817 Prevalence and Severity of Gastrointestinal Symptoms in Cirrhosis

p=0.002], malnutrition [HR 2.661 (95% CI 1.285-5.511), p=0.008], and log-transformed serum adiponectin level [HR 1.491 (95% CI 1.021-2.176), p=0.039] were associated with the combined endpoint of death or liver transplantation. In the multivariate model, only INR [HR 2.451 (95% CI 1.223-4.911), p=0.011], malnutrition [HR 2.233 (95% CI 1.0044.967), p=0.049], and log-transformed serum adiponectin level [HR 1.527 (95% CI 1.0283.367), p=0.036] were independently associated with the combined endpoint of death or liver transplantation. The median transplant-free survival time was shorter in malnourished patients [145 days (IQR 82-273 days) vs. 535 days (IQR 194-722 days), p =0.006]. Conclusions: Malnutrition and adiponectin are associated with decreased transplant-free survival in hospitalized cirrhotic patients. These findings highlight the importance of adipose tissue on clinical outcomes in end-stage liver disease. Future studies are ongoing to validate these findings in other populations.

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Background: Hepatic encephalopathy (HE) may occur after transjugular intrahepatic porto systemic shunt (TIPS) placement. Multimodal MRI, combining morphologic sequences, diffusion tensor imaging (DTI), and H proton magnetic resonance spectroscopy (MRS), is modified in cirrhotic patients even in the absence of patent HE, and may predict HE development. Aims: (1) To assess if TIPS induces changes in multimodal MRI; (2) To correlate changes to the development of HE after TIPS. Methods: All consecutive patients with cirrhosis and an indication for TIPS were prospectively screened. Exclusion criteria were: common contra-indication to MRI, active drinking, overt HE. Neurocognitive evaluation using Psychometric HE test score (PHES) was assessed at baseline, the day of MRI, and 3 months after TIPS. MRI combined morphologic sequences, DTI, and MRS. DTI data were processed with standard tools of FSL5 including eddy current correction and the tensor metrics (Fractional Anisotropy, FA and Mean Diffusivity, MD) computation. Averaged measures of FA and MD were calculated within the 48 regions of the ICBM-DTI-81 white-matter labels atlas. Results: 23 consecutive patients were prospectively analysed (age 57 ± 8, male gender 68 %, Child-Pugh score 7.8 ± 1.6, MELD score 12 ± 4, cause of cirrhosis: OH/ virus/others 14/4/5, indication for TIPS placement: ascites/secondary prophylaxis of variceal bleeding: 20/3, HE status: no HE/minimal HE (MHE)/patent HE: 18/5/0. 8/23 patients developed HE after TIPS (1 MHE, 7 patent HE). Baseline metabolites were not predictive of the development of HE after TIPS. TIPS induced significant changes in MRS metabolites as compared to baseline, in patients without or with HE: decrease in creatinin, inositol, glycerophosphocholine; increase in glu/gln and GABA. After TIPS, metabolites were significantly different between patients with or without HE: increase in glu/gln and decrease in N-acetylaspartate, glycerophosphocholine. TIPS did neither modify FA nor MD. However, baseline FA was significantly lower in patients who developed HE in cingulate gyrus, in internal and external capsule and in fronto-occipital regions. Conclusion: TIPS induced significant changes in cerebral metabolites, even in the absence of the development of HE. DTI findings before TIPS could help predicting the development of HE after TIPS. This finding could help refining a population where prophylactic treatment of HE before TIPS is warranted.

817 Prevalence and Severity of Gastrointestinal Symptoms in Cirrhosis Alice Zhang, Christopher V. Almario, William D. Chey, Brennan Spiegel Background: Individuals with cirrhosis are at risk for well-known complications of portal hypertension, such as ascites, variceal bleeding, and hepatic encephalopathy. However, less is known about the distribution and severity of common GI symptoms in communitydwelling cirrhotic patients, such as abdominal pain, diarrhea, constipation, and heartburn, among others. We hypothesized that patients with cirrhosis have a higher GI symptom burden and severity vs. those without the disease. To test this hypothesis, we used data from the "National GI Survey" - a population-based audit of GI symptoms in over 71,000 Americans - to compare the prevalence and severity of GI symptoms between those with and without cirrhosis. Methods: To evaluate the burden of GI symptoms in the US, we conducted the National GI Survey in October 2015 using My Gi Health, a mobile app that employs a previously validated computer algorithm called AEGIS (Automated Evaluation of GI Symptoms) to systematically collect patient GI symptoms. We partnered with Cint®, a survey research firm, to recruit a representative sample of Americans to complete AEGIS. AEGIS guided participants through NIH GI Patient Reported Outcome Measurement Information System (PROMIS®) surveys along with questions about relevant comorbidities and demographics. We compared the GI symptom burden and severity between individuals with and without cirrhosis. The exposed group consisted of those who were age ‡18 years and reported a physician diagnosis of cirrhosis. We paired each cirrhotic patients with up to 50 age- and sex-matched controls without cirrhosis. Our outcomes were (1) presence of GI symptoms and (2) symptom severity as measured by NIH GI PROMIS scores. We used regression models to adjust for confounding factors. Results: A total of 71,813 individuals completed AEGIS, of which 435 (0.6%) reported a physician diagnosis of cirrhosis. There were 18,009 age- and sex-matched controls without cirrhosis. Overall, 89.9% of cirrhotic patients had ‡1 GI symptom in the past week vs. 61.7% for matched controls (adjusted p<.001). Patients with cirrhosis were more likely to report abdominal pain, bowel incontinence, bloating, diarrhea, nausea, and dysphagia vs. controls ( Table 1); there was no difference in heartburn/reflux and constipation between groups. Among symptomatic individuals, cirrhotic patients had higher PROMIS scores for all 8 GI PROMIS symptoms versus matched controls (Table 2). Conclusions: In this population-based survey, we found that community-dwelling individuals with cirrhosis have a significantly higher burden and severity of common GI symptoms when compared to those without cirrhosis. These data suggest that in addition to evaluating for portal hypertensive complications, clinicians should also screen for and manage common GI symptoms that can negatively impact quality of life.

816 Malnutrition and Serum Adiponectin Levels Are Independent Predictors of Transplant-Free Survival in Hospitalized Cirrhotic Patients Amy Lu, Jaideep Behari, Vikrant Rachakonda Background and Aims: Malnutrition is a common complication of chronic liver disease. While current definitions are based on skeletal muscle measurements, we recently demonstrated that adipose-derived factors, including serum leptin levels, are associated with the d e v e l o p m e n t o f m a l n u t r i t i o n in ho sp it al iz ed ci rr ho ti c p at ie nt s ( He pa to lo gy 2015;62(S1):940A). The aim of this study was to determine the influence of nutritional factors on transplant-free survival in this cohort. Methods: This was a prospective observational cohort study of 52 hospitalized cirrhotic patients who were classified either as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference<23 cm and dominant handgrip strength<30 kg (Liver Transpl 2000; 6(5):575-81). Nutritional biomarkers were collected, and patients were assessed for the combined endpoint of death or liver transplantation. Transplant-free survival was analyzed using Kaplan-Meier methods, and Cox proportional hazards analysis was used to determine nutritional parameters associated with decreased survival. Results: Median age was 57.5 years (IQR 50.5 - 62.5 years), and 42.3% were women. Cirrhosis etiologies included viral hepatitis (32.6%), alcoholic liver disease (46.2%), non-alcoholic fatty liver disease or cryptogenic cirrhosis (32.7%), and others (5.7%). The median follow-up time was 205 days (IQR 82.0−534.25 days). Thirty-three patients (63.5%) died (n =22) or underwent liver transplantation (n=11) during the followup period. Univariate Cox analysis demonstrated that prior transjugular intrahepatic portosystemic shunt (TIPS) placement [HR 0.214 (95% CI 0.051-0.899), p=0.035], Model for EndStage Liver Disease (MELD) Score [HR 1.084 (95% CI 1.012-1.161), p=0.021], Child Pugh Score [HR 1.219 (95% CI 1.043-1.424), p=0.013], INR [HR 2.703, 95% CI (1.455-5.022),

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AASLD Abstracts

Transjugular Intra Hepatic Porto Systemic Shunt (TIPS) Placement Induces Modifications of Cerebral Multimodal MRI in Cirrhotic Patients, Even in the Absence of Development of Hepatic Encephalopathy (HE) Marika Rudler, Nicolas Weiss, Vincent Perlbarg, Maxime Mallet, Simona Tripon, Damien Galanaud, Dominique Thabut

AASLD Abstracts

Table 1. Prevalence of GI symptoms

Fig 1. Overall 90-day survival rate (%) across MELD scores stratified based on Hepatic Encephalopathy (bold arrows represent range of scores with higher magnitude of difference in survival).

AASLD Abstracts

(a) Experienced within the past 7 days. (b) The logistic regression model adjusted for age, sex, race/ethnicity, education level, marital status, employment status, household income, and number of medical comorbidities (non-cirrhosis). The reference group was non-cirrhotic individuals. Table 2. NIH GI PROMIS scores

(a) Experienced within the past 7 days. (b) GI PROMIS score for individual symptoms is on a 0-100 percentile scale. (c) The linear regression model adjusted for age, sex, race/ ethnicity, education level, marital status, employment status, and household income. The reference group was non-cirrhotic individuals.

Fig 2. Overall 90-day survival rate (%) among four MELD score cohorts in No HE vs. Grade 3-4 HE (error bars represent standard error).

940 818 Death Is Rare and Progression to Transplant Is Slow, Despite a Burden of Portal Hypertension, in Longitudinal Outcomes of Alpha-1-Antitrypsin Deficiency From the Children Cohort Jeffrey Teckman, Anna Conlon, Philip Rosenthal, Lee Bass, Karen F. Murray, Kasper Wang, John C. Magee, Catherine Spino

Hepatic Encephalopathy (HE): Impacting Waitlist Survival and Implications in Current Organ Allocation Policy for Liver Transplantation (LT) Avin Aggarwal, Robert J. Wong, Ryan B. Perumpail, Zobair M. Younossi, Aijaz Ahmed Background: Organ allocation has always aimed to prioritize LT for the sickest people on the waitlist. With increasing number of waitlisted patients wait times have increased and hence increased waitlist removals due to mortality or morbidity is a growing concern. Model for End Stage Liver Disease (MELD) was adopted as a measure of objective scale of disease severity incorporating measurement of serum creatinine, total bilirubin and INR. Currently HE is not considered in allocation prioritization and has been shown to be an independent predictor of mortality in various studies. Methods: Utilizing United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS/OPTN) registry from 2003-2012, we compared the overall 90-day survival among LT waitlist registrants with no HE vs. Grade 3-4 HE (based on West Haven Criteria) for MELD scores >20. Survival data was further stratified into four groups (MELD score: 21-25; 26-30; 31-35; and ‡ 35). Results: Overall 90-day LT waitlist survival was significantly lower among waitlist registrants with Grade 3-4 compared to those with no HE among all the groups, especially at MELD score ‡30 (Fig.1). Among MELD 31-35 mean survival was 73.04% in no HE vs. 47.86% in Grade 3-4 HE (p-value 0.0003). Among MELD >35 mean survival was 60.26% vs. 36.64% (pvalue 0.012) respectively (Fig.2). Most interestingly patients with grade 3-4 HE with MELD 30-34 had lower mean survival percentage of 52.24% vs 62.97% in those without HE but MELD ‡35 (p-value 0.01). Conclusions: Among MELD score cohorts, there is a significantly higher mortality in waitlisted registrants with Grade 3-4 HE, especially at MELD ‡30. This remarkable difference clearly demonstrates the patient population that is much sicker and is already at disadvantage with the current allocation system, especially in Donation Service Areas (DSAs) like California and New York that transplant at much higher MELD scores than the national median of 27. Further a large subgroup (with Grade 3-4 HE and MELD 30-34) does not benefit from regional organ sharing while continuing to have higher mortality. Further investigation is warranted to examine whether considering exception criteria for HE could reduce the existing disparity in waitlist mortality.

AASLD Abstracts

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Background: The Childhood Liver Disease Research Network (ChiLDReN) is a longitudinal study of pediatric liver diseases, including subjects with alpha-1-antitrypsin deficiency (AAT), aiming to document the natural history in North America, identify predictors of clinical outcomes and identify disease modifiers. Objective: Summarize and identify predictors of clinical outcomes, including portal hypertension (PHT), liver transplantation and death, in AAT subjects with native liver. Methods: PIZZ and PISZ subjects, 0-25y, have enrolled since Nov. 2007 at 14 North American tertiary care centers, with liver disease as defined by having one of: neonatal cholestasis, chronically elevated AST, ALT or GGT (>1.25xULN), chronic hepatomegaly, clinical findings or complications of PHT or cirrhosis, impaired liver synthetic function, or liver biopsy abnormalities other than globular inclusions. Baseline visits recorded data from medical records, history, physical exam, laboratory, imaging and other information obtained as part of routine clinical care, that were updated at prospective annual visits. PHT was defined as: (1) history of a complication of PHT (variceal hemorrhage, ascites, or hepatopulmonary syndrome) or (2) clinical findings consistent with PHT (splenomegaly [spleen > 2 cm below the costal margin] or thrombocytopenia [platelet count < 150,000]). PHT was "absent" if none of the criteria were met. Available clinical studies (liver biopsies, ultrasounds, endoscopies) were then examined to confirm the PHT assignment. Kaplan-Meier methods and Generalized Estimating Equations (GEE) were used to analyze time to event and correlated longitudinal dichotomous outcomes. Results: 284 subjects enrolled with native liver (61% male). 209 (74%) entered the cohort without PHT, and approximately 3% of these developed PHT per year. 21 of 284 had liver transplants during 1672 person-years of follow up. 19 of the 21 subjects transplanted entered the cohort with PHT. Only one death is reported. No physical exam or laboratory measure predicted PHT (p>0.05). Significantly lower weight-Z scores and mid arm circumference were seen after development of PHT compared to those without PHT (p<0.05), but the cohorts were not different for height, BMI, triceps skin fold, or head circumference. No physical exam or laboratory measures predicted progression to liver transplant or death, although power was limited by low numbers of transplants. Conclusions: Young AAT patients at tertiary care centers have a significant burden of PHT, affecting growth parameters, but progress slowly to liver transplant. Death is very rare in the transplant era. PHT almost always precedes transplant by several years. Clinical parameters collected during conventional provision of care did not predict PHT or transplant, suggesting an important role of unidentified genetic and environmental modifiers.

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