Chewing the Fat on Fatty Liver Mike Kolber MD, CCFP, MSc PEIP 2018

Transcription

1 Chewing the Fat on Fatty Liver Mike Kolber MD, CCFP, MSc PEIP 2018 Faculty/Presenter Disclosure Faculty: Michael Kolber Relationships with financial sponsors: Grants/Research Support: Alberta College of Family Physicians; Toward Optimized Practice Speakers Bureau/Honoraria: Alberta College of Family Physicians; Alberta Health Consulting Fees: N/A Patents: N/A Other: Employee University of Alberta; NAFMASC; Alberta College of Family Physicians; EMPRSS 1

2 Disclosure of Financial Support This program does not receive financial support. This program is presented by the ACFP without financial support. The ACFP provides a speaker fee and expense support for presenting at the event. This program does not receive in-kind support. This program is presented by the ACFP without in-kind support. Mitigating Potential Bias Material/Learning Objectives and/or session descriptions were developed and reviewed by the Planning Committee composed of experts/family physicians/ allied care professionals responsible for overseeing the program s needs assessment and subsequent content development to ensure accuracy and fair balance. Consideration was given by the Planning Committee to identify when speakers personal or professional interests may compete with or have actual, potential, or apparent influence over their presentations. Information and/or recommendations in the program are evidence- and/or guidelines-based, and the opinions of the independent speakers will be identified as such. 2

3 Personal Bias: Last time I had non-insurance screening lab tests: 1992 Due to my heritage and physique: I probably have an abnormal ALT and NAFLD Fatty Liver: Poll Audience What best describes your current understanding of fatty liver or abnormal LFTs? Most of my patients have Fatty Liver and none have died so I don t care NAFLD, NASH and cirrhosis really confuses me, can you teach me? I can confidently predict which of my patients with abnormal LFTs have something wrong, so I think I will go get a coffee I do the LFT chase : order LFTs àabn results à confront about ETOH, order more tests (don t remember which) + US à walk away when don t find anything. 3

4 Best Lecture in Med School - RJ Bailey 1994 Only 4 things get the liver ( ALT) Alcohol Medications Viruses Infiltrative Malignancy Bonus: Hemochromatosis, Wilsons, A1AT, Autoimmune Best Lecture in PEIP - Kolber 2018 Only 5 things get the liver ( ALT) NAFLD Alcohol Viruses Medications Infiltrative Malignancy Bonus: Hemochromatosis, Wilsons, A1AT, Autoimmune 4

5 ~20% Liver Tests in Primary Care are Abnormal Study Patients Tests Abnormal Ultimate Findings Scotland k patients AST,ALT, ALP GGT, Bili albumin 22% 1% had Liver disease Italy AST, ALT GGT 21% 2% viral hepatitis Italy AST, ALT GGT 18% 18% viral hepatitis 1 Family Practice 2009; 26: 251, 2 Hepatology 1994; 20: Hepatology 2005;41 :1151 ~20% Liver Tests in Primary Care are Abnormal Study Patients Tests Abnormal Ultimate Findings Scotland k patients AST,ALT, ALP GGT, Bili albumin 22% 1% had Liver disease Italy AST, ALT GGT 21% 2% viral hepatitis Italy AST, ALT GGT 18% 18% viral hepatitis 1 Family Practice 2009; 26: 251, 2 Hepatology 1994; 20: Hepatology 2005;41 :1151 5

6 Abnormal LFTs (UK) à Search for Liver Disease 1290 AbN LFTs (AST/ALT, ALP, GGT, Bili, albumin, globulin, protein) 1,2 Ordered for chronic disease management (70%), symptoms (30%) 55 yo, 56% men, 30% 15 drinks /week ETOH; HT/Wt, abd circ., additional lab tests + US à Diagnosis Ultimate Diagnosis Viral Hepatitis, Hemochromatosis, PBC 4% Malignancy 1% NAFLD 40% Alcohol or no disease ~50% 2 BMJ Open 2013;3:e003099, Health Tech Assess 2013;17(28) Elevated ALT in Primary Care ~10% Country Patients ALT Associations / Notes USA NHANES ( ) 8% 69% unexplained by ETOH, viruses or abnormal iron studies USA NHANES ( ) 9% Associated: Waist size,, BMI, Mexican American Scotland Tayside cohort 95,000 patients 7% No info on ETOH, obesity 12-15% if BMI 35 or ETOH 2/day 4 1 Clark Am J Gastro 2003: 960, 2 Am J Gastro 2006; 101: 76 3 Family Practice 2009; 26: 251, 4 Euro J Gastro Hep 2015, 27:1 6

7 Obesity ETOH Viral hepatitis Adapted from: Alcohol Consumption WHO 2014, Obesity WHO 2016, Hepatitis Lancet 2015; 386: adult patients in your practice 7

8 100 will have abnormal ALT 40 will have nafld 8

9 5 will have nash What the heck is NAFLD? (Non-Alcoholic Fatty Liver Disease) NAFLD: comprised of: 1. NAFL: simple steatosis (fat in liver) ~30% of population, benign Associated with obesity, NIDDM Likely 40% of abn ALTs 2 2. NASH (Non-alcoholic steatohepatitis) = fat + inflammation Proportion of NAFLD will have NASH Fibrosis (liver damage) stages: F0 - F4 (cirrhosis) 20% develop cirrhosis, #2 cause of Liver transplant 3 Hepatology 2018; 67(1): 328, 2 BALLET 2013, 3 Dig Dis Sci 2017; 62:2915 9

10 Good News: 57 years for NAFL à cirrhosis ~10 years to proceed between each fibrosis stage 2 BMJ 2016;354:i4428 doi: Clinical Gastro and Hepatology 2015;13:643 The Other NASH: Non-Abstinent Steatohepatitis 10

11 LT Follow up of NAFLD Patients: Systematic Review Sys Rev: 11 cohorts, including 411 patients with biopsy proven NAFLD 1 Differing FU periods: 50% same, 30% progressed, 20% improved 50% of patients had or developed DM in 8 years 5 Majority do not develop liver complications 5 NAFLD patients die from: 3,4 CVD Malignancy Liver disease (depending on fibrosis stage) 1 Clinical Gastro Hepatology 2015;13: Annals Medicine, 2011; 43: NEJM 2010;363: Journal Hepatology 2017; 67: Adams, GASTRO 2005;129:113 So A lot of people have abnormal ALTs Many of whom are obese, have DM and a few have NASH: Most don t end up having significant liver disease Fibrosis stage (F ) determines prognosis: 10 years between each stage Maybe it would be good to know if F0/1/2 or F3/4? So what do we do? Don t investigate abnormal ALTs (concentrate on their diabetes?) Telling everyone to exercise anyways? Try figure out who has fibrosis / NASH? 11

12 Where s NASH (Fibrosis)? NASH diagnostic gold standard = liver biopsy Liver Biopsy: painful (no repeat customers), 2-3% admitted Need non-invasive method of finding NASH from NAFL Annals of Medicine, 2011; 43: 617 Gastro 2017;152:1536 Diagnostic Test Characteristics: Undifferentiated patients (abnormal ALTs) à test (score, lab, DI) à compare (blinded) to gold standard (liver biopsy) Prevalent condition, simple (acceptable), affordable, reproducible test Differentiate disease from no disease (good Likelihood ratios) Problem with diagnostic tests for NAFLD: Many don t face diagnostic uncertainty (ex. liver bx à go back and look at test), unsure agreement between different test evaluators Spectrum / referral bias: none from primary care 12

13 Approach to Mildly Elevated ALT Bailey 1994, Am Fam Phys 2017; 96(11):709 BMJ 2018;362:k2734, Hepatology 2018; 67 (1); 328 Ultrasound = Fat Other etiologies of fat on ultrasound Common Causes of Fat in Liver on Ultrasound: NAFLD alcohol Meds: (MTX, Amiodarone, Tamoxifen) NICE 2016 NAFLD Guidelines 13

14 Forget the Evidence Kolber: I m trying to retire soon, should I buy a Fibroscan? NAFLD Fibrosis Prediction Tools: NAFLD score, FIB-4 Good for ruling out (and finding) fibrosis

15 Non-Invasive Tests for Detecting Fibrosis (Advanced F3) Test Cut Off Likelihood Ratio+ Likelihood Ratio - Notes Fib-4 < Need AST > % of results are in between NAFLD Score < Need albumin, BMI, DM > % are in between Fibroscan Shear Wave Elastography Depends on Disease 1 Clin Gastro Hep 2009;7:1104, 2 Annals of Medicine, 2011; 43: 617, 3 BMJ Open 2018;8:e % incomplete 2 to obesity Can tell amount of fat Variable % of SWE not completed What do the Test Results Mean? Test Result Means Response Fib-4 or NAFLD score Low (negative) result Rules out fibrosis don t refer: Exercise, weight loss, treat CV risks High (positive) result Probably has fibrosis Consider referral for Fibroscan or SWE Intermediate Result May have fibrosis Consider referral for Fibroscan or SWE Fibroscan / SWE Low Risk Result Unlikely Fibrosis Back to primary care. Exercise, weight loss, treat CV risks High Risk result Likely fibrosis Exercise, Wt. loss, treat CV risks Look for complications of LD Kolber

16 NAFLD Score, Fib-4 Calculations Negative Result NAFLD Score, Fib-4 Calculations Positive Result 16

17 I diagnosed NAFLD What now? Rule out Associated Conditions: DM Treat CV Risk Factors: BP, statins ( Treatment: Exercise and Weight loss Medications: Vit E, pioglitazone no clinical outcomes 1-4 Repeat SWE in 3 years(?): if F0/1 à 40 years for cirrhosis: I would not repeat SWE NICE 2016 NG Guidelines, Calgary Enhance Primary Care NAFLD Pathway 2018: 1 Cochrane 2017 CD011640, 2 European J Gastro & Hep 2017, 29:e8, 3 BMJ 2017;359:j5024, 4 Clinical Gastro Hep 2017;15:1940 Abnormal ALT Look for other non-nafld causes 1. Alcohol: AST/ ALT ratio, IGA 2. Viruses: HBsAg, Anti-HBC 3. Medications: livertox.nlm.nih.gov 4. Infitrative Malignancy: imaging 5. Inherited: ferretin, Iron saturation, serum ceruloplasmin, A1AT 6. Other: celiac (ATTG), Autoimmune (IGG, ANA, Antismooth muscle AB) Fatty Liver on Ultrasound 1. NAFLD 2. Medications: methotrexate, Amiodarone, Tamoxifen 3. Alcohol 17

18 In NAFLD à look for DM, consider CV risk calculator Non-Invasive Testing for Fibrosis in NAFLD Fib-4 Results NAFLD Score Low Unlikely Fibrosis Exercise, wt. loss Interm./High Possible Fibrosis Exercise, wt. loss refer for fibroscan/swe References: BMJ 2018; 362: k2734 doi: , Am Fam Physician 2017; 96(11):709. HEPATOLOGY 2018; 67 (1); 328 Thank you! 18

19 NAFLD HANDOUT: Kolber PEIP Oct 2018 Abnormal ALT Fatty Liver on Ultrasound Look for other non-nafld causes 1. Alcohol: AST/ ALT ratio, IGA 2. Viruses: HBsAg, Anti-HBC 3. Medications: livertox.nlm.nih.gov 4. Infitrative Malignancy: imaging 5. Inherited: ferretin, Iron saturation, serum ceruloplasmin, A1AT 6. Other: celiac (ATTG), Autoimmune (IGG, ANA, Anti-smooth muscle AB) 1. Alcohol 2. Medications: methotrexate, Amiodarone, Tamoxifen 3. NAFLD In NAFLD à look for DM, consider CV risk calculator Non-Invasive Testing for Fibrosis in NAFLD Fib-4 NAFLD Score Results Low Unlikely Fibrosis Exercise, weight loss Interm./High Possible Fibrosis Exercise, weight loss refer for fibroscan/swe References: BMJ 2018; 362: k2734 doi: , Am Fam Phys 2017; 96(11):709 Hepatology 2018; 67 (1); 328