Sorting out the Diagnostics

Sorting out the Diagnostics

Ed Marino, PA
Ed Marino, PA
-
-
C
C
Porter Adventist Hospital
Porter Adventist Hospital
Liver Transplant Services
Liver Transplant Services
Denver, CO
Denver, CO
Acknowledgements
Acknowledgements
Thanks to the organizers for my invitation
Thanks to the organizers for my invitation
Especially
Especially
Corinna
Corinna
Dan, RN, MPH
Dan, RN, MPH
Staff at Hepatitis Foundation International
Staff at Hepatitis Foundation International
Staff at Porter Hospital Liver Transplant
Staff at Porter Hospital Liver Transplant
Service for allowing me time away for this
Service for allowing me time away for this
Educational Objectives
Educational Objectives
Review the most common liver lab tests
Review the most common liver lab tests
Determine true liver synthetic function
Determine true liver synthetic function
Review viral hepatitis lab values
Review viral hepatitis lab values
Discuss follow up for above labs
Discuss follow up for above labs
Hepatic Physiology
Hepatic Physiology
Liver:
Liver:
Largest solid organ in the body
Largest solid organ in the body
Performs over 500 chemical processes
Performs over 500 chemical processes
Produces over 160 different proteins
Produces over 160 different proteins
Makes clotting factors for the blood
Makes clotting factors for the blood
Stores & releases sugar as glycogen
Stores & releases sugar as glycogen
Metabolizes, detoxifies, synthesizes
Metabolizes, detoxifies, synthesizes
The Anatomy of the Liver
The Anatomy of the Liver
CT
CT
Liver Histology
Liver Histology
Defining Terms
Defining Terms
Hepatitis: refers to any swelling,
Hepatitis: refers to any swelling,
inflammation, or irritation of the liver
inflammation, or irritation of the liver
Over 100 causes including:
Over 100 causes including:

Viruses, alcohol, enzyme deficiencies

Viruses, alcohol, enzyme deficiencies

Iron or copper overload,

Iron or copper overload,
microvesicular
microvesicular
fat
fat

Genetic disorders, licit & illicit drugs, toxins

Genetic disorders, licit & illicit drugs, toxins

Hypotension (shock liver / reperfusion)

Hypotension (shock liver / reperfusion)
Defining Terms
Defining Terms
Inflammation that lasts long enough will
Inflammation that lasts long enough will
create fibrosis
create fibrosis
Extreme fibrosis is called cirrhosis
Extreme fibrosis is called cirrhosis
Cirrhosis can be either compensated or
Cirrhosis can be either compensated or
decompensated
decompensated
Compensated cirrhosis can be subtle
Compensated cirrhosis can be subtle
Decompensated
Decompensated
cirrhosis is more obvious
cirrhosis is more obvious
Normal Liver
Normal Liver
Cirrhotic Liver
Cirrhotic Liver
Defining Terms
Defining Terms
Normal Lab Values: 95% of normal,
Normal Lab Values: 95% of normal,
asymptomatic patients have numbers in
asymptomatic patients have numbers in
this range on a
this range on a

bell shaped curve

bell shaped curve

Abnormal Labs: By definition, 2.5% of

Abnormal Labs: By definition, 2.5% of
normal patients have lab values either
normal patients have lab values either
above or below the
above or below the

normal
normal

range
range
Liver
Liver

Function
Function

Tests
Tests
ALT: alanine aminotransferase (SGPT)
ALT: alanine aminotransferase (SGPT)
AST: aspartate aminotransferase (SGOT)
AST: aspartate aminotransferase (SGOT)
Alkaline Phosphatase & Bilirubin
Alkaline Phosphatase & Bilirubin
Known as LFT
Known as LFT

s (but they
s (but they

re really not)
re really not)
Liver Synthetic Function
Liver Synthetic Function
Total Protein and serum albumin
Total Protein and serum albumin
Total
Total
Bilirubin
Bilirubin
Prothrombin Time (PT / INR)
Prothrombin Time (PT / INR)
These are
These are

true
true

tests of liver function

tests of liver function
Traditional LFT
Traditional LFT

s
s
ALT:
ALT:
Found primarily in hepatocytes
Found primarily in hepatocytes
Released when cells are hurt or destroyed
Released when cells are hurt or destroyed
Normal levels depend on the reference
Normal levels depend on the reference
range which actually differs lab to lab
range which actually differs lab to lab
Considered normal between 5
Considered normal between 5
-
-
40 U/L
40 U/L
Probably should be half of this (5
Probably should be half of this (5
-
-
20?)
20?)
Traditional LFT
Traditional LFT

s
s
AST:
AST:
Found in many sources, including liver,
Found in many sources, including liver,
heart, muscle, intestine, pancreas
heart, muscle, intestine, pancreas
Not very specific for liver disease
Not very specific for liver disease
Often follows ALT to a degree
Often follows ALT to a degree
Elevated 2 or 3:1 (vs. ALT) in alcoholics
Elevated 2 or 3:1 (vs. ALT) in alcoholics
Normal range: 8
Normal range: 8
-
-
20 U/L
20 U/L
Traditional LFT
Traditional LFT

s
s
Alkaline Phosphatase:
Alkaline Phosphatase:
Found in liver (especially biliary tract),
Found in liver (especially biliary tract),
bones, intestines, & placenta
bones, intestines, & placenta

Fractionated
Fractionated

or
or

isoenzymes
isoenzymes

to source
to source
Liver AP rises with obstruction or
Liver AP rises with obstruction or
infiltrative diseases (i.e., stones or tumors)
infiltrative diseases (i.e., stones or tumors)
Normal range: 20
Normal range: 20
-
-
70 U/L
70 U/L
Traditional LFT
Traditional LFT

s
s
Bilirubin: two primary sources
Bilirubin: two primary sources
Indirect (unconjugated): old red cells,
Indirect (unconjugated): old red cells,
removed by the spleen, sent to the liver
removed by the spleen, sent to the liver
Liver
Liver

adds
adds

glucuronic acid, making these

glucuronic acid, making these
cells water soluble for excretion; now
cells water soluble for excretion; now
called direct (or conjugated)
called direct (or conjugated)
Normal range: less than 0.8 mg/dL
Normal range: less than 0.8 mg/dL
Traditional LFT
Traditional LFT

s
s
Bilirubin: Indirect and direct
Bilirubin: Indirect and direct
Direct (conjugated): Total bilirubin includes
Direct (conjugated): Total bilirubin includes
both direct and indirect types
both direct and indirect types
Excreted in the bile, down the common
Excreted in the bile, down the common
bile duct, into the small intestine
bile duct, into the small intestine
Normal range: 0.3
Normal range: 0.3

1.0 mg/ dL
1.0 mg/ dL
Patterns of Abnormal
Patterns of Abnormal
Elevations in ALT & AST only: suggests
Elevations in ALT & AST only: suggests
cellular injury
cellular injury
Elevations in Alk Phos & Bilirubin:
Elevations in Alk Phos & Bilirubin:
suggests cholestasis or obstruction
suggests cholestasis or obstruction
Mixed pattern: ALT, AST, AP & Bili:
Mixed pattern: ALT, AST, AP & Bili:
probably the most common scenario
probably the most common scenario
Patterns of Abnormal
Patterns of Abnormal
Consider degree of elevation:
Consider degree of elevation:
Very high ALT and AST usually only come
Very high ALT and AST usually only come
from a couple of sources:
from a couple of sources:
Acute viral hepatitis (A,B,C, HSV)
Acute viral hepatitis (A,B,C, HSV)
Acetominophen
Acetominophen
toxicity / overdose
toxicity / overdose

Shock Liver
Shock Liver

; cardiac or surgical event?

; cardiac or surgical event?
Most other items don
Most other items don

t cause huge levels

t cause huge levels
Viral Hepatitides
Viral Hepatitides
Hepatitis A, B, C, D, E, G
Hepatitis A, B, C, D, E, G
Cytomeglovirus (CMV)
Cytomeglovirus (CMV)
Herpes Virus (HSV)
Herpes Virus (HSV)
West Nile Virus (WNV)
West Nile Virus (WNV)
Viral Hepatitides
Viral Hepatitides
Hepatitis A (HAV):
Hepatitis A (HAV):
Food, water borne; heat labile
Food, water borne; heat labile
Fecal
Fecal
-
-
oral contamination; contagious
oral contamination; contagious
Usually self limited, lasting days to weeks
Usually self limited, lasting days to weeks
99% spontaneous recovery, no treatment
99% spontaneous recovery, no treatment
Tests: HAV IgM antibody = acute infection
Tests: HAV IgM antibody = acute infection
HAV total antibody (
HAV total antibody (
IgM
IgM
& IgG) = exposure
& IgG) = exposure
only, could be post infection or vaccination
only, could be post infection or vaccination
Viral Hepatitides
Viral Hepatitides
Hepatitis B (HBV):
Hepatitis B (HBV):
Blood, semen, saliva, vaginal secretions
Blood, semen, saliva, vaginal secretions
Highly contagious; sexually transmitted
Highly contagious; sexually transmitted
90
90
-
-
95% self limited over 6 months
95% self limited over 6 months
Chronic infection: >6 months
Chronic infection: >6 months
DNA virus: incorporates into host with
DNA virus: incorporates into host with
chronic infection
chronic infection
Viral Hepatitides
Viral Hepatitides
HBV Lab Tests:
HBV Lab Tests:
HBV s Ag: surface antigen; + infection
HBV s Ag: surface antigen; + infection
HBV s Ab: surface antibody;
HBV s Ab: surface antibody;
-
-
infection
infection
HBV c Ab: core antibody IgM, IgG; only
HBV c Ab: core antibody IgM, IgG; only
+ with infection,
+ with infection,
not
not
vaccination
vaccination
HBV e Ag: envelope antigen; if + actively
HBV e Ag: envelope antigen; if + actively
replicating virus
replicating virus
HBV DNA: actual viral load in blood
HBV DNA: actual viral load in blood
Viral Hepatitides
Viral Hepatitides
Hepatitis C (HCV):
Hepatitis C (HCV):
Blood borne, not in food or water; not
Blood borne, not in food or water; not
highly sexually transmitted*
highly sexually transmitted*
Not highly contagious
Not highly contagious
20% self clearing; 80%
20% self clearing; 80%
chronicity
chronicity
RNA virus: does
RNA virus: does
not
not
incorporate into host
incorporate into host
Can cause HCC; #1 cause of transplant
Can cause HCC; #1 cause of transplant
Viral Hepatitides
Viral Hepatitides
HCV Ab: + means past exposure; can take
HCV Ab: + means past exposure; can take
3
3
-
-
6 months to form; not found if acute
6 months to form; not found if acute
RIBA / ELISA: used to confirm Ab; + rules
RIBA / ELISA: used to confirm Ab; + rules
out false positives
out false positives
HCV PCR RNA: confirms actual viral
HCV PCR RNA: confirms actual viral
presence in blood; can be +/
presence in blood; can be +/
-
-
or a viral
or a viral
count (qualitative vs. quantitative)
count (qualitative vs. quantitative)
HCV Genotype: there are at least six (6)
HCV Genotype: there are at least six (6)
different (
different (
geno)types
geno)types
of HCV virus
of HCV virus
Viral Hepatitides
Viral Hepatitides
HCV Genotypes: different mutations of
HCV Genotypes: different mutations of
same virus (different branches, same tree)
same virus (different branches, same tree)
Can vary by global geography
Can vary by global geography
Not
Not
predicative of damage or symptoms
predicative of damage or symptoms
Can
Can
predict response to treatment
predict response to treatment
Can
Can
be used to determine who is the best
be used to determine who is the best
treatment candidate
treatment candidate
G1 & 4: most stubborn; G2 & 3: most
G1 & 4: most stubborn; G2 & 3: most
responsive; G5 & 6: most rare
responsive; G5 & 6: most rare
Evaluation Strategy
Evaluation Strategy
Hepatocellular Injury:
Hepatocellular Injury:
Liver biopsy remains the
Liver biopsy remains the

Gold Standard
Gold Standard

for diagnosis
for diagnosis
Biopsy is second only to a good history
Biopsy is second only to a good history
If a biopsy is obtained, you
If a biopsy is obtained, you

ll need a very
ll need a very
experienced pathologist to read it
experienced pathologist to read it
Consider sending it out if your local
Consider sending it out if your local
expertise is suspect
expertise is suspect
Evaluation Strategy
Evaluation Strategy
Advanced Imaging:
Advanced Imaging:
If RUQ US is questionable, and you
If RUQ US is questionable, and you

re
re
looking at a mixed picture:
looking at a mixed picture:
Consider an MRCP: non
Consider an MRCP: non
-
-
invasive,
invasive,
sensitive for
sensitive for
ductal
ductal
dilation (CBD,
dilation (CBD,
pancreatic ducts). Diagnostic, but non
pancreatic ducts). Diagnostic, but non
-
-
therapeutic.
therapeutic.
ERCP: Therapeutic, risk of pancreatitis,
ERCP: Therapeutic, risk of pancreatitis,
not available everywhere
not available everywhere
Spider
Spider
Angiomata
Angiomata
Spider Nevi
Spider Nevi
Nail Clubbing
Nail Clubbing
Dupuytren's Contracture
Ascites
Ascites
J aundice or
J aundice or
Scleral
Scleral
Icterus
Icterus
Evaluation Strategy
Evaluation Strategy
Clinical Pearls:
Clinical Pearls:
Acute hepatitis panels
Acute hepatitis panels
never
never
consider acute
consider acute
HCV. If you have a IVDA pt, consider an HCV
HCV. If you have a IVDA pt, consider an HCV
PCR for acute hepatitis C. HIV?
PCR for acute hepatitis C. HIV?
Consider celiac
Consider celiac
sprue
sprue
for abnormal LFT
for abnormal LFT

s,
s,
especially if you get a vague history of
especially if you get a vague history of
dyspepsia. Order TTG (tissue
dyspepsia. Order TTG (tissue
transglutaminase
transglutaminase
antibodies) with AGA (anti
antibodies) with AGA (anti
gliadin
gliadin
antibodies).
antibodies).
Summary
Summary
Liver tests are numerous and somewhat
Liver tests are numerous and somewhat
confusing
confusing
Not all liver disease is associated with
Not all liver disease is associated with
abnormal test results
abnormal test results
Some of the worst liver disease has
Some of the worst liver disease has
relatively normal appearing LFT
relatively normal appearing LFT

s and can
s and can
only be noticed with a look at synthetic
only be noticed with a look at synthetic
functions
functions
Summary
Summary
All
All
abnormal liver tests should be
abnormal liver tests should be
investigated
investigated
Referral to an expert is absolutely needed
Referral to an expert is absolutely needed
Liver biopsy is the
Liver biopsy is the

Gold Standard
Gold Standard

for
for
diagnosis
diagnosis
Family histories of liver disease should be
Family histories of liver disease should be
noted:
noted:

.
.

my grandmother died of
my grandmother died of
cirrhosis, but she never drank
cirrhosis, but she never drank

.
.

Thank You!
Thank You!
My contact information:
My contact information:
Ed Marino, PA
Ed Marino, PA
-
-
C
C
Porter Hospital Liver Transplant Service
Porter Hospital Liver Transplant Service
2535 S. Downing St., Suite #380
2535 S. Downing St., Suite #380
Denver, CO 80210
Denver, CO 80210
edwardmarino@centura.org
edwardmarino@centura.org
Wk. 303.778.5797 Fax 303.778.5205
Wk. 303.778.5797 Fax 303.778.5205