At Least 1 in 5 Patients in Your Practice Have Fatty Liver

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1 At Least 1 in 5 Patients in Your Practice Have Fatty Liver What Can You Tell Your Patients Magnus McLeod MD FRCPC Assistant Professor Dalhousie University 30-NOV-2017

2 NAFLD Non-Alcoholic Fatty Liver Disease

3 Disclosures Consultant/Advisor for Intercept and Gilead Principal Investigator in NASH Clinical Trials involving Genfit, Novo Nordisk, and Shire

4 Histological Images Courtesy of Dr. Ashley Stueck

5 Objectives Does my patient have NAFLD? What is NAFLD? What to tell my patient? When should I refer?

6 Case 39 year old man presents with some nonspecific abdominal discomfort. He has a history of DM2 on Metformin and has dyslipidemia(triglycerides 1.8, LDL 3.5, and HDL 0.9) on atorvastatin 20mg daily.

7 AST 45 ALT 135 ALP 65 GGT 200 Ultrasound shows hypoechoic liver

8 Presentation Most are asymptotic RUQ pain and fatigue Hepatomegaly Elevated liver transaminases(alt>ast, high GGT) Incidental finding on imaging

9 Does My Patient Have NAFLD?

10 Diagnosis 1. Hepatic steatosis by imaging or histology 2. No significant alcohol consumption 3. No competing etiologies for hepatic steatosis 4. No coexisting causes for chronic liver disease

11 Canada Low Risk Alcohol Drinking Guidelines

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13 Ongoing or recent alcohol consumption >21 standard drinks on average per week in men and >14 standard drinks on average per week in women is a reasonable threshold for significant alcohol consumption in patients with NAFLD

14 Rule Out Other Causes of Steatosis Drugs - Methotrexate, Amiodarone, Tamoxifen Wilson Disease HCV Celiac disease

15 Investigate for Other CLD HBV and HCV Autoimmune Hepatitis(ASMA) Hemochromatosis(HFE gene test) A1AT Deficiency

16 Comorbidities Obesity(BMI) Diabetes(HgbA1c, glucose) Dyslipidemia(Cholesterol panel) OSA(Level 3 sleep test) TSH PCOS Age appropriate cancer screening

17 What is NAFLD?

18 20-30% NAFLD Torres DM et al. Clin Gastro Hepatol 2012;10: % Non-Alcoholic Fatty Liver (NAFL)

19 20-30% Torres DM et al. Clin Gastro Hepatol 2012;10: NAFLD 20-25% Non-Alcoholic Steatohepatitis (NASH)

20 NAFLD 20-30% 20-25% NASH F3 F2 20% F1 F4/CIRRHOSIS Torres DM et al. Clin Gastro Hepatol 2012;10:

21 Does my Patient Have NASH?

22 ALT is Useless Serum ALT can be NORMAL in up to 60-80% of NAFLD patients with NASH ALT can be increased in up to 53% of NAFLD patients without NASH ALT is not a reliable indicator of NASH or fibrosis Mofrad P, et al. Hepatology 37: , Fracanzanni et al. Hepatology 2008;48;792-8 Torres et al. Nat Rev Gastroenterol Hepatol 2013;10: Verma et al. Liver Int 2013;33:

23 NASH Risk Factors Men >50 Postmenopausal females Diabetes Metabolic Syndrome Obstructive Sleep Apnea Angulo et al., Hepatology 1999 Ratziu et al., Gastroenterology 2000

24 Metabolic Syndrome Increased waist circumference Men >101cm; women >87cm Triglycerides >1.6 mmol/l HDL <1 mmol/l in men; <1.3 mmol/l in women SBP >129 and/or DBP >84 Fasting glucose >5.5 mmol/l

25 Does My Patient Have Fibrosis?

26 Fibrosis Stage is the Most Important Determinant of Outcomes in NASH Fibrosis is the only independent predictor of clinical outcomes 1 Survival of NASH patients stratified by fibrosis stage 2 Fibrosis Stage Liver-Related Events Hazard Ratio (95% CI) 0 1.6% 1.0 (reference) 1 2.8% 2.3 ( ) Control F0-F % 6.7 ( ) % 13.4 ( ) F3-F % 52.9 ( ) MORE FIBROSIS = WORSE PROGNOSIS 1. Angulo P, et al. Gastroenterology 2015:149:389-97, 2. M. Ekstedt et al. Hepatology 2015; 61(5):

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28 Fibroscan: Vibration Elastrography

29 Summary Algorithm

30 LOW RISK PROFILE -BMI <29.9 -Absent DM2 -Absent Metabolic Syndrome -Low NAFLD FS -Normal ALT INTERMEDIATE RISK PROFILE -BMI >29.9-1/2 Metabolic Syndrome parameters -Indeterminate NAFLD FS -elevated ALT NAFLD Non-Invasive Risk Stratification HIGH RISK PROFILE -Age>50 -DM2 -Metabolic Syndrome -High NAFLD FS -AST=ALT VERY HIGH RISK -Splenomegaly -Abnormal Liver Function

31 LOW RISK PROFILE -BMI <29.9 -Absent DM2 -Absent Metabolic Syndrome -Low NAFLD FS -Normal ALT Lifestyle Intervention Control CV Risk Factors Recheck NAFLD Risk Profile in 3-5 years

32 INTERMEDIATE RISK PROFILE -BMI >29.9-1/2 Metabolic Syndrome parameters -Indeterminate NAFLD FS -elevated ALT Lifestyle intervention Control CV Risk Factors Refer to Hepatology for Fibroscan

33 HIGH RISK PROFILE -Age>50 -DM2 -Metabolic Syndrome -High NAFLD FS -AST=ALT VERY HIGH RISK -Splenomegaly -Abnormal Liver Function Refer to Hepatology Involvement in Clinical Trial

34 Treatment

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36 Lifestyle Intervention Limit simple sugars(fructose and sucrose) Avoid large meals(decrease total calories by ) Include protein in every meal Use healthy oils in limited amounts Avoid prolonged fasting

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38 Exercise Intentional walking is a start Goal of min aerobic/resistance training 3d/week Avoid sedentary lifestyle

39 Cardiovascular Risk Top cause of death in patients with NAFLD/NASH Statins are safe and recommended Metformin is safe Limit DM2 medications associated with weight gain if possible(sulfonylureas, insulin)

40 Referral of Intermediate or High Risk Fibroscan vs Liver Biopsy Clinical Trial if NASH and F2/F3 Disease Possible use of Vitamin E or Pioglitazone Cirrhosis - Antifibrotic clinical trials Aggressive Lifestyle and CV Risk Modification

41 Questions