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Abnormal LFTs

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Abnormal LFTs Michele Ritter Argy Resident February, 2007 Liver Function Test Albumin Bilirubin: Total Bilirubin Direct Bilirubin (conjugated bilirubin) Serum ... – PowerPoint PPT presentation

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Title: Abnormal LFTs


1
Abnormal LFTs
  • Michele Ritter
  • Argy Resident February, 2007

2
Liver Function Test
  • Albumin
  • Bilirubin
  • Total Bilirubin
  • Direct Bilirubin (conjugated bilirubin)
  • Serum aminotransferases
  • Aspartate aminotransferase (AST)
  • Alanine aminotransferase (ALT)
  • Alkaline Phosphatase
  • Prothrombin time

3
Albumin
  • Synthesized in the liver
  • Production is controlled by multiple factors
    including nutritional status, serum oncotic
    pressure, cytokines, and hormones
  • A serum albumin may be reflection of the
    synthetic function of the liver.

4
Bilirubin
5
Bilirubin
  • Used to determine livers ability to clear
    endogenous/exogenous substances from the
    circulation
  • Indirect (unconjugated) bilirubin
  • Elevated with hemolysis, hepatic disease
  • Direct (conjugated) bilirubin
  • Elevated with biliary obstruction and
    hepatocellular disease.
  • Jaundice usually develops with a bilirubin 3
    mg/dL

6
Biliary Tract
7
Aminotransferases
  • Hepatic enzymes that are usually intracellular,
    but are released from hepatocytes with
    hepatocellular injury.
  • Includes aspartate aminotransferase (AST) and
    alanine aminotransferase (ALT)
  • AST/ALT ratio
  • Normal is 0.8
  • In alcoholic hepatitis, is usually gt 2

8
Alkaline Phosphatase
  • A group of enzymes that catalyze the hydrolysis
    of a large number of organic phosphate esters.
  • In liver, believed to play an active role in
    down-regulating the secretory activities of the
    intrahepatic biliary epithelium
  • Found in
  • Liver
  • Bone
  • intestine
  • First trimester placenta
  • Kidney
  • Gamma-glutamyl transpeptidase (GGT)
  • Liver origin Elevated GGT
  • Bone origin Normal GGT

9
Prothrombin Time (PT)
  • Liver is in charge of the synthesis of many
    clotting factors
  • Factor I (fibrinogen)
  • Factor II (prothrombin)
  • Factor V
  • Factor VII
  • Factor IX
  • Factor X
  • Factors XII and XIII
  • Elevated PT may be reflection of decreased
    synthetic activity of liver.

10
(No Transcript)
11
Assessing the patient with abnormal Liver
Function Tests
  • Most of the time, the cause of elevated LFTs can
    be illicited without invasive testing (biopsy)
  • If no cause of abnormality is found, most
    frequently the cause is alcohol liver disease,
    steatosis, or steatohepatitis
  • Certain patterns exist with LFTs
  • Hepatocellular Injury Very high AST, ALT with
    mild/moderately elevated alkaline phosphatase.
  • Cholestatis mild/moderately elevated AST/ALT
    with very high alkaline phosphatase
  • Bilirubin can be elevated with both combinations.

12
Hepatocellular Injury
  • Medications
  • History Need to assess temporal relationship
    with drug, see if patient improves once
    medication removed
  • NSAIDs, antibiotics, statins, anti-tuberculosis
    medications, anti-epileptic drugs, acetaminophen
  • Frequently cause isolated elevated
    aminotransferases
  • Acetaminophen overdose
  • Toxicity is likely to occur with single
    ingestions greater than 250 mg/kg or those
    greater than 12 g over a 24-hour period
  • AST/ALT elevations is first sign of liver damage
    (usually 24-hours after ingestion)
  • Alcohol Use
  • Frequently have ASTALT ratio 21
  • History Need accurate assessment of alcohol
    intake, including CAGE questions.

13
Hepatocellular Injury
  • Hepatitis A
  • Acute infection
  • History travel, recent outbreak, MSM nausea,
    vomiting, jaundice
  • Labs Hepatitis A IgM, frequent elevated
    bilirubin
  • Hepatitis B
  • Can be acute or chronic
  • History See if patient from Asia, Subsaharan
    Africa Sexual history, Drug use
  • Labs Hepatitis B surface antigen, surface
    antibody, core antibody
  • Hepatitis C
  • History IV drug abuse, blood transfusion prior
    to 1992, Sexual history, Tattoos
  • Labs Hepatitis C antibody (Hepatitis C viral
    load if HIV positive or immunocompromised)
  • HIV
  • Often causes isolated elevated aminotransferases
  • History Sexual History, IV drug use
  • Labs HIV Antibody test (ELISA with reflex
    Western Blot)

14
Hepatocellular Injury
  • Hereditary Hemochromatosis
  • History Family history of liver disease?
    Diabetes? Heart Failure? Bronze skin?
  • Labs
  • Serum iron, TIBC
  • Calculate iron saturation serum iron/TIBC
  • If iron saturation gt 45, check ferritin
  • Ferritin
  • If gt 400 ng/mL in men, or gt 300 ng/mL in women,
    then need to check liver biopsy or genetic
    testing
  • Liver biopsy
  • Homozygous hereditary hemochromatosis if iron
    index gt 1.9
  • If under age 40, and positive genetic testing, no
    biopsy needed.
  • Genetic Testing

15
Hepatocellular Injury
  • Hepatic steatosis/Non-alcoholic steatohepatitis
    (NASH)
  • Increase in AST/ALT are usually less than 4-fold.
  • Ratio of AST/ALT is usually lt 1
  • History Female, obesity, diabetes
  • Labs
  • Labs to rule out other causes of hepatitis
  • Abdominal Ultrasound look for fatty
    infiltration of liver

16
Hepatocellular Injury
  • Autoimmune Hepatitis
  • History Young to middle-aged female
  • Labs
  • Serum protein electrophoresis (SPEP) if
    polyclonal increase in gamma globulin
  • Anti-nucleur antibody Positive
  • Anti-smooth-muscle antibody (SMA)
  • Liver biopsy should be performed if the above
    are negative, but autoimmune hepatitis still
    suspected.

17
Hepatocellular Injury
  • Alpha-1-antitrypsin deficiency
  • History Family history, emphysema, young age
  • Labs
  • Alpha-1-antitrypsin level/phenotype
  • Treatment
  • Intravenous alpha-1 antiprotease helps with lung
    disease, but liver transplant is ultimately only
    treatment for liver disease.

18
Hepatocellular Injury
  • Wilsons Disease
  • A genetic disorder of biliary copper excretion
  • History Age (usually age 5 25, but up to age
    40), family history of liver disease
    neuropsychiatric disease
  • Evaluation
  • Serum ceruloplasmin Low
  • Opthalmologist Exam for Kayser-Fleisher rings
  • 24-hour urine copper
  • Liver biopsy Evaluate liver copper levels
  • Treatment
  • Copper chelating agents
  • Zinc
  • In some cases, ultimately liver transplant

19
Wilsons Disease Kayser-Fleisher Rings
20
Hepatocellular Injury
  • Shock Liver (ischemic hepatitis)
  • Etiology Shock, severe hypotension
  • Severely elevated AST/ALT (50 times normal)
  • Treatment Re-establish good blood
    pressure/perfusion.
  • Prognosis Usually patients recover, but can
    progress to fulminant liver failure requiring
    transplant.

21
Hepatocellular Injury
  • Non-Hepatic Causes
  • Usually only mild increase in AST/ALT
  • Muscle disorders
  • Hypothyroidism/Hyperthyroidism
  • Celiac Disease
  • Adrenal Insufficiency
  • Anorexia nervosa

22
Hepatocellular Injury
  • What if work-up is negative and AST/ALT remain
    elevated?
  • Observe
  • Patients with two-fold or less increase in
    AST/ALT and no hyperbilirubinemia
  • Liver Biopsy
  • Patients with gt two-fold increase in AST/ALT, or
    abnormalities of other liver function tests.

23
Cholestatic Pattern
  • Predominantly elevated alkaline phosphatase
  • Need to check GGT to see if bone or liver in
    origin
  • Blood types O and B can have elevated serum
    alkaline phosphatase after eating a fatty meal
    due to an influx of intestinal alkaline
    phosphatase
  • Need to determine if the cholestasis is
    intrahepatic or extrahepatic in origin.

24
Cholestatic Pattern - Intrahepatic
  • Drugs
  • Anabolic steroids, contraceptives, antibiotics
  • Total parenteral nutrition (TPN)
  • Cirrhosis
  • Viral hepatitis (Hepatitis B, C)
  • Alcohol hepatitis

25
Cholestatic Pattern - Intrahepatic
  • Primary Biliary Cirrhosis
  • Autoimmune disease
  • Predominately in women, usually ages 35-65
  • May have history of other autoimmune disease
  • Symptoms Prurutis, fatigue, hyperpigmentation,
    musculoskeletal complaints
  • Labs
  • RUQ Ultrasound
  • Anti-mitochondrial antibody
  • Liver biopsy to verify diagnosis

26
Cholestatic Pattern Both Intrahepatic and
Extrahepatic
  • Primary Sclerosing Cholangitis
  • chronic progressive disorder of unknown etiology
    that is characterized by inflammation, fibrosis,
    and stricturing of medium size and large ducts in
    the intrahepatic and extrahepatic biliary tree
  • 90 have inflammatory bowel disease, especially
    ulcerative colitis
  • Symptoms Pruritus, fatigue, RUQ pain
  • Diagnosis
  • Ultrasound
  • Cholangiogram multifocal stricturing and
    dilation of intrahepatic and/or extrahepatic bile
    ducts
  • Prognosis
  • Poor average life expectancy after diagnosis is
    12 years
  • 10-15 risk of developing cholangiocarcinoma
  • Liver transplant is ultimate only treatment

27
Cholangiogram of Primary Sclerosing Cholangitis
28
Cholestatic Pattern - Extrahepatic
  • Choledocholithiasis (gall stones!)
  • History
  • The 3 Fs
  • RUQ colicky abdominal pain
  • Diagnosis/Treatment Ultrasound, ERCP (to remove
    stones)
  • Malignancy
  • Cholangiocarcinoma
  • Pancreatic
  • Metastatic cancer
  • Diagnosis Ultrasound, MRCP
  • Treatment ERCP, biliary stent

29
Cholestatic Pattern - Extrahepatic
  • Chronic Pancreatitis
  • History Recurrent pancreatitis
  • Symptoms Abdominal pain, frequently referred to
    back
  • HIV Cholangiopathy
  • Usually seen in AIDS patients with CD4 count well
    below 100/mm3
  • Usually caused by Cryptosporidium.
    Microsporidium, CMV
  • Symptoms RUQ pain, Diarrhea, Occassional fever,
    Occassional jaundice
  • Diagnosis
  • ERCP
  • Cholangiography shows multifocal strictures of
    extrahepatic biliary tree

30
Isolated Hyperbilirubinemia
  • Unconjugated (indirect) hyperbilirubinemia
  • Overproduction of bilirubin
  • Hemolysis
  • Dubin-Johnson Syndrome and Rotor Syndrome
  • Decrease in uptake, conjugation, or excretion of
    bilirubin
  • Increased unconjugated (indirect) bilirubin
  • Liver Disease

31
Isolated Unconjugated Hyperbilirubinemia
  • Drugs
  • Probenecid, Rifampicin
  • Gilberts Disease
  • Autosomal recessive disorder
  • 3 to 7 of population
  • Most common in white males
  • Jaundice, increased unconjugated bilirubin
    (always lt 6)
  • Occurs when patient under stress/infection
  • Crigler-Najjar type II
  • Caused by gene mutation
  • Reduced activity of Bilirubin UDP glucuronosyl

32
SUMMARY
  • Hepatocellular Injury mostly ? AST/ALT
  • Drugs
  • Alcohol hepatitis
  • Hepatitis A
  • Hepatitis B
  • Hepatitis C
  • Steatohepatitis (NASH)
  • Autoimmune hepatitis
  • Wilsons Disease
  • Hereditary Hemochromatosis
  • Alpha-1 antitrypsin deficiency

33
SUMMARY
  • EXTRAHEPATIC
  • Gall stones
  • Primary Sclerosing Cholangitis
  • Malignancy
  • Chronic pancreatitis
  • HIV cholangiopathy
  • Cholestatic Pattern
  • INTRAHEPATIC
  • Drugs
  • Hepatitis A, B, C
  • Alcoholic hepatitis
  • TPN
  • Primary Sclerosing Cholangitis
  • Primary Biliary Cirrhosis

34
SUMMARY
  • Isolated elevated indirect (unconjugated)
    bilirubin
  • Hemolysis
  • Drugs
  • Gilberts Disease
  • Crigler-Najjar type II

35
Scenario 1
  • A 43-year old woman who has consumed a pint of
    80-proof whiskey daily for 18 years presents with
    right upper quadrant pain. The pain began
    approximately a week ago and has been transiently
    relieved by her taking two extra-strength
    acetaminophen tablets every 4 hours for the past
    4 days. She has had some nausea and vomiting but
    no fever. There is no history of jaundice or
    cholelithiasis. The patient used intravenous
    drugs and shared needles during her late teen
    years.

36
Scenario 1
  • Physical Exam
  • Enlarged tender liver that percusses to 17 cm in
    the right midclavicular line and a tattoo on the
    right buttock
  • Labs
  • Bilirubin 2 mg/dL AST 3800
  • Alk. Phos 198
  • PT normal

37
Scenario 1
  • The most likely diagnosis is
  • (A) Alcoholic hepatitis
  • (B) Acute cholecystitis
  • (C) Acetaminophen hepatotoxicity
  • (D) Acute viral hepatitis B
  • (E) Acute viral hepatitis C

38
Scenario 2
  • A 54-year old asymptomatic man volunteers to
    donate blood and is found to have elevated
    aminotransferase levels. He has no known medical
    problems and no history of hepatitis. He drinks
    no alcohol, takes no medications, and has not
    seen a physician in more than 10 years. He is
    active, works as a truck driver, and has noted no
    change in his physical condition. He has no
    family history of liver disease.

39
Scenario 2
  • Physical Exam
  • Obesity Ht 5 10, 115 kg
  • Labs
  • AST 45 ALT 85 Alk. Phos 90
  • Hepatitis serologies (A, B, C) negative
  • ESR normal ANA negative
  • Smooth muscle antibody negatie
  • Total chol 260 LDL 225 Triglycerides 830
  • Liver biopsy
  • Large-droplet steatosis without significant
    inflammatory reaction and no fibrosis.
    Ultrasonography shows a mildly enlarged fatty
    liver.

40
Scenario 2
  • The appropriate management of this patient would
    be
  • Interferon therapy for presumed chronic non-B,
    non-C hepatitis
  • Alcohol rehabilitation and counseling
  • Weight loss and therapy for hyperlipidemia
  • Endoscopic retrograde cholangiopancreatography
    (ERCP) to evaluate the biliary tree
  • Corticosteroid therapy

41
Scenario 3
  • A 43-year old woman complains of itching that
    keeps her awake at night. Physical examination
    is normal except for the liver, which is felt 7
    cm below the right costal margin.
  • CBC is normal
  • Creatinine 0.8 mg/dL, Bilirubin 0.6 mg/dL
  • ALT 78 U/L, Albumin 4.2 g/dL
  • Alkaline Phosphatase 450 U/L
  • Cholangiogram normal

42
Scenario 3
  • Which test would be most accurate in diagnosing
    her underlying disorder?
  • (A) Serum protein electrophoresis
  • (B) Anti-Smooth Muscle Antibody
  • (C) Antimitochondrial antibody
  • (D) Technetium-99m liver-spleen scan
  • (E) Endoscopic retrograde cholangiopancreatography
    (ERCP)
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