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Clinical update on Approach to Abnormal Liver Profiles_CME Accredited Material_Prashant V. Krishnan, MD_COPYRIGHTED MATERIAL

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Dr. krishnan final protected

  1. 1. Approach to Abnormal Liver Profiles Prashant Krishnan, M.D. Gastroenterologist! Medical Director! Peak Gastroenterology Associates! Front Range Endoscopy Centers! ! GI Section Chair! Memorial Gastroenterology Department ! Clinical Associate Professor! Rocky Vista University Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  2. 2. Overview Initial Testing! Cholestatic Diseases! Interpretation! Fulminant Hepatic Failure! Hepatocellular Diseases Other Considerations Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  3. 3. Initial Testing Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  4. 4. Important Initial Tests Liver profile! Coagulation profile! CBC! Possibly imaging studies! PATTERN RECOGNITION!!! Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  5. 5. The Liver Profile AST & ALT! Alkaline phosphatase! Total and direct bilirubin! Total protein and albumin Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  6. 6. The Aminotransferases Where are they located?! Markers of liver cell injury (Hepatocellular disease)! AST is located in various extrahepatic tissue! • Skeletal and cardiac muscle and more! • Not as specific to liver Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  7. 7. Alkaline Phosphatase Where is this located?! Membrane bordering hepatocytes and bile canaliculi! Also found in bone and placenta! How can you tell if elevation in alkaline phosphatase is from liver vs. other?! GGT or fractionated alkaline phosphatase Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  8. 8. Bilirubin Unconjugated = Indirect (Water insoluble)! Conjugated = Direct (Water soluble)! Unconjugated becomes conjugated! Indirect bilirubin flows to liver! Hepatocytes conjugate bilirubin with glucuronic acid! Bile becomes water soluble and excreted in bilirubin Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  9. 9. Albumin Abnormality typically indicates severe liver disease! Short half life! If no overt liver disease, think about:! Urinary losses! GI losses Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  10. 10. Coagulation Profile Prothrombin Time (PT) and INR! Abnormality indicates severe liver disease! PT is dependent on vitamin K and vitamin K dependent factors! Vitamin K dependent factors synthesized in liver Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  11. 11. CBC Why should you look at this?! Thrombocytopenia! • What does this tell you? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  12. 12. Interpretation Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  13. 13. Synthetic Function Liver profile is different from liver function tests (LFTs)! Function is determined by:! Bilirubin! Albumin! Is the liver working? PT/INR Aminotransferases Is the liver dying? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  14. 14. Understanding Time Frames You order the labs and get the results...now what?! Look to the past! Is this new or chronic?! Does the person have chronic liver disease with something new superimposed?! Patterns give you hints as to what could be going on Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  15. 15. Primary Process Is this primarily a hepatocellular process?! Aminotransferases (AST & ALT)! Is this primarily a cholestatic process?! Alkaline phosphatase and bilirubin! Is this a mixed picture? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  16. 16. Hepatocellular Diseases Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  17. 17. Case # 1 75 y/o female in MVA found unconscious! Has subdural hematoma! Intubated for airway protection! Sent to ICU where you pick up patient! No documented hypotension! Labs are checked - Mild troponin elevation and renal failure Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  18. 18. Case # 1 Continued Liver profile! AST = 4528! ALT = 2350! Alkaline phosphatase = 145! Total bilirubin = 3.2! Direct bilirubin = 1.2! Total protein = 7.4! Albumin = 3.5! Hepatocellular, cholestatic, or mixed? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  19. 19. Case # 1 Continued What do you think is going on with her liver?! Why do you think so?! What information supports your suspicion?! What information would offer you further support? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  20. 20. Case # 1 Continued ANSWER = Ischemic liver injury! Ischemia not only refers to hypovolemia, but also decrease oxygen delivery to tissues! S0 could be euvolemic with hypoxemia leading to liver injury! Evidence for ischemia! Elevation in troponin and ARF - Ischemia to other organs Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  21. 21. Case # 1 Continued With ischemia, rapid rise in aminotransferases and a rapid decline! Treatment is IV fluids and improve oxygenation, if hypoxemic Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  22. 22. Aminotransferases > 1000 Viral hepatitis! Hepatitis A, B, and C! EBV, CMV, and HSV! Drugs - Acetaminophen (Tylenol)! Ischemic hepatopathy! Trauma! Autoimmune hepatitis! Choledocholithiasis (Rare) Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  23. 23. Aminotransferases > 1000 Viral hepatitis - Social and sexual history is important! HSV, Tylenol, and ischemia can elevate aminotransferases extremely high! Drugs - Check acetaminophen level! Ischemia - Hypovolemia or hypoxemia! Trauma - History! Autoimmune - ANA, ASMA, ALKM, quantitative immunoglobulins! Choledocholithiasis (Rare) - Imaging Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  24. 24. Case # 2 52 y/o Caucasian female with h/o HTN, hypercholesterolemia, and DM! New to your clinic from another state! Has 2 tattoos and is a “love machine”! No h/o blood transfusions! Physical exam - Obesity! You draw some labs and find elevations in her liver profile Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  25. 25. Case # 2 Continued Liver profile! AST = 75! ALT = 135! Alkaline phosphatase = 78! Total bilirubin = 0.7! Direct bilirubin = 0.1! Total protein = 7.9! Albumin = 4.1! Coags and CBC normal! Hepatocellular, cholestatic, or mixed? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  26. 26. Case # 2 Continued How do you want to proceed?! Check viral hepatitis screen - If negative, recheck in 3-6 months! Still elevated...now what? - Exclude causes! Inquire about EtOH history! Hepatitis B and C screen, if not done! Hemochromatosis (Caucasians) - Iron studies and ferritin! Wilson’s disease - Probably too old but can check ceruloplasmin! Autoimmune hepatitis - ANA, ASMA, ALKM, quantitative immunoglobulins! Alpha 1 Anti-trypsin deficiency - Check level and phenotype! DILI - Check medication list! NASH - Can check fasting lipid profile and recommend weight loss Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  27. 27. Case # 2 Continued Drinks 1-2 beers only on weekends! Hepatitis B and C screen negative! Autoimmune workup negative! Iron studies, ferritin, and ceruloplasmin negative! A1AT is normal! LDL = 178 Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  28. 28. Case # 2 Continued Why is her liver profile abnormal?! NASH - Diagnosis of exclusion! What is the difference between NAFLD and NASH?! Can image liver to evaluate for fatty deposition! Treatment:! Weight loss! Treat DM and hypercholesterolemia! • Okay to use statins as long as aminotransferases < 3x upper limit of normal Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  29. 29. Chronic Hepatitis So what are the causes of chronic hepatitis?! EtOH! Hepatitis B and C! Hemochromatosis! Wilson’s disease! Autoimmune hepatitis! A1AT deficiency! DILI! NASH Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  30. 30. Case # 3 35 y/o male comes to your clinic - Physical exam shows scleral icterus and jaundice! Liver profile! AST = 250! ALT = 110! Alkaline phosphatase = 88! Total bilirubin = 7.4! Direct bilirubin = 4.8! Total protein = 7! Albumin = 3.1! Hepatocellular, cholestatic, or mixed? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  31. 31. Case # 3 Continued What further information would you want from him?! What do you suspect and why?! How do you treat him? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  32. 32. Alcoholic Hepatitis Social history is extremely important! Patients underestimate consumption level! Classic 2:1 ratio and aminotransferases < 400! Bilirubin increased out of proportion to aminotransferases! Treatment:! Counseling and chemical dependency! Many improve off EtOH! Hydration and monitoring liver profile/coags periodically! Consider pentoxifylline or steroids Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  33. 33. Cholestatic Diseases Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  34. 34. Case # 4 45 y/o new female patient with no medical problems! Complains of fatigue! Has some itching from time to time! Physical exam is normal! Labs checked Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  35. 35. Case # 4 Continued Liver profile! AST = 45! ALT = 40! Alkaline phosphatase = 240! Total bilirubin = 2.2! Direct bilirubin = 1.6! Total protein = 7.6! Albumin = 4.1! Ultrasound is done - No biliary dilation or cholelithiasis Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  36. 36. Case # 4 Continued Hepatocellular, cholestatic, or mixed! What do you suspect and why?! How would you confirm this?! What else would be in your differential?! How do you treat this? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  37. 37. Primary Biliary Cirrhosis Middle aged females are predominantly affected! Complaints include fatigue and pruritus! Smaller intrahepatic bile ducts are mainly affected! Diagnosis confirmed by AMA, although 5-10% could be negative for AMA and still have PBC! Treat with Ursodiol (Actigall)! May eventually need a liver transplant Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  38. 38. Other Considerations Gallstones - U/S not suggestive & no biliary colic! Difference between cholelithiasis and choledocholithiasis! PSC - Affects large extrahepatic ducts! More common in men! Associated with ulcerative colitis (Board Question)! Diagnose with ERCP or MRCP! DILI - Withdraw medication and should improve! SEPSIS - See many ICU patients with this! Infiltrative disorders - CT or MRI to image the liver! Lymphoma, other malignancies, amyloidosis, and sarcoidosis Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  39. 39. Case # 5 38 y/o male presents with RUQ and epigastric pain x 2 days! RUQ pain began first, intermittently for 30 min to 3 hours! Some nausea and clear emesis! Had chills at home but did not check temperature! Stools are slightly lighter in color Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  40. 40. Case # 5 Continued Temp = 38.5oC! Physical exam! Tenderness in epigastrium and RUQ! Jaundice! U/S - 9 mm CBD and cholelithiasis! No pericholecystic fluid or GB wall thickening Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  41. 41. Case # 5 Continued Liver profile! AST = 55! ALT = 52! Alkaline phosphatase = 235! Total bilirubin = 6.2! Direct bilirubin = 4.4! Total protein = 7.8! Albumin = 3.6! Lipase = 527 Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  42. 42. Case # 5 Continued What do you suppose is the problem?! How should you work up this patient?! Is an ERCP necessary?! How would you treat this patient? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  43. 43. Gallstone Pancreatitis and Cholangitis Most likely sequence of events! Cholelithiasis leads to choledocholithasis! Pancreatitis, biliary stasis, and bacterial growth! Patient develops cholangitis! • Charcot’s triad and Raynaud’s pentad! Cholangitis is a SERIOUS problem! Act fast and act early! Aggressive IV hydration and antibiotics Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  44. 44. Gallstone Pancreatitis and Cholangitis If still obstructed, needs ERCP for intervention! Persistent pain, dilated ducts, persistent fevers! If not obstructed, would postpone ERCP! One of the complications is pancreatitis! Pain control! Call surgery for cholecystectomy Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  45. 45. Fulminant Hepatic Failure Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  46. 46. Case # 6 56 y/o female brought in by boyfriend for confusion! Had a fight 2 weeks ago - Extremely depressed! Thinks she may have taken a “medicine” with EtOH! Does not drink regularly! 1.5 weeks ago - Slightly yellow and become progressively worse! Last night - Very confused! She is not able to provide any history Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  47. 47. Case # 6 Continued Physical exam:! Jaundice and asterixis! Patient is very lethargic and drowsy! No spider angiomata or caput medusae! No known varices or prior liver disease Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  48. 48. Case # 6 Continued Ammonia = 120! Liver profile! AST = 163! PT = 18.3! ALT = 137! INR = 2.34! Alkaline phosphatase = 254! Platelets = 428 Total bilirubin = 24.3! Direct bilirubin = 16.8! Total protein = 7.8! Albumin = 2.8 Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  49. 49. Case # 6 Continued What do you think the “medicine” was she ingested?! What is happening to her now?! Her aminotransferases decrease - Is she getting better?! What do you need to do? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  50. 50. Case # 6 Continued She probably overdosed on Acetaminophen! Check acetaminophen level! Start N-acetylcysteine immediately! She is in fulminant hepatic failure! Decreased synthetic function! Hepatic encephalopathy! Hepatic burnout Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  51. 51. Case # 6 Continued Management needs to be deliberate and fast! Address code status! Move patient to ICU IMMEDIATELY - Intubation may be necessary for airway protection! Call the transplant center IMMEDIATELY! CT head and rule out infection (BCx, UA, UCx, CXR) - Minimize narcotics and sedation! • If elevated intracranial pressure, move to SICU and a bolt should be placed IMMEDIATELY - Can also try Mannitol! Lactulose and Rifaximin - Goal of 3-4 bowel movements per day! Supportive care Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  52. 52. Fulminant Hepatic Failure Acute liver failure with encephalopathy within 8 weeks of onset of jaundice in a patient with no prior liver disease! Encephalopathy - Cerebral edema! Hypoglycemia! Renal and electrolyte disturbances! Lactic acidosis! Infections Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  53. 53. Other Considerations Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  54. 54. Case # 7 85 y/o cirrhotic female from NASH falls at home and fractures her femur! Seen by Ortho who wants to manage her nonsurgically with brace since she is cirrhotic! Bone displacement occurs even with brace so patient taken to the OR Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  55. 55. Case # 7 Continued On physical exam, she has multiple ares of ecchymosis Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  56. 56. Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  57. 57. Case # 7 Continued What’s going on with her?! What information supports your conclusion?! Indirect hyperbilirubinemia! Ecchymosis! Elevated BUN! How do you treat her? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  58. 58. Indirect Hyperbilirubinemia Breakdown or resorption of heme from RBCs! Look at the BUN - Can give you a clue! Think of hemolysis! Bilirubin, LDH, haptoglobin, retic count, peripheral smear Possibly Coomb’s test! Think of resorption of hematomas! Gilbert’s syndrome - Everything else is normal! Normal variant Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  59. 59. Thank You Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.
  60. 60. Any Questions? Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.

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