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Rifaximin for Prevention of Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome in Cirrhosis: A Systematic Review and Meta-Analysis
Demographic and clinical characteristics of patients with cirrhosis receiving intensive care, comparing survivors with those who died during hospitalization.
Su1498
Background: Liver transplantation (LT) centers often receive requests for inpatient transfers from other institutions. Anecdotally, these patients have high mortality, particularly if they are new to the accepting LT center with acute-on-chronic liver failure (ACLF). Very little is known about ACLF in this unique transfer cohort. Purpose: The purpose of this study is to examine the characteristics and outcomes of inpatient hospital transfers with ACLF to a high volume LT center in New York City. Methods: Using a prospectively maintained database from July 2011 to July 2013, consecutive referrals for adult inpatient hospital transfer to our LT center were retrospectively examined. Patients seen by a liver provider at our center prior to transfer and repeat transfers of the same patient were excluded. The primary outcome for analysis was inpatient mortality. Secondary outcomes were LT and discharge. ACLF was defined by the North American Consortium for Study of End-stage Liver Disease (NACSELD) criteria (two of the following: shock, grade III-IV hepatic encephalopathy, ventilator dependence, and need for renal replacement therapy (RRT)) and the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria (one of the following: creatinine (Cr) >2, need for RRT, non-renal organ failure (total bilirubin >12, shock, grade III-IV hepatic encephalopathy) and renal compromise (Cr>1.5) or two nonrenal organ failures) at the time of transfer. Statistical analyses were performed. Results: Over a 2-year period, a total of 512 patients were transferred to our center, 221 (43%) of which were never seen previously (new-to-center). These new-to-center patients had a mean age of 53 years, a median MELD of 25 and a slightly male predominance. The most common reason for transfer was ACLF (15%), followed by alcoholic hepatitis (14%). Of the 33 patients transferred for ACLF, 4 (12%) met NACSELD criteria for ACLF and 33 (100%) met EASL-CLIF criteria. The most common identified cause of acute decompensation was infection (n=22, 66%). The overall inpatient hospital mortality rate was 33%. ACLF patients experienced higher 30-day inpatient mortality rates compared to non-ACLF patients (73% vs 26%, respectively; hazard ratio, 1.85; 95% confidence interval 1.12-3.03; p=0.01). As predictors of inpatient mortality, the NASCELD criteria had 17% sensitivity and 100% specificity, while EASL-CLIF criteria demonstrated 100% sensitivity and 0% specificity. Of patients transferred for ACLF, 7 (22%) were listed for LT and 3 (9%) underwent LT during the index hospitalization. Conclusions: ACLF is the most common reason for inpatient transfer to our LT center and is associated with increased mortality but significant eligibility for LT. The EASL-CLIF criteria outperformed NACSELD in predicting inpatient mortality and could be used to triage transferred patients.
Su1497 CHARACTERISTICS AND OUTCOMES OF INTENSIVE CARE IN PATIENTS WITH CIRRHOSIS AT SAFETY-NET HOSPITAL: A MULTICENTER STUDY V. V. Pavan Kedar Mukthinuthalapati, Samuel A. Akinyeye, Zachary P. Fricker, Maya Balakrishnan, Michelle T. Long, Eric Orman, Naga P. Chalasani, Marwan S. Ghabril Background. Critically ill cirrhotics suffer high disease severity, morbidity and healthcare resource utilization, with in-hospital mortality rates that range from 40-80% as reported by tertiary care centers. Safety-net hospitals provide care for vulnerable urban populations with distinct racial and socioeconomic make-up, and face unique challenges in providing critical care to this population. Aims. To characterize intensive care in patients with cirrhosis and associated outcomes at safety-net hospitals. Methods. Data from the ongoing multicenter study ‘Cirrhosis in Urban Safety-net Hospital' (CrUSH) of hospitalized cirrhotics in 20122013 were analyzed (Eskenazi Health Hospital (Indiana University (IU)), Ben Taub Hospital (Baylor College of Medicine (BCM)) and Boston Medical Center (Boston University (BU))). Demographic and clinical data were summarized and compared based on hospital mortality in patients admitted to the intensive care unit (ICU) (Chi square for categorical variables and Mann-Whitney test for continuous variables). Model for end stage Liver disease (MELD) and Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scores were calculated on ICU admission. Results. In 2012, 116 of 555 hospitalized cirrhotics received ICU care at the 3 study centers (55 IU, 35 BCM, 26 BU). Mean age was 54±8, 62% were male, 50% Caucasian, 27% Black and 20% Hispanic. Etiologies of cirrhosis were alcohol 63%, viral hepatitis 47%, fatty liver 4% and cryptogenic disease 5%. Indications for ICU care included: gastrointestinal (GI) bleeding 41%, encephalopathy 16%, respiratory failure 12%, sepsis 4%, shock 3%, and other 21%. Mean MELD was 19±8 and CLIF-SOFA was 6±4. Advanced interventions included mechanical ventilation in 47%, vasopressors in 16%, and dialysis in 8%. The 28 patients (24%) who died during hospitalization had similar age, gender and liver disease etiologies compared with survivors (differences are described in table 1). In 68 patients with available data, CLIF-SOFA and MELD predicted hospital mortality with a c-statistic of 0.87 [95%CI 0.74-.99] and 0.77 [95%CI 0.65-0.89] respectively. Conclusions. Cirrhotics receiving intensive care at safety-net hospitals predominantly suffer from alcoholic and viral liver disease, and are most commonly admitted for GI bleeding. Disease severity (general and liver) and mortality are lower than generally reported by academic centers. Nevertheless, hospital mortality is associated with non-GI bleeding indications for ICU admission and infections, and is predicted by CLIF-SOFA and MELD on ICU admission.
Su1499 RIFAXIMIN FOR PREVENTION OF SPONTANEOUS BACTERIAL PERITONITIS AND HEPATORENAL SYNDROME IN CIRRHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS Faisal Kamal, Muhammad Ali Khan, George Cholankeril, Zubair Khan, Wade M. Lee, Chiranjeevi Gadiparthi, Aijaz Ahmed, Colin W. Howden, Satheesh Nair, Sanjaya K. Satapathy Background Spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS) are associated with high morbidity and mortality in cirrhotics. Prophylactic antibiotics (quinolones) have been recommended in patients with a previous history of SBP. Recently, there has been interest in the use of rifaximin, as it is a poorly absorbed from the GI tract and produces selective decontamination of the gut. It may also decrease IL-6 and TNFα production thereby lowering bacterial translocation and the risks of SBP and HRS. Aims To evaluate rifaximin in the prevention of SBP and HRS in patients with cirrhosis and ascites Methods We searched several databases from inception through October 18, 2016 to identify comparative observational studies and randomized controlled trials (RCTs) evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed pre-determined sub-group analyses based on type of control group (quinolones or no antibiotics), design of study (RCT or observational) and type of prophylaxis (primary or secondary). Pooled odds ratios (OR) were calculated using a random effects model. We used the GRADE framework to interpret our findings. Results We included 10 studies (4 RCTs and 6 observational) with 1483 patients (rifaximin 544, controls 939) in the meta-analysis of SBP prevention. Pooled OR (95% confidence interval) was 0.50(0.25, 1.01), with considerable heterogeneity (I2=61%). We performed a sensitivity analysis after excluding two outlier studies with disproportionately high Child Class C patients in the rifaximin group; adjusted OR was 0.33 (0.21, 0.52),(I2= 0%) in favor of rifaximin. Subgroup analysis based on type of control: in quinolone group, pooled OR was 0.47 (0.11, 1.98),(I2=66%); in no antibiotic group, pooled OR was 0.52(0.21, 1.28), (I2=65%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (0.14, 0.70), (I2=12%) for the quinolone comparison and, 0.33 (0.19,
S-1151
AASLD Abstracts
AASLD Abstracts
ACUTE-ON-CHRONIC LIVER FAILURE IS THE MOST COMMON REASON FOR INPATIENT TRANSFER TO A LIVER TRANSPLANT CENTER AND IS ASSOCIATED WITH HIGH MORTALITY Alexander S. Vogel, Jonathan Nahas, Gene Y. Im
0.59), (I2=0%) for the comparison with no antibiotics. For RCTs alone, the pooled OR was 0.41 (0.22, 0.75), (I2=13%); for observational studies it was 0.52 (0.15, 1.77), (I2=73%). For subgroup analysis based on primary and secondary prophylaxis the pooled OR was 0.32 (0.17, 0.61) and 0.20 (0.07, 0.59), respectively. Four studies with 486 patients evaluated rifaximin for the prevention of HRS; pooled OR was 0.30 (0.15, 0.60), (I2=0%) in favor of rifaximin. Conclusions Initially, we only found a trend towards a protective effect of rifaximin against the development of SBP in patients with cirrhosis and ascites. However, the quality evidence as per the GRADE framework was low. After adjusting for outliers, rifaximin was found to be effective in reducing the risk of SBP. RCTs with rifaximin were more likely to show an advantage than uncontrolled, observational studies. Rifaximin appeared effective for the prevention of HRS.
ICPs, 4 endoscopic interventions for variceal hemorrhage, 8 other procedures (e.g., TIPS, arterial embolization). No evidence of procedure-related hemorrhage and thromboembolic complications were identified. Conclusions: rFVIIa appears to be safe and effective method in improving coagulopathy in patients with liver failure in the ICU setting. It enables patients to undergo invasive procedures and a significant decrease in requirement of blood products transfusion. No thromboembolic events and procedure related hemorrhage were identified in any patient regardless of the dose administered.
Su1501 NON-NEUTROCYTIC BACTERASCITES IN AN OUTPATIENT SETTING: IS ANTIBIOTIC TREATMENT NEEDED? Alireza Meighani, Vijay Jarodiya, Mohammad Arsalan Siddiqui, Kimberly Christensen, Anas Kutait, Vinay Katukuri, Mayur Ramesh, Syed-Mohammed Jafri
AASLD Abstracts
Introduction: Non-neutrocytic bacterascites (NNB) is defined as a positive ascitic fluid bacterial culture but with polymorphonuclear neutrophil (PMN) count <250 cells/mm3. Unlike spontaneous bacterial peritonitis (SBP), there are currently no guidelines on optimal management of NNB in an outpatient setting. We reviewed management of non-neutrocytic bacterascites and compared outcomes with or without antibiotic therapy for complications including 6-month mortality, recurrent infection and hospitalization. Methods: We reviewed records of all patients with liver cirrhosis who underwent outpatient paracentesis in a single urban transplant center from January 2012 to December 2015. Patients with NNB, defined as a positive ascitic fluid bacterial culture with PMN count <250 cells/mm3, were identified. Data was reviewed for development of SBP, recurrent infection, Model for end stage liver disease-sodium (MELD-Na) score and mortality within 6 months of bacterascites. We compared the outcomes of patients who were treated with antibiotics at the time of diagnosis of NNB with patients who were not treated. Results: A total of 100 patients had NNB during the study period. Mean age of our patients was 59 years with 70% being male. Mean MELD-Na at the time of inclusion was 21. The organisms identified in ascitic fluid cultures were Gram-positive cocci (60%), Gram-positive bacilli (22%), Gram-negative bacilli (14%) and mixed Gram-positive/ Gram-negative organisms (4%). Twenty-one patients (21%) were symptomatic at the time of paracentesis with abdominal pain, altered mental status and/ or shortness of breath. Twenty-five patients (25%) received antibiotic treatment after initial diagnosis of NNB. Patients with symptoms at the time of paracentesis were more likely to receive antibiotics (36.0% vs 16.4%, p= 0.040). Also, patients with Gram-positive cocci in ascitic fluid were marginally less likely to receive antibiotics (65.8% vs 44%, p=0.055). Around 11% had another episode of non-neutrocytic bacterascites within 6 months. Recurrence rate was 10.1% for those who did not receive antibiotics and 15% in those who did. Mortality rate was 19.4%, which was 16.9% for those who did not receive antibiotics, and 24% for those who did. Only one patient was diagnosed with SBP in the repeat paracentesis done 1 week after the initial NNB. This subject was symptomatic at the time but did not receive antibiotic treatment. Overall there was no statistically significant difference in the outcomes, including NNB recurrence and mortality between patients who received antibiotics for treatment of NNB and those who did not. Conclusion: In NNB, patients are usually asymptomatic and gram-positive organisms are common in ascitic fluid culture. In our population asymptomatic NNB did not require antibiotic therapy given lack of SBP or positive cultures on repeat evaluation.
Fig. 1 A: Forest plot evaluating association between rifaximin and SBP B: Forest plot after sensitivity analysis.
Su1502 CHARACTERIZATION OF INFECTIONS AND THEIR IMPACT ON PATIENTS WITH CIRRHOSIS ADMITTED TO URBAN SAFETY-NET HOSPITALS: A MULTI-CENTER STUDY Zachary P. Fricker, Samuel A. Akinyeye, V V Pavan Kedar Mukthinuthalapati, Maya Balakrishnan, Naga P. Chalasani, Marwan S. Ghabril, Michelle T. Long Background Infections are a common and morbid complication of cirrhosis and have a major impact on the health of these patients. Previous work has suggested proton-pumpinhibitor (PPI) use is associated with an increased risk of infection. Furthermore, many patients with cirrhosis are prescribed antibiotics for a prolonged interval for prophylaxis against spontaneous bacterial peritonitis (SBP) or hepatic encephalopathy (HE). We aimed to characterize the nature of infections among patients with cirrhosis admitted to safety-net hospitals, as well as risk-factors and outcomes associated with infection. Methods Data from the ongoing multi-center study ‘Cirrhosis in Urban Safety-net Hospitals' (CrUSH) of hospitalized cirrhotics in 2012-2013 were analyzed (Eskenazi Hospital (Indiana University (IU)), Ben Taub Hospital (Baylor College of Medicine (BCM)) and Boston Medical Center (Boston University (BU))). Infections diagnosed within 3 days of hospital admission, baseline clinical and demographic subject characteristics, and clinical outcomes were recorded. Comparison of categorical variables was made via Fischer's Exact test and continuous variables via Mann-Whitney U-test. Results Among 555 unique subjects included, there were 145 infections on admission, distributed across 126 subjects (23%). Infections were distributed relatively evenly across anatomical sites (Table). In-hospital mortality varied with anatomic site of infection (Figure). Pre-admission PPI use was not associated with infection (p=0.75). Subjects with infection on hospital admission had worse outcomes compared to those without infection, including longer length of stay (LOS) (8 vs 6 days, p<0.001) and increased inhospital mortality (13% vs. 5%, p=0.002). Admission MELD score (p<0.001) and history of complicated diabetes mellitus (p=0.002) were associated with presence of infection. Of 66 cases with antibiotic-sensitivity testing data available, 26 (39%) had any resistance to antibiotics. In-hospital mortality rate was higher in cases of infection with an antibiotic resistant organism (19% vs. 6%, p=0.007). Neither use of pre-admission antibiotics of any type (SBP prophylaxis, rifaximin, or other antibiotics for HE prophylaxis) nor use of prophylactic antibiotics against SBP alone was associated with resistant infection. Conclusions Infections are common among patients with cirrhosis, with a high-rate of antibiotic resistance. Increased MELD score is strongly associated with the presence of infection. No association was observed between use of long-term antibiotics and antibiotic resistance or PPI use and infection. Clinical outcomes are poor among patients with infection, as marked by increased LOS and in-hospital mortality. Further study to better identify at-risk patients and improve prevention of infections is needed in this population.
Fig.2 A: Forest plot evaluating association of rifaximin with SBP based on RCTS and observational studies. B: Forest plot evaluating association of rifaximin with HRS
Su1500 THE ROLE OF RECOMBINANT FACTOR VIIA FOR PATIENTS WITH ADVANCED LIVER DISEASE IN ICU SETTING Annu Gupta, Kamal Amer, Kaivalya Deshpande, Michael Elias, Nikolaos T. Pyrsopoulos Background and Aims: Coagulopathy is an important cause of morbidity and mortality in patients with liver failure. The benefits of traditional therapies to correct coagulopathy is often limited. Recombinant activated factor VIIa (rFVIIa) has shown to be effective in improving coagulopathy in a variety of disorders; its use in patients with liver failure is rather limited. The main objective of our study is to review administration of rFVIIa in patients with liver failure in the ICU setting. Methods: A retrospective chart review study from January 2008 to March 2016 was performed to identify patients 18 to 80 years old hospitalized in the ICU setting with evidence of liver failure who received rFVIIa. 30 patients were included in the study. The INR was monitored at 2 and 4 hours after administration of rFVIIa. Two-sample assuming unequal variance T tests was used to see significance between the two populations. The number and type of invasive procedures were identified. Procedure-related complications such as hemorrhage and thrombosis potentially related to rFVIIa were analyzed. Results: The median rFVIIa dose was 63.75 mcg/kg. There was a significant difference in INR levels prior to rFVIIa administration (median=3.7) compared with 2 and 4 hours after rFVIIa treatment (median=1.20 and median=1.45 respectively) with P= 0.0035. Following rFVIIa administration, 65.4% of patients did not require any blood products transfusion. 19 patients underwent invasive procedures which included 7
AASLD Abstracts
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Su1498
Background: Liver transplantation (LT) centers often receive requests for inpatient transfers from other institutions. Anecdotally, these patients have high mortality, particularly if they are new to the accepting LT center with acute-on-chronic liver failure (ACLF). Very little is known about ACLF in this unique transfer cohort. Purpose: The purpose of this study is to examine the characteristics and outcomes of inpatient hospital transfers with ACLF to a high volume LT center in New York City. Methods: Using a prospectively maintained database from July 2011 to July 2013, consecutive referrals for adult inpatient hospital transfer to our LT center were retrospectively examined. Patients seen by a liver provider at our center prior to transfer and repeat transfers of the same patient were excluded. The primary outcome for analysis was inpatient mortality. Secondary outcomes were LT and discharge. ACLF was defined by the North American Consortium for Study of End-stage Liver Disease (NACSELD) criteria (two of the following: shock, grade III-IV hepatic encephalopathy, ventilator dependence, and need for renal replacement therapy (RRT)) and the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria (one of the following: creatinine (Cr) >2, need for RRT, non-renal organ failure (total bilirubin >12, shock, grade III-IV hepatic encephalopathy) and renal compromise (Cr>1.5) or two nonrenal organ failures) at the time of transfer. Statistical analyses were performed. Results: Over a 2-year period, a total of 512 patients were transferred to our center, 221 (43%) of which were never seen previously (new-to-center). These new-to-center patients had a mean age of 53 years, a median MELD of 25 and a slightly male predominance. The most common reason for transfer was ACLF (15%), followed by alcoholic hepatitis (14%). Of the 33 patients transferred for ACLF, 4 (12%) met NACSELD criteria for ACLF and 33 (100%) met EASL-CLIF criteria. The most common identified cause of acute decompensation was infection (n=22, 66%). The overall inpatient hospital mortality rate was 33%. ACLF patients experienced higher 30-day inpatient mortality rates compared to non-ACLF patients (73% vs 26%, respectively; hazard ratio, 1.85; 95% confidence interval 1.12-3.03; p=0.01). As predictors of inpatient mortality, the NASCELD criteria had 17% sensitivity and 100% specificity, while EASL-CLIF criteria demonstrated 100% sensitivity and 0% specificity. Of patients transferred for ACLF, 7 (22%) were listed for LT and 3 (9%) underwent LT during the index hospitalization. Conclusions: ACLF is the most common reason for inpatient transfer to our LT center and is associated with increased mortality but significant eligibility for LT. The EASL-CLIF criteria outperformed NACSELD in predicting inpatient mortality and could be used to triage transferred patients.
Su1497 CHARACTERISTICS AND OUTCOMES OF INTENSIVE CARE IN PATIENTS WITH CIRRHOSIS AT SAFETY-NET HOSPITAL: A MULTICENTER STUDY V. V. Pavan Kedar Mukthinuthalapati, Samuel A. Akinyeye, Zachary P. Fricker, Maya Balakrishnan, Michelle T. Long, Eric Orman, Naga P. Chalasani, Marwan S. Ghabril Background. Critically ill cirrhotics suffer high disease severity, morbidity and healthcare resource utilization, with in-hospital mortality rates that range from 40-80% as reported by tertiary care centers. Safety-net hospitals provide care for vulnerable urban populations with distinct racial and socioeconomic make-up, and face unique challenges in providing critical care to this population. Aims. To characterize intensive care in patients with cirrhosis and associated outcomes at safety-net hospitals. Methods. Data from the ongoing multicenter study ‘Cirrhosis in Urban Safety-net Hospital' (CrUSH) of hospitalized cirrhotics in 20122013 were analyzed (Eskenazi Health Hospital (Indiana University (IU)), Ben Taub Hospital (Baylor College of Medicine (BCM)) and Boston Medical Center (Boston University (BU))). Demographic and clinical data were summarized and compared based on hospital mortality in patients admitted to the intensive care unit (ICU) (Chi square for categorical variables and Mann-Whitney test for continuous variables). Model for end stage Liver disease (MELD) and Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scores were calculated on ICU admission. Results. In 2012, 116 of 555 hospitalized cirrhotics received ICU care at the 3 study centers (55 IU, 35 BCM, 26 BU). Mean age was 54±8, 62% were male, 50% Caucasian, 27% Black and 20% Hispanic. Etiologies of cirrhosis were alcohol 63%, viral hepatitis 47%, fatty liver 4% and cryptogenic disease 5%. Indications for ICU care included: gastrointestinal (GI) bleeding 41%, encephalopathy 16%, respiratory failure 12%, sepsis 4%, shock 3%, and other 21%. Mean MELD was 19±8 and CLIF-SOFA was 6±4. Advanced interventions included mechanical ventilation in 47%, vasopressors in 16%, and dialysis in 8%. The 28 patients (24%) who died during hospitalization had similar age, gender and liver disease etiologies compared with survivors (differences are described in table 1). In 68 patients with available data, CLIF-SOFA and MELD predicted hospital mortality with a c-statistic of 0.87 [95%CI 0.74-.99] and 0.77 [95%CI 0.65-0.89] respectively. Conclusions. Cirrhotics receiving intensive care at safety-net hospitals predominantly suffer from alcoholic and viral liver disease, and are most commonly admitted for GI bleeding. Disease severity (general and liver) and mortality are lower than generally reported by academic centers. Nevertheless, hospital mortality is associated with non-GI bleeding indications for ICU admission and infections, and is predicted by CLIF-SOFA and MELD on ICU admission.
Su1499 RIFAXIMIN FOR PREVENTION OF SPONTANEOUS BACTERIAL PERITONITIS AND HEPATORENAL SYNDROME IN CIRRHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS Faisal Kamal, Muhammad Ali Khan, George Cholankeril, Zubair Khan, Wade M. Lee, Chiranjeevi Gadiparthi, Aijaz Ahmed, Colin W. Howden, Satheesh Nair, Sanjaya K. Satapathy Background Spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS) are associated with high morbidity and mortality in cirrhotics. Prophylactic antibiotics (quinolones) have been recommended in patients with a previous history of SBP. Recently, there has been interest in the use of rifaximin, as it is a poorly absorbed from the GI tract and produces selective decontamination of the gut. It may also decrease IL-6 and TNFα production thereby lowering bacterial translocation and the risks of SBP and HRS. Aims To evaluate rifaximin in the prevention of SBP and HRS in patients with cirrhosis and ascites Methods We searched several databases from inception through October 18, 2016 to identify comparative observational studies and randomized controlled trials (RCTs) evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed pre-determined sub-group analyses based on type of control group (quinolones or no antibiotics), design of study (RCT or observational) and type of prophylaxis (primary or secondary). Pooled odds ratios (OR) were calculated using a random effects model. We used the GRADE framework to interpret our findings. Results We included 10 studies (4 RCTs and 6 observational) with 1483 patients (rifaximin 544, controls 939) in the meta-analysis of SBP prevention. Pooled OR (95% confidence interval) was 0.50(0.25, 1.01), with considerable heterogeneity (I2=61%). We performed a sensitivity analysis after excluding two outlier studies with disproportionately high Child Class C patients in the rifaximin group; adjusted OR was 0.33 (0.21, 0.52),(I2= 0%) in favor of rifaximin. Subgroup analysis based on type of control: in quinolone group, pooled OR was 0.47 (0.11, 1.98),(I2=66%); in no antibiotic group, pooled OR was 0.52(0.21, 1.28), (I2=65%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (0.14, 0.70), (I2=12%) for the quinolone comparison and, 0.33 (0.19,
S-1151
AASLD Abstracts
AASLD Abstracts
ACUTE-ON-CHRONIC LIVER FAILURE IS THE MOST COMMON REASON FOR INPATIENT TRANSFER TO A LIVER TRANSPLANT CENTER AND IS ASSOCIATED WITH HIGH MORTALITY Alexander S. Vogel, Jonathan Nahas, Gene Y. Im
0.59), (I2=0%) for the comparison with no antibiotics. For RCTs alone, the pooled OR was 0.41 (0.22, 0.75), (I2=13%); for observational studies it was 0.52 (0.15, 1.77), (I2=73%). For subgroup analysis based on primary and secondary prophylaxis the pooled OR was 0.32 (0.17, 0.61) and 0.20 (0.07, 0.59), respectively. Four studies with 486 patients evaluated rifaximin for the prevention of HRS; pooled OR was 0.30 (0.15, 0.60), (I2=0%) in favor of rifaximin. Conclusions Initially, we only found a trend towards a protective effect of rifaximin against the development of SBP in patients with cirrhosis and ascites. However, the quality evidence as per the GRADE framework was low. After adjusting for outliers, rifaximin was found to be effective in reducing the risk of SBP. RCTs with rifaximin were more likely to show an advantage than uncontrolled, observational studies. Rifaximin appeared effective for the prevention of HRS.
ICPs, 4 endoscopic interventions for variceal hemorrhage, 8 other procedures (e.g., TIPS, arterial embolization). No evidence of procedure-related hemorrhage and thromboembolic complications were identified. Conclusions: rFVIIa appears to be safe and effective method in improving coagulopathy in patients with liver failure in the ICU setting. It enables patients to undergo invasive procedures and a significant decrease in requirement of blood products transfusion. No thromboembolic events and procedure related hemorrhage were identified in any patient regardless of the dose administered.
Su1501 NON-NEUTROCYTIC BACTERASCITES IN AN OUTPATIENT SETTING: IS ANTIBIOTIC TREATMENT NEEDED? Alireza Meighani, Vijay Jarodiya, Mohammad Arsalan Siddiqui, Kimberly Christensen, Anas Kutait, Vinay Katukuri, Mayur Ramesh, Syed-Mohammed Jafri
AASLD Abstracts
Introduction: Non-neutrocytic bacterascites (NNB) is defined as a positive ascitic fluid bacterial culture but with polymorphonuclear neutrophil (PMN) count <250 cells/mm3. Unlike spontaneous bacterial peritonitis (SBP), there are currently no guidelines on optimal management of NNB in an outpatient setting. We reviewed management of non-neutrocytic bacterascites and compared outcomes with or without antibiotic therapy for complications including 6-month mortality, recurrent infection and hospitalization. Methods: We reviewed records of all patients with liver cirrhosis who underwent outpatient paracentesis in a single urban transplant center from January 2012 to December 2015. Patients with NNB, defined as a positive ascitic fluid bacterial culture with PMN count <250 cells/mm3, were identified. Data was reviewed for development of SBP, recurrent infection, Model for end stage liver disease-sodium (MELD-Na) score and mortality within 6 months of bacterascites. We compared the outcomes of patients who were treated with antibiotics at the time of diagnosis of NNB with patients who were not treated. Results: A total of 100 patients had NNB during the study period. Mean age of our patients was 59 years with 70% being male. Mean MELD-Na at the time of inclusion was 21. The organisms identified in ascitic fluid cultures were Gram-positive cocci (60%), Gram-positive bacilli (22%), Gram-negative bacilli (14%) and mixed Gram-positive/ Gram-negative organisms (4%). Twenty-one patients (21%) were symptomatic at the time of paracentesis with abdominal pain, altered mental status and/ or shortness of breath. Twenty-five patients (25%) received antibiotic treatment after initial diagnosis of NNB. Patients with symptoms at the time of paracentesis were more likely to receive antibiotics (36.0% vs 16.4%, p= 0.040). Also, patients with Gram-positive cocci in ascitic fluid were marginally less likely to receive antibiotics (65.8% vs 44%, p=0.055). Around 11% had another episode of non-neutrocytic bacterascites within 6 months. Recurrence rate was 10.1% for those who did not receive antibiotics and 15% in those who did. Mortality rate was 19.4%, which was 16.9% for those who did not receive antibiotics, and 24% for those who did. Only one patient was diagnosed with SBP in the repeat paracentesis done 1 week after the initial NNB. This subject was symptomatic at the time but did not receive antibiotic treatment. Overall there was no statistically significant difference in the outcomes, including NNB recurrence and mortality between patients who received antibiotics for treatment of NNB and those who did not. Conclusion: In NNB, patients are usually asymptomatic and gram-positive organisms are common in ascitic fluid culture. In our population asymptomatic NNB did not require antibiotic therapy given lack of SBP or positive cultures on repeat evaluation.
Fig. 1 A: Forest plot evaluating association between rifaximin and SBP B: Forest plot after sensitivity analysis.
Su1502 CHARACTERIZATION OF INFECTIONS AND THEIR IMPACT ON PATIENTS WITH CIRRHOSIS ADMITTED TO URBAN SAFETY-NET HOSPITALS: A MULTI-CENTER STUDY Zachary P. Fricker, Samuel A. Akinyeye, V V Pavan Kedar Mukthinuthalapati, Maya Balakrishnan, Naga P. Chalasani, Marwan S. Ghabril, Michelle T. Long Background Infections are a common and morbid complication of cirrhosis and have a major impact on the health of these patients. Previous work has suggested proton-pumpinhibitor (PPI) use is associated with an increased risk of infection. Furthermore, many patients with cirrhosis are prescribed antibiotics for a prolonged interval for prophylaxis against spontaneous bacterial peritonitis (SBP) or hepatic encephalopathy (HE). We aimed to characterize the nature of infections among patients with cirrhosis admitted to safety-net hospitals, as well as risk-factors and outcomes associated with infection. Methods Data from the ongoing multi-center study ‘Cirrhosis in Urban Safety-net Hospitals' (CrUSH) of hospitalized cirrhotics in 2012-2013 were analyzed (Eskenazi Hospital (Indiana University (IU)), Ben Taub Hospital (Baylor College of Medicine (BCM)) and Boston Medical Center (Boston University (BU))). Infections diagnosed within 3 days of hospital admission, baseline clinical and demographic subject characteristics, and clinical outcomes were recorded. Comparison of categorical variables was made via Fischer's Exact test and continuous variables via Mann-Whitney U-test. Results Among 555 unique subjects included, there were 145 infections on admission, distributed across 126 subjects (23%). Infections were distributed relatively evenly across anatomical sites (Table). In-hospital mortality varied with anatomic site of infection (Figure). Pre-admission PPI use was not associated with infection (p=0.75). Subjects with infection on hospital admission had worse outcomes compared to those without infection, including longer length of stay (LOS) (8 vs 6 days, p<0.001) and increased inhospital mortality (13% vs. 5%, p=0.002). Admission MELD score (p<0.001) and history of complicated diabetes mellitus (p=0.002) were associated with presence of infection. Of 66 cases with antibiotic-sensitivity testing data available, 26 (39%) had any resistance to antibiotics. In-hospital mortality rate was higher in cases of infection with an antibiotic resistant organism (19% vs. 6%, p=0.007). Neither use of pre-admission antibiotics of any type (SBP prophylaxis, rifaximin, or other antibiotics for HE prophylaxis) nor use of prophylactic antibiotics against SBP alone was associated with resistant infection. Conclusions Infections are common among patients with cirrhosis, with a high-rate of antibiotic resistance. Increased MELD score is strongly associated with the presence of infection. No association was observed between use of long-term antibiotics and antibiotic resistance or PPI use and infection. Clinical outcomes are poor among patients with infection, as marked by increased LOS and in-hospital mortality. Further study to better identify at-risk patients and improve prevention of infections is needed in this population.
Fig.2 A: Forest plot evaluating association of rifaximin with SBP based on RCTS and observational studies. B: Forest plot evaluating association of rifaximin with HRS
Su1500 THE ROLE OF RECOMBINANT FACTOR VIIA FOR PATIENTS WITH ADVANCED LIVER DISEASE IN ICU SETTING Annu Gupta, Kamal Amer, Kaivalya Deshpande, Michael Elias, Nikolaos T. Pyrsopoulos Background and Aims: Coagulopathy is an important cause of morbidity and mortality in patients with liver failure. The benefits of traditional therapies to correct coagulopathy is often limited. Recombinant activated factor VIIa (rFVIIa) has shown to be effective in improving coagulopathy in a variety of disorders; its use in patients with liver failure is rather limited. The main objective of our study is to review administration of rFVIIa in patients with liver failure in the ICU setting. Methods: A retrospective chart review study from January 2008 to March 2016 was performed to identify patients 18 to 80 years old hospitalized in the ICU setting with evidence of liver failure who received rFVIIa. 30 patients were included in the study. The INR was monitored at 2 and 4 hours after administration of rFVIIa. Two-sample assuming unequal variance T tests was used to see significance between the two populations. The number and type of invasive procedures were identified. Procedure-related complications such as hemorrhage and thrombosis potentially related to rFVIIa were analyzed. Results: The median rFVIIa dose was 63.75 mcg/kg. There was a significant difference in INR levels prior to rFVIIa administration (median=3.7) compared with 2 and 4 hours after rFVIIa treatment (median=1.20 and median=1.45 respectively) with P= 0.0035. Following rFVIIa administration, 65.4% of patients did not require any blood products transfusion. 19 patients underwent invasive procedures which included 7
AASLD Abstracts
S-1152