Sorting out the Diagnostics

1
Sorting out the Diagnostics

• Ed Marino, PA-C
• Porter Adventist Hospital
• Liver Transplant Services
• Denver, CO

2
Acknowledgements

• Thanks to the organizers for my invitation
• Especially Corinna Dan, RN, MPH
• Staff at Hepatitis Foundation International
• Staff at Porter Hospital Liver Transplant Service
  for allowing me time away for this

3
Educational Objectives

• Review the most common liver lab tests
• Determine true liver synthetic function
• Review viral hepatitis lab values
• Discuss follow up for above labs

4
Hepatic Physiology

• Liver
• Largest solid organ in the body
• Performs over 500 chemical processes
• Produces over 160 different proteins
• Makes clotting factors for the blood
• Stores releases sugar as glycogen
• Metabolizes, detoxifies, synthesizes

5
The Anatomy of the Liver

6
CT
7
Liver Histology
8
Defining Terms

• Hepatitis refers to any swelling, inflammation,
  or irritation of the liver
• Over 100 causes including
• Viruses, alcohol, enzyme deficiencies
• Iron or copper overload, microvesicular fat
• Genetic disorders, licit illicit drugs, toxins
• Hypotension (shock liver / reperfusion)

9
Defining Terms

• Inflammation that lasts long enough will create
  fibrosis
• Extreme fibrosis is called cirrhosis
• Cirrhosis can be either compensated or
  decompensated
• Compensated cirrhosis can be subtle
• Decompensated cirrhosis is more obvious

10
Normal Liver
11
Cirrhotic Liver
12
Defining Terms

• Normal Lab Values 95 of normal, asymptomatic
  patients have numbers in this range on a bell
  shaped curve
• Abnormal Labs By definition, 2.5 of normal
  patients have lab values either above or below
  the normal range

13
Liver Function Tests

• ALT alanine aminotransferase (SGPT)
• AST aspartate aminotransferase (SGOT)
• Alkaline Phosphatase Bilirubin
• Known as LFTs (but theyre really not)

14
Liver Synthetic Function

• Total Protein and serum albumin
• Total Bilirubin
• Prothrombin Time (PT / INR)
• These are true tests of liver function

15
Traditional LFTs

• ALT
• Found primarily in hepatocytes
• Released when cells are hurt or destroyed
• Normal levels depend on the reference range which
  actually differs lab to lab
• Considered normal between 5-40 U/L
• Probably should be half of this (5-20?)

16
Traditional LFTs

• AST
• Found in many sources, including liver, heart,
  muscle, intestine, pancreas
• Not very specific for liver disease
• Often follows ALT to a degree
• Elevated 2 or 31 (vs. ALT) in alcoholics
• Normal range 8-20 U/L

17
Traditional LFTs

• Alkaline Phosphatase
• Found in liver (especially biliary tract), bones,
  intestines, placenta
• Fractionated or isoenzymes to source
• Liver AP rises with obstruction or infiltrative
  diseases (i.e., stones or tumors)
• Normal range 20-70 U/L

18
Traditional LFTs

• Bilirubin two primary sources
• Indirect (unconjugated) old red cells, removed
  by the spleen, sent to the liver
• Liver adds glucuronic acid, making these cells
  water soluble for excretion now called direct
  (or conjugated)
• Normal range less than 0.8 mg/dL

19
Traditional LFTs

• Bilirubin Indirect and direct
• Direct (conjugated) Total bilirubin includes
  both direct and indirect types
• Excreted in the bile, down the common bile duct,
  into the small intestine
• Normal range 0.3 1.0 mg/ dL

20
Patterns of Abnormal

• Elevations in ALT AST only suggests cellular
  injury
• Elevations in Alk Phos Bilirubin suggests
  cholestasis or obstruction
• Mixed pattern ALT, AST, AP Bili probably the
  most common scenario

21
Patterns of Abnormal

• Consider degree of elevation
• Very high ALT and AST usually only come from a
  couple of sources
• Acute viral hepatitis (A,B,C, HSV)
• Acetominophen toxicity / overdose
• Shock Liver cardiac or surgical event?
• Most other items dont cause huge levels

22
Viral Hepatitides

• Hepatitis A, B, C, D, E, G
• Cytomeglovirus (CMV)
• Herpes Virus (HSV)
• West Nile Virus (WNV)

23
Viral Hepatitides

• Hepatitis A (HAV)
• Food, water borne heat labile
• Fecal - oral contamination contagious
• Usually self limited, lasting days to weeks
• 99 spontaneous recovery, no treatment
• Tests HAV IgM antibody acute infection
• HAV total antibody (IgM IgG) exposure
• only, could be post infection or vaccination

24
Viral Hepatitides

• Hepatitis B (HBV)
• Blood, semen, saliva, vaginal secretions
• Highly contagious sexually transmitted
• 90-95 self limited over 6 months
• Chronic infection 6 months
• DNA virus incorporates into host with chronic
  infection

25
Viral Hepatitides

• HBV Lab Tests
• HBV s Ag surface antigen infection
• HBV s Ab surface antibody - infection
• HBV c Ab core antibody IgM, IgG only with
  infection, not vaccination
• HBV e Ag envelope antigen if actively
  replicating virus
• HBV DNA actual viral load in blood

26
Viral Hepatitides

• Hepatitis C (HCV)
• Blood borne, not in food or water not highly
  sexually transmitted
• Not highly contagious
• 20 self clearing 80 chronicity
• RNA virus does not incorporate into host
• Can cause HCC 1 cause of transplant

27
Viral Hepatitides

• HCV Ab means past exposure can take 3-6
  months to form not found if acute
• RIBA / ELISA used to confirm Ab rules out
  false positives
• HCV PCR RNA confirms actual viral presence in
  blood can be /- or a viral count (qualitative
  vs. quantitative)
• HCV Genotype there are at least six (6)
  different (geno)types of HCV virus

28
Viral Hepatitides

• HCV Genotypes different mutations of same virus
  (different branches, same tree)
• Can vary by global geography
• Not predicative of damage or symptoms
• Can predict response to treatment
• Can be used to determine who is the best
  treatment candidate
• G1 4 most stubborn G2 3 most responsive
  G5 6 most rare

29
Evaluation Strategy

• Hepatocellular Injury
• Liver biopsy remains the Gold Standard for
  diagnosis
• Biopsy is second only to a good history
• If a biopsy is obtained, youll need a very
  experienced pathologist to read it
• Consider sending it out if your local expertise
  is suspect

30
Evaluation Strategy

• Advanced Imaging
• If RUQ US is questionable, and youre looking at
  a mixed picture
• Consider an MRCP non-invasive, sensitive for
  ductal dilation (CBD, pancreatic ducts).
  Diagnostic, but non-therapeutic.
• ERCP Therapeutic, risk of pancreatitis, not
  available everywhere

31
Spider Angiomata
32
Spider Nevi
33
Nail Clubbing
34
Dupuytren's Contracture
35
Ascites
36
Jaundice or Scleral Icterus
37
Evaluation Strategy

• Clinical Pearls
• Acute hepatitis panels never consider acute HCV.
  If you have a IVDA pt, consider an HCV PCR for
  acute hepatitis C. HIV?
• Consider celiac sprue for abnormal LFTs,
  especially if you get a vague history of
  dyspepsia. Order TTG (tissue transglutaminase
  antibodies) with AGA (anti gliadin antibodies).

38
Summary

• Liver tests are numerous and somewhat confusing
• Not all liver disease is associated with abnormal
  test results
• Some of the worst liver disease has relatively
  normal appearing LFTs and can only be noticed
  with a look at synthetic functions

39
Summary

• All abnormal liver tests should be investigated
• Referral to an expert is absolutely needed
• Liver biopsy is the Gold Standard for diagnosis
• Family histories of liver disease should be
  noted .my grandmother died of cirrhosis, but
  she never drank.

40
Thank You!

• My contact information
• Ed Marino, PA-C
• Porter Hospital Liver Transplant Service
• 2535 S. Downing St., Suite 380
• Denver, CO 80210
• edwardmarino_at_centura.org
• Wk. 303.778.5797 Fax [phone]