Patrick Northup, MD, MHS - Wyoming Medical Center Northup: Abnormal LFTS What would your next step...

Click here to load reader

download Patrick Northup, MD, MHS - Wyoming Medical Center Northup: Abnormal LFTS What would your next step be?

of 40

  • date post

    30-May-2020
  • Category

    Documents

  • view

    0
  • download

    0

Embed Size (px)

Transcript of Patrick Northup, MD, MHS - Wyoming Medical Center Northup: Abnormal LFTS What would your next step...

  • Abnormal Liver Enzymes

    Patrick Northup, MD, MHS Medical Director, Liver Transplantation

    Program Director, GI and Hepatology Fellowship

    University of Virginia liver@virginia.edu

  • 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

    http://images.google.com/imgres?imgurl=http://s88741803.onlinehome.us/weblog/Images/jaundice.jpg&imgrefurl=http://s88741803.onlinehome.us/weblog/&h=216&w=216&sz=22&tbnid=GGis_lRmo7EJ:&tbnh=101&tbnw=101&hl=en&start=2&prev=/images%3Fq%3Djaundice%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN

  • 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 to hepatologist

    Stop meds / EtOH repeat

    chemistry in 3 months

    Repeat chemistries,

    HBs-Ag, HCV- Ab, Iron, TIBC,

    ferritin

    above plus RUQ

    ultrasound

    above plus abdominal 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 (

  • Initial more detailed workup

    Probably the most cost-effective and efficient initial workup for

  • Last Case

    43 yo female with many years of MS. Multiple medications used f