Dis isclosures Jordan Feld: • Research: Abbott, Abbvie, Gilead, Janssen, Merck Approach to App o Abn Abnormal Liv Liver Test: • Consulting: Abbvie, Contravir, Gilead, Merck Approach to App o live liver en enzymes Hemant Shah: • Consulting Fees: Abbvie, Gilead, Merck, Intercept, Lupin Hemant Shah MD MScCH Jordan J Feld MD MPH HPTE Toronto Centre for Liver Disease Sandra Rotman Centre for Global Francis Family Liver Clinic Health @hepatoMD Learn Le arning Obje bjectives Outl utline • Brief intro to ECHO 1. Appreciate the significance of different patterns of abnormal liver enzymes • Liver enzyme patterns • Work-up for 2. Develop an approach to the initial work-up of • Hepatocellular pattern abnormal liver enzymes in primary care • Cholestaic pattern • Mixed pattern • Liver enzymes over 1000! The father of ECHO ECHO (Extension for Community Health Outcomes) 1
Made in New Mexico The Methods Project ECHO Use Technology to leverage scarce resources - Linking PCPs to specialists - Facilitates Sharing “best practices” to reduce disparities Nurses linkage to care - Allows people to Other care providers be treated by Case based learning to master complexity Primary Care MDs people and in settings they Web-based database to monitor outcomes know & trust Perfected in Canada! Arora NEJM 2011 Arora S, Acad Med. 2007 Feb;82(2): 154-60. ECH CHO in in Ca Canada Th The ECHO Hub Hub Team am • First proposed to do ECHO Hepatitis in Canada • Hepatology: Jordan Feld & Hemant Shah - Toronto • Limited interest and no support from MOH • Family Medicine/Addiction: Craig Kuhn - Niagara • Developed HepC Net program – Hemant Shah – similar model • Nursing: Magdalena Kuczynski, Elizabeth Lee to support HCV treatment teams around Ontario • Pharmacist: Ruifen Su • 2014 – ECHO Pain • Chronic pain team led by Andrea Furlan • ECHO Team: Rhonda Mostyn – Project Manager • Support from MOH Ralph Fabico – Program Coordinator • Highly successful Jane Zhao – Research Coordinator • 2016 – Add ECHO Hepatitis + Arthritis…initially only HCV Shamini Martin- Eduation Coordinator • 2018 – expanded ECHO hepatitis to cover liver disease Ashley Grilo – Admin Coordinator Th The Sess Sessions After the Af he Cu Curr rriculum • ‘Didactic session’ • Welcome to join any time! • HCV curriculum – 15 topics • Bring cases or just participate in the discussion • Hub + ‘guest’ speakers – 40 min + discussion • With time…the goal is that everyone becomes a • Case presentations local HCV expert but still value in joining the • Community site sessions • Key points and clear question • Updates from meetings • Discussion – community sites + hub • New literature • Collective consensus on best strategies • Challenging cases • Follow-up of previous cases • Pre + Post questionnaires + survey 2
Wha hat do do you call all the hese tests? • ALT App Approach to o Abn Abnormal al Liv Liver Tes est: • AST Ap Approach to liver en enzymes • ALP • GGT Hemant Shah MD MScCH Jordan J Feld MD MPH Liver enzymes NOT LFTs HPTE Toronto Centre for Liver Disease Sandra Rotman Centre for Global Francis Family Liver Clinic ALT - Alanine aminotransferase | AST – Aspartate aminotransferase Health @hepatoMD ALP - Alkaline phosphatase | GGT - Gamma-glutamyl transferase Why? r tests/enzymes ≠ LFTs Liver Liv 56 yo man awaiting liver transplant • Liver Functions ALT 17 • Synthesis: AST 27 • Protein – Albumin, Clotting factors (INR) GGT 43 • Glucose – gluconeogenesis (only impaired very late) ALP 93 • Metabolism: • Bilirubin conjugation “LFTs” are “Normal”!! • Ammonia breakdown (encephalopathy) • Drug/toxin breakdown • (Portal Hypertension) • Ascites Actually – not true – LFTs VERY abnormal • Varices INR 2.4 • Encephalopathy Bilirubin 4.8 g/dL Liver function tests : INR, albumin, bilirubin (direct) Albumin 2.8 g/dL INR – International normalized ratio | LFT – Liver function tests Wha hat do do the he live liver r enz nzymes mean? Ca Categori rization • Most useful relative to upper limit of normal • Ongoing injury • Hepatocellular injury • Hepatocellular pattern (ALT/ULN >> ALP/ULN) • ALT (SGPT) – L for Liver specific (small amount muscle) • Cholestatic/infiltrative pattern (opposite) • AST (SGOT) – lots of other sources (RBC, muscle, heart) • Normal for both lower than the labs! • Mixed (ALT/ULN ≈ ALP/ULN) • Men – ALT 30 • Women – ALT 19 • Helps with narrowing a broad differential • Cholestatic/infiltrative injury or obstruction • Height & duration of elevation also important • ALP (alkaline phosphatase) • Check trend i.e. historical labs • GGT ULN - Upper Limit of Normal 3
Hep Hepatocellular r Pattern rn Infectious (AL ALT/AST) • Organization is key Screen EVERYONE! Common enough • HBV (HBsAg, anti-HBc, anti-HBs) to screen even if • Infectious • HCV (anti-HCV Ab) ALT normal • Toxic This should be the focus • Metabolic Screen Selectively • Genetic • HAV – very high ALT (>1000, exposure hx) – IgM • Autoimmune • CMV/EBV – immunosuppressed, ALP elevated Probably leave this stuff for us to do • Other CMV – Cytomegalovirus | EBV - Epstein – Barr virus | IgM - Immunoglobulin G | HAV - Hepatitis A virus Alc lcohol l – ho how muc uch is is too oo muc uch? Toxi xin • History is everything • AST>ALT (2:1) (+GGT) • Medications, medications, medications • CAGE questionnaire • Almost any drug can do it • Trust your patients (mostly) • Take a good history may have stopped the drug • If ALT>500 not alcohol alone (ask about drugs in past 3 months) • Antibiotics (Amox/Clav!!, minocycline, nitrofurantoin) Men: 1-2 per day • Don’t forget herbals, OTC and recreational drugs – Women: 1 per day need to ask Avoid binge drinking Avoid daily drinking Metabolic – fatty liv Me liver Genetic Gen • Hemochromatosis • Not rare in Caucasians (think Vikings – northern Europe) • ALT> AST (+ GGT) • Fe Sat > 50%, Ferritin • Metabolic risk factors • But both can be up in ETOH or Fatty liver disease • DM, HTN, lipids • Again…not mutually exclusive! • Weight gain or loss • More likely if also DM, arthritis, bronzing of the skin… etc • Still screen for HCV, HBV & ETOH – not • Wilson Disease mutually exclusive! • Screen all if < 30 and maybe all up to age 50 • More to come… • Ceruloplasmin • Bad to miss this – deadly disease that is treatable 4
Autoimmune?? Aut A few ‘general’ rules • Diagnosis is not straightforward • ALT>AST – most liver diseases • Viral hepatitis • Variable presentation from asymptomatic liver test • NAFLD/NASH abnormalities to fulminant liver failure • Most drug induced liver injury • Useful diagnosis because it has a bad prognosis and it’s treatable! • AST>ALT • Start with IgG if high, follow with ANA, SMA (and • Alcohol – >2:1 ratio LKM if children) and biopsy (or just refer!) • Ischemia (low flow or congestion) • Wilson disease (hemolysis – 4:1) • Cirrhosis!! (AST>ALT but <2:1) IgG - Immunoglobulin G | ANA - Antinuclear antibody So bo So bottom line line – AL ALT/AST Wha hat abo about hig high ALP ALP? • First prove it’s from the liver GGT (usually up), ALP • Etiology Search isoenzymes • History – meds, alcohol & other drugs • GGT is pretty useless on its own – VERY non-specific (almost any liver disease) and inducible (by meds) • HBV, HCV for everyone, (HAV, other viruses in context) • Fe Sat/ferritin for everyone • Cholestatic • (ceruloplasmin) • Extra-hepatic obstruction (stone/tumor) • (IgG – if persistent) • Intrahepatic duct disease • Severity assessment • Cholestasis (poor bile flow) – e.g. alcohol!! • CBC – low platelets suggest cirrhosis or acute alcohol • Infiltrative • Bilirubin, INR, Albumin (if persistent) • Granulomatous • Ultrasound (if persistent) • Mass / tumor Cho Cholestatic Gr Granulomatous/Infi filtrative • Rule out obstruction US usually adequate • Granulomatous (biopsy) • If painless jaundice need to see pancreas (CT or MRCP) • Sarcoid • TB/Fungal • Schistosomiasis – even years after leaving endemic area • If no obstruction (this is where we come in…): • Large Ducts: Primary/Secondary Sclerosing Cholangitis • Infiltrative (imaging +/- biopsy) (stones, IgG4) MRCP • Lymphoma • Small Ducts : Primary Biliary Cholangitis, vanishing bile duct syndrome, portal biliopathy (PV thrombosis) biopsy • Mass lesion (HCC, mets, abscess, hydatid cyst) • Drugs (or alcohol) history +/- biopsy 5
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