Chronic Transaminitis
Dr. Danny Panisko
UHN/MSH AIMGP Seminar Series
March 2007
Chronic Transaminitis: Objectives
At the end of this seminar you will be able to:
 Define chronic transaminitis
 List an underlying differential diagnosis
 Understand relevant features on History
 Conduct a relevant Physical Exam
 Describe a guideline-based Investigation
approach
Chronic Transaminitis: Outline
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Objectives/Outline and Guidelines/References
Cases
Differential Diagnosis
Medical History
Physical Examination
Initial Laboratory Evaluation
Diagnostic Algorithm
Revisit Objectives
Chronic Transaminitis:
Guidelines
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AGA Medical Position Statement: Evaluation of Liver Chemistry Tests.
Gastroenterology 2002; 123: 1364-66. Also available at www.gastro.org
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AGA Technical Review on the Evaluation of Liver Chemistry Tests.
Gastroenterology 2002; 123: 1367-84. At www.gastro.org
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National Academy of Clinical Biochemistry’s Laboratory Guidelines for
the Screening, Diagnosis, and Monitoring of Hepatic Injury 2000;
Section 4; Chronic Hepatic Injury; pp.31-8. At www.nacb.org
Chronic Transaminitis:
Useful References
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Pratt DS and Kaplan MM. Evaluation of abnormal liver-enzyme results
in asymptomatic patients. N Eng J Med 2000; 342: 1266-71
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Role of PCR and liver biopsy in the evaluation of patients with
asymptomatic transaminitis: implications in diagnostic approach. J
Gastroenterol Hepatol 2004; 19(11): 1291-9
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O’Neil J and Powell L. Clinical aspects of hemochromatosis. Sem
Liver Dis 2005; 25(4): 381-91
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Giannini EG et al. Liver enzyme alteration: A guide for clinicians.
CMAJ 2005; 172: 367-79
Chronic Transaminitis: Cases
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Ms. A. Viral, Miss B. Immune, and Mrs. C. Metaltoxin are
three asymptomatic 35 year old women coincidently
referred to your AIMGP clinic on the same day.
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They were noted to have elevated transaminases (AST 100125, ALT 100-125 [N<35]; and N ALP and Tbili) by their
family MD’s on routine bloodwork 6 months ago. Repeat
bloodwork, miraculously performed on the same day,
revealed similar values 2 months ago and also one week
ago.
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The women have been well with no symptoms. They look
surprisingly similar to you – maybe identical triplets lost at
birth !
Chronic Transaminitis: Cases
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Do these mysterious women have chronic
transaminitis?
Chronic Transaminitis: Cases
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Do these mysterious women have chronic
transaminitis?
Yes. This entity is defined as persistence of
elevated ALT for more than 6 months, either
after an episode of acute hepatitis or without
another explanation.
Chronic Transaminitis: Cases
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Why is the time frame of 6 months important ?
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In general terms, what is the sensitivity this definition for
chronic hepatic injury ?
Chronic Transaminitis: Cases
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Why is the time frame of 6 months important ?
It defines a clinical entity with a limited differential and
eliminates a variety of short-lived causes of liver injury that
do not have long term consequences or considerations.
Work up of mild asymptomatic transaminitis that does not
persist is not indicated in a patient without risk factors.
Work up of chronic asymptomatic transaminitis is
conducted in the hope of preventing progression to
cirrhosis.
Cirrhosis:
Chronic Transaminitis: Cases
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In general terms, what is the sensitivity of this definition for
chronic hepatic injury ?
While generally sensitive and specific, it is not perfect.
For example, some patients with chronic Hepatitis C
infection do not mount elevated ALT’s.
Also, a patient with primary biliary cirrhosis or sclerosing
cholangitis may only have an elevated ALP earlier in the
course of their disease.
Chronic Transaminitis: Dxdx
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In terms of broad disease categories, what is a
differential diagnosis of potential etiologies of
chronic transaminitis ?
Chronic Transaminitis: Dxdx
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In terms of broad disease categories, what is a differential
diagnosis of potential etiologies of chronic transaminitis ?
Viral
Immune
Metal deposition / Toxic
Other – including non-hepatic !
Can you provide more detail for this differential before
viewing the answers on the next slide?
Chronic Transaminitis: Dxdx
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Which medications, herbs, street drugs can lead
to transaminitis and liver injury ?
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(Note: chronic recurrent use can lead to chronic
liver injury)
Chronic Transaminitis: Dxdx
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Which Immune causes of liver disease can lead
to chronic transaminitis ?
Chronic Transaminitis: Dxdx
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Which Immune causes of liver disease can lead
to chronic transaminitis ?
“True” Auto-immune hepatitis
Primary Biliary Cirrhosis
Sclerosing Cholangitis
Chronic Transaminitis: History
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Given the previously discussed differential
diagnosis, what are important historical features
to explore in a patient with chronic transaminitis ?
Chronic Transaminitis: History
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Symptoms of liver injury: fatigue, weakness, icterus,
pruritis, dark urine, possible stool colour lightening,
nausea, vomiting, RUQ discomfort, intolerance to dietary
protein or cigarette smoke
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Symptoms of the consequences of cirrhosis: bleeding,
cachexia, edema, ascites, encephalopathy, skin changes,
gynecomastia etc.
Chronic Transaminitis: History
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Risk factors / etiology:
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fecal/oral and blood/body fluid exchange risks for
viral hepatitis
drugs, medications, herbs, toxins, alcohol [CAGE],
acetaminophen (primary or co-toxin)
obesity, dieting, obesity surgery, bullemia, diabetes as
risks for non-alcoholic steatohepatitis (NASH)
Family history: for diseases with symptoms
consistent for hemochromatosis, Wilson’s, alpha-1
antitrypsin, or autoimmune
Chronic Transaminitis: Physical
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What physical exam features should be
emphasized in a patient with chronic
transaminitis ?
(Can you identify the physical signs on the following slides ?)
Chronic Transaminitis: Physical
Obviously trivia…..
 Dermatitis herpetiformis: chronic herpetiform lesions on
extensor surfaces (in this case, elbows) in patients with
Celiac Disease
 Kayser-Fleischer Rings, best appreciated with a slit
lamp, as brown pigmentary deposits on the periphery of
the cornea, in patients with Wilson’s disease
 Tendon xanthomata, on the Achilles, in patients with
hyperlipidemia due to cholestasis in liver disease that
also can have chronic transaminitis such as primary
biliary cirrhosis
Chronic Transaminitis: Physical
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Findings of liver injury and structural change:
hepatomegaly, RUQ tenderness
Findings of liver dysfunction: icterus/jaundice, edema,
bleeding, bruising, edema, encephalopathy, asterixis,
fetor hepaticus
Findings of portal hypertension: splenomegaly, caput
medusa, hemorrhoids, ascites
Stigmata of chronic liver disease
Findings of Etiologic disease processes: bronze
diabetes, mental status changes/psychoses,
malnutrition/malabsorption, vasculitic purpura (what
are the connections with these signs ?)
Chronic Transaminitis:
Case History and Physical
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No additional history or physical exam data was
contributory for none of the suspiciously similar Ms.
A. Viral, Miss B. Immune, nor Mrs. C. Metaltoxin….
except that Ms. A. Viral received a transfusion of
2 units of pRBC’s after a car accident in 1986,
and Mrs. C. Metaltoxin underwent a total
hysterectomy because of fibroids at age 30
Chronic Transaminitis: Initial Labs
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What are considered relevant initial laboratory
investigations by several expert consensus
guidelines ?
Chronic Transaminitis: Initial Labs
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What are considered relevant initial laboratory
investigations for chronic transaminitis by
several expert consensus guidelines ?
Liver enzymes, INR, Albumin, CBC with
platelets, Hepatitis B S Ag, Hepatitis B S Ab,
Hepatitis C IgG, % Iron Saturation and/or Ferritin
Chronic Transaminitis: Initial Labs
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Ms. A. Viral was found to have Hepatitis C IgG
positive. Therefore, a diagnosis of Chronic Hepatitis
C was made. She was referred to a hepatologist for
consideration of antiviral therapy.
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Mrs. C. Metaltoxin was found to have an iron
saturation of 58% (n<45%) and a ferritin of 850 mcg/l
(n = 22-322) …
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What is her diagnosis ?
Does she need further diagnostic testing ?
What are the broad principles in her management ?
Chronic Transaminitis:
Mrs. C. Metaltoxin
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She likely has hereditary hemochromatosis, was not on iron
supplements, & did not take alcohol to excess (why is this relevant ?)
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Some physicians like to confirm the degree of iron overload definitively
with liver biopsy
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She and her first degree relatives should receive genetic screening,
with HFE mutation analysis, to facilitate decision making for treatment
of family members and genetic counseling
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Treat with phlebotomy get Fe saturation below 50%, & assess for
cirrhosis and other systemic involvement of Fe overload
Chronic Transaminitis:
Diagnostic Algorithm
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Miss B. Immune had (N) initial investigations
apart from a repeat of the transaminases which
were minimally elevated as before…
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What should be done now ?
Chronic Transaminitis:
Diagnostic Algorithm
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The AGA algorithm suggests abdominal ultrasound,
ANA, Ceruloplasmin, anti-smooth muscle antibody,
anti-gliadin antibody, anti-endomysial antibodies and
alpha-1 antitrypsin level.
(What entities do these investigations test for ?…
see answer on next slide)
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The algorithm also suggests further confirmatory
liver biopsy if any of these results are abnormal.
Many hepatologists would also do a liver biopsy at
this point if there was still no diagnosis.
(See algorithm on 2nd slide following)
Chronic Transaminitis:
Miss B. Immune
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Miss B. Immune had a positive ANA at a titre of
1:640.
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A liver biopsy confirmed autoimmune hepatitis
with no evidence of cirrhosis.
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She was referred to a hepatologist and started
on Prednisone therapy.
Chronic Transaminitis: Objectives
Hopefully, you are now able to:
 Define chronic transaminitis
 List an underlying differential diagnosis
 Understand relevant features on History
 Conduct a relevant Physical Exam
 Describe a guideline-based Investigation
approach