Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE...

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

Transcript of Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE...

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

NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER

25th Annual Southwestern Conference on Medicine

Archita P. Desai, MD Assistant Professor of Medicine University of Arizona

Page 2: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Outline

¨  Pathophysiology

¨  Natural History

¨  Scope of the problem

¨  Diagnosis & Staging of Disease

¨  Management

Page 3: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Pathophysiology: Overview

Adapted from: Marchesini G, et al. Hepatology. 2016:1-11. doi:10.1002/hep.28392. McCullough AJ. J Clin Gastro. 2006. doi:10.1097/01.mcg.0000168645.86658.22

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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

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Natural history

Clinical progression limited to those with fibrosis

Spengler EK, Loomba R. Mayo Clin Proc. 2015. doi:10.1016/j.mayocp.2015.06.013. Angulo P, et al. Gastroenterology. 2015;149(2):389-397.e10. doi:10.1053/j.gastro.2015.04.043

Controls

F0-F2

F3-F4

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Prevalence

¨  10–35% prevalence rate ¨  Wide variation with the study population and the

modality used to diagnose

Vernon G, et al. Aliment Pharmacol Ther. 2011. doi:10.1111/j.1365-2036.2011.04724.x.

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Prevalence

Torres DM, et al. Clin Gastroenterol Hepatol. 2012. doi:10.1016/j.cgh.2012.03.011.

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Impact on Liver Transplantation

Page 9: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Diagnosis

¨  Accurate Diagnosis

¨  Stage of Disease ¤ NAFLD vs. NASH ¤ Fibrosis ¤ Cirrhosis

Page 10: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Abnormal Liver Tests

¨  Liver Enzymes – Alk Phos, AST, ALT ¤ Do not effectively assess the actual function of the liver

¨  Liver Function – Bilirubin, Albumin, PT/INR

Normal ALT: < 30 for males

<19 for females

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Diagnosis

Abnormal Liver Enzymes

Steatosis by imaging

Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol. 2016. doi:10.1038/nrgastro.2016.3.

AST/ALT ratio < 1 Obesity Diabetes

Metabolic Syndrome

Viral hepatitis Medications

Hemochromatosis Autoimmune Hepatitis

Page 12: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Risk Stratification

¤ NAFLD vs. NASH

¤ Stage of Fibrosis n Cirrhosis?

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Non-invasive Staging

¨  Serologic markers

¨  Transient Elastography

¨  MRI +/- Elastography

Page 14: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Non-invasive Staging

Page 15: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Non-invasive Staging

Sebastiani G, et al. PLoS One. 2015;10(6):e0128774. doi:10.1371/journal.pone.0128774.

Page 16: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

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

Page 17: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Non-invasive Staging

Loomba R, et al. Am J Gastroenterol. 2016;(October 2015):1-9. doi:10.1038/ajg.2016.65.

MRE

vs.

Live

r bi

opsy

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Risk-based Staging

Page 19: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Risk-based Staging

Page 20: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

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

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Weight Loss

http://www.chronicliverdisease.org/disease_focus/slide_details.cfm?topic=LIVERSUMMIT2015_NASH-NAFLD

Page 22: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Lifestyle Modifications

Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol. 2016. doi:10.1038/nrgastro.2016.3.

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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;362:1675-1685. doi:10.1056/NEJMoa0907929.

Page 24: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Bariatric Surgery

Mummadi RR, et al. Clin Gastroenterol Hepatol. 2008;6(12):1396-1402. doi:10.1016/j.cgh.2008.08.012.

Improvement or resolution of steatohepatitis

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

Bariatric Surgery

Improvement or resolution of fibrosis

Mummadi RR, et al. Clin Gastroenterol Hepatol. 2008;6(12):1396-1402. doi:10.1016/j.cgh.2008.08.012.

Page 26: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

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):7352-7379. doi:10.3390/ijms15057352.

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Future therapies

http://www.nashbiotechs.com/nash-biotech-analysis/biotechs-targeting-nash/RiskReward.html

Page 28: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

Current Management

Corey KE, et al. Dig Dis Sci. 2016;61(5):1387-1397. doi:10.1007/s10620-016-4083-8.

¨  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

Page 29: Archita P. Desai, MD University of Arizona · NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER 25th Annual Southwestern Conference on Medicine Archita P. Desai, MD

¨ Thank you!


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