424 Background: Racial/ethnic (R/E) minorities and patients of low socioeconomic (SE) status are reported to have higher mortality related to HCC than their counterparts. However, prior studies are limited to administrative datasets without annotation for clinical covariates or represent single-center data with limited generalizability. The aim of this analysis was to characterize geographic, R/E, and SE disparities in HCC presentation, treatment, and survival among a representative sample of HCC patients in the US. Methods: TARGET-HCC is an observational, retrospective/prospective study of patients with HCC from academic and community sites. Complete medical records from consented patients are abstracted into a secure database. Multivariable logistic regression with random intercepts for site and Cox proportional hazard models with frailty adjustment were fit with adjustment for age, sex, BMI, liver disease etiology (LDE) and history of alcohol abuse to identify factors associated with early HCC detection, receipt of curative-intent therapy (CIT) and overall survival. Results: 925 patients with HCC (63% non-Hispanic white, 21% black, and 8% Hispanic) were consented from 42 sites in the US (22% Northeast, 27% Southeast, 21% Midwest, 14% South, and 16% West). Median age was 64 years and 76% were men. The most common LDE was hepatitis C (72%), and 72% had Child Pugh A cirrhosis. Most patients were diagnosed with early-stage HCC (72% Barcelona Clinic Liver Cancer 0/A). CIT was the initial therapy in 249 (32%), including 32% of BCLC 0/A. Although early tumor detection and CIT did not differ by region or R/E, there were SE disparities in CIT. Among those with early stage HCC, patients with private insurance [OR = 0.51, 95% CI (0.29, 0.91)] or Medicaid [OR = 0.50, 95% CI (0.25, 0.97)] were significantly less likely to undergo CIT. Overall survival was associated with BCLC stage and type of HCC treatment, with no significant association with region, R/E, or insurance. Conclusions: In this sample of HCC patients, there were no geographic or R/E disparities in early detection, treatment, and survival although SE disparities in administration of CIT were identified and warrant further study.

Nonalcoholic fatty liver disease (NAFLD) has quickly become the most common chronic liver disease in children in many countries around the world.1–5 Estimates in Europe range from 1.3% to 22.5% of children being affected.2,6–9 In the United States, 9.6% of all children and 38.0% of obese adolescents are estimated to have NAFLD.10,11 In China, 45% of obese adolescents are estimated to have NAFLD.12 Certain populations have notable predisposition; for example, in the United States, the highest prevalence is found in Mexican Americans.

Background: Evaluation of drug-induced serious hepatotoxicity (eDISH) is a tool used to assess and identify potential cases of drug-induced liver injury.eDISH was used to evaluate obeticholic acid (OCA) and placebo profiles in 2 double-blind (DB), placebo-controlled studies in patients with nonalcoholic steatohepatitis (NASH).FLINT was a 72-week study, which demonstrated statistically significant improvements in hepatocellular ballooning, steatosis, lobular inflammation, and fibrosis in patients treated with OCA compared to placebo.CONTROL was a 16-week study, which showed that the addition of low-dose atorvastatin reversed OCA-associated changes in LDL-C.The objective of this analysis was to use eDISH to determine if patients with NASH treated with OCA show increased markers of liver injury or whole liver dysfunction.Methods: eDISH methodology was applied to 278 patients treated with placebo (n=140) or 25mg OCA (n=138) from FLINT and 84 patients treated with placebo (n=21), 5mg OCA (n=20), 10mg OCA (n=21), or 25mg OCA (n=22) from CONTROL.Individual subject peak values of alanine aminotransferase (ALT) and total bilirubin throughout the DB treatment phase were plotted on an x-y chart as logarithm 10 values of multiples of elevations above the upper limit of the normal reference ranges (x ULN).Results: Overall, no OCA-treated patients were in the Hy's law quadrant (>3x ULN for ALT and >2x ULN for total bilirubin) compared with 1 placebo-treated patient in FLINT.The proportion of patients with peak ALT and total bilirubin values in the lower left quadrant (representing normal or near normal range) was higher in OCA-treated patients compared with placebo (FLINT: 91% OCA vs 84% placebo; CONTROL: 91% OCA vs 86% placebo).8% of OCA-treated patients from both FLINT and CONTROL presented in the Temple's corollary quadrant (>3x ULN for ALT and <2x ULN for total bilirubin) vs 14% (in both studies) for the placebo-treated patients.Across both studies (N=362), 4 patients were in the cholestasis quadrant (>2X ULN total bilirubin and <3X ULN for ALT); 1 placebotreated patient and 3 OCA-treated patients, including 1 patient with Gilbert's syndrome.Conclusions: In these 2 placebo-controlled, DB NASH studies, the eDISH analysis showed no trend for liver injury with OCA at doses up to and including 25 mg. Su1509

Background:The pathophysiological relationship between Metabolic Syndrome Severity (MSS) and Severe Hepatic Steatosis (SHS) is not fully understood.Studies have shown the degree of MSS to be associated with increased odds of mortality.However, no study to date has examined the relationship between MSS and the presence of SHS, and if such association varies by gender, race and their interaction.The Metabolic Syndrome Severity Score (MetS) is a validated summary score that captures the effects of all 5 metabolic features.This study aims to use the MetS 1) to investigate the association between MSS and the presence of SHS and 2) to quantify racial and gender disparities in such association.Methods: The study sample included 8,495 adults age 20 to 74 years who participated in the Third National Health and Nutrition Examination Survey.Ultrasound was used to classify hepatic steatosis into normal, mild, moderate and severe.In turn, two dichotomous categories were defined for hepatic steatosis (severe vs. moderate, mild or normal).Participants with hepatitis B, hepatitis C, iron overload and excessive drinking were excluded.All 5 metabolic features were used to calculate gender-race specific MetS Z-scores, which were then transformed to 4 percentiles-based categories (none 0-50, low 51-75, moderate 76-90, high 90+).Multivariable logistic regression models adjusting for age, gender, education, smoking, BMI, physical activity, diet index, race and alcohol intake were used to test the associations between MSS and occurrence of SHS.Race-by-MSS and race-by-gender-by MSS terms were added to test disparities in the relationship between MSS and SHS.Results: A total of 977 participants had SHS.The prevalence of moderate and high MSS were 13.62 (95% CI; 12.25, 14.98) and 9.55 (95% CI; 8.52, 10.59), respectively.MSS was a significant predictor of higher odds of SHS in all adjusted models.A dose-response was observed with one level increase in MSS was associated with higher odds of SHS (Table ).Among all participants, those with high MSS had Adjusted Odds Ratio (AOR) of 9.78 (95% CI; 4.58, 20.90) compared to no MSS.Both racial and racial-gender interactions with MSS were statistically significant, with White non-Hispanics having the highest odds of SHS AOR 12.13 (95% CI; 4.92, 29.93) for high versus none MSS.Among White non-Hispanics females, the odds of SHS were highest for high vs. no MSS AOR 14.58 (95% CI; 5.50, 38.64).Among all three racial groups, the odds of SHS were lowest for Black non-Hispanics.For Black non-Hispanic females, the effects of MSS on SHS odds were only significant for the highest severity group.Conclusion: Both racial and racial-gender disparities in the association between MSS and SHS were observed.The effect of MSS on odds of SHS is more significant for White non-Hispanic Females and lower for Black non-Hispanic females.Odds Ratios and 95% CI for the Association Between Metabolic Syndrome Severity and Severe Hepatic Steatosis By Race and Gender NHANES III (n=8,495) †Reference to no metabolic severity † † CI = Confidence Interval Su1524

Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, steatohepatitis (NASH), is an increasingly common problem in patients with T2DM and is associated with progression to cirrhosis and extrahepatic complications (i.e., cardiovascular disease [CVD]). There is limited information on the clinical profile of T2DM patients with NASH in “real world” practice. Accordingly, we studied the clinical profile of participants (pts) with NASH, with or without T2DM (nonDM), enrolled in TARGET-NASH, a large longitudinal observational study of patients with NAFLD followed at 54 sites (39 academic/15 community) across the U.S. Data collected from medical records (including lab data, imaging, pathology, procedures, and outcomes) is sent to a central database utilizing novel data abstraction technology. Among 1743 pts studied to date in TARGET-NASH, 1261 had NASH diagnosed by biopsy or clinical criteria (699 T2DM and 562 nonDM). Pts with T2DM and NASH were older (median 61 vs. 56 years) and had a higher BMI than nonDM (34.0 vs. 32.0 kg/m2, both p<0.01). The prevalence rates of hypertension (68 vs. 41%), dyslipidemia (42 vs. 25%), CVD (26 vs. 17%) all p <0.001, and cancer (17 vs. 12% p=0.015), were higher in T2DM compared to nonDM. Median ALT in T2DM was lower than nonDM (33 vs. 38 U/L, p<0.001). Among pts with a liver biopsy, advanced fibrosis was seen in 55% of T2DM vs. 35% nonDM, including 38 vs. 19% with cirrhosis, respectively (both p<0.001). Among pts with a biopsy and NAFLD Activity Score total, more T2DM had severe steatohepatitis than nonDM (38 vs. 23% p<0.01). In this large cohort of NASH pts managed in standard clinical practice, pts with T2DM had substantially different clinical profiles compared to nonDM. ALT, only modestly elevated in most pts with NASH, is not a reliable marker for NASH. Diagnosis requires reliance on clinical features and additional testing. Further investigation of independent risk factors and long-term outcomes is ongoing. Disclosure K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc. A.S. Barritt: Consultant; Self; Targetpharma solutions. Consultant; Spouse/Partner; Targetpharma solutions, Takeda Pharmaceuticals U.S.A., Inc., AbbVie Inc.. V. Clark: None. R.J. Firpi: None. S. Klein: Stock/Shareholder; Self; Aspire Bariatrics. Consultant; Self; Pfizer Inc.. Research Support; Self; Merck & Co., Inc., Johnson & Johnson Services, Inc., REMD Biotherapeutics. A. Lok: None. R. Loomba: Research Support; Self; Adheron, Arora, BMS, Daiichi-Sankyo Inc., Galectin, Galmed, GE, Genfit, Gilead, Immuron, Intercept, Kinemed, Madrigal, Merck, NGM, Promedior, Prometheus, Siemens, Sirius, Tobira. Advisory Panel; Self; Arrowhead Research, Conatus, Galmed, Gilead, Intercept, NGM, Nimbus, Octeta, Tobira. Consultant; Self; Alnylam, Bird Rock Bio, BMS, Boehringer Ingleheim, Celgene, Conatus, DeuteRx, Eli Lily, Enanta, Fibrogen, Genkyotex, Gilead, GRI Bio, ISIS, Janssen Inc.Kirin, Madrigal, Metacrine, NGM, Nitto Denko, Pf, Sanofi,Scholar Rock, Shire, Tasly, Viking, Yuhan Pharmaceuticals, Zafgen. L. Malahias: None. B. Neuschwander-Tetri: None. C. Schoen: None. K. Reddy: Advisory Panel; Self; Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc.. Other Relationship; Self; Novartis AG, Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc., Mallinckrodt Pharmaceuticals, Conatus Pharmaceuticals Inc., Intercept Pharmaceuticals, Inc.. J.L. Taunk: None. K. Wyne: Research Support; Self; Sanofi. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company. A.J. Sanyal: Stock/Shareholder; Self; Sanyal Bio, Genfit, Durect, Indalo, Exhalenz. Consultant; Self; Gilead, Boehringer Ingelheim, Intercept. Advisory Panel; Self; Galectin, NGM. Consultant; Self; Pfizer.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown. TARGET-NASH is a 5-year, longitudinal, observational study of patients with NAFLD designed to evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. A biological specimen repository is included in TARGET-NASH for translational studies of genomics and biomarkers of disease activity. Patients are enrolling at adult and pediatric sites representing multiple specialties. All patients being managed for NAFLD are eligible, whereas those in other NASH registries or clinical trials will be excluded. Enrolled patients range in age from 6 and up and will have 3years of clinical data reviewed. Patient comorbidities, concomitant medications, disease progression and off-label interventions will be assessed, and adverse outcomes, monitored. Confirming the use, safety and effectiveness of NAFLD interventions in children and adults and establishing pragmatic methods of assessing disease progression under real-world conditions are key study outcomes. Ultimately, TARGET-NASH will establish a large, diverse registry of NAFLD patients at academic and community practices to be leveraged to improve health and reduce development of cirrhosis and hepatocellular carcinoma.