378 Total Body Weight Loss of ≥10% Is Associated With Improved Hepatic Fibrosis in Patients With...
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Cirrhosis Predicts Mortality in Hospitalized Patient Requiring Dialysis forAcute Kidney Injury (AKI) and Is an Independent Risk Factor for NewHemodialysisMuhammad Ali, Shahryar Ahmad, Nilay Kumar, Gagan Kumar, Kia Saeian
Introduction: Acute kidney injury (AKI) affects hospitalized patient and increases mortality.Cirrhotics have fragile hemodynamics and are prone to AKI from multiple reasons includinghepatorenal syndrome. Patients who do not improve with AKI require renal replacementtherapy with hemodialysis (HD). Our aims for the study were 1) to look at the differencesbetween cirrhotics and non-cirrhotics requiring HD, 2) to determine if cirrhosis was anindependent risk factor for mortality in this population, 3) to determine effect of cirrhosison odds of receiving dialysis. Materials and Methods: Nationwide Inpatient Sample (NIS)from year 2008 was used to select patients with a discharge diagnosis of AKI. AppropriateICD-9 codes were used to identify patients with cirrhosis as well as those requiring HD.Students t-test was used for categorical variables, Chi square was used to compare categoricalvariables. Logistic regression was for adjusted analysis. Results: There were about 6.8 milliondischarges in 2008. Out of those, 100,516 (14.6%) were associated with AKI whereas140,095 (2%) were associated with cirrhosis. Prevalence of AKI in non cirrhotics was lessthan that in cirrhotics (6.65% vs. 14.63%, p,0.001). Only 16% of AKI admissions amongcirrhotics were also associated with hepatorenal syndrome. On unadjusted analysis, amongpatients with AKI, more cirrhotics required new hemodialysis as compared to non-cirrhotics(11.37% vs. 6.5%, p,0.001). On unadjusted analysis, among patients requiring HD, morecirrhotics were in the 35-65 age group (69% vs 41% p ,0.001), were male (65% vs 56%,p.0.001), were hispanic (16.5% vs. 8.5%, p.0.001) and had higher mortality (41.8% vs.20.1%, p.0.001). Non cirrhotics had more Medicare as insurance (60.0% vs. 37.8%,P.0.001), were admitted to non-teaching hospitals (47.7% vs. 32.9%, p .0.001) and haddischarge disposition of home (41.4% vs. 36.2%, p.0.001). Cirrhotics had longer lengthof stay (19.2 vs. 16.5 days, p.0.001) and had increased hospitalization cost ($203k vs.$141k, p.0.001). On adjusted analysis, cirrhosis was associated with about 3 times oddsof dying (OR 3.08, 95% confidence interval 2.78-3.34) in patient requiring HD. Afteradjusting for various demographic variables, cirrhosis was found to be an independent riskfactor for new HD among hospitalized patients with AKI (OR 1.46, 95% CI 1.39-1.53).Conclusion: In this nationally representative analysis, cirrhosis is a risk factor for receivingnew dialysis in patients with acute kidney injury, as well as being an independent risk factorfor mortality in this population. Further studies looking into the factors associated withthese findings are warranted.
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Impact of Malnutrition on Clinical Outcomes in Hospitalised Patients WithChronic Liver DiseaseDep Huynh, Shane P. Selvanderan, Hugh A. Harley, Richard H. Holloway, Nam Q.Nguyen
Malnutrition is common in patients with chronic liver disease. The prevalence is dependenton disease severity and the population examined (reported range 16-90%). Evidence forthe impact of malnutrition on morbidity and mortality has mostly been derived from datain the liver transplant population. The aim of this study is to examine the impact ofmalnutrition on outcome in hospitalised patients with cirrhosis, in a non-liver transplanttertiary hospital Method: Data related to hospitalized patients with liver cirrhosis who hadformal dietetic assessment, at the Royal Adelaide Hospital, over 20 months were reviewed.Patients' demographics, disease severity, nutritional status and assessment, biochemistry,and clinical outcomes were collated. Nutritional status was assessed by a dietician anddetermined by subjective global assessment. Median duration of follow up was 11 (0-28)months. Results: Of the 98 cirrhotic patients (69 males, age 56 ± 1.4 year, 4% Childs A,39% Childs B, 57% Childs C) who had dietician review and subjective global assessment,54 (55%) were deemed to have malnutrition. There was no difference in Childs Pugh score(10.1 vs 9.9, p=0.55) or MELD score (18.5 vs 17.4, p=0.45) between patients with malnutri-tion and normal nutritional status. Although malnutrition was not associated with prolongedhospital stay (median: 9(1-113) vs. 9.5(1-100) days, p=0.67), greater 1-year readmissionrate (1.9±0.4 vs. 2.1±0.5; p=0.67) or more infectious complications (31% vs 25%, p=0.5),both 28-day (19% vs. 5%, p=0.06) and 1-year (50% vs. 18%, p=0.001) mortality werehigher in cirrhotic patients with malnutrition than those without. The overall relative riskof death from malnutrition in these patients was 2.8 (1.4-5.4). The presence of malnutritiondid not influence the occurrence of ascites (80% vs 84%, p=0.61 versus no malnutritionrespectively) and hepatic encephalopathy (56% vs 57%, p=1.0). Conclusions: Malnutritionis common amongst hospitalized patients with chronic liver disease and is associated withhigher short and long-termmortality without affecting the related morbidities, hospital lengthof stay or re-admissions. The role of aggressive nutritional support during hospitalization andafter discharge warrants further evaluation in these patients.
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Total Body Weight Loss of ≥10% Is Associated With Improved HepaticFibrosis in Patients With NASH: Data From a Population With Serial LiverBiopsiesLisa M. Glass, Rolland C. Dickson, Joseph C. Anderson, Arifa Toor
BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a significant and increas-ing cause of liver disease. Advanced fibrosis has been associated with several factors, includingage, BMI, glucose intolerance, elevated ferritin, and tobacco use. AASLD guidelines recom-mend that patients lose 10% of their total body weight (TBW) for NASH management, asthis has been shown to correlate with histologic improvement in steatosis, inflammation,and NAFLD activity score. The effect of weight loss on hepatic fibrosis is less well understood.The AIM of this study was to determine the predictors associated with changes in hepaticfibrosis in NASH patients undergoing serial liver biopsies. METHODS: This was a retrospec-tive cohort study of NASH patients who underwent serial biopsies from 1999 to 2011 in
S-946AASLD Abstracts
order to monitor disease progression. Patients with significant alcohol use or concomitantliver disease were excluded. Liver biopsies were scored according to the NASH ClinicalResearchNetwork guidelines: fibrosis stage 0-4. Regression of fibrosis was defined as improve-ment in fibrosis score of at least 1 stage. Univariate analysis utilized Fischer's exact test forcategorical data and two-tailed student's t-test for continuous variables. Multivariate regres-sion models were performed to determine independent predictors for regression of fibrosis.RESULTS: 46 NASH patients with serial biopsies collected at 1-7 year intervals were includedin the study. At the time of the first biopsy, the average age was 47 years (28-69), with anaverage BMI of 39.5 (26.0-66.7). 27.7% of patients were male, and 63.8% had glucoseintolerance or diabetes mellitus. The average initial fibrosis stage was 2 (0-4), and 1 patienthad histologic cirrhosis. Univariate analysis revealed a higher rate of fibrosis regressionamong patients who lost ≥10% TBW (63.2% vs. 15.4%; p =0.002). There was a trendtoward fibrosis regression among patients with hypertriglyceridemia at their first liver biopsywho normalized their triglyceride levels at the time of second liver biopsy (50% vs. 7.7%;p=0.05). Factors such as age, gender, glucose intolerance, tobacco use, elevated ferritin, andA1AT heterozygosity did not influence fibrosis regression. On multivariable analysis onlyweight loss of ≥10% TBW remained a predictor of fibrosis regression (OR 10.8, 95% CI2.4-47.5). CONCLUSION: This study suggests a primary focus of NASH treatment shouldbe TBW loss of ≥10%, as recommended by the AASLD guidelines. Treatment of triglyceridesmay also be of benefit. Regression of fibrosis, a key disease end point, gives strongersupport for the AASLD weight loss guidelines which are currently based on studies showingimprovement in NAFLD activity score.
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Novel Genetic Loci Associated With Steatohepatitis and Fibrosis in HispanicBoys With Nonalcoholic Fatty Liver DiseaseJoel E. Lavine, Naga P. Chalasani, Xiuqing Guo, Soonil Kwon, Jeffrey Schwimmer, Jean P.Molleston, Rohit Loomba, Elizabeth M. Brunt, Yii-Der Ida Chen, Mark O. Goodarzi, KentD. Taylor, Katherine P. Yates, Aynur Unalp, Jerome I. Rotter
Background: Children with nonalcoholic fatty liver disease (NAFLD) may be at greater riskfor progression with more penetrant genetic traits than found in adults. Adolescent Hispanicboys are at greatest risk. No genome-wide association scan data exist on children withNAFLD. Aim: To identify gene loci associated with predisposition to nonalcoholic steatohepa-titis (NASH) and fibrosis in Hispanic boys characterized by the NASH Clinical ResearchNetwork. Methods: 234 Hispanic boys 2-17y with clinical, laboratory and histological datafrom liver biopsy were analyzed for 624,297 single nucleotide polymorphisms (SNPs) overall 22 autosomal chromosomes. After elimination of 4 with outlier SNPs and 22 with crypticrelatedness, association analyses were performed on DNA from 208 subjects with liverhistology scored by NASH CRN pathologists. Genotyping was performed using IlluminaOmniExpress chips. Genotypes were determined based on clustering of the raw intensitydata using Illumina BeadStudio software. Analyses of logistic regression for qualitative traitsand linear regression for quantitative traits were conducted. Traits of interest includedNAFLD Activity Score (NAS), NASH vs. NAFLD without NASH, and fibrosis. A two-tailedp-value ,10e-6 was deemed significant, using only minor allele frequencies for reportedtraits .0.05. Results: The median age and BMI z-score were 12.0 years (interquartile range,11.0 to 14.0) and 2.4 (interquartile range, 2.1 to 2.6), respectively. NAS (scores 1-4 vs. 5-8) associated with SNP rs11166927 on chromosome 8 in the C8orf17/potassium channel,subfamily K, member 9 region (p = 8.7e-07). A linear regression model for NAS associatedrs1546740, rs12476047, and rs9879289 for NAS (scores 1-8) on chromosomes 7 (p=7.7e-06), 2 (p=8.5e-06) and 3 (p=9.2e-06) respectively. Degree of fibrosis associated with SNPrs128907 on chromosome 20 within actin-related protein 5 homolog (p=9.9e-07). TwoSNPs were associated with NASH versus NAFLD without NASH on logistic regression: SNPrs6571631 on chromosome 14 near Rho guanine nucleotide exchange factor ARHGEF40(p=6.5e-06), and rs6660749 on chromosome 1 near C1orf94 (p=8.2e-06). The intentionalhomogeneity of the cohort regarding ethnicity, gender and age are strengths for a GWASthis size. Conclusions: In this pilot GWAS study of well-characterized Hispanic boys wefound significant novel relations on histologic factors associated with NASH and fibrosisthat are distinct from those previously reported in adults. Pediatric NAFLDmay have a distinctgenetic susceptibilities. Validation of these traits in larger GWAS studies and mechanisticcharacterization of their role in etiopathogenesis will advance our knowledge of early onsetNAFLD in vulnerable Hispanic populations.
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Hepatic Steatosis Is an Independent and a Strong Predictor of CoronaryArtery Disease in Asymptomatic Patients, Beyond That Expected FromConventional Framingham Risk Factors and Metabolic SyndromeRajiv Chhabra, Harshal Patil, Shaya Ansari, Linda Lee, Randall Thompson, James H.OKeefe, Kevin Kennedy, John H. Helzberg
BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) may be at increasedrisk of developing coronary artery disease (CAD) beyond that expected from conventionalFramingham risk factors. The risk of developing CAD in asymptomatic patients with hepaticsteatosis has not been evaluated. Using a coronary calcium score (CCS) . 100 Agatstonunits to define significant coronary calcification and CAD,we prospectively examinedwhetherNAFLD, as determined from non-contrast computed tomography (CT), is predictive of CADin asymptomatic patients. METHODS: 377 asymptomatic patients self-referred for screeningnon-contrast CT to determine CCS were studied. Upper abdominal CT images were usedto determine the presence of hepatic steatosis measuring the difference in liver and spleenattenuation of . 10 Hounsfield units by a blinded radiologist. Metabolic syndrome wasdefined using the ATP III or WHO criteria. Patients underwent a single fasting bloodprocurement to evaluate liver chemistries, lipid profile, and exposure to hepatitis B and C.Patients were excluded if they consumed five or more alcoholic beverages per week. AnAPRIORI model was created to predict CCS.100 based on traditional Framingham riskfactors: age, male gender, smoking, LDL, hypertension, diabetes mellitus and also metabolicsyndrome. Hepatic steatosis was then added to this model. Computation of the odds ratiofor hepatic steatosis, c-statistic, and the integrated discrimination improvement (IDI) was