patrick northup, md, mhs - wyoming medical center · northup: abnormal lfts what would your next...
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Abnormal Liver Enzymes
Patrick Northup, MD, MHS Medical Director, Liver Transplantation
Program Director, GI and Hepatology Fellowship
University of Virginia [email protected]
Case presentation
43 year old man
Needs to start statin
AST 64, ALT 72, ALP 88, TB 1.0
No new meds/herbs
One drink EtOH per day
No high risk practices or h/o transfusion
Question one
Northup: Abnormal LFTS
What would your next step be?
A. Viral hepatitis serologies, ferritin, iron studies, ANA, AMA
B. above plus RUQ ultrasound
C. Advise patient to stop EtOH and recheck LFTs in 3 months
D. Refer to hepatology
E. Schedule f/u visit with your partner next week when you are on vacation
10
Results
Northup: Abnormal LFTS
0
0.2
0.4
0.6
0.8
1
1.2
A B C D E F
Overview
• Definition of abnormal LFTs
• Abnormal AST and ALT • Less than 5x upper limits of normal
• Greater than 15x upper limits of normal
• Elevations of ALP and total bilirubin
• Initial approach to workup
• When to refer?
What are the LFTs?
ALT / AST Hepatocellular damage
TBili / ALP Cholestasis, impaired
conjugation, or biliary
obstruction
PT-INR / ALB Synthetic function
GGT / 5’-NT Cholestasis or biliary
obstruction
LDH Hepatocellular damage, not
specific for hepatic disease
What is abnormal?
You think you are here
You may be here
What is abnormal?
19,877 US Air Force recruits, 99 (0.5%) had confirmed ALT elevations
• Only 12 had identifiable liver disease
• Most people with abnormal LFTs have no identifiable liver disease
Kundratos Dig Dis Sci 1993
What is abnormal?
1033 blood donors, 186 with HCV, 40 patients treated for HCV Piton
Hepatology 1998
All tested once for level of ALT
Blood
Donors
Active
HCV
Cured
HCV
96%
27%
42%
Percent with NORMAL
LFTs
Normal ALT does not guarantee “normal” liver
What is normal?
Normal ranges at UVAHS:
Test Lower limit
normal
Upper limit
normal
T. Bili (mg/dL) 0.3 1.2
ALP (U/L) 40 150
AST (U/L) 0 35
ALT (U/L) 0 55
Hepatocellular injury
Primarily elevations of AST and or ALT
1. Mild: less than 5x ULN
2. Moderate: 5-15x ULN
3. Severe: greater than 15x ULN
Could be due to
causes from
either group
AST/ALT less than 5x ULN
Most common clinical scenario
Widest differential diagnosis
Consider non-hepatic causes
• Hemolysis
• Myopathy
• Thyroid disease
• Acute muscle injury due to strenuous exercise
AST/ALT less than 5x ULN
Chronic viral (B and C)
Acute viral (CMV, EBV)
Steatohepatitis / NAFLD
Hemochromatosis
Medications / toxins
Autoimmune hepatitis
Alpha-1 antitrypsin
Wilson’s disease
Celiac disease
Cirrhosis
There is more alcohol than you think…
AST/ALT less than 5x ULN - Meds
Augmentin
Amiodarone
Anticonvulsants
Glyburide
Niacin
Nitrofurantoin
NSAIDS
Sulfonamides
Glitazones
Herbs
Anabolic steroids
Cocaine
Ecstasy
PCP
Carbon tetrachloride
Hydrazine
Toluene
Chloroform
livertox.nih.gov
Suspected NAFLD/NASH
Suspected NAFLD/NASH
• Rule out other liver diseases (? specialist referral)
• In young you must think about Wilson’s dz and AIH
• In polypharmacy, look at meds (amiodarone, corticosteroids)
• If all negative, manage metabolic syndrome aggressively, recheck in 4-6 months
Case presentation
• 21 yo male student
• RUQ pain, nausea, “hungover”
• 12-14 beers per day for the past week
• Returned from spring break in Cancun
• TB 7.9, ALT 1089, AST 2036, ALP 199
Question two
Northup: Abnormal LFTS
Which is least likely to be the source of these findings?
1. Acute hepatitis A
2. Acetaminophen toxicity
3. Amanita toxicity
4. Acute alcoholic hepatitis
5. Acute hepatitis B
10
Results
Northup: Abnormal LFTS
0
0.2
0.4
0.6
0.8
1
1.2
AST/ALT more than 15x ULN
Much smaller differential diagnosis
More likely to have an acute symptomatic presentation
History and physical exam are key
When associated with encephalopathy and coagulopathy termed liver failure
*Alcohol alone is rarely (if ever) solely responsible for this degree of elevation
AST/ALT more than 15x ULN
• Acute viral infection (A-E, HSV)
• Medication or toxin
• Acetaminophen
• Rx meds
• Amanita
• Ischemia
• Hypotension
• Budd-Chiari
• Autoimmune hepatitis
• Acute bile duct obstruction
• Wilson’s disease (rare)
• Acute hepatic artery ligation or clot
Enzymes > 15x ULN
• Can be life threatening
• Can progress rapidly, sometimes in as little as 48 hours
• Limited differential diagnosis
• Need to assess for synthetic dysfunction
• INR
• Bilirubin
• Altered mentation
Isolated increased bilirubin
Unconjugated (indirect)
Gilbert’s syndrome (rarely >4)
Hemolysis (heart valve, vascular prosthesis)
Ineffective erythropoiesis
Hematoma resorption
TIPS shunt
Neonatal / Crigler-Najjar
Isolated increased ALP
Hepatobiliary causes Biliary obstruction
PBC / PSC
Medications
Infiltrating disease
• TB
• Sarcoid
• Fungal
Metastases
Nonhepatic Bone disease / trauma
Pregnancy
Chronic renal disease
Non-liver malignancy
CHF
Normal childhood growth
Chronic inflammation
Increased ALP and TBili
Biliary obstruction
Medications
Chronic viral hepatitis
PBC / PSC
Sepsis
TPN
Pregnancy diseases
Cirrhosis
Meds causing cholestasis
Anabolic steroids
Allopurinol
Augmentin
ACE-inhibitors
Anticonvulsants
Erythromycin
Estrogens
HIV meds
NSAIDS
TMP-sulfa
Doxy / tetracycline
Question three
Northup: Abnormal LFTS
What is your initial lab/radiology workup of abnormal liver chemistries?
A. Referral to hepatologist
B. Stop meds / EtOH repeat chemistry in 3 months
C. Repeat chemistries, HBs-Ag, HCV-Ab, Iron, TIBC, ferritin
D. above plus RUQ ultrasound
E. above plus abdominal CT
10
Results
Northup: Abnormal LFTS
0
0.2
0.4
0.6
0.8
1
1.2
Referral tohepatologist
Stop meds /EtOH repeat
chemistry in 3months
Repeatchemistries,
HBs-Ag, HCV-Ab, Iron, TIBC,
ferritin
above plusRUQ
ultrasound
above plusabdominal CT
Costs of labs / radiology
51
37
129
80
93
108
920
600
Hepatic Panel
Hepatitis ABC
HCV VL and geno
Abd U/S
Charge Medicare Reimb
Based on 2001 USD. Green Gastroenterol 2002: 1367-1384
Initial workup of abnormal enzymes
• History and physical exam can help narrow the workup
• Marked abnormalities in chemistries, signs of chronic liver disease or cirrhosis should prompt expedited workup
• Extensive workup can be exhaustive and expensive and may be unnecessary in some cases
Initial workup of abnormal enzymes
• An isolated minor abnormality (<1.5 times upper limit of normal) in an asymptomatic individual should prompt retesting in 1 to 3 months, particularly after addressing potential causes or modifiable risk factors.
• Screen for HCV if in the right age group
• Disease specific tests including auto-antibodies, copper and iron studies, alpha-fetoprotein (AFP), and other specific viral markers should only be obtained in appropriate circumstances and usually in consultation with a specialist.
Initial more detailed workup
Probably the most cost-effective and efficient initial workup for <5x normal:
• Stop EtOH/meds, recheck chem panel in 6-8 weeks
• If normal, recheck again in 6-8 weeks
• If abnormal: HBsAg, HCV-Ab, ferritin, TIBC, +/- ultrasound
• If no findings and persistent increase, then refer
Last Case
43 yo female with many years of MS. Multiple medications used for therapy
• Avonex, Copaxone distant past: poor tolerance
• Betaseron stopped 2008
• Gilenya 2011: fatigue
• Tysabri in past, restarted April 2013
Labs
• ALP 468, ALT 1039, AST 682 • Significant abdominal pain, N/V, poor po intake
Other workup
• HBV studies negative
• Hepatitis C positive
• Anti-nuclear ab positive 1:80
• RUQ U/S showed no abnormalities
• No recent acetaminophen use
What to do now?
Liver Biopsy
Summary
• Abnormal liver enzymes can be caused by many things • Less than 5x upper limits of normal is rarely an
emergency and requires a lot of detective work
• Greater than 15x upper limits of normal can be immediately life threatening
• Think about the common things, especially medications and don’t panic about a single value
• If things don’t get better or clarify themselves, call me
Questions?