Clinical Outcome in Hospitalized Cirrhotic Patients with Bacterial Infections Treated with Empirical or Antibiogram-Guided Therapy

POSTER PRESENTATIONS study in outpatients with cirrhosis aimed to assess whether food intake is adequate to the needs of their specific clinical condition according to the current nutritional guidelines. Methods: Patients were consecutively screened by using a scored algorithm for the Risk of Alterated Nutrition (RAN), adapted from the Royal Free Hospital Nutritional Prioritizing Tool and including both anthropometric and clinical parameters (altered BMI, recent body weight changes, presence of diabetes, ascites or hepatic encephalopathy) as risk factors. Patients were categorized in low, moderate and high risk according the number of risk factors. Those with at least a moderate risk were offered evaluation by a certified nutritionist and were asked to fill up a weekly food diary (DAS) and to perform a hand-grip strength (HGS) test to assess muscle wasting. Results: 121 out of the 144 pts screened (Child A/B/C: 52/40/8%) were at risk for altered nutrition (53 moderate and 68 high-risk). As expected, Child and MELD scores paralleled the risk severity. 86/121 patients accepted nutritional evaluation and all performed the HGS test, which indicated significant muscle wasting in 56% of patients (Child A/B/C: 44/41/79%). 56/86 patients properly returned the DAS. Despite patients had received general nutritional indications by their hepatologist, DAS showed that 70% has an insufficient intake of calories and 40–60% inadequate water and sodium intake. Furthermore, the weekly intake of macronutrients was insufficient in 70–95% of cases, with the exception of sugar, which was excessive in 87% of cases including diabetic patients. Conclusions: The intake of total calories and different macronutrients is inadequate in almost 90% of outpatients with cirrhosis, due to both scarce adherence to the indications given by the hepatologist and the low knowledge of nutritional facts. Malnutrition is often associated to muscle wasting even in less advanced disease. This highlights the need of a personalized nutritional approach, including educational and motivational aspects. THU-326 IN-HOSPITAL MORTALITY AND ECONOMIC BURDEN OF GASTROINTESTINAL BLEEDING IN CIRRHOSIS PATIENTS F. Wubiee1, C. Howell1, B. Tesfaye1, A. Kibreab1. 1Medicine, Howard University, Washington, DC, United States E-mail: [email protected] Background and Aims: Gastrointestinal (GI) bleeding is a major complication of cirrhosis and causes substantial mortality, morbidity and health care resource utilization. Methods: We used the weighted Nationwide Inpatient Sample (NIS) from 2007 to 2011 to characterize adult (age 18 years and above) patients with both cirrhosis and GI bleeding among the discharge diagnoses. We determined the national trends in hospitalization, inpatient mortality and morbidity, and resource utilization. Results: The number of inpatient cases with cirrhosis and GI bleeding ranged from 71,391 in 2007 to 87,861 in 2011 ( p < 0.001), comprising approximately 0.2% of all US hospitalizations. About 15.7% of inpatients with cirrhosis had GI bleeding compared to 2.2% of the general admissions. Thirty-five percent of the cirrhotic bleeders had variceal bleeding. The incidence rate of GI bleeding and cirrhosis steadily increased from 0.18% in 2007 to 0.23% in 2011( p < 0.001). Among cirrhotics, the mortality rate for GI bleeders was 10.8%, almost twice as much as non-bleeders (5.6%), ( p < 0.001). Non-variceal bleeders had a higher mortality rate than variceal bleeders (11.3% versus 9.9%, p < 0.001) (Table). Mortality in GI bleeders declined from 11.7% in 2007 to 10.2% in 2011 ( p < 0.001). The average length of inpatient stay during the same period declined form 6.8 days to 6.4 days ( p < 0.001). On the other hand, average total inpatient charges increased from $49,327 in 2007 to $ 64,912 in 2011 per case per hospitalization ( p < 0.001). In multivariate analysis, independent predictors of mortality were the presence of hepatic encephalopathy (OR = 1.73, 95% CI, 1.68–1.77), alcoholic cirrhosis (OR = 1.31, 95% CI, 1.12–1.48), male sex, (OR = 1.16, 95% CI, 1.13–1.19) and number of procedures per admission (OR = 1.28, 95% CI, 1.27–1.28).

Conclusions: There was a gradual increase in the incidence and number of cases hospitalized for cirrhosis and GI bleeding and resource utilizations in the US from 2007 to 2011. The inpatient mortality rate was significantly higher for GI bleeders than nonbleeders, but showed a decline over time. Non-variceal bleeders had a higher risk of mortality than variceal bleeders. THU-327 CLINICAL OUTCOME IN HOSPITALIZED CIRRHOTIC PATIENTS WITH BACTERIAL INFECTIONS TREATED WITH EMPIRICAL OR ANTIBIOGRAM-GUIDED THERAPY G. Caccamo1, S. Maimone1, R. Filomia2, M.S. Franze3, S. Tomeo2, R. Spinella2, T. Lembo2, A. Alibrandi4, P. Mondello5, C. Saitta1, I. Cacciola2, G. Squadrito6, G. Raimondo2. 1Division of Clinical and Molecular Hepatology; 2Division of Clinical and Molecular Hepatology, Department of Clinical and Experimental Medicine; 3University School of Medicine of Messina; 4Department of Economics, University of Messina; 5Unit of Infectious Disease, University Hospital of Messina; 6 Division of Clinical and Molecular Hepatology, Department of Human Pathology, University Hospital of Messina, University Hospital of Messina, Messina, Italy E-mail: [email protected] Background and Aims: Bacterial infections (BI) in cirrhosis are associated with high rate of liver decompensation and mortality. Aim of this study was to evaluate the short-term mortality in a cohort of cirrhotic patients treated with empirical versus antibiogram-guided antibiotic therapy. Methods: We retrospectively evaluated 200 episodes of BI occurring in 186 cirrhotics [56.5% male; mean age 65.8 ± 12.1 years; 45 with hepatocellular carcinoma (HCC)] consecutively hospitalized from January 2009 to March 2015. Child-Pugh (CP) classes A/B/C and MELD score at the initiation of empirical antibiotic treatment (EAT) were 41/ 108/51 and 14.2 ± 7.3, respectively. Microbiological cultures were performed before starting EAT in all the cases. Therapy was modified both in patients with positive cultures (Cpos) according to antibiogram and in patients with negative cultures (Cneg) but without clinical or laboratory evidence of EAT effectiveness. Mortality was evaluated one month (M-1) and 3 months (M-3) after starting EAT. Results: Cultures tested positive in 111/200 BI episodes (55.5%). Bacterial isolated were Gram-negative in 48.8%, Gram-positive in 42.6%, mixed in 8.6%. EAT was changed in 37/111 (33.3%) Cpos and in 35/89 (39.3%) Cneg BI episodes ( p = 0.5). Overall mortality at M-1 and M-3 was 17% and 26.5%, respectively, being significantly higher in Cneg than in Cpos patients (M-1: 25.8% Cneg vs 9.9% Cpos, p = 0.001; M-3: 38.2% Cneg vs 17.1% Cpos, p = 0.008)]. At Cox-regression analysis, independent risk factors for M-1 mortality were: HCC (HR:2.93, 95%CI:1.46–5.89, p = 0.003); higher CP score (HR:2.22, 95% CI: 1.21–4.06, p = 0.01); creatinine values (HR:1.64, 95%CI:1.27– 2.13, p = 0.0001); C-reactive proteine (C-rp) (HR:1.11, 95%CI:1.01– 1.22, p = 0.036); Cneg (HR: 0.46, 95%CI:0.22–0.98, p = 0.045). Creatinine values, C-rp and Cneg were significant risk factors of mortality also when HCC patients were excluded. M-3 mortality risk

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POSTER PRESENTATIONS factors were: HCC (HR: 2.42, 95%CI: 1.36–4.3, p = 0.003); creatinine values (HR: 1.37, 95%CI: 1.06–1.76, p = 0.016); sodium levels (HR:0.94, 95%CI:0.89–0.99, p = 0.041); Cneg (HR: 0.54, 95%CI: 0.3–0.98, p = 0.044). When HCC patients were excluded from the analysis, risk factors of mortality were Cneg, diabetes and lenght of stay. Conclusions: Cirrhotic patients with BI and negative microbiological cultures have a significantly higher mortality rate compared to cirrhotics with positive cultures, and this independently of HCC co-existence.

Conclusions: Our findings demonstrate that PPIs and milder antacids are associated with an increased risk of bacterial infections. PPIs, but not milder antacids, are a risk factor for SBP. There are two possible explanations: 1) Antacids of all kinds increase the risk of bacterial infections. 2a) Users of antacids have a higher risk of bacterial infections because they have worse liver function in ways that are not described by our confounders, but 2b) PPIs increase the risk of SBP. This study provides unparalleled evidence that PPIs increase the risk of SBP and, possibly, other bacterial infections.

THU-328 PROTON PUMP INHIBITORS INCREASE THE RISK FOR INFECTIONS IN CIRRHOSIS PATIENTS WITH ASCITE G. Dam1, H. Vilstrup1, H. Watson2, P. Jepsen1,3. 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2Sanofi Asia-Pacific R&D, Chilly-Mazarin, France; 3 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected]

THU-329 EMBOLIZATION OF A SPONTANEOUS PORTOSYSTEMIC SHUNT FOR POST-TIPS REFRACTORY HEPATIC ENCEPHALOPATHY W. Wu1, L. Zheng1, M. Li2, C. He1, W. Guo1, Z. Wang1, Z. Yin1, J. Niu1, D. Fan1, G. Han1. 1Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an; 2Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Fourth Military Medical University, China E-mail: [email protected]

Background and Aims: Approximately 40% of cirrhosis patients with ascites use proton pump inhibitors (PPIs). PPIs predispose to bacterial overgrowth and translocation. Our aim was to determine whether PPI use and mild acid reduction with other antacids are risk factors for infections in cirrhosis patients with ascites. Methods: We used the complete original data from three randomized trials of satavaptan treatment of ascites (N = 1198 patients). All infections diagnosed during the one-year follow-up were recorded. The rates of first-time infection during follow-up were similar for patients randomized to satavaptan or placebo. In our analysis, we followed the patients until their first infection, irrespective of its agent (bacterial, viral, fungal, or unknown) and site. We compared rates of first-time infection between current users vs. non-users of PPIs and other antacids. We used Cox regression to adjust for differences in gender, age, cirrhosis etiology, current MELD score, current serum albumin, current serum sodium, diabetes, current use of lactulose, refractory ascites, and current hospitalization. Results: There were 446 first-time infections during the follow-up; 104 were SBP, and 32 were other bacterial infections. Most infections had no identified pathogen (N = 263). At randomization, 524 patients (44%) used PPIs, and 121 others used them at some point during follow-up. Current PPI use increased the rate of first-time infection (adjusted hazard ratio = 1.38, 95% CI 1.13–1.68). PPIs were a risk factor for bacterial infections of all kinds, but not for viral or fungal infections (Figure 1). Compared to PPIs, other antacids were equally bad with respect to development of urinary tract infection, lower respiratory tract infections and gastroenteritis (Figure 1). PPIs were a strong risk factor for SBP (HR = 1.81, 95% CI 1.81–2.74) whereas other antacids were not.

Background and Aims: The role of spontaneous portosystemic shunt (SPSS) embolization during transjugular intrahepatic portosystemic shunt (TIPS) placement in cirrhotic patients remains obscure. This retrospective cohort study aimed to assess whether adjunctive SPSS embolization could improve post-TIPS refractory HE for cirrhotic patients with variceal bleeding. Methods: Between May 2004 and November 2012, 69 cirrhotic patients with SPSS who underwent TIPS implantation for the prevention of variceal rebleeding were enrolled. Results: The TIPS patients were divided into two groups: the adjunctive SPSS embolization group (TIPS + E group, n = 61) and the TIPS-only group (n = 8). Media duration of follow-up was 2.3 years. The cumulative risk of refractory HE was significantly decreased in the TIPS + E group than in the TIPS-only group (P = 0.029). The univariate and multivariate analysis also demonstrated that SPSS embolization (hazard ratio [HR] = 0.249; 95% confidence interval [CI]: 0.064-0.964) was the only significant predictor associated with refractory encephalopathy. The cumulative rates free of shunt dysfunction, was higher in the TIPS + E group (P = 0.042). SPSS embolization (HR = 0.398; 95% CI: 0.158–0.999) may be a protective predictor of shunt dysfunction. Meanwhile, the cumulative risk of rebleeding was not significant increase in the TIPS + E group (P = 0.063). Albumin (HR = 2.307; 95%CI: 1.055–5.044) was the only independent predictor. Survival and liver function did not differ between both groups. Conclusions: Adjunctive SPSS embolization may benefit the prophylaxis of refractory HE and shunt dysfunction without significant increasing the risk of rebleeding. Future large scale, randomized, controlled trials are warranted. THU-330 HEPATIC MYELOPATHY AFTER TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT: PREVALENCE, RISK FACTORS, AND LONGTERM OUTCOME S. Ren1, Y. Lv1, Z. Wang1, M. Bai1, W. Zhang1, J. Niu1, Z. Yin1, C. He1, W. Guo1, B. Zhang1, X. Meng1, J. Cai1, G. Han1. 1Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China E-mail: [email protected] Background and Aims: Hepatic Myelopathy (HM) is a central neural dysfunction associated with chronic liver disease and/or portal systemic shunt. Data on HM is extremely limited. We sought to evaluate the prevalence, risk factors of onset and survival, and long-term outcome of HM in a cohort of cirrhotic patients with symptomatic portal hypertension treated successfully by TIPS. Methods: From January 2005 and December 2014, 1101 consecutive cirrhotic patients with symptomatic portal hypertension undergoing TIPS were retrospectively included. All the patients were followed up in 1, 3, 6 months after TIPS and every half year subsequently. A

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Journal of Hepatology 2016 vol. 64 | S213–S424