regression model. Results: Mean shear wave velocities were 1.18 ± 0.09 m/sec in subjects with non-fatty liver (n = 163), 1.07 ± 0.11 m/sec in those with mild fatty liver (n = 74), and 1.02 ± 0.12 m/sec in those with moderate fatty liver (n = 24), respectively (p , 0.001). An increase in the number of risk factors for metabolic syndrome was strongly associated with decreased velocities (p , 0.001). Multivariate analysis demonstrated that the factors independently related to a decreased velocity were the presence of fatty liver, elevated BMI, elevated fasting plasma levels of glucose and triglycerides, hypertension, and the homeostasis assessment model ratio. Conclusions: These results suggest that insulin resistance and disorders of glucose and lipid metabolism are associated with a decrease in liver stiffness in young, non-obese individuals. ARFI sonoelastography may be a useful marker for detecting individuals at a high risk for development of metabolic syndrome at a young age. Mo1022 Proton Pump Inhibitors Independently Increase Mortality in Cirrhotic Patients With Spontaneous Bacterial Peritonitis Jee Hye Kwon, Seong-Joon Koh, Ji Won Kim, Kook Lae Lee, Byeong Gwan Kim

Mo1019 Adipose Tissue Insulin Resistance and Lipotoxicity Drive Disease Phenotype and Decline in Pancreatic Beta Cell Function in Nonalcoholic Fatty Liver Disease Mohammad S. Siddiqui, Velimir A. Luketic, Puneet Puri, Carol C. Sargeant, Sherry Boyett, Melissa J. Contos, Michael O. Idowu, Arun J. Sanyal BACKGROUND: The histologic spectrum of NAFLD extends from fatty liver (FL) to steatohepatitis (SH). NAFLD, especially steatohepatitis, has also been associated with an increased risk of developing type 2 diabetes mellitus (T2DM) (Hanley Diabetes 2005) and T2DM is associated with more advanced SH stage. The basis for this association is unknown. HYPOTHESIS: We tested the hypothesis that increasing exposure to circulating free fatty acids due to adipose tissue insulin resistance produces lipotoxicity and thus leads to both more severe liver disease i.e. SH and pancreatic beta cell dysfunction leading to T2DM. METHODS: Nondiabetic subjects with histologically characterized (by NASH CRN classification) NAFLD (n=101 with SH) were compared to lean or obese controls (defined clinically and persistently normal liver enzymes). The homeostatic model (HOMA-IR), β cell-HOMA (HOMA-β) and adipose tissue insulin resistance (adipo-IR) were used to assess insulin resistance, β cell function and adipose tissue insulin resistance respectively. Intergroup differences were assessed by ANOVA or a distribution-free test and corrections for multiple testing as appropriate. RESULTS: 140 subjects each were studied in the three groups. The mean BMI were: NAFLD 34kg/m2, obese controls 34kg/m2 and lean controls 23kg/m2 (p ,0.05 lean vs NALFD/Obese). Liver enzymes were significantly higher in the NAFLD group as expected. Mean fasting glucose was similar in lean and NAFLD groups (93 vs 91 mg/dl) and lower than in obese controls (104 mg/dl, p , 0.05). Hemoglobin A1C, fasting insulin and HOMAIR were similar in obese and NAFLD subjects and higher than lean controls. [FFA] was higher in NAFLD subjects compared to lean and obese controls resulting in higher AdipoIR (4.8v10.9v17.2; p,0.05). HOMA-β increased progressively lean to obese controls to NAFLD (124% vs 214% vs 520%, p , 0.05). However, when HOMA- β was related to NAFLD phenotype, it was significantly lower in those with SH (444%) compared to those with FL (719%; p, 0.001). [FFA] and adipo-IR were inversely related to SH. Steatohepatitis was also inversely related to HOMA-β. CONCLUSIONS: Development of NAFLD is associated with increasing insulin resistance and need for increased β cell insulin output. Increasing adipo-IR is associated with SH and declining β cell function suggesting a role of FFA lipotoxicity in development of SH and T2DM.

AASLD Abstracts

S-1014

Backgrounds & aims: Spontaneous bacterial peritonitis (SBP) is one of the most serious complications in cirrhotic patients. It has been reported that acid suppressants such as PPIs or H2RAs might cause small intestine bacterial overgrowth and bacterial translocation. However, little information is available whether acid suppression increases the risk of SBP and affects mortality rate in patients with advanced cirrhosis. Therefore, we designed a multi-center, cohort study that included a large number of cirrhotic patients to evaluate whether acid suppressive therapy increases the risk of SBP and to define the factors associated with mortality after SBP in cirrhotic patients with ascites. Methods: A total of 1437 consecutive cirrhotic patients with ascites from January 2003 to December 2010 were reviewed in this study. Patients with GI bleeding or antibiotics use within 14 days prior to admission and those who undergone organ transplant were excluded. Those patients were divided into two groups according to the presence or absence of SBP. Factors associated with the development of SBP were analyzed. Mortality rates during hospitalization or within 30 days after SBP and the factors associated with mortality were also analyzed. Results: One thousand one hundred forty patients (Median age, 62; Men, 75%; model for end-stage liver disease (MELD) score, 17) were included. Five hundred thirty three patients were identified as having SBP. In the logistic regression analysis, the use of histamine-2 receptor antagonists (H2RAs), the use of proton pump inhibitors (PPIs), a high admission MELD score, and old age were associated with the development of SBP. The mortality rate during hospitalization or within 30 days after SBP was higher in SBP patients with acid suppressive therapy compared to those without acid suppressive therapy. In the Cox regression analysis, the use of PPIs within 7 days (HR, 1.684; 95% CI, 1.126 to 2.519), the use of PPIs within 8 to 30 days (HR, 2.095; 95% CI, 1.097 to 4.001), and a higher admission MELD score (HR, 1.038; 95% CI, 1.024 to 1.054) were associated with mortality after SBP. Conclusion: Acid suppressive therapy is associated with the development of SBP in cirrhotic patients with ascites. The use of PPIs is a risk factor of mortality after SBP independent of the severity of the underlying liver disease. Mo1023 Exposure to Ionizing Radiation From Evaluation to Liver Transplantation Ser Yee Lee, Alyson N. Fox, Sonja K. Olsen, Daniel Cherqui, Michael D. Kluger INTRODUCTION:Radiation exposure has been linked to development of both solid tumors and leukemias. Patients considered for transplantation undergo extensive radiographic investigations, and are subject to immunosuppression post-transplantation. The objective of this study was to examine radiation exposure in liver transplant candidates. METHODS:A 1year cohort of patients transplanted or evaluated for transplantation was reviewed. Effective dose (mSv) for all diagnostic imaging and interventional procedures were obtained, and categorized according to standard parameters. Effective dose reflects risk in terms of whole body exposure and potential biological detriment. Statistical analyses were performed using the Student's t-test.RESULTS:74 patients received imaging as part of their pre- or peritransplantation care during the 2010 calendar year. 69% were male and the median age was 57 years. The most common indication for liver transplantation was hepatitis C (55%), and 20% had hepatocellular carcinoma (HCC) (30%). 1,826 imaging studies were performed, and 22% (n= 408) involved ionizing radiation. Most studies (Figure 1) occurred during the evaluation period, with a greater utilization of nuclear studies and fluoroscopy or angiography (i.e. trans-arterial embolization, cardiac catheterization, ERCP) (p,0.01). Additionally, there was a proportional increase in the utilization of computed tomography in the post-operative period. Patients received a median [IQR] annualized effective dose of 51 mSv [19,126]. Based on annualized exposure rates, 51% (Table 1) were exposed to very high doses of ionizing radiation (.50 mSv), with 10% being exposed to almost twice the amount of