93rd Annual Dalhousie Fall Refresher · •Develop a practical and economical approach to evaluate...
Transcript of 93rd Annual Dalhousie Fall Refresher · •Develop a practical and economical approach to evaluate...
There is No Normal Abnormal Liver Test
Magnus McLeod MD FRCPC
Assistant Professor
Associate Program Director Internal Medicine
Dalhousie University
November 29/2019
93rd Annual Dalhousie Fall Refresher
Halifax, NS
Objectives
• Develop a practical and economical approach to evaluate abnormal serum liver tests
• Demonstrate appropriate use of hepatic imaging
• Discuss the use of liver biopsy in evaluation
93rd Annual Dalhousie Fall Refresher 2019Conflict Disclosures
Company/Organization Details
Advisory Board or equivalent Intercept
Gilead
Novartis
PBC/NASH
HCV/NASH
CHF
Grant(s) or an honorarium Intercept
Gilead
Lupin
PBC
HCV/NASH
IBS
Participating or participated in a clinical trial Genfit
Shire
NovoNordisk
Intercept
Gilead
NASH
NASH
NASH
NASH
NASH
PSC
Definitions
• LFTs is a misnomer
• Liver enzyme abnormalities reflect injury to either hepatocytes or cholangiocytes
• Can be referred to as liver injury tests
• Liver function tests reflect liver synthetic function(INR, Bilirubin, albumin)
The Common Patient
• 57 year old man with Hypertension
Obstructive Sleep Apnea
BMI 37
Dyslipidemia
HgbA1c 6%
Rare social alcohol
No symptoms
Labs
• AST 39(nl <45)
• ALT 31(nl <45)
• ALP 68 (nl <150)
• Albumin 40 (nl >35)
• Total bilirubin 12 (nl <20)
• Platelets 160 (nl 150-350)
Question 1
• What should be the next best step in evaluating this patient?
A. Liver ultrasound and possibly Hepatology referral
B. Liver biopsy
C. Check full liver panel- ANA, Ceruloplasmin, A1AT, AMA, HBV, HCV
D. Reassurance
Labs
• AST 39
• ALT 31
• ALP 68
• Albumin 40
• Total bilirubin 12
• Platelets 160
What evaluation is
indicated in this
patient?
Many conditions are clinical
diagnoses
Directed Approach
Back to Our Case
• AST 39
• ALT 31
• ALP 68
• Albumin 40
• Total bilirubin 12
• Platelets 160
Further work up
• HBsAg -ve
• HBsAb -ve
• HCV -ve
• Ultrasound shows MildHepatic steatosis
Prognosis
• How would you counsel this patient in regards to his prognosis?
A. Low risk; refer to Hepatology when ALT>2x
ULN
B. Impossible to know prognosis without biopsy
C. High risk; Refer to Hepatology
ALT
AST
ALT
AST
TIME
120
30
40
33
Available Non-Invasive Tests
HCV
Fibrotest
Forms Index
AST to Platelet Ratio(APRI)
Fibrospectll
MP3
Enhanced Liver Fibrosis Test(ELF)
Fibrosis Probability Index(FPI)
Hepascore
Fibrometer
Lok Index
Gotaborg University Cirrhosis Index(GUCI)
Virahep-C Model
HALT-C model
HBV
Hui score
Zeng score
HCV-HIV
FIB-4
SHASTA Index
NAFLD
NAFLD Fibrosis Index
BARD Score
Transient Elastography Magnetic Resonance
Elastography
NAFLD Referral
High RiskLow Risk
Fibroscan
Age
AST
ALT
Platelet count
BMI
Albumin
Impaired glucose tolerance
FIB4
NAFLD Fibrosis
Score
FIB4 EFFECT NPV/PPV%
<1.3Rules out
fibrosis95
>3.25Predicts
Fribrosis75
NFS EFFECT NPV/PPV%
<-1.455Rules out
fibrosis88-93
>0.676Predicts
Fribrosis82-90
8.5
>-1.455
>1.3
Case Cont’d
Age
AST
ALT
Platelet count
BMI
Albumin
Impaired glucose tolerance
57
39
31
160
37
40
Yes
Case Cont’d
Age
AST
ALT
Platelet count
BMI
Albumin
Impaired glucose tolerance
57
39
31
160
37
40
Yes
Fibroscan
ALT
AST
ALT
AST
TIME
120
30
40
33
8 10 12 14
Case Summary
• Given high Liver stiffness biopsy done
• Showed NASH cirrhosis
• EGD showed high risk varices
• HCC surveillance initiated
Case 2
• 37 year old man who works in sales
• No PMHx
• No alcohol
• Has family history of diabetes
• Complains of epigastric discomfort after spicy food and coffee
• BMI 37
Labs• CBC normal(platelets 280)
• Albumin 48
• Total bilirubin 10
• ALP 60
• ALT 124 (repeat 100)
• AST 101 (repeat 70)
• Normal HCV, HBV, iron indices, A1AT, ceruloplasmin, ASMA, AMA, TTG
What is the next best step?
A. Reassurance
B. Check more blood work
C. Liver biopsy
D. MRCP
E. Do more extensive history
A liver biopsy was performed
Referred to me
Pre-Visit
• 37 year old man who works in sales
• No PMHx
• No alcohol
• Has family history of diabetes
• Complains of epigastric discomfort after spicy food and coffee
• BMI 37
Non-Hepatic Causes• Muscle Injury: Rhabdomyolysis, seizures, dermatomyositis, long
distance running
– Check CK level
• Thyroid disease
• Celiac Disease
• Anorexia nervosa
• Adrenal Insufficiency
• Hemolysis
Case 3
• A 60 year old woman
• AST 190
• ALT 80
• ALP 300
• Bilirubin 120
• Ferritin 4500
• TS 60%
Shotgun Approach Used
• HBV and HCV negative
• AMA and ASMA negative
• A1AT normal
• Ceruloplasmin normal
• Iron studies as per previous
• HFE Heterozygous C282Y/H63D
What is the best therapeutic approach?
A. Needs a liver biopsy to say
B. Therapeutic phlebotomy
C. Iron chelation therapy
D. Antibiotics
E. None of the above
Hereditary Hemochromatosis
Complications
• After 3rd phlebotomy had syncopal episode
• Hip fracture
• Lost to follow up
• 6 months later presented with a variceal bleed and ascites complicated by spontaneous bacterial peritonitis
Typical Labs of AH
• AST >50 but <400
• AST:ALT >1.5
• ALT <200
• Bilirubin >51
• ALP/GGT usually high
Case 4
• 76 year old man
• Dark urine, jaundice, fatigue after bout of acute sinusitis
• ALT 450
• Bilirubin 180
• INR 1.3
Tests
• Tested for:
• HBV, HCV, EBV, HSV, CMV, Parvovirus
• ASMA, ANA, AMA
• Ceruloplasmin, HFE gene test
• A1AT
EBV IgM positive
What do you do during the next bout of sinusitis
A. Monitor liver tests closely
B. Reassure patient(EBV should not cause repeat
infxn)
C. Treat with NAC
D. Give different antibiotic than last time
Drug Induced Liver Injury(DILI)
• Amoxicillin/Clavulinic acid
• Most common cause of antibiotic induced ALF
• No diagnostic test
• Will recur and should never be given again
• EBV IgM has high false positive rate
Case 5
• 72 year old woman
• Fatigue, anorexia
• ALT 1200
• Bilirubin 40
• INR 1.0
CAD s/p MI
BP 110/60, HR 110
Cool legs
Acute Hepatocellular Liver Injury
What needs treatment NOW
Is this ALF
Tylenol? NAC
Hep B? Tenofovir
AIH Steroids
Testing for Inpatients with Severe Liver Injury
ALT/AST >10xULNClear History
Cardiogenic shock(cool extremities) +/-
hypotension
Ischemic
Hepatitis
Characteristic abdominal pain,
pancreatitis, feverBiliary causes
IV drug use, immunosuppression Viral hepatitis
Excessive acetaminophen, new
antibiotic or anti epileptic DILI
ALT/AST >10xULNUnclear History
STEP 1
Physical exam and evaluate for cardiac
failure
Ischemic
Hepatitis
Liver U/S vs cross sectional imaging Biliary causes
HBsAg, HBV PCR, HCV Ab, HCV PCR Viral hepatitis
Drug/ingestion history, withhold meds DILI
ALT/AST >10xULNUnclear History
STEP 2/3
Antismooth muscle Ab, IgG levelAutoimmune
hepatitis
Age<55, Ceruloplasmin and urine CuWilson’s
Disease
Not clear and above Liver biopsy
Case 6
• A 54 year old woman saw her primary care physician for an annual visit
• She complains of mild itching and fatigue
• Patient never had any surgeries and her only medications are calcium and vitamin D
• Her exam is unremarkable apart from below
Labs
• Alk Phos 426
• AST 40
• ALT 54
• Total bilirubin 17
January 2017 January 2018
• Alk Phos 398
• AST 39
• ALT 58
• Total bilirubin 19
Elevated ALP
GGT Normal
GGT Elevated
Investigate Non-Hepatic Causes of ALP
ALP of Hepatobiliary origin
AST/ALT Elevated
ALP of Hepatobiliary Origin: What is the Next Best Test To Determine the
Diagnosis?
A. Liver Biopsy
B. Anti-Smooth Muscle Antibody Titre
C. Abdominal U/S
D. HIDA Scan
ALP of Hepatobiliary Origin
• Next best step is Liver Ultrasound
• Differentiates Intrahepatic from Extrahepatic Cholestasis
ALP of Hepatic Origin
RUQ Ultrasound
Intrahepatic Biliary Dilatation or Irregular bile ducts
Normal U/S
Intrahepatic Cholestasis
Extrahepatic Cholestasis
Chronic Extrahepatic Cholestasis
Chronic Intrahepatic Cholestasis
Our Case Patient
• Chronic Cholestatic Liver Injury
• Normal Liver Ultrasound
• Intrahepatic Cholestasis
Intrahepatic Cholestasis
Antimitochondrial Antibody(AMA)
MRCP
Liver Biopsy
Primary Biliary Cholangitis(PBC)
+-
Thank You
Questions?