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?