Clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Slideset on: Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty.

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clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Slideset on: Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140: NAFLD and NASH Prevalence in US Cohort Higher Than Previously Estimated This program is supported by educational grants from

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Background and Rationale  NAFLD a manifestation of metabolic syndrome –Common cause of abnormal liver enzymes –Increases risk for diabetes and coronary artery disease –Linked to presence of obesity and diabetes, both increasing in the US –Most clinically relevant subset of NAFLD patients is those with NASH  Previous estimates of NAFLD prevalence vary widely depending on study population and diagnostic technique (liver biopsy, imaging, liver enzymes)  Estimates of NASH difficult to establish due to need for liver biopsy  Current study prospectively determined prevalence of both NAFLD and NASH in US adult outpatients without known liver disease Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Summary of Study Design  Outpatients aged yrs recruited from Brooke Army Medical Center in Texas during primary care visits or visits for colon cancer screening from January March 2010 –Exclusion criteria: history of chronic liver disease, HIV infection, receipt of medications associated with fatty liver (eg, steroids, tamoxifen), alcohol use > 20 g/day  Baseline questionnaire: queried about medical history, current medications, current/past alcohol consumption, dietary habits  Standard right upper quadrant ultrasound: liver images independently reviewed by expert staff radiologist for presence of steatosis based on echogenic features  Laboratory analyses and percutaneous liver biopsy for patients identified as having fatty liver by ultrasound –Liver biopsies reviewed by expert hepatopathologist; steatohepatitis graded and staged according to Brunt system, if present Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Main Findings  46% of patients had NAFLD according to evidence from ultrasound and liver biopsy (if performed) –22 of these 151 patients refused liver biopsy, but NAFLD still assumed  Highest prevalence of NAFLD observed in Hispanics (58.3%), followed by whites (44.4%) and blacks (35.1%) CharacteristicNAFLD (n = 151) No NAFLD (n = 177) P Value Mean age, yrs (SD)55.9 (6.48)53.5 (7.87).004 Male, % Mean BMI (SD)32.4 (5.30)27.6 (4.94)<.0005 Obese (BMI ≥ 30), % < Hypertension, % < Diabetes, % < Fast food (≥ 1 time/wk), % Exercise (≥ 30 min/wk), % Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Main Findings  12.2% of all patients had NASH according to liver biopsy –29.9% prevalence of NASH among subset of patients with fatty liver identified by ultrasound  Highest prevalence of NASH observed in Hispanics (19.4%), followed by blacks (13.5%) and whites (9.8%) –Difference in prevalence between Hispanics and whites statistically significant (P =.03) CharacteristicNASH (n = 40) No NASH (n = 89) P Value Mean BMI (SD)34.4 (5.41)31.7 (5.34).01 Obese (BMI ≥ 30), % Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Main Findings  Insulin and ALT found to independently predict for NASH –These variables used in an equation to predict NASH with receiver operating characteristic curve of (95% CI: ; P <.001) –Cutoff value of derived from equation yielded sensitivity and specificity of ~ 75%, enabling creation of probability curve using insulin and ALT to detect NASH Laboratory ParameterNASH (n = 40) No NASH (n = 89) P Value Mean quantitative insulin-sensitivity check index (SD) 0.30 (0.02)0.33 (0.03)<.0005 Mean insulin, µIU/mL (SD)23.2 (13.0)14 (8.4)<.0005 Mean ALT, U/L (SD)50.9 (19.55)36.2 (15.73)<.0005 Mean AST, U/L (SD)36.3 (13.05)25.6 (7.44)<.0005 Mean HDL cholesterol, mg/dL (SD)44.3 (9.01)49.2 (15.65).03 Mean adiponectin, ng/mL (SD)7815 (4811)11,028 (13,078).02 Mean hsCRP, ng/mL (SD)7351 (6397)5355 (5537).04 Mean cytokeratin-18, U/L (SD)307.1 (233.1)210.3 (118.0).02 Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Other Outcomes  Diabetics (16.5% of cohort) significantly older, heavier, more likely to be hypertensive, and exercised less than nondiabetics –74.0% of diabetics had NAFLD and 22.2% had NASH –All individuals with NASH were obese and hypertensive CharacteristicDiabetic (n = 54) Nondiabetic (n = 274) P Value Mean age, yrs (SD)59.1 (6.66)53.7 (7.16)<.0005 Mean BMI (SD)32.8 (4.77)29.2 (5.62)<.0005 Hypertension, % < Exercise (≥ 30 min/wk), % Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Other Outcomes  9 of 40 patients diagnosed with NASH had significant fibrosis (stages 2-4), accounting for 2.7% of total cohort –These patients had significantly greater insulin resistance vs patients with mild fibrosis –Mean AST trended higher vs patients with mild fibrosis (43.4 vs 34.3 U/L; P =.062) –Fast food consumption trended higher vs patients with mild fibrosis (P =.09) Williams CD, et al. Gastroenterology. 2011;140:

clinicaloptions.com/hepatitis NAFLD and NASH Prevalence in US Cohort Summary of Key Conclusions  Prevalence of NAFLD and NASH 46% and 12%, respectively, in cohort of asymptomatic middle-aged individuals in Texas [1] –NAFLD estimate markedly higher than that reported in previous studies (ie, 31%) [2] despite use of ultrasound for detection, a less sensitive method –Higher prevalence possibly because of increasing rates of obesity and diabetes  Hispanics and diabetics at greatest risk for NAFLD and NASH  Presence of NAFLD associated with lifestyle factors including minimal exercise and fast food consumption 1. Williams CD, et al. Gastroenterology. 2011;140: Browning JD, et al. Hepatology. 2004;40: