Disclosure. Objectives. Smash the Nash: A practical approach to fatty liver disease

Transcription

1 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

2 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, (6) 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

3 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

4 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:

5 Prevalence 5.5% between 1988 and % between 1999 and % 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 Clinical Gastroenterology Hepatology. 2011; 9: Risk Factors Obesity Diabetes mellitus Insulin resistance Hypertriglyceridemia Dyslipidemia The hepatic component of the metabolic syndrome Pathophysiology 15 15

6 Pathophysiology Pathophysiology 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

7 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): Proposed Second Hit Players Hemochromatosis Excess hepatic iron Leptin Decreased adiponectin Small intestinal bacterial overgrowth 21 21

8 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): Hypothyroidism Hypopituitarism Additional Risk Factors Hypogonadism Polycystic ovary syndrome Sleep apnea Rapid weight loss 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

9 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: 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)

10 Differentiating Between NAFLD and NASH NAFLD fibrosis score Age, BMI, hyperglycemia, platelet count, albumin, AST/ALT ratio Score < 1.455: 90 sensitivity and 60% specificity to exclude advanced fibrosis Score >0.676: 67% sensitivity and 97% specificity to predict advanced fibrosis Management of Fatty Liver Disease Identify and treat the underlying cause Obesity/sleep apnea Diabetes Hypertriglyceridemia Hyperlipidemia Hypothyroidism Obesity Slow, gradual weight loss 1 2 pounds ( 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

11 Weight Loss Carbohydrates: 4 kilocalories/gram Proteins: 4 kilocalories/gram Alcohol: 7 kilocalories/gram Fats: 9 kilocalories/gram 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 Weight Loss 3 5% body weight reduction improves hepatic steatosis. Up to 10% may be necessary to decrease inflammation in NASH 33 33

12 Pharmacologic Therapy Treat diabetes, hyperlipidema, hypertriglyceridemia, and hypothyroidism with appropriate agents. Statins can be used to treat dyslipidemia in those with NAFLD and NASH Studies of Pharmacologic Therapy Pioglitazone mg daily Improved steatosis, inflammation and liver enzymes Weight gain Long-term effects in non-diabetics are unknown 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

13 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 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 If cirrhosis is identified Ultrasound and alpha fetoprotein every 6 months for hepatoma screening Vaccinate for hepatitis A and hepatitis B 39 39

14 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: unit/l) ALT 129 unit/l (N: unit/l) Alkaline phosphatase 131 unit/l (N: unit/l) Remainder of liver panel is normal 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 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

15 Case Study #1 Physical exam was normal. Lab results Hemoglobin A1C: 4.9% (N: <6.0) proportion (N: <0.06) Cholesterol: 152 mg/dl (N: ) 3.94 mmol/l (N: ) Triglycerides: 472 mg/dl (N: ) 5.33 mmol/l (N: ) 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 Case Study #1 What now? What differentiates AFLD from NAFLD? What differentiates between NAFLD and NASH? 45 45

16 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: ) Remainder of liver panel is normal 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 Case Study #2 His past medical history Hyperlipidemia Hypertriglyceridemia Hypertension Obesity (BMI 37 kg/m 2 ) Type 2 diabetes mellitus 48 48

17 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 Case Study #2 - Medications Medications Metformin (Glucophage ) 500 mg BID Lisinopril (Zestril ) 30 mg daily Simvastatin (Zocor ) 20 mg daily Case Study #2 Lab results Hemoglobin A1C: 9.2% (N: <6.0) 0.09 proportion (N: <0.06) Cholesterol: 342 mg/dl (N: ) 8.86 mmol/l (N: ) HDL: 37 mg/dl (N: >40) 0.96 mmol/l (N: >1.04) 51 51

18 Case Study #2 Lab results (cont.) LDL: 196 mg/dl (N: ) 5.08 mmol/l (N: ) Triglycerides: 472 mg/dl (N: ) 5.33 mmol/l (N: ) Physical exam Normal, other than central adiposity 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 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

19 End of Presentation Thank you for your time and attention. Bruce D. Askey, MS, ANP-BC 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

20 Statement of Liability The information in this program has been thoroughly researched and checked for accuracy. However, clinical practice and techniques are a dynamic process and new information becomes available daily. Prudent practice dictates that the clinician consult further sources prior to applying information obtained from this program, whether in printed, visual or verbal form. disclaims any liability, loss, injury or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents of this presentation Flagship Drive North Andover, MA Fax Website: fhea.com Learning & Testing Center: fhea.com/npexpert 59