1 / 76

ASSESEMENT OF ABNORMAL LIVER TESTS

ASSESEMENT OF ABNORMAL LIVER TESTS. Prof. Eli Zuckerman, M.D. Liver Unit Haifa and Western Galilee District and Carmel Medical Center Clalit Health Services. Liver tests. ALT. AST, LDH. ALT (GPT) AST (GOT) LDH ALP (alkaline phosphatase) GGT bilirubin albumin

ricky
Download Presentation

ASSESEMENT OF ABNORMAL LIVER TESTS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ASSESEMENT OF ABNORMAL LIVER TESTS Prof. Eli Zuckerman, M.D.Liver UnitHaifa and Western Galilee District and Carmel Medical CenterClalit Health Services

  2. Liver tests ALT AST, LDH • ALT (GPT) • AST (GOT) • LDH • ALP (alkaline phosphatase) • GGT • bilirubin • albumin • P.T (prothrombin time) • globulin • CBC

  3. CLINICAL ASSESSMENT OF ABNORMAL LIVER TESTS Blood tests • Acute/recent vs. chronic liver disease • Hepatocellular vs. cholestatic injury • Etiology of liver disease (ALD, viral…) • Severity of liver disease (cirrhotic vs. non-cirrhotic)

  4. Markers of Hepatocellular damage(Transaminases) • AST- liver, heart skeletal muscle, kidneys, brain, RBCs • In liver 20% activity is cytosolic and 80% mitochondrial • Clearance performed by sinusoidal cells, half-life 17hrs ALT– more specific to liver, v.low concentrations in kidney and skeletal muscles. • In liver totally cytosolic. • Half-life 47hrs

  5. Gamma-GT – hepatocytes and biliary epithelial cells, pancreas, renal tubules and intestine • Very sensitive but Non-specific • Raised in ANY liver disease hepatocellular or cholestatic • Usefulness limited • Confirm hepatic source for a raised ALP • Alcohol • Isolated increase does not require any further evaluation, suggest watch and rpt 3/12 only if other LFT’s become abnormal then investigate

  6. Markers of Cholestasis • ALP– liver and bone (placenta, kidneys, intestines) • Hepatic ALP present on surface of bile duct epithelia and accumulating bile salts increase its release from cell surface. Takes time for induction of enzyme levels so may not be first enzyme to rise and half-life is 1 week. • ALP isoenzymes, 5-NT or gamma GT may be necessary to evaluate the origin of ALP

  7. CLINICAL ASSESSMENT OF LIVER DISEASE SEVERITY Physical examination (I) Peripheral signs of CLD (“stigmata”): • spider angiomata • Dupuytren’s contracture • palmar erythema • testicular atrophy • gynecomastia

  8. Physical examination (II) Significant liver disease and/or portal HTN • Enlarged Lt. Lobe • Firm liver (fibrosis/cirrhosis) • Abdominal collaterals (portal HTN) • Splenomegaly (portal HTN) • Ascites (high SAAG, portal HTN) • Muscle wasting

  9. Bilirubin, Albumin and Prothrombin time (INR) • Useful indicators of liver synthetic function • In primary care when associated with liver disease abnormalities should raise concern • Thrombocytopenia is a sensitive indicator of liver fibrosis

  10. Patterns of liver enzyme alteration • Hepatic vs cholestatic • Magnitude of enzyme alteration (ALT >10x vs minor abnormalities) • Rate of change • Nature of the course of the abnormality (mild fluctuation vs progressive increase)

  11. CLINICAL ASSESSMENT OF LIVER DISEASE SEVERITY Case 1. ALT (GPT) 1890 AST (GOT) 1750 LDH 880 ALP 180 GGT 170 bilirubin 1.0 albumin N P.T 1.4 (60%) globulin 4.3 CBC N

  12. Admission?

  13. Differential diagnosis?

  14. Acute hepatitis (ALT>10xULN) • Viral • Ischaemic • Toxins • Autoimmune • Acute Budd-Chiari • Early phase of acute obstruction • Metastatic liver-diffuse (extremely rare)

  15. Comments * Extremely high AST & LDH: ischemic, toxic (paracetamol, ecstasy) *“Hit and run” pattern: (AST 17h, ALT 47h): ischemic, toxic, CBD stone * Relatively preserved appetite:AIH, drug- induced * Alcoholic hepatitis: AST/ALT >1 (92%) AST <300 (98%)

  16. “Hit and Run” pattern of liver enzymes AST ALT

  17. Diagnostic blood tests?

  18. Diagnostic tests: acute hepatitis * HAV-IgM, HBsAg, HBc-IgM, HCV (± HCV RNA) *Anti smooth muscle Ab, ANA, anti-LKM-1 * Ultrasound * CMV-IgM, EBV-IgM * Additional: toxic screen, Doppler US (hepatic veins)

  19. IgG 2430 mg/ml • anti-smooth muscle +++ • ANA 1:160

  20. Liver biopsy?

  21. Interface hepatitis

  22. Lobular Hepatitis

  23. Plasma cell infiltration

  24. Case 2. 28 y/o male, asymptomatic, BMI 27.7, •ALT (GPT) 132 AST (GOT) 51 • LDH 467 • ALP 66 • GGT 95 • bilirubin 0.6 • albumin 4.3 • P.T 1.1 • globulin N • CBC N • Cholesterol 277 (LDL-C 170) • TG 304

  25. Differential diagnosis?

  26. CLINICAL ASSESSMENT OF ABNORMAL LIVER TESTS Case 2. • D.D • Fatty liver or NASH (non alcoholic steatohepatitis) (DM II, HLP, obesity, insulin resistance) • Chronic viral hepatitis (HBV, HCV) • Alcoholic liver disease(AST>ALT, MCV , GGT ) • Autoimmune hepatitis (ANA, aSMA, LKM-1) • Wison’s disease(age < 55) (hemochromatosis, A1AT) • Drug induced liver injury • Celiac disease, Addison.

  27. Diagnostic blood tests?

  28. Diagnostic tests case 2: asymptomatic abnormal LT (X2-5) *Viral serology: HBsAg, HCV (± HCV RNA) *Autoimmune screen: anti-smooth muscle Ab, ANA, anti-LKM-1, (anti mitochondrial) *Metabolic (age < 50):ceruloplasmin, ferritin, transferin, iron, α1 anti-trypsin *NAFLD: lipids, HbA1c, insulin resistance, glucose *US *Additional: celiac(anti-transglutaminase, endomysial)

  29. All diagnostic blood tests negative except anti-smooth muscle Ab ±

  30. Imaging features US sensitivity depends on hepatic fat content- >30% fat, sensitivity 80% 10-19% fat, sensitivity 55% Morbid obesity – sensitivity 49%, specificity 75%

  31. MANAGEMENT OF NAFLD•TO BIOPSY OR NOT TO BIOPSY ?•WHOM TO BIOPSY ?

  32. NASH - RISK FACTORS FOR FIBROSIS AND CIRRHOSIS Independent risk factors in several studies: • Age >45 • ALT > 2x normal • AST/ALT ratio > 1 • Obesity, particularly truncal , BMI > 27 • Type 2 diabetes • Insulin Resistance • Hyperlipdemia (trigycerides > X1.7) NB: Studies are in selected groups; may not apply to all patients

  33. Case 3. 48 y/o male, asymptomatic, BMI 36 •ALT (GPT) 100 AST (GOT) 125 • LDH 467 • ALP 66 • GGT 95 • bilirubin 0.6 • albumin 3.7 • P.T 1.1 • globulin 4.0 • PLT 138000 • Cholesterol 277 (LDL-C 170) • TG 304

  34. HIT # 1

  35. NAFLD-”simple” steatosis

  36. NASH Fibrosis

  37. NASH cirrhosis

  38. Management?

  39. Treatment of NAFLD Weight reduction Diet + exercise* Pharmacological: orlistat, Bariatric surgery * Insulin sensitizing agentsthioglitazones* (pio-, rosi-) metformin* Anti-oxidantsVit E, betain CytoprotectiveUrsodeoxicholic acid Lipid lowering agents HMG-CoA RI’s ? Fibrates ?

  40. Surgery

  41. Case 4. 61 y/o male, asymptomatic, BMI 27.7, IHD (PTCA + stent RCA), HTN, US: “fatty liver” •ALT (GPT) 87 AST (GOT) 51 • ALP 66 • GGT 95 • bilirubin 0.6 • albumin 4.3 • P.T 1.1 • globulin N • CBC N • Cholesterol 277 (LDL-C 170) • TG 304 Statins?

  42. After 12 weeks of Rx with statins •ALT (GPT) 220 AST (GOT) 110 • ALP 100 • GGT 95 • bilirubin 1.0 • albumin 4.3 • Cholesterol 210 (LDL-C 123) • TG 220

  43. FOR THE PHYSICIAN Continued treatment 3. Fulminant hepatitis ALAT 2. Chronic liver disease 5 ULN 1. Adaptation 1 ULN DRUG

  44. Black, Gastroenterology , 1975;69:289 0.1% Death CLINICAL 1% Jaundice INFRA- CLINICAL ALT > 10 ULN Unfractionated heparin Isoniazid 30%  Transaminases 15%  Transaminases Monreal, Eur J Clin Pharmacol 1989;37:415 Huang, Hepatology 2002;35:883-889

More Related