1. Acute liver failure Tutorial Ayman Abdo MD, FRCPC

2. Objectives To identify common causes of acute liver failure through history and examination To recognize common presentations To be familiar with medical management To know when to refer a patient for transplantation

3. Acute Liver Failure Definition 1. Rapid hepatocellular dysfunction 2. Encephalopathy 3. No pre-existing liver disease

4. Common causes of acute liver failure Viral hepatitis: Hep A, Hep B Toxin/drugIschemic Autoimmune hepatitis Wilson disease

5. Pt 1: Initial history 66 y old female Chronic abdominal pain and constipation Otherwise healthy 3 day history of jaundice and confusion

6. Patient 1 What other questions are you going to ask?

7. Important questions on history Recent travel Sexual exposure IVDU Contact with jaundiced pt Detailed drug history including herbs Autoimmune features Neurological symptoms Recent hypotension or sepses

8. Pt 1 : More history Dx to have IBS Started on herbal medication 1 week ago No viral hepatitis risk factors No hypercoagulable disorder No new medications

9. Patient 1 What physical signs are you going to look for?

10. Physical examination Vital signs Level of conciseness Flapping tremor Stigmata of chronic liver disease Ophthalmology exam if indicated Full abdominal examination Full neurological examination

11. Patient 1 What labs are you going to order?

12. Important labs CBC and electrolytes Liver enzymes : ALT, AST, ALP, GGT, LDH Liver function tests: INR, Albumine, Bili Viral hep serology= HAV IgM, Hep B cAb IgM, HCV RNA Toxic screen: Acetaminophen level AIH markers: ANA, ASMA Wilson: Ceruloplasmin, urine cupper Others

13. Causes of acute liver failure Viral hepatitis: Hep A, Hep B Toxin/drugIschemic Autoimmune hepatitis Wilson disease

17. Lab investigations CBCElectrolytes Liver enzymes (ALT, AST, ALP, GGT, LDH) Liver function tests (Bili, Albumin, INR) Hep A (IgM, IgG), Hep B (HBsAG, HBcIgM) Acetaminophen level ANA Cerulopasmin, 24 h copper collection

18. Pattern in Ischemic hepatitis

19. Ischemic vs. viral

20. Get more information ?

21. Complications & Management

23. Specific therapy Viral:Ischemic:Toxic: Acetaminophen (N-acetyl cystein) AutoimmuneWilson

24. Which pt will recover with intensive medical therapy and which pt requires transplantation?

25. King’s College Criteria Acetaminophen pH < 7.3 or Grade III or IV HE and –INR > 6.5 –Creatinine > 300 Non-acetaminophen INR > 6.5 or any 3/6 –Age 40 yrs –Bili > 300 –Coagulopathy: INR > 3.5 –Duration of jaundice > 7 days before HE –Etiology: Non A-E, other drug O’Grady et al. Gastroenterology 1989;97:439

27. MARS : Molecular adsorbents recycling system

29. More quick cases

30. Case 2 A 33 y old female Just came back from Umrah Has 2 day history of dark urine and yellow eyes No new medications

31. Patient 2 What are the possible causes of this presentation?

32. Case 2 No physical signs except for jaundice No encephalopathy ALT=2300, AST=1700, ALP=480, GGT=789, INR=2.1

33. Patient 2 How would you manage this patient?

34. Patient 3 55 y old male Massive acute MI Successful resuscitation Cardiac condition stable 5 days later: ALT=2300, AST=2000, LDH=4500

35. Patient 3 What is the most likely cause?

36. Patient 3 How would you manage this patient?

37. Patient 4 22 y old male Previously healthy 1 week history of jaundice ALT=1500, AST=3400, ALP=450, INR=1.8 CBC= HB=7.8, WBC=10.8, PLt=340

38. Patient 4 What is the most likely cause?

39. Patient 4 Cerulopasmin= very low 24 urinary cupper= very high Ophthalmology exam= KFR

40. Conclusion The most important three causes of acute liver failure are : viral hepatitis, toxic hepatitis, and ischemic hepatitis Less likely causes include: Autoimmune hepatitis, Wilson disease, malignant infiltration Early recognition and treatment of the cause Medical management of complication Decide early about transplantation