1 / 45

Acute Liver Failure

Acute Liver Failure. Common Causes & Management José L. González, R3 John A . Donovan, MD. Why Acute Liver Failure?. Why did I choose this topic and why is it important for clinicians? Identification of ALF Regenerative properties Interventions Liver Transplant. Presentation Outline.

kagami
Download Presentation

Acute Liver Failure

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. Acute Liver Failure Common Causes & Management José L. González, R3 John A. Donovan, MD

  2. Why Acute Liver Failure? • Why did I choose this topic and why is it important for clinicians? • Identification of ALF • Regenerative properties • Interventions • Liver Transplant

  3. Presentation Outline • Introduction • Acetaminophen Toxicity • Idiosyncratic Drug Reactions • Viral Hepatitis • Complications and Management • Liver Transplant & Conclusion • N-Acetylcysteine for non-acetaminophen causes of acute liver failure by Dr. Donovan.

  4. Learning Objectives • Recognize Acute Liver failure • Understand Acetaminophen toxicity & apply appropriate treatment • Understand common causes of Viral ALF and identify the interventions that improve outcomes • Know which groups of drugs commonly cause liver injury • Identify prognostic criteria • Manage complications of ALF

  5. Defining Acute Liver Failure • INR > 1.5 • Altered mental status • Illness of < 26 weeks duration • Hyperacute < 7 days • Acute 7-21 days • Subacute > 21 days and < 26 weeks • Fulminant (2 wks) vssubfulminant (2-12 wks)

  6. What are the common causes of liver failure? • Acetaminophen 39% • Indeterminite 17% • Idiosynchratic drug rxns 13% • Viral hepatitis 12% • HBV > HAV > HEV, HSV • Autoimmune 4-5% • Wilson’s Disease 2-3% • Mushroom Poisoning • Herbal Medications • Vascular • Bud-Chiarri • Ischemic • Hepatic Vein Thrombosis • Reye’s Syndrome • Fatty Liver of Pregnancy • HELLP

  7. Acetaminophen Toxicity

  8. para- acetylaminophenol

  9. Treatment Nomogram

  10. Acetaminophen Toxicity: Treatment • GI decontamination – activated charcoal • N-Acetylcysteine • 20 hour IV protocol • 72 hour PO protocol • Liver Transplant

  11. Indications for Liver Transplant: King’s College Criteria for Acetaminophen Toxicity • Arterial pH < 7.30 after adequate fluid resuscitation OR • Grade III/IV encephalopathy AND • PT > 100 sec AND • Cr > 3.3

  12. Idiosyncratic Drug Reactions

  13. Idiosyncratic Drug Reactions • Idiosyncratic: unpredictable and dose-independent • Pattern of injury varies • Cholestatic (alkaline phosphotase) • Hepatocellular (ALT) • Mixed • Mechanism of Action • Covalent bonds disruption of cell membrane • Inhibition of cellular pathways • Abnormal bile flow • Pump dysfunction • Apoptosis via TNF and fas pathways • Inhibition of mitochondrial synthesis

  14. Idiosyncratic Drug Reactions: MOA #1 antimicrobials #2 CNS agents #3 herbal supplements - weight loss - muscle building

  15. Idiosyncratic Drug Reactions • What factors influence susceptibility? • <10 and >40 yoa, obesity, female gender, DM, etoh use, genetic variability • Importance of discontinuing medication after liver injury. • Likelihood of progression to liver failure is dependent on how long you continue to take the drug after identification of liver injury. • What is the clinical course and natural history of disease? • Repair varies : days to weeks to months

  16. Viral Causes of Acute Liver Failure

  17. Viral Causes of Acute Liver Failure • Hepatitis B: 8% +/- Hepatitis D • Hepatitis A: 4% • Hepatitis C: does not cause ALF • Hepatitis E: in developing countries • HSV, EBV

  18. Acute Hepatitis B leading to ALF • HBV: DNA virus • Antivirals: nucleoside or nucleotide analogs • Lamivudine, adefovir, tenofovir, entecavir • Lamivudine Treatment Improves the Prognosis of Fulminant Hepatitis B: • Serologies for acute Hep B: IgM anti-hepatitis B virus core antibody • Retrospective cohort study, n = 33 • 10 patients received lamivudine • Endpoints: 1 week, overall survival • 1wk: 90% vs 65% Overall: 70% vs 26%

  19. Lamivudine Treatment Improves the Prognosis of Fulminant Hepatitis B

  20. Acute Hepatitis B: Factors associated with increased mortality

  21. Management and Prognosis Acute Liver Failure

  22. What are the potential outcomes? • 1. Recovery because of a successful intervention • NAC for acetaminophen toxicity • Antivirals for acute hepatitis B • 2. Spontaneous recovery with supportive care • 3. Death • 4. Rescue by liver transplant

  23. Predicting Outcomes in Acute Lifer Failure • Most important predictive factors: • Degree of encephalopathy • Suggested laboratory markers: • Factor V • AFP • Serum Phosphate • VII/V ratio > 30 • Gc globulin • Clinical algorithms: • King’s College Criteria • APACHE II

  24. King’s College Criteria, non-acetaminophen • INR > 6.5 OR • Any 3 of the following 5: • Age < 10 or > 40 • Serum bilirubin > 18 • Jaundice to encephalopathy interval > 7 days • INR > 3.5 • Unfavorable Etiology • Non-A, non-B hepatitis, halothane, idiosyncratic drug reaction, Wilson’s

  25. APACHE II Scoring Table

  26. Predicting Outcomes • Which variable or clinical algorithm do we use? • Meta-analysis of Prognostic Criteria • No prospective trials as of yet • Why is sensitivity important? • False negatives: death due to withholding liver transplants • Why is specificity important? • False positives: liver transplants in those that don’t need them

  27. Meta-analysis of Prognostic Criteria: Need for Transplant • Reviewed raw data • Arterial pH, PT, Cr, Factor V, Gc-globulin • King’s College Criteria, APACHE II score • Prospective study needed

  28. Clinical Course and Management Common Complications of Acute Liver Failure

  29. Complications of Acute Liver Failure: • CNS disturbances • Hepatic encephalopathy • Cerebral edema • Hemodynamic Collapse • Infections • Coagulopathy and bleeding • Renal failure • Metabolic derangements

  30. Cerebral Edema • (astrocytes) NH3 glutamine + edema • Degree of encephalopathy correlates w/ cerebral edema • Grade I-II: 25-35% risk • Grade III: 65% risk • Grade IV: 75% risk • Uncalherniation • Compromises cerebral blood flow  hypoxic brain injury

  31. Intracranial Pressure • CPP = MAP – ICP • CPP > 60mmHg • ICP < 20mmHg

  32. Intracranial Pressure • CPP = MAP – ICP • CPP > 60mmHg • ICP < 20mmHg

  33. Treatments for raised ICP: How useful are they? • HOB > 30º • Decreased patient stimulation • Hyperventilation • Barbiturates • Mannitol • Corticosteroids • Hypertonic Saline • Hypothermia (32-33ºC)

  34. Hemodynamic Failure • Decreased SVR • Renal failure, pulmonary failure and cardiovascular collapse • Restoration of hemodynamics: • Crystalloid initially • Once euvolemic, studies show albumin is better than crystalloid • Pressors • Alpha adrenergics (epi- and norepi-) • Not used: Dopamine, Vassopressin • No benefit of NAC, prostaglandins and steroids

  35. Infections • Etiology • Bacterial (90%): gram negative organisms, staphylococci • Fungal (30%) • SIRS has been shown to decrease survival rate • Should we use prophylactic antibiotics? • Decrease # of infections • But no improvement in outcomes • Routine surveillance blood, sputum, urine cultures and CXR

  36. Coagulopathy • Coagulopathies: • Prolonged PT • Platelet dysfunction • Reduction in factors II, VII, IX and X • Defective production of procoagulant factors: • Proteins C and S • Antithrombin III • Upregulation of factor VIII • End Result: • Clinically significant spontaneous bleeding is relatively unusual in ALF, even during liver transplant. • Overuse of blood products

  37. Correction of coagulopathies: • Vitamin K • Platelets if clinically significant bleeding or < 10k • Limited role for prophylactic FFP, platelets, cryoprecipitate • Giving FFP takes away your best prognostic indicator • Recombinant VII

  38. Renal Failure • RF contributes to mortality and overall poor prognosis • Multi-factorial • Pre-renal • ATN (from prolonged pre-renal state vs nephrotoxic agents) • HRS • CVVD > HD

  39. Metabolic Disturbances • Lactic acidosis w/ compensatory respiratory alkalosis • Hypokalemia • Hypoglycemia (40%) • Hypophosphatemia • Hypomagnasemia • Early nutrition is important

  40. Liver Transplant

  41. Liver Transplant • Indicated when prognostic criteria suggest a high likelihood of death • 2004 UNOS data • 5845 transplants 491 for acute liver failure = 8.4% • Of patients w/ ALF, 29% receive a transplant. • Survival rates in pre-transplant era ~ 15% vs 40% now • Better prognosis: acetaminophen, HAV, ischemia, AFLP • Worse prognosis: HBV, AIH, Wilson’s, Bud-Chiari

  42. Variations of Transplants • Orthotopic Liver Transplant • Auxiliary liver transplant • Xenotransplantation • Artificial / Bioartificial Hepatic Assist Devices • Detoxify, metabolize and synthesize • Hepatocyte Transplantation

  43. Summary • ALF: INR > 1.5, AMS, < 26 weeks duration • Acetaminophen: charcoal, NAC • Idiosyncratic drugs  ALF: 1. antimicrobials, 2. CNS agents, 3. herbal supplements. • Viral: HBV>HAV, tx w/ antivirals • ID Prognostic criteria: APACHE II vs King’s College, Age, AMS, etiology • Manage complications: increased ICP, hemodynamic instability, RF, coagulopathies, metabolic derrangements

  44. American Association for the Study of Liver Diseaseswww.aasld.orgSpecial Thanks to Dr. Donovan

  45. Bibliography • Bailey, B., Amre, D., and Gaudreault, P. Fulminant hepatic failure secondary to acetaminophen poisoning: A systemic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med 2003; 31: 299-305 • Craig, D.G.N, Lee, A., Hayes, P.C. et al, Review article: the current management of acute liver failure. Alimentary Pharmacology and Therapeutics 2010; 31: 345-348 • Ganem, D., and Prince, A. Hepaitis B Virus Infection – Natural History and Clinical Consequences. N Engl J Med. 2004; 350: 1118-29 • Ghabril, M., Chalasani, N., Bjornsson, E. Drug-induced liver injury: a clinical update. Current Opinion in Gastroenterology 2010; 26:222-226 • Goldberg, Eric et al. Acute liver failure: Prognosis and management. www.uptodate.com2011 • Gotthardt, D., Riediger, C. Weiss, K.H., et al. Fulminant hepatic failure: etiology and indications for liver transplantation. Nephrology Dialysis Transplantation 2007; 22: viii5-viii8 • Heard, K. and Dart, R. Acetaminophen poisoning in adults: Treatment. www.uptodate.com2011 • Miyake, Y., Iwasaki, Y., Takaki, A. Lamivudine Treatment Improves the Prognosis of Fulminant Hepatitis B. Inter Med 2008; 47: 1293-1299 • Navarro, Victor J. and Senior, John R. Drug Related Hepatotoxicity. N Engl J Med. 2006; 345: 731-739 • Ostapowicz, G., Fontana, R.J., Shiodt, F.V. Results of a prospective study of acute liver failure a 17 tertiary care centers in the United States. Ann Intern Med 2002; 137: 947-954. • Polson, Julie and Lee, William M. AASLD Position Paper: The Management of Acute Liver Failure. www.aasld.org2005

More Related