1 / 36

OGDEN SURGICAL-MEDICAL SOCIETY 68 TH ANNUAL CONFERENCE - 2013

OGDEN SURGICAL-MEDICAL SOCIETY 68 TH ANNUAL CONFERENCE - 2013. What the LFTs are Telling You Avoiding Common Mistakes. Norman L. Sussman, MD Baylor College of Medicine Houston, Texas. OGDEN SURGICAL-MEDICAL SOCIETY 68 TH ANNUAL CONFERENCE - 2013.

ivory
Download Presentation

OGDEN SURGICAL-MEDICAL SOCIETY 68 TH ANNUAL CONFERENCE - 2013

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. OGDEN SURGICAL-MEDICAL SOCIETY68TH ANNUAL CONFERENCE - 2013 What the LFTs are Telling YouAvoiding Common Mistakes Norman L. Sussman, MD Baylor College of Medicine Houston, Texas

  2. OGDEN SURGICAL-MEDICAL SOCIETY68TH ANNUAL CONFERENCE - 2013 • This presentation has no commercial content, promotes no commercial vendor and is not supported financially by any commercial vendor. • I receive no financial remuneration from any commercial vendor related to this presentation

  3. Question 1: Acute or Chronic? • Injury • ALT/AST • Cholestasis • AlkPhos • GGT • 5’NT • Biliary imaging • U/S, MRCP, ERCP • Cirrhosis • Platelets • Imaging • Chronicity & severity • Prior studies • Albumin • Bilirubin • INR

  4. Question 2: Hepatocellular or Cholestatic ALT/ULN AP/ULN • >5 = hepatocellular • <2 = cholestatic Or, just look at the fold increase of ALT and AP • Normal ALT • Women < 19 IU/mL • Men < 30 IU/mL

  5. Aspartate Aminotransferase (AST/SGOT)Alanine Aminotransferase (ALT/SGPT)Markers of Cell Destruction • ALT is more specific to the liver • Usually higher in chronic liver injury (steady state) • Viral hepatitis, AIH, NAFLD • AST may be higher than ALT • Cirrhosis • Alcohol (pyridoxine deficiency) • Early phase of acute liver injury • Other organ damage – eg rhabdomyolysis, tumors

  6. Acute Liver injury Acetaminophen, Shock, IV AmiodaroneDynamic AST/ALT Ratio • Peak injury about 48 hrs • AST is initially 2x ALT • Differential clearance • AST – 50%/day • ALT – 33%/day • Equalize at about 96 hrs • Bilirubin, INR, and creatinine are key to assessing survival Remien et al., Hepatology 2012

  7. MALDModel of Acetaminophen-related Liver Damage Remien et al., Hepatology 2012

  8. Biliary Architecture - Bile Flow

  9. Epithelial Cells are Polarized Liver Hollow Organ Lumen = Bile Canaliculus = Brush Border Basolateral Aspect

  10. Alkaline Phosphatase • Located on the bile canliculus • Three genes • Liver/kidney/bone • Intestine • Placenta (man and great apes) • PI-glycan anchor (PI-g tailed proteins) • GGT, 5’-nucleotidase • GGT is inducible by alcohol • Access to the sinusoid (blood side of the cell) • Low in patients with Wilson disease Phospholipase C cleavage site

  11. Albumin & AFP • Proteins – made by the liver • AFP is the fetal analogue of albumin • Made when cells revert to a fetal phenotype – part of a coordinated switch to fetal genes • Liver regeneration (eg recovery from ALF) • Inflammation (injury with regeneration) • Liver cancer

  12. Prealbumin • Actually Transthyretin • Transports thyroxine and retinol • Used to assess nutrition • 2-4 day half life • Affected by inflammation • Mis-folded TTR is the most common protein in amyloid

  13. Bilirubin Transport

  14. Bilirubin • Organic anion derived from hemoglobin • Measured by diazo (Van Den Bergh) reaction • Direct (conjugated) vs. indirect • Indirect – albumin-bound • Direct – water soluble (urine) • Delta (albumin-bound) – clears slowly • Liver disease  conjugated bilirubinemia • Jaundice may occur in right heart failure

  15. Y = sufate, glucuronate Z = glycine, taurine NTCP – Na Taurocholate Cotransporting Polypeptide MRP2 – Multidrug Resistance Protein 2 BSEP – Bile Salt Export Protein OATP – Organic Anion Transport Protein

  16. Unknown FIC1 – PFIC1 Bile acids BSEP – PFIC2 Sterols ABC G5/G8 – Sitosterolemia MDR3 – PFIC3 Phospholipids MRP2 – Dubin-Johnson Conjugated Bilirubin & other conjugates Canalicular Transporters & Diseases

  17. Coagulation FactorsLiver makes factors I, II, V, VII, IX, X • PT/INR: I, II, V, VII, X • Prolonged PT/INR: • Congenital • Liver failure • Vitamin K deficiency • Warfarin • Vitamin K dependent factors: II, VII, IX, X • FV – shortest half-life and not vitamin K dep. • Vitamin K replacement

  18. Ammonia • Not especially useful • Occasional adult with urea cycle defect

  19. MELD FormulaThe Basis for Organ Allocation since Feb 2002 • 6.3 + ([0.957 x log creat] + [0.378 x log bili] + [1.12 x log INR] + 0.643) x 10

  20. The 2g Sodium DietSpot urine Na+>K+ predicts >78 mmol sodium excretion with 90% accuracy • 2g Na+ = 88 mmole • 78 mmol urinary + 10 mmol involuntary loss • Patients who excrete >78 mmol/24h can be treated with 2g dietary restriction alone • Assess excretion with 24h urinary sodium • 24h creatinine excretion to test completeness • 15 mg/kg for men) or 10 mg/kg for women • If spot urine Na+>K+, the patient is excreting >78 mmol Na+ (i.e. consuming >2 Na+ per day)

  21. Hyponatremia997 consecutive patients from 28 centers in Europe, North and South America, and Asia for 28 days • Inpatients and outpatients with cirrhosis and ascites Angeli P et al. Hepatology. 2006;44:1535–1542.

  22. Hyponatremia – MELD-Na Kim et al, NEJM 2008;359:1018-26

  23. Liver Failure • Portal hypertension • Ascites/edema • Encephalopathy • Varices • Renal failure • Cardiomyopathy • Pulmonary Disease • Liver injury • ALT & AST • Synthetic failure • INR, F-V, F-VII • Albumin • Bilirubin

  24. Viral Hepatitis • Acute hepatitis panel • Anti-HAV IgM, anti-HBcIgM, HBsAg, anti-HCV • The rest • HAV immunity: anti-HAV (total) • Anti-HBc (total), anti- HBs • Viral titers: HBV DNA, HCV RNA

  25. Hepatitis B • Anti-HBc • IgM – current infection or flare • IgG – prior infection • HBsAg: current infection • Anti-HBs: immunity (titer) • HBeAg and anti-HBe: stage of disease

  26. Autoimmune Markers • AIH • Usual: ANA, ASMA, anti-actin, LKM • Unusual: SLA, ASGP, ANCA • Increased IgG • PBC • AMA • Increased IgM • PSC: None • IgG4

  27. *Adaptedfrom Alvarez F, Berg PA, Bianchi FB, et al. J. Hepatology 1999;31:929-938.

  28. AMA-Positive & AMA-Negative PBC Vierling JM. Clin Liver Dis. 2004; 8:177-94

  29. FibroTest/Fibrosure® • Five serum tests • a-2 macroglbulin • Haptoglobin • GGT • T-bilirubin • Apolipoprotein A1 • For a cutoff of 0.31, the negative predictive value for excluding significant fibrosis = 91%

  30. 49 year old female • Admitted through the ER with jaundice, fever, chills, and RUQ pain for past three days • Pain worse when the car hit a bump • U/S: thickened gall bladder, large liver • Murphy sign during u/s

  31. Does this patient need a cholecystectomy? • History • Gallstones – mother and grandmother • Works from home • Drinks – 1-2 glasses of Scotch daily • Diagnosis – acute alcoholic hepatitis

  32. Summary • ALT/AST = liver injury • ALT is higher in hepatitis • AST his higher in acute liver injury and cirrhosis • AP/GGT/5’NT = cholestasis • Wilson disease = low AP • AFP is an analogue of albumin = regeneration

  33. Summary • Bilirubin • Direct = cholestasis & liver injury • Indirect = hemolysis, Gilbert • Serum ammonia has little utility • Occasional urea cycle defect • PT/INR – higher in zone 3 necrosis • Severe liver injury • Hyperbilirubinemia • Abnormal clotting

More Related