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Chronic Transaminitis Objectives

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					   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
   Objectives/Outline and Guidelines/References
   Cases
   Differential Diagnosis
   Medical History
   Physical Examination
   Initial Laboratory Evaluation
   Diagnostic Algorithm
   Revisit Objectives
    Chronic Transaminitis:
    Guidelines
   AGA Medical Position Statement: Evaluation of Liver Chemistry Tests.
    Gastroenterology 2002; 123: 1364-66. Also available at www.gastro.org

   AGA Technical Review on the Evaluation of Liver Chemistry Tests.
    Gastroenterology 2002; 123: 1367-84. At www.gastro.org

   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
   Pratt DS and Kaplan MM. Evaluation of abnormal liver-enzyme results
    in asymptomatic patients. N Eng J Med 2000; 342: 1266-71

   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

   O’Neil J and Powell L. Clinical aspects of hemochromatosis. Sem
    Liver Dis 2005; 25(4): 381-91

   Giannini EG et al. Liver enzyme alteration: A guide for clinicians.
    CMAJ 2005; 172: 367-79
    Chronic Transaminitis: Cases
   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.

   They were noted to have elevated transaminases (AST 100-
    125, 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.

   The women have been well with no symptoms. They look
    surprisingly similar to you – maybe identical triplets lost at
    birth !
Chronic Transaminitis: Cases
   Do these mysterious women have chronic
    transaminitis?
Chronic Transaminitis: Cases
   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
   Why is the time frame of 6 months important ?




   In general terms, what is the sensitivity this definition for
    chronic hepatic injury ?
    Chronic Transaminitis: Cases
   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
   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
   In terms of broad disease categories, what is a
    differential diagnosis of potential etiologies of
    chronic transaminitis ?
    Chronic Transaminitis: Dxdx
   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
   Which medications, herbs, street drugs can lead
    to transaminitis and liver injury ?

       (Note: chronic recurrent use can lead to chronic
        liver injury)
Chronic Transaminitis: Dxdx
   Which Immune causes of liver disease can lead
    to chronic transaminitis ?
Chronic Transaminitis: Dxdx
   Which Immune causes of liver disease can lead
    to chronic transaminitis ?

    “True” Auto-immune hepatitis

    Primary Biliary Cirrhosis

    Sclerosing Cholangitis
Chronic Transaminitis: History
   Given the previously discussed differential
    diagnosis, what are important historical features
    to explore in a patient with chronic transaminitis ?
Chronic Transaminitis: History
   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

   Symptoms of the consequences of cirrhosis: bleeding,
    cachexia, edema, ascites, encephalopathy, skin
    changes, gynecomastia etc.
Chronic Transaminitis: History
   Risk factors / etiology:
       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
   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
   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


   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
   What are considered relevant initial laboratory
    investigations by several expert consensus
    guidelines ?
Chronic Transaminitis: Initial Labs
   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
   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.

   Mrs. C. Metaltoxin was found to have an iron
    saturation of 58% (n<45%) and a ferritin of 850 mcg/l
    (n = 22-322) …
       What is her diagnosis ?
       Does she need further diagnostic testing ?
       What are the broad principles in her management ?
    Chronic Transaminitis:
    Mrs. C. Metaltoxin
   She likely has hereditary hemochromatosis, was not on iron
    supplements, & did not take alcohol to excess (why is this relevant ?)

   Some physicians like to confirm the degree of iron overload definitively
    with liver biopsy

   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

   Treat with phlebotomy get Fe saturation below 50%, & assess for
    cirrhosis and other systemic involvement of Fe overload
Chronic Transaminitis:
Diagnostic Algorithm
   Miss B. Immune had (N) initial investigations
    apart from a repeat of the transaminases which
    were minimally elevated as before…

   What should be done now ?
Chronic Transaminitis:
Diagnostic Algorithm
   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)


   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
   Miss B. Immune had a positive ANA at a titre of
    1:640.

   A liver biopsy confirmed autoimmune hepatitis
    with no evidence of cirrhosis.

   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

				
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