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Chronic Mildly Elevated LFT’s and Nonalcoholic Fatty Liver Disease (NAFLD)

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Chronic Mildly Elevated LFT s and Nonalcoholic Fatty Liver Disease (NAFLD) Josh Spencer AM Report 11-26-2007 Liver Function Tests Enzyme Tests Serum ... – PowerPoint PPT presentation

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Title: Chronic Mildly Elevated LFT’s and Nonalcoholic Fatty Liver Disease (NAFLD)


1
Chronic Mildly Elevated LFTs and Nonalcoholic
Fatty Liver Disease (NAFLD)
  • Josh Spencer
  • AM Report
  • 11-26-2007

2
Liver Function Tests
  • Enzyme Tests
  • Serum aminotransferases (ALT,AST) GGT, AP
  • Tests of synthetic function
  • Serum albumin, prothrombin time
  • Hepatic Transport Capability
  • Serum Bilirubin

3
Frequency of Elevated LFTs
  • Many routine screening tests include LFTs
  • Survey between 1999-2002
  • 8.9 had elevated LFTs
  • Serious underling disease is uncommon
  • Many times diagnosis can be made noninvasively
  • Tests can be guided by pretest probablity of
    certain liver diseases
  • False positives high with low pretest probability

4
Work-up of elevated LFTs
  • History
  • Exposure, duration of increased LFTs, presence
    of symptoms (ex. Jaundice, arthralgias, abd pain
    etc), transfusions, IVDU, sexual history, ETOH
    USE
  • Physical Exam
  • Presence of liver disease stigmata of CLD,
    abdominal exam, ascites?
  • Labs
  • Suggestive of hepatocellular injury serum
    aminotransferases higher than AP
  • Suggestive of cholestasis AP higher than ALT
  • Look at synthetic function
  • Going to look at w/u of mild elevation of serum
    aminotransferases

5
Mild Chronic Elevation of Serum Aminotransferases
  • Six months
  • Mild elevation lt4X ULN of ALT,AST, or both
  • Stepwise w/u
  • 4 steps
  • HP can raise/lower pretest probability

6
Step I
  • Meds/supplement use
  • ETOH use
  • Viral hep B and C
  • Hemochromatosis
  • Fatty Liver

7
Meds
  • Almost any med and Dx can be difficult
  • NSAIDS, ABX, Statins, anti-sz, anti-TB
  • Herbals and illicits
  • Tylenol even at recommended doses can raise LFTs
  • Features may lead to Drug cause as Dx lack of
    elevation before drug, elevation after drug use,
    improvement after stopping

8
ETOH
  • Many patients hide this history
  • Questionnaires
  • AST/ALT ratio gt21
  • Twofold increase in GGT when above ratio is seen

9
Hep B
  • History or parental exposures and being from high
    risk areas
  • Hep B surface antigen
  • Hep B surface Ab
  • Hep B core antibody

10
Hep C
  • History
  • Hep C antibody (sens 92-97)

11
Hereditary Hemochromatosis (HHC)
  • Common Genetic Disorder
  • Heterozygotes 10 of Caucasians
  • 5/1000 homozygous
  • Screen with serum iron, TIBC which helps
    calculate iron sat
  • Iron saturation of gt45 Dx but to support get
    ferritin (remember ferritin AFR)
  • Ferritin gt400ng/ml men, gt300 women

12
Hepatic Steatosis and Steatohepatitis
  • Fatty liver and NASH
  • History (more on this later)
  • LFTs lt4X elevation
  • Ratio of AST/ALT lt1
  • Ultrasound, CT, MRI
  • Differentiate NASH and NAFLD (more later) by
    biopsy

13
Step II Non-hepatic causes
  • Muscle disorders
  • ALT and AST can be high in muscle injury
  • Look for elevations in CK, LDH, aldolase
  • Thyroid disorders
  • TSH and history
  • Celiac disease
  • History diarrhea, Iron def
  • Ab screening serum anti endomysal IgA, anti
    tissue transglutaminase IgA
  • Adrenal insufficiency
  • Anorexia
  • History

14
Step III Rare Liver Diseases
  • Autoimmune Hepatitis
  • Young women, hx autoimmune disorders
  • SPEP gt2 fold elevation in polyclonal IGs
  • Also can order ANA, Anti SM ab, liver-kidney
    microsomal ab
  • Biopsy
  • Wilsons
  • Billary copper excretion, age lt40
  • Serum ceruloplasmin reduced
  • Call optho for Kayser-Fleischer rings
  • 24 hour urine quant copper (gt250mcg/gm)
  • Alpha-1-antitrypsin def
  • History of emphysema (early)
  • Alpha-1-antitrypsin phenotype

15
Step IV Liver Biopsy
  • Observation
  • If ALT and AST less than two fold elevated
  • No stigmata chronic liver disease
  • Biopsy
  • AST ALT persistently gt2x elevated
  • Strong suspicion of liver disease

16
NAFLD
  • Spectrum of disorders from simple hepatic
    steatosis to NASH and ESLD (steatohepatitis)
  • From simple fat accumulation in hepatocytes w/o
    inflammation or fibrosis to steatohepatitis with
    necroinflammatory changes with associated
    fibrosis
  • Macrovesicular hepatic steatosis with absence of
    excessive ETOH use
  • gt5 hepatic steatosis
  • Approximately 30 of population
  • Major cause of hepatic related morbitity/mortality
  • Directly proportional to body weight
  • With increasing obesity becoming major public
    health concern

17
NAFLD RISK FACTORS
  • Obesity
  • Diabetes and other insulin resistance
  • High triglycerides
  • Extreme wt. loss
  • Drugs
  • Increasing incidence as obesity increases

18
Pathogenesis
  • Not totally certain exact cause
  • Insulin resistance seems to be most popular
    theory with strong epidemiological and
    biochemical evidence showing link
  • Increased lipolysis, increased TG synthesis,
    increased liver uptake of FFA, increased
    accumulation of hepatic TG
  • Second hit mechanism
  • Oxidative injury
  • Hepatic iron, anti-oxidant def, intestinal
    bacteria
  • Host factors

19
Pathogenesis Causes of Fat Accumulation
  • Hepatic steatosis is TG acculmulation in liver
  • Excessive importation of FFA from tissues to
    liver
  • Increased delivery (obesity)
  • Excessive conversion of carbs and protein to fat
    (TPN, overfeeding)
  • Diminished fat export by VLDL
  • Impaired VLDL synthesis
  • Impaired beta-oxidation of FFA

20
NAFLD Treatment
  • Treatment of metabolic syndrome
  • Improving insulin resistance
  • Modification of diet
  • Exercise
  • Weight loss
  • Bariatric surgery?
  • Wt loss too quickly can worsen liver disease
  • Identify patients at risk for more significant
    liver disease
  • Biopsy
  • Pharmacological therapy

21
Who to Biopsy
  • No firm recommendations
  • Individual basis
  • Age gt45
  • Presence of DM and/or obesity
  • AST/ALT gt1

22
References
  • Mendez-Sanchez, Nahum et al. Treating
    Nonalcoholic Fatty Liver Disease. Liver
    International. ISSN 1478-3223.
  • UpToDate. AGA guideline Nonalcoholic fatty
    liver disease.
  • Tendler, David A MD. Pathogenesis of
    nonalcoholic fatty liver disease. UpToDate.
    2007.
  • Kaplan, Marshall M MD. Approach to the patient
    with abnormal liver function tests. UpToDate.
    2007.
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