NAFLD: evidence-based management. Curso de residentes AEEH Salvador Augustin, MD Liver Unit Vall d Hebron Hospital Barcelona, Spain
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1 NAFLD: evidence-based management Curso de residentes AEEH 2017 Salvador Augustin, MD Liver Unit Vall d Hebron Hospital Barcelona, Spain
2 Clinical case - 55 yo female - Sent for incidental steatosis at abdominal US - History: hypertension (losartan 50 mg/d) - Physical Exam: height 1.54, weight 86 kg (BMI 36.2) - Blood: AST 34, ALT 24, GGT 129, plat , Glu 112, TC 161, TGC 206
3 Clinical case -LS 13.9 kpa, IQR 1.0 -CAP 363, IQR 56 -SR 10/10
4 NAFLD (Non-Alcoholic Fatty Liver Disease) NAFL (Non-Alcoholic Fatty Liver) NASH (Non-Alcoholic Steato-Hepatitis) Adapted from Rinella, JAMA 2015
5 NAFLD Natural History FAST PROGRESSORS (20%, 1 STAGE F/2-3y) SLOW PROGRESSORS (80%, 1 STAGE F/7y)
6 NASH: disease or phenotype? DIET SEDENTARISM COMORBIDITIES INSULIN RESISTANCE IRON METABOLISM LIPOTOXICITY INFLAMMATION FIBROSIS GENETICS EPIGENETICS GUT MICROBIOME
7 NASH: disease or phenotype? 70 yo BMI 30 T2DM 40 yo BMI yo BMI 32 PNPLA3 rs yo BMI 29 Ferritin yo Asian BMI 26, body fat 28%
8
9 Scenario #1: Liver Clinics 1. Confirm STEATOSIS 2. Identify RISK FACTORS 3. EXCLUDE other causes 4. STAGE (FIBROSIS)
10 LIVER FIBROSIS is the main determinant of severity and progression Angulo et al., Gastroenterology 2015
11 LIVER FIBROSIS is the main determinant of severity and progression Liver-related mortality All-cause mortality Dulai, et al. Hepatology 2017
12 Scenario #1: Liver Clinics 1. Confirm STEATOSIS 2. Identify RISK FACTORS 3. EXCLUDE other causes 4. STAGE (FIBROSIS)
13 Scenario #1: Liver Clinics Classic tools are not valid US - Only when steatosis >30% - No correlation withseverity ALT, AST - No correlation withseverity: 75% high ALT do not have advanced fibrosis 10-30% normal ALT have advanced fibrosis 30% advanced fibrosis have normal ALT Kwok, et al. Gut 2015
14 Scenario #1: Liver Clinics 1. Confirm STEATOSIS 2. Identify RISK FACTORS 3. EXCLUDE other causes 4. STAGE (FIBROSIS) 5. BIOPSY?
15 Scenario #2: Risk Populations Diabetes, Obesity, Cardiovascular Risk Prevalence: NAFLD 60-80%, Advanced Fibrosis 10-15% Rule OUT SEROLOGIC MARKER High Sn / NPV Low-Risk Intermediate High-Risk Referring specialist IMAGING TECHNIQUE High Sp / PPV Low-Risk Intermediate High-Risk Rule IN Hepatologist?
16 Scenario #2: Risk Populations High Sn / NPV SEROLOGIC MARKERS High Sp / PPV Low-Risk Intermediate High-Risk - AST / ALT ratio - FIB-4 - NFS - HEPASCORE - Proprietary: ELF, Fibrotest, OWL-Fiber
17 Scenario #2: Risk Populations Diabetes, Obesity, Cardiovascular Risk Prevalence: NAFLD 60-80%, Advanced F 10-15% Rule OUT FIB-4 (age-adjusted) High Sn / NPV Low-Risk Intermediate High-Risk Referring specialist Fibroscan (with CAP) High Sp / PPV Low-Risk Intermediate High-Risk Rule IN Hepatologist?
18 Scenario #3: General Population Primary Care Prevalence: NAFLD 25-30%, Advanced Fibrosis 5% DEFINE TARGET POPULATION Risk Factors, Age, Others? Low-Risk High-Risk Primary Care Rule OUT SEROLOGIC MARKER High Sn / NPV Low-Risk Intermediate High-Risk IMAGING TECHNIQUE High Sp / PPV Low-Risk Intermediate High-Risk Rule IN Referral to Hepatologist
19
20 NAFLD: evidence-based treatment & surveillance 1. Weight loss - Lifestyle interventions (nutrition, exercise) - Bariatric surgery 2. Drug therapy 3. Screening varices / HCC
21 Lifestyle Interventions Bariatric Procedures
22 WEIGHT LOSS IMPACT ON NASH 0% 3% 5% 7% >10% Steatosis ALT HbA1c/risk T2DM NAS NASH resolution Fibrosis
23 WEIGHT LOSS Impact on NASH histology Romero-Gómez et al. J Hep 2017 adapted from Vilar-Gómez et al., Gastroenterology 2015
24 Caloric restriction >> macronutrient composition Fats: MUFA/PUFA > SFA Coffee is OK Alcohol is NOT OK Sucrose is TOTALLY NOT OK
25 Avoid sedentarism (Increase physical activity) Exercise - Aerobic / Resistance - Sitting time: total time, breaks - Intensity - Apps / wearables - Consistency
26 - Low % responders - Non-lasting effects - Effect in advanced stages?
27 Bariatric Surgery - NASH Improves NASH NASH Resolution 80% Fibrosis Improvement 34% Lassailly et al., Gastroenterology 2015
28 Bariatric Surgery - NASH Improves overall mortality Arterburn et al., JAMA 2015
29
30 NO DRUG APPROVED FOR NASH BUT: - Vitamin E - Liraglutide - Pioglitazone
31 Vitamin E in NASH PIVENS trial (phase 3): improves NASH, but NOT Fibrosis (2 years, non-diabetics) 50% 40% p= % p=.12 41% 30% 31% 20% 19% 10% 0% NASH Resolution FIBROSIS Improvement Placebo Vit E Sanyal et al., N Eng J Med 2010
32 Liraglutide in NASH LEAN trial (phase 2b): improves NASH & Fibrosis (1 year, non-diabetics & diabetics) 50% 40% 30% p=.019 p=.46 p=.04 39% 36% 26% 20% 10% 9% 14% 9% 0% NASH Resolution FIBROSIS Improvement FIBROSIS Worsening Placebo Liraglutide Armstrong et al., Lancet 2015
33 Pioglitazone in NASH Meta-analysis: improves F (especially in F3-F4, even in non-diabetics) Musso et al., Hepatology 2017
34 NEW NASH TARGETS Ampuero et al., GastroHepatol 2017
35
36 Screening HCC- NASH VA USA, N=1419 HCC ( ) % Cirrhosis % Correct Surveillance HCC 72% 60 58% Virus OH NAFLD Virus OH NAFLD Mittal, Clin Gastro Hepatol 2015
37 Screening Varices- NASH BAVENO VI CRITERIA: platelets >150 & LS <20 kpa - Risk of missing varices needing treatment (VNT) <2% - Spared endoscopies 21% - Viral etiology EXPANDED-BAVENO VI CRITERIA: platelets <110 & LS 25 kpa VNT missed Spared endoscopies HCV, n= % 40% NASH, n=90 2.2% 49% Augustin et al., Hepatology 2017
38 Clinical case Dx: NASH NAS central: 7, local: 5 F4 (central=local)
39 Clinical case - DIET + EXERCISE (Nutrition Unit) - November 2017: Weight 62 Kg (!!!!!) - Blood: platelets 236, AST 22, ALT 23, AP 107, GGT 18, glycemia 71, total cholesterol 132, triglycerides 70 - Liver US: no steatosis
40 Clinical case -LS 5.2 kpa, IQR 0.3 -CAP 239, IQR 16 -SR 10/10
41 We need multidisciplinary teams with experts
42 Take-home messages Sequential diagnostic approach Weight Loss: able to improve NASH histology if WL >7-10%, but: - Low % responders / non-lasting effects / advanced stages - Multidisciplinary teams Drug therapy: Vitamin E / Pioglitazone / Liraglutide Consider bariatric surgery in selected patients Screening varices / HCC Multidisciplinary teams
43
44
45 Non-Invasive assessment of NASH improvement After Lifestyle Interventions N=141 AUC=0.956 Vilar-Gómez et al., Hepatology 2016
46 Non-Invasive assessment of NASH improvement After Lifestyle Interventions N=141 Vilar-Gómez et al., Hepatology 2016
47 IMPACT OF WEIGHT LOSS ON NASH N=293, 1 YEAR 80% NASH resolution...in 9% of the cohort 9% WL>10% Vilar-Gómez et al., Gastroenterology % WL<5%
48
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