NON-ALCOHOLIC FATTY LIVER DISEASE:

Transcription

1 NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER Archita P. Desai, MD Assistant Professor of Medicine University of Arizona 25 th Annual Southwestern Conference on Medicine

2 Outline Pathophysiology Natural History Scope of the problem Diagnosis & Staging of Disease Management

3 Pathophysiology: Overview Adapted from: Marchesini G, et al. Hepatology. 2016:1-11. doi: /hep McCullough AJ. J Clin Gastro doi: /01.mcg

4 Spectrum of Disease NAFLD Spectrum Non-Alcoholic Fatty Liver macrovesicular fat accumulation in more than 5% of hepatocytes simple steatosis No inflammation Non-Alcoholic Steatohepatitis Lobular inflammation, hepatocellular ballooning à hepatocyte necrosis No fibrosis NASH with Fibrosis Chronic inflammation Liver regeneration Fibrosis à cirrhosis

5 Natural history Clinical progression limited to those with fibrosis Spengler EK, Loomba R. Mayo Clin Proc doi: /j.mayocp Angulo P, et al. Gastroenterology. 2015;149(2): e10. doi: /j.gastro

6 Prevalence 10 35% prevalence rate Wide variation with the study population and the modality used to diagnose Vernon G, et al. Aliment Pharmacol Ther doi: /j x.

7 Prevalence Torres DM, et al. Clin Gastroenterol Hepatol doi: /j.cgh

8 Impact on Liver Transplantation

9 Diagnosis Accurate Diagnosis Stage of Disease NAFLD vs. NASH Fibrosis Cirrhosis

10 Abnormal Liver Tests Liver Enzymes Alk Phos, AST, ALT Do not effectively assess the actual function of the liver Normal ALT: < 30 for males <19 for females Liver Function Bilirubin, Albumin, PT/INR

11 Diagnosis Abnormal Liver Enzymes Steatosis by imaging AST/ALT ratio < 1 Obesity Diabetes Metabolic Syndrome Viral hepatitis Medications Hemochromatosis Autoimmune Hepatitis Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol doi: /nrgastro

12 Risk Stratification NAFLD vs. NASH Stage of Fibrosis n Cirrhosis?

13 Non-invasive Staging Serologic markers Transient Elastography MRI +/- Elastography

14 Non-invasive Staging

15 Non-invasive Staging Sebastiani G, et al. PLoS One. 2015;10(6):e doi: /journal.pone

16 Non-invasive Staging Transient Elastography: MR Elastography: US probe delivers shear wave, velocity is mesaured and converted mathematically into a liver stiffness measurement (LSM), which is depicted in kilopascals (kpa) External vibrators are used to generate shear or compression waves wave propagation measured for whole liver

17 Non-invasive Staging MRE vs. Liver biopsy Loomba R, et al. Am J Gastroenterol. 2016;(October 2015):1-9. doi: /ajg

18 Risk-based Staging

19 Risk-based Staging

20 Management There are NO FDA approved therapies for NASH GI and Liver society guidelines recommend 2 pharmacologic therapies Limited impact on fibrosis Lifestyle modifications Management of other risk factors Bariatric Sugery

21 Weight Loss topic=liversummit2015_nash-nafld

22 Lifestyle Modifications Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol doi: /nrgastro

23 Pharmacologic therapy PIVENS Trial (2010): Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis Only NON-Diabetics with NASH Pioglitazone lead to modest weight gain Long term safety and efficacy of pioglitazone in patients with NASH is not established Sanyal AJ, et al. N Engl J Med. 2010;362: doi: /nejmoa

24 Bariatric Surgery Improvement or resolution of steatohepatitis Mummadi RR, et al. Clin Gastroenterol Hepatol. 2008;6(12): doi: /j.cgh

25 Bariatric Surgery Improvement or resolution of fibrosis Mummadi RR, et al. Clin Gastroenterol Hepatol. 2008;6(12): doi: /j.cgh

26 Future therapies Over 150 ongoing trials Several drugs in phase 2b or 3 Mostly non-cirrhotic NASH Future targets: Farsenoid receptor X agnoist - Obeticholic acid PPARα/δ agonist Genfit, Elefibranor ASK1 Inhibitors Lysyl Oxidase-Like 2 inhibitors Takaki A, et al. Int J Mol Sci. 2014;15(5): doi: /ijms

27 Future therapies

28 Current Management Weight loss - Exercise + Diet Sustain weight loss Nutritionist, Weight Watchers Consider Bariatric surgery if other indications Aggressive management of metabolic risk factors Don t stop statin Consider aspirin Vit E 800 IU/daily - α-tocopherol Caffeine? If Fibrosis, send to a center with on-going clinical trials Corey KE, et al. Dig Dis Sci. 2016;61(5): doi: /s

29 Thank you!