1. Interpreting Your Test Results
William Carey, MD MACG FAASLD
PSC Partners Seeking A Cure
June 23, 2017
3PM – 4PM

2. Where to learn more

3. http://www. clevelandclinicmeded

4. Within the liver cell the enzyme alkaline phosphatase is located close to the bile cannaliculus

5. Patterns of Liver Injury
Liver Disease Category
Test
Hepatocelluar
Cholestatic
Infiltrative
AST, ALT higher than alk phos
Typical
Alk phos higher than AST, ALT
Alk phos high and near normal AST ALT

6. Liver Enzymes Sensitive for hepatic injury
Not very specific to identify the cause of liver injury

7. Non Hepatic Sources of Select Lab Tests
Notes
Bilirubin
Red blood cells
Hemolysis, intra abdominal bleed, hematoma
AST
Skeletal, cardiac muscle, red blood cells
Muscle injury
ALT
Skeletal, cardiac muscle, kidneys
Not liver specific
LDH
Heart, red blood cells
Alkaline phosphatase
Bone, first trimester placenta, kidneys, intestine
Interpret with caution in pregnancy, acute kidney injury, when bone disease may be present

8. Acute vs. Chronic 6 months duration
New onset elevation of LFT in a chronic condition. “Acute on chronic liver disease”

9. Acute Chronic Viral infection (HAV, HEV, EBV, CMV, etc.)
Drug-induced injury
Alcoholic hepatitis
Ischemic
Fatty Liver Disease
Hepatitis C, B
PSC
A1AT deficiency
Alcoholic cirrhosis
more
Wilson Disease
HCV, HBV, AIH

10. Why Is My Bilirubin Elevated?

11. Bilirubin Nomenclature
Fraction
In Serum As
Measured As
Present in Urine
Unconjugated
Albumin-bound
Indirect-reacting bilirubin
Never
Conjugated
Unbound
Direct-reacting bilirubin
Yes, when serum bilirubin level is elevated

12. Disease That Principally Affect The Bile Ducts (Cholestatic Liver Disease)

13. Cholangiography (ERCP)

14. Cholangiography (ERCP/MRCP)

15. Commonest Liver Diseases USA 2017
More than one liver disease can occur in the same person !!!
Commonest Liver Diseases USA 2017
Fatty Liver Disease
Hepatitis C

16. What Is Fatty Liver?

18. Hepatitis C

19. Tests of Hepatic Fibrosis

20. Complications of Liver Biopsy
Pain
(84% of all biopsies)
Bleeding
(clinically significant*-1:2,500-1:10,000)
Death
Mostly due to bleeding
Reported in 1:10,000
* Requiring transfusion, intervention or hospitalization

21. Evolution of Diagnosis of Cirrhosis From Biopsy to Elastography

22. Elastography
Fibroscan (Echosens)
ARFI (Siemens)
MRI elastography

23. M/S to kPa units E=3xV2
F2: Cut-off 1.34 m/s x (1.34)^2 = E = kPa
F3: Cut-off 1.55 m/s 3 x (1.55)^2 = E = 7.2 kPa F4: Cut-off 1.80 m/s 3 x (1.83)^2 = E = kPa

24. Compensated Advanced Chronic Liver Disease (Cirrhosis)
TE [kPA]values:
< 10 in the absence of other known clinical signs RULES OUT cirrhosis
10 – 15 Suggestive of cirrhosis
> 15 highly suggestive of cirrhosis

25. Serum Fibrosis Biomarkers
Patented
Not Patented
FibroTest ®
APRI
Fibrospectl ®
14 others
Fibrometer®
Fibrosis Probability Index ®
Cales et al.Liver Inter 2008; 28:1352
Degos et al. J Hepatol 2010; 53: 1013
Zarski et al. J Hepatol 2012: 56:55
Castera et al. Gastro 2005; 128: 343

26. Some Limitations of
Liver Biopsy
Elastography
Serum Markers
MRI
Size/ diameter
Unable to discern intermediate stages of fibrosis
Further validation vs. TE
Unrepresentative
Applicability lower than serum markers. Failure 3% -16%
Parameters not liver specific
Time
Inter-observer variation
False positives in: obesity, ascites, congestion, inexperienced operator, acute hepatitis, cholestasis, food intake, xs alcohol
Hemolysis, Gilberts, inflammation
Not valid if iron overload
Costly
Costly (capital)
Costly*
Costly (capital)
Invasive
Requires MRI facility
Toxicity
HCP and patient aversion

27. Non Invasive Assessment
Fatty Liver

28. NAFLD Fibrosis Score The most studied and validated biomarker
What is it:
Limitations: performs best in Caucasians
NAFLD Fibrosis Score =
x age(yr) x BMI x IFG/diabetes [yes=1; no = 0) x AST/ALT ratio – x platelet count (x 10^9/L) – 0.66 x albumin (g/dl)

29. NAFLD Fibrosis Score Age Platelet count Impaired glucose tolerance
Albumin
BMI
AST/ALT ratio
Results
Fibrosis
<
F0 –F2
to ≤ 0.675
Indeterminate score
> 0.675
significant fibrosis (F3-F4 fibrosis)
Angulo et al. Hepatology2007;45:846

30. Serum Fibrosis Biomarkers APRI SCORE
APRI score greater than 1.0 has a sensitivity of 76% and specificity of 72% for predicting cirrhosis.
APRI score greater than 0.7 had a sensitivity of 77% and specificity of 72% for predicting significant hepatic fibrosis.
APRI score calculator:
Comparing patented vs. APRI scores AUROC values for significant fibrosis – no difference in performance
Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:

31. Cirrhosis: Know the Score

34. Serum Sodium Concentration and the Relative Risk of Death after Adjustment for the MELD Score
Figure 1. Serum Sodium Concentration and the Relative Risk of Death after Adjustment for the MELD Score.
MELD NA and UNOS
Kim WR et al. N Engl J Med 2008;359:

35. Summary Liver tests usually need to be interpreted as a pattern
Blood tests can identify with certainty hepatitis B, C and some other conditions
PSC cannot be accurately diagnosed by blood tests.
MRCP has replaced ERCP to a large extent
Liver biopsy is used much less frequently
When cirrhosis is present, Childs Pugh and MELD gauge remaining liver reserves

36. Thank you

37. Hepatitis B Tests of Interest
HBsAg
Anti HBc
Anti HBs
Interpretation + -
Chronic HBV
Prior infection
No current or prior infection
immunization