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Elevated Liver Function Tests

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stage 2-3 fibrosis and/or grade 3-4 necrosis/ inflammation on liver biopsy. stage 4 fibrosis (cirrhosis) with compensated liver function ... – PowerPoint PPT presentation

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Title: Elevated Liver Function Tests


1
Elevated Liver Function Tests
  • Senior talk 2009
  • MAISSAA JANBAIN, MD

2
BACKGROUND
  • Abnormal LFTs are frequently detected in
    asymptomatic patients (1-4).
  • They do not always reflect liver diseases.
  • They may be a marker of worse health outcomes.

3
BACKGROUND
  • A diagnosis can be established noninvasively in
    the majority of cases and usually guided by
    pretest probability as well as the pattern of
    abnormalities.
  • A complete history is very important duration,
    degree, associated symptoms and exposure to
    medications, chemicals, alcohol or recent travel
    history.

4
Isolated elevation of transaminases 1.common
hepatic causes
  • Medications (NSAIDs, Anitbiotics, statins,
  • antiepileptics and herbal preparations)
  • Alcohol (AST/ALT gt21, twofold elevation
  • of GGT)
  • Hereditary hemochromatosis (Caucasian, iron,
  • TIBC, ferritin /- liver biospy)

5
Isolated elevation of transaminases 1.common
hepatic causes
  • Viral hepatitis HBV ( HBsAg, anti HBsAg, anti
    HBc) and HCV ( ELISA, RIBA, PCR )
  • Hepatic steatosis and NASH ( AST/ALTlt1,
    ultrasound, CT or MRI)

6
Isolated elevation of transaminases 2.
Nonhepatic causes
  • Muscular disorders (AST/ALTgt3 if immediately
    after injury, CK, LDH, aldoalse)
  • Thyroid diseases (TSH)
  • Celiac disease (ALTgtAST, reversible with gluten
    free diet)
  • Adrenal insufficency ( reversible within week of
    treatment)
  • Anorexia nervosa

7
Isolated elevation of transaminases 3.Rare liver
diseases
  • Wilson s disease (age 5-25, serum ceruloplasmin,
    24hr urine for copper, liver biopsy)
  • Autoimmune hepatitis ( SPEP, ANA , SMA, LKMA,
    liver biopsy)
  • Alpha 1 antitrypsin (associated emphysema,
    protein electrophoresis)

8
Isolated elevation of transaminases 3.Rare liver
diseases
  • If no cause was identified and ALT, AST elevation
    is less than tow fold, no more investigations.
  • Biopsy is done otherwise eventhough it is less
    likely to provide diagnosis or lead to changes in
    management.

9
Isolated Hyperbilirubinemia
  • Unconjugated
  • Hemolysis (smear, retic count, haptoglobin) can
    be inherited or acquired. Rarely exceeds 5mg/dl
  • Impaired uptake or conjugation, drugs, Crigller
    Najjar and Gilberts syndrome.
  • Conjugated
  • Dubin Johnson with altered excretion
  • Rotor syndrome with defective storage.

10
Isolated elevation of alkaline phosphatase
  • Alk phos is derived from liver, bones, intestins
    and placenta.
  • Levels vary with age, more elevated in children.
  • To determine the source we check GGT or 5
    nucleotidase.
  • Initial evaluation includes U/S and AMA followed
    by ERCP v/s liver biopsy.

11
Isolated elevation of GGT
  • Very sensisitive for hepatobiliary disease but
    not specific.
  • Can reflect pancreatic disease, MI, renal
    failure, diabetes, COPD, alcoholism.

12
Cholestasis
  • The first step is to obtain ultrasound.
  • 2 big categories intrahepatic and extrahepatic.
  • Absence of biliary dilatation suggests
    intrahepatic cholestasis.

13
Extrahepatic cholestasis
  • u/s shows biliary dilatation, and usually is
    followed by ERCP v/s CT scan.
  • Choleodocholithiasis is the most common.
  • Other causes include malignancies, PSC, chronic
    pancreatitis and HIV cholangiopathy due to CMV or
    cryptosporidium (usually with no jaundice)

14
Intrahepatic cholestasis
  • Viral hepatitis (A, B, C, EBV, CMV)
  • Alcoholic hepatitis
  • PBC
  • Drugs (anabolic and OCPs, usually reversible)
  • Vanishing bile duct syndrome, adult bile
    ductopenia (chronic rejection, sarcoidosis)
  • Benign recurrent cholestasis (AR)
  • Pregnancy
  • TPN, sepsis, post-op, Stauffers syndrome

15
Hepatitis A
  • RNA virus with 4 genotypes but one serotype.
  • Fecal-oral route but also sexual (homosexual!),
    IVDA, and most common in USA international
    travel.
  • Incidence has significantly decreased with
    vaccination.

16
Hepatitis A
  • Usually acute self limited rarely fulminant
    especially if associated with chronic hep C.
  • Manifestations vary with age, more silent in
    children.
  • Incubation period of 30 days followed by abrupt
    prodromal symptoms then jaundice.
  • Extrahepatic manifestations vasculitis, optic
    neuritis, thrombocytopenia, aplastic anemia,
    transverse myelitis.

17
Hepatitis A
  • IgM anti HAV is the gold standard for diagnosis.
  • Start at the onset of symptoms and remain
    positive 4-6 months.
  • Infected individuals are contagious during
    incubation and for a week after jaundice appears.
  • Handwashing is very important !!! As HAV survives
    for up to 4 hrs on fingertips.

18
Hepatitis A
  • Treatment is usually supportive.
  • Prevention is mainly by good hygiene and
    vaccination ( travel to high risk areas).
  • IM Immunoglobulin are available for people
    allergic to vaccine and immunocompromised, they
    provide passive immunity for up to 6 months.

19
Hepatitis C
20
Hepatitis C
  • Flaviviridae family the prototype Hepacivirus
  • Rapid replication rate
  • High mutation rate that allows him to escape the
    immune recognition.
  • Hep C infection can present as acute hepatitis,
    chronic hepatitis, cirrhosis, HCC or extrahepatic

21
Hepatitis C
  • Incubation period 6-7 weeks and seroconversion
    time 8-9 weeks.
  • Acute symptomatic cases occur in 10-30 while
    fulminant hepatitis occurs almost exclusively in
    patients with HBV.
  • Most cases progress slowly to chronic infection.
    Mechanism is unknown. Viral, host and other
    factors play role.

22
Hepatitis C
  • Host factors
  • HLA-DRB1, DQB1
  • Low peak levels of HCV during acute infection
  • Age
  • Ethnicity
  • Coinfections (HIV, Hep B)
  • High BMI

23
Hepatitis C
  • Viral factors
  • Genotype 1B
  • Coinfection with gt1 HCV genotype
  • Other Factors
  • Marijuana
  • Alcohol
  • Amount of inflammation and fibrosis on liver bx
  • Corticosteroids

24
Chronic Hepatitis C
  • Symptoms if present are nonspecific Fatigue most
    common
  • Lack of correlation between symptoms and serum
    enzymes/liver histology.
  • ALT is mostly normal to mildly elevated used by
    some to monitor interferon therapy, while others
    are more interested in AST/ALT 1 as predictor of
    cirrhosis.

25
Cirrhosis/Complications
  • 20-50 (different studies) of chronic infections
    progress into cirrhosis where most complications
    of Hepatitis C are usually confined and survival
    is impaired.
  • Hepatic decompensation is manifested usually as
    ascites, followed by varcieal bleeding and
    jaundice
  • Hepatocellular carcinoma 0-3 of cases. More with
    genotype 1B
  • Once these complications occur, transplant is the
    only effective therapy

26
Extrahepatic manifestations
  • Hematologic (mixed cryoglobulenimia, lymphoma)
  • Renal (membranoproliferative GN)
  • Autoimmune (thyroiditis)
  • Dermatologic ( porphyria cutanea tarda, Lichen
    palnus)
  • Diabetes mellitus.

27
Exposure (acute phase)
HIV, HBV, Alcohol
55-85 (55-85)
15-45 (15-45)
Chronic
Resolved
20 (9-14)
80 (44-68)
Cirrhosis
Stable
25 (2-3)
75 (7-11)
Slowly Progressive
HCC Transplant Death
28
Hepatitis C Diagnosis
  • Who should be tested? AASLD recommendations
  • Abnormal ALT
  • IVDU hx
  • Blood transfusion lt 1992
  • Clotting factors lt1987
  • Kids to HCV infected mothers
  • Current sexual partners to HCV infected subjects
  • Needle stick

29
Hepatitis C Diagnosis
  • Elisa
  • RIBA
  • PCR-RNA
  • Genotype
  • Liver biopsy

30
Treatment
  • Counseling
  • Diet NO alcohol
  • Smoking controversial
  • Zofran for fatigue 4 mg bid
  • The mainstay of treatment is Interferon and
    ribavirin
  • Goals of treatment
  • eradicate HCV infection, slow disease
    progression,
  • improve hepatic histology (function) and
  • prevent hepatocellullar carcinoma

31
Interferon
  • Glycoproteins produced by cells in response to
    infection
  • Biological properties of interferons
  • anti-viral
  • immunostimulatory
  • anti-proliferative
  • anti-angiogenic

32
Pegylated Interferon
  • covalent attachment of variably configured
    polyethylene glycol (PEG) chains to sites on the
    interferon molecule
  • delays absorption
  • decreases clearance rate
  • allows once per week dosing
  • alters properties and activity of parent compound
  • prolongs immune activation and cytokine-derived
    antiviral effects
  • two pegylated interferons are now FDA-approved
  • peginterferon alfa-2a (Pegasys - Roche)
  • peginterferon alfa-2b (PEG-Intron - Schering)

33
Ribavirin
  • guanosine analogue
  • active against many viruses in vitro and in vivo
  • mechanism of action against HCV unclear
  • depletion of intracellular triphosphate pools
  • inhibition of viral-dependent polymerase
  • immunomodulatory
  • mutational deletions

34
Indications for treatment
  • stage 2-3 fibrosis and/or grade 3-4 necrosis/
  • inflammation on liver biopsy
  • stage 4 fibrosis (cirrhosis) with compensated
    liver function
  • genotype 2 or 3, viral load lt 2 million IU/mL
  • severe symptoms related to cirrhosis or
    extrahepatic symptoms (e.g., cryoglobulinemia)
  • desire to be pregnant without risk of vertical
    transmission

35
Contraindications for treatment
  • pregnancy or breast feeding
  • unwilling to practice reliable birth control
  • anemia (hemoglobin lt11 g/dL)
  • uncontrolled cardiac or cerebrovascular disease
  • renal failure
  • unstable neuropsychiatric disease
  • active alcohol or drug use
  • allergy or hypersensitivity to IFN or ribavirin

36
Recommended Regimen
  • genotype 1a/b and 4
  • pegylated interferon alfa-2a or 2b (see below)
    plus ribavirin (1000-1200 mg/d) for 48 weeks
  • genotypes 2, 3
  • pegylated interferon alfa-2a plus ribavirin (800
    mg/d) for 24 weeks
  • If viral load does not drop by a factor of at
    least 2 logs within the first 12 weeks of
    treatment, therapy should be discontinued.
  • e.g., viral load of 1,000,000 IU/mL must decrease
    to 10,000 IU/mL to indicate an early viral
    response.
  • Early viral response (EVR) predicts sustained
    viral response (SVR)

37
Investigational Therapies
  • Albuferon (longer half life, but same side
    effects and efficacy)
  • Thymus an extract of thymus gland
  • Interleukin 10, 11
  • resiquimod (receptor TLR7)
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