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

Where to learn more http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/guide-to-common-liver-tests/

http://www. clevelandclinicmeded http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/cirrhosis-cholangitis-other-cholestatic-liver-disease/

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

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

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

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

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

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

Why Is My Bilirubin Elevated?

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

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

Cholangiography (ERCP)

Cholangiography (ERCP/MRCP)

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

What Is Fatty Liver?

Hepatitis C

Tests of Hepatic Fibrosis

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

Evolution of Diagnosis of Cirrhosis From Biopsy to Elastography

Elastography Fibroscan (Echosens) ARFI (Siemens) MRI elastography

M/S to kPa units E=3xV2 F2: Cut-off 1.34 m/s 3 x (1.34)^2 = E = 5.4 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 = 10.04 kPa

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

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

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

Non Invasive Assessment Fatty Liver

NAFLD Fibrosis Score The most studied and validated biomarker What is it: Limitations: performs best in Caucasians NAFLD Fibrosis Score = -1.65+0.037 x age(yr) + 0.094 x BMI + 1.13 x IFG/diabetes [yes=1; no = 0) + 0.99 x AST/ALT ratio – 0.013 x platelet count (x 10^9/L) – 0.66 x albumin (g/dl)

NAFLD Fibrosis Score Age Platelet count Impaired glucose tolerance Albumin BMI AST/ALT ratio Results Fibrosis < - 1.455 F0 –F2 -1.455 to ≤ 0.675 Indeterminate score > 0.675 significant fibrosis (F3-F4 fibrosis) http://nafldscore.com/ Angulo et al. Hepatology2007;45:846

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: www.thecalculator.co/health/AST-to-Platelet-Ratio-Index-APRI-Calculator-700.html 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;53:726-36.

Cirrhosis: Know the Score

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;359:1018-1026

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

Thank you

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