NONALCOHOLIC FATTY LIVER DISEASE. Non-Alcoholic Fatty Liver Disease (NAFLD) Primary NAFLD. April 13, 2012

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1 NONALCOHOLIC FATTY LIVER DISEASE Kiran Bambha, MD University of Colorado Denver April 13, 2012 Non-Alcoholic Fatty Liver Disease (NAFLD) Primary NAFLD

2 Simple Steatosis Fatty hepatocytes Intracellular fat deposition NonAlcoholic SteatoHepatitis (NASH) Intracellular fat deposition Necrosis Fibrosis Fat deposits Inflammation Fibrosis with necrosis Cirrhosis Regenerative nodule Fibrosis Nodules surrounded by fibrosis

3 Non-Alcoholic Fatty Liver Disease (NAFLD) NAFLD is Associated with the Metabolic Syndrome Obesity Diabetes Dyslipidemia Neuschwander-Tetri BA. Hepatology 2010; 52(2):

4 Dallas Heart Study Results Liver fat < 5.5% Liver fat > 5.5% Steatosis = 34%* *Exptrapolated to the Dallas Co. population Liver enzymes NORMAL in most (79%) with steatosis Hepatology 2004;40:1387 NAFLD AND NASH PREVALENCE IN US COHORT HIGHER THAN PREVIOUSLY ESTIMATED Prevalence of NAFLD and NASH among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study Williams CD, Stengel J, Asike MI, et al. Gastroenterology. 2011;140: Main Findings 46% of patients had NAFLD according to evidence from ultrasound and liver biopsy (if performed) 22 (of 151) refused liver biopsy, but NAFLD assumed Highest prevalence of NAFLD observed in Hispanics (58.3%), followed by whites (44.4%) and blacks (35.1%) Williams CD, et al. Gastroenterology. 2011;140:

5 NAFLD in High-Risk Populations Type 2 Diabetes Mellitus Prevalence of NAFLD is high Several studies have documented a higher prevalence of NAFLD among patients with DM compared with non-dm Prevalence estimates 40-70% Case-control study using NMR Individuals with DM have 80% more hepatic fat compared with age-, weight- and sex-matched controls AST and ALT are not reliable markers of liver disease severity or degree of steatosis J Gastro Hepatol 2004;19: Ann Intern Med 2004; 141: Prevalence of Hepatic Steatosis Varies with Ethnicity and Race Fatty liver Prevalence (%) 45% 33% 24% Latino Caucasian African American Natural History of NAFLD Natural history depends upon the histologic subtype of NAFLD SS generally benign prognosis NASH may develop fibrosis leading to cirrhosis

6 Risk Factors for Cirrhosis Age > years Obesity Diabetes

7 NAFLD and Cardiovascular Disease Patients with NAFLD have multiple risk factors for CVD CVD is much more common than liver disease as a cause of death, esp with NASH NAFLD is linked to increased risk of CV events in patients with and without diabetes Management Issues Who Might Have NAFLD?

8 Rule out other liver diseases No specific serologic markers for NAFLD/NASH Caveats Standard imaging tests may under- or overestimate liver fat content Steatosis on imaging test does not exclude other liver diseases Positive tests for other liver diseases do not necessarily exclude NAFLD - autoantibody positivity (ANA 25%, ASM 15%) Assess the Severity of the Liver Disease Clinical prognosis depends on histology Simple Steatosis generally benign Steatohepatitis increases risk for progressive disease and advanced fibrosis Cirrhosis

9 Assess the Severity of the Liver Disease Imaging Studies Cannot distinguish SS from NASH or reliably distinguish stages of fibrosis Stigmata of portal HTN suggest cirrhosis May detect unsuspected HCC Assess the Severity of the Liver Disease Laboratory Tests Aminotransferase levels Limited utility Can be normal in advanced fibrosis or NASH AST/ALT ratio may be suggestive Elevated in cirrhosis Thrombocytopenia suggests cirrhosis Bili, albumin later findings in cirrhosis No specific markers for NASH are avail for routine use Liver Biopsy

10 Specific pharmacotherapy for NAFLD - Shown to be beneficial in studies Insulin sensitizers : TZDs >> metformin Vitamin E : PIVENS Trial PIVENS: VITAMIN E SUPERIOR TO PLACEBO FOR IMPROVING NONALCOHOLIC STEATOHEPATITIS IN NONDIABETIC PATIENTS Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis Sanyal AJ, Chalasani N, Kowdley KV, et al. N Engl J Med. 2010;362: PIVENS Vitamin E vs Pioglitazone vs Placebo Wk 96 Nondiabetic patients with possible/definite NASH (N = 247) Vitamin E 800 IU QD + Pioglitazone-like Placebo (n = 84) Pioglitazone 30 mg QD + Vitamin E-like Placebo (n = 80) Pioglitazone- + Vitamin E-like Placebos QD (n = 83) Sanyal AJ, et al. N Engl J Med. 2010;362:

11 Management Options Weight loss (at least 7%) Gastric Bypass Surgery Reduce steatosis, gen beneficial for steatohepatitis, inconsistent in fibrosis Dietary Changes Decrease fructose consumption and saturated fats and simple CHO and trans fats Increased fructose consumption (>7 servings/week) is associated with increased fibrosis, inflammation and ballooning in NAFLD patients Increase PUFAs and Omega 3 FA Increased physical activity Improved cardiorespiratory fitness, even in absence of weight loss, has been shown to improve NASH histology Summary NAFLD is very prevalent in the US adult population Insufficient evidence to support routine screening of the general population Recommend screening of individuals at greatest risk in the primary care setting, diabetes clinics and cardiology clinics Management is dictated by the clinical scenario