Smash the Nash: A practical approach to fatty liver disease Bruce D. Askey, MS, ANP-BC Associate Lecturer North Andover, MA Adult Nurse Practitioner Dept. of Hepatology/Gastroenterology Guthrie Clinic Sayre, PA/Ithaca, NY Disclosure No real or potential conflict of interest to disclose No off-label, experimental or investigational use of drugs or devices will be presented. 2 Objectives By the end of the presentation, the participant will be able to: Describe the meaning of fatty liver disease. Differentiate between hepatic steatosis and steatohepatitis. State the risk factors for fatty liver disease. 3
Information was obtained from Chalasani, N et al. The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. June, 2012. 55(6). 2005-2023. http://www.gastro.org/journals- publications/gastroenterology/nafld_guideline_6-12.pdf 4 Fatty Liver Disease A clinical condition in which fat accumulates in the hepatocytes 5 Definitions Fatty liver disease: The accumulation of fat in the hepatocyte Alcoholic fatty liver disease (AFLD) Non-alcoholic fatty liver disease (NAFLD) Hepatic steatosis Another way of saying fatty liver disease 6 6
Definitions Steatohepatitis Fatty liver disease that has resulted in inflammation of the liver Non-alcoholic steatohepatitis (NASH) Fatty liver disease that has resulted in inflammation of the liver in the absence of routine alcohol ingestion Increased risk of cirrhosis 7 7 8 8 9 9
10 10 11 11 Prevalence NAFLD in the United States 10 46% NASH in the United States 3 5% Source: Williams 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; 140:124. 12 12
Prevalence 5.5% between 1988 and 1994 9.8% between 1999 and 2004 11% between 2005 and 2008 Source: Younossi, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 2008. Clinical Gastroenterology Hepatology. 2011; 9:524. 13 13 Risk Factors Obesity Diabetes mellitus Insulin resistance Hypertriglyceridemia Dyslipidemia The hepatic component of the metabolic syndrome 14 14 Pathophysiology 15 15
Pathophysiology 16 16 Pathophysiology 17 17 Pathophysiology Insulin resistance results in increased load of free fatty acids to the liver, which are then stored as fat, resulting in hepatic steatosis (NAFLD). The cause of the stored fat resulting in inflammation (NASH) has not yet been fully elucidated, but likely results in a metabolic second hit. 18 18
Prevalence 19 Pathophysiology The cause of the stored fat resulting in inflammation (NASH) has not yet been fully elucidated, but likely results in a metabolic second hit. Source: Schuppan, D. and Schattenberg, J. Nonalcoholic steatohepatitis: Pathogenesis and novel therapeutic approaches. Journal of Gastroenterology Hepatology. 2013; 28 (Suppl. 1):68-76. 20 20 Proposed Second Hit Players Hemochromatosis Excess hepatic iron Leptin Decreased adiponectin Small intestinal bacterial overgrowth 21 21
Proposed Second Hit Players Reactive oxygen species (ROS) Chemically reactive molecules containing oxygen Oxidative stress Imbalance between ROS and the system s inability to detoxify them Source: Basaranoglu, et al. From fatty liver to fibrosis: A tale of a second hit. World Journal of Gastroenterology. 2013; February 28; 19(8):1158-1165. 22 22 Hypothyroidism Hypopituitarism Additional Risk Factors Hypogonadism Polycystic ovary syndrome Sleep apnea Rapid weight loss 23 23 Diagnosis Fatty liver disease is generally incidentally identified during a workup for elevated liver enzymes, during cholecystectomy or at the time of imaging, usually for abdominal pain. 24 24
Diagnosis Ultrasound Noninvasive No contrast or radiation risks Inexpensive Not sensitive with <30% steatosis via liver biopsy Source: Ahmed, et al. Nonalcoholic fatty liver disease review: Diagnosis, treatment and outcomes. Clinical Gastroenterology Hepatology. 2015; 13:2062-2070. 25 25 26 26 Differentiating Between NAFLD and NASH A liver biopsy is necessary to differentiate between fatty liver disease without inflammation and NASH (fatty liver disease with inflammation). 27 27
Differentiating Between NAFLD and NASH NAFLD fibrosis score Age, BMI, hyperglycemia, platelet count, albumin, AST/ALT ratio http://nafldscore.com Score < 1.455: 90 sensitivity and 60% specificity to exclude advanced fibrosis Score >0.676: 67% sensitivity and 97% specificity to predict advanced fibrosis 28 28 Management of Fatty Liver Disease Identify and treat the underlying cause Obesity/sleep apnea Diabetes Hypertriglyceridemia Hyperlipidemia Hypothyroidism 29 29 Obesity Slow, gradual weight loss 1 2 pounds (0.05 1 kg) per week Rapid weight loss results in liberation of free fatty acids, which are presented to the liver, resulting in worsening of fatty liver disease 30 30
Weight Loss Carbohydrates: 4 kilocalories/gram Proteins: 4 kilocalories/gram Alcohol: 7 kilocalories/gram Fats: 9 kilocalories/gram 31 31 Weight Loss 3500 kilocalories=1 pound (0.5 kg) 3500 kilocalories/7 days per week=500 kilocalories per day In order to lose 1 pound (0.5 kg) per week, one has to either decrease daily intake by 500 kilocalories or burn 500 extra kilocalories through exercise daily. 32 32 Weight Loss 3 5% body weight reduction improves hepatic steatosis. Up to 10% may be necessary to decrease inflammation in NASH 33 33
Pharmacologic Therapy Treat diabetes, hyperlipidema, hypertriglyceridemia, and hypothyroidism with appropriate agents. Statins can be used to treat dyslipidemia in those with NAFLD and NASH. 34 34 Studies of Pharmacologic Therapy Pioglitazone 30 45 mg daily Improved steatosis, inflammation and liver enzymes Weight gain Long-term effects in non-diabetics are unknown. 35 35 Studies of Pharmacologic Therapy Vitamin E 800 international units/day Improved liver histology in non-diabetic adults with biopsy-proven NASH Ursodeoxycholic acid Found to be ineffective and is not recommended 36 36
Bariatric surgery is not contraindicated in those with NAFLD and NASH, who do not have cirrhosis, but is not considered an established option for management at this time. Bariatric Surgery 37 37 Alcohol Use Those with NAFLD or NASH should not consume heavy amounts of alcohol and there is no established safe amount of alcohol in this setting. 38 38 If cirrhosis is identified Ultrasound and alpha fetoprotein every 6 months for hepatoma screening Vaccinate for hepatitis A and hepatitis B 39 39
Case Study #1 42-year-old female has been noted to have elevated liver enzymes which have persisted over 6 months. AST 267 unit/l (N: 15 46 unit/l) ALT 129 unit/l (N: 13 69 unit/l) Alkaline phosphatase 131 unit/l (N: 38 126 unit/l) Remainder of liver panel is normal 40 40 Case Study #1 Serologic workup is negative for Infectious hepatitis A, B, and C Autoimmune hepatitis Hemochromatosis Wilson s disease Alpha-1 antitrypsin deficiency Primary biliary cirrhosis Celiac disease 41 41 Case Study #1 PMH-Unremarkable per patient Social/family history Both parents alcohol abusers Lives with her boyfriend, no children Consumes a fifth of whiskey daily for years Smokes 2-packs per day Does not exercise, unemployed Currently on no medications 42 42
Case Study #1 Physical exam was normal. Lab results Hemoglobin A1C: 4.9% (N: <6.0) 0.049 proportion (N: <0.06) Cholesterol: 152 mg/dl (N: 118 200) 3.94 mmol/l (N: 3.06 5.18) Triglycerides: 472 mg/dl (N: 10 150) 5.33 mmol/l (N: 0.113-1.7) 43 43 Case Study #1 Ultrasound indicated No evidence of mass No evidence of cholelithiasis No evidence of biliary ductal dilatation Increased echogenicity of the liver consistent with fatty infiltration 44 44 Case Study #1 What now? What differentiates AFLD from NAFLD? What differentiates between NAFLD and NASH? 45 45
Case Study #2 54-year-old male has been noted to have elevated liver enzymes which have persisted over 6 months. AST 63 unit/l (N: 15 46) ALT 112 unit/l (N: 13 69) Alkaline phosphatase 131 unit/l (N: 38 126) Remainder of liver panel is normal 46 46 Case Study #2 Serologic workup is negative for Infectious hepatitis A, B, and C Autoimmune hepatitis Hemochromatosis Wilson s disease Alpha 1 antitrypsin deficiency Primary biliary cirrhosis Celiac disease 47 47 Case Study #2 His past medical history Hyperlipidemia Hypertriglyceridemia Hypertension Obesity (BMI 37 kg/m 2 ) Type 2 diabetes mellitus 48 48
Case Study #2 Social/family history Adopted: No knowledge of FMH Married and has 3 teenage children Does not consume alcohol Does not smoke Does not exercise Employed as a writer for a newspaper 49 49 Case Study #2 - Medications Medications Metformin (Glucophage ) 500 mg BID Lisinopril (Zestril ) 30 mg daily Simvastatin (Zocor ) 20 mg daily 50 50 Case Study #2 Lab results Hemoglobin A1C: 9.2% (N: <6.0) 0.09 proportion (N: <0.06) Cholesterol: 342 mg/dl (N: 118 200) 8.86 mmol/l (N: 3.06 5.18) HDL: 37 mg/dl (N: >40) 0.96 mmol/l (N: >1.04) 51 51
Case Study #2 Lab results (cont.) LDL: 196 mg/dl (N: 92 160) 5.08 mmol/l (N: 2.38 4.14) Triglycerides: 472 mg/dl (N: 10 150) 5.33 mmol/l (N: 0.11 1.7) Physical exam Normal, other than central adiposity 52 52 Case Study #2 Ultrasound indicated No evidence of mass No evidence of cholelithiasis No evidence of biliary ductal dilatation Increased echogenicity of the liver consistent with fatty infiltration 53 53 Case Study #2 What now? What differentiates AFLD from NAFLD? What differentiates between NAFLD and NASH? What do you get when you cross an elephant with a rhino? 54 54
End of Presentation Thank you for your time and attention. Bruce D. Askey, MS, ANP-BC www.fhea.com bruce@fhea.com 55 Images/Illustrations: Unless otherwise noted, all images/ illustrations are from open sources, such as the CDC or Wikipedia or property of FHEA or author. All websites listed active at the time of publication. 56 Copyright Notice Copyright by All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording or any information storage and retrieval system, without permission from Fitzgerald Health Education Requests for permission to make copies of any part of the work should be mailed to: 85 Flagship Drive North Andover, MA 01845-6184 57
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