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Acute Liver Failure - Dr. Mutchnick.ppt
- 1. Milton G. Mutchnick,M.D. Professor of Medicine Chief, Division of Gastroenterology Wayne State University School of Medicine ACUTE LIVER FAILURE
- 2. Acute Liver Failure Rapiddeterioration of liver function resulting in altered mentation and coagulopathy in a patient without preexisting cirrhosis and with an illness of less than 26 weeks duration.
- 3. Acute Liver Failure….AKA •Fulminant hepatic failure • Fulminant hepatitis • Subfulminant liver failure • Subacute hepatic necrosis • Subacute liver failure • Hyperacute liver failure
- 4. Index of Suspicionfor ALF • Clinical signs of moderate to severe hepatitis • Laboratory findings including an increase in the prothrombin time of 4-6sec.(INR ≥ 1.5). • Altered sensorium INR ≥ 1.5 + Altered Mental Status = ALF
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- 6. Etiology of ALF •Acute viral hepatitis (A - E) • Mushroom poisoning • Acetaminophen • Acute fatty liver of pregnancy •Chemical agents
- 7. • Drug-induced hepatitis •Budd-Chiari Syndrome • VOD of liver • Wilson’s disease • AIH
- 8. ALF Etiologies • Viral • Drug •Poisoning • Ischemia • VOD • Malignant Infiltrate • Wilson’s Disease • Microvesicular steatosis • AIH • Hyperthermia • OLT • Partial hepatectomy
- 9. Etiology of ALFin 342 Cases (University Hospital, London UK) Drugs-Overdose Other Acetaminophen 250 Wilson’s 3 Ecstasy 2 Fatty liver of pregnancy 7 Lymphoma/ Viral Hepatitis malignant infiltrate 7 HAV 8 Sepsis 2 HBV 8 Budd-Chiari 5 Non A-E 28 Ischemia 9 Miscellaneous 6 Idiosyncratic Drug Reactions Lamotrigine, cyproterone, NSAID, chloroguine, rifampin/ INH halothane, flucloxacillin
- 10. U.S. ALF STUDYGROUP 2003 (308 Patients, 73% Women) 0 5 10 15 20 25 30 35 40 ACM HBV HAV Indet Other
- 11. Viral • Acute HepatitisA-E • Reactivation of HBV Chemotherapy Immunosuppresion • Herpes simplex • Varicella-Zoster • EBV
- 12. Acute HAV andALF • ALF uncommon • Frequency 0.01% - 0.1% in jaundiced patients • ALF occurs early • Survival (transplant- free) 75% • Age related survival
- 13. Acute HBV andALF • HBV alone or with HDV co-infection (rare) • Transplant-free survival is 23% • Overall survival 77% because of transplantation
- 14. HBV Markers inALF IgM Anti HBc 100% HBsAg 90% HBV DNA (Abbott) 10% *Absence of HBsAg favors better prognosis (47% v 17%). Higher frequency ALF with mutant HBV form
- 15. Drug Induced ALF •Many drugs implicated Acetaminophen Halothone and derivatives INH/ Rifampin Tricyclics/ MAO inhibitors Phenytoin/ NSAID • Increased risk: acetaminophen (as little as 2gms) + ETOH median dose: 13 gm • Increased risk if drug continued after jaundice appears
- 16. Poisoning and ALF •Amanita mushrooms (amanatoxins) - LD = 50 gms (3 mushrooms) - Toxins not destroyed by cooking - Rapid onset of HE in 4-8 days following severe emesis and diarrhea • Solvents - chlorinated hydrocarbons • Herbal remedies • Yellow phosphorus
- 17. Ischemic Hepatitis andALF • Liver cell necrosis - massive scale • Cardiac tamponade • Acute heart failure • Pulmonary embolus • Hepatic artery thrombosis
- 18. Obstruction of HepaticVeins and ALF • Budd-Chiari syndrome and thrombosis of hepatic veins • VOD - Post BMT Chemotherapy, Irradiation
- 19. Massive Malignant Infiltration ofthe Liver • Attributed to ischemic changes • Leukemia, lymphoma • Malignant histiocytosis • Metastatic Replacement
- 20. Other Etiologic Causesof ALF • Wilson’s Disease can be presenting feature usually in patients <20 yrs can occur if patient discontinued D-penicillamine for a few years
- 21. Other Etiologies (2) •Microvesicular steatosis Acute fatty liver of pregnancy Reye’s syndrome Drug Induced - Valproic acid • AIH May appear as an acute hepatitis on initial presentation More common if anti-LKMI antibody present ASMA usually not present
- 22. Other Etiologies (3) •Hyperthermia (Heat stroke) Direct thermal injury Hepatic ischemia due to -DIC -Perfusion defect • OLT Poor presentation of donor liver Acute graft rejection Thrombosis - hepatic artery, hepatic vein, portal vein • Partial hepatectomy Removal of 80% or more of healthy liver Removal of 50% or less in hepatic dysfunction
- 23. Evaluation & Diagnosis ofImpending ALF History! History! History! Sexual contacts IDU Risk Factors Pregnancy Mushrooms Medications Travel Toxic exposures
- 24. HISTORY • Family memberswith liver disease? • Recent cold sores • Onset of jaundice • Work environment- toxic agents • Hobbies • Herbal products/dietary supplements
- 25. Physical Exam Determine presenceor absence of pre-existing liver disease Hepatic tenderness Hepatic decompensation
- 26. Laboratory Tests (1) Drugscreening ALT, AST, Alk Phos, Glu, Bilirubin Lytes, Albumin, Mg, Phos., CBC with differential Coags: PT, PTT Anti HAV IgM Anti HBc IgM/ Anti HBsAg/ Anti-HCV
- 27. Laboratory Tests (2) Ifunder 35 years of age Ceruloplasmin Serum & urine copper Arterial blood gas Arterial lactate Pregnancy test Autoimmune markers – ANA, ASMA, Ig levels HIV status Amylase & lipase
- 28. Liver Biopsy Reserved fordiagnostic dilemma - AIH, HS (Transjugular approach)
- 29. Diagnosis of ALF Hallmarks- occurs simultaneously or in succession • Altered mentation Clinical EEG Arterial Ammonia • Coagulopathy PT 4 sec prolonged (INR≥ 1.5) • Arterial pH<7.3 if acetaminophen ingested (cause for immediate transfer for OLT)
- 30. Management of ALF (1) •Directed towards prevention of complications • ICU setting Central line(s)-10% dextrose Pulmonary artery pressure and CO • Inform Transplant Service and transfer with onset of HE • Monitor VS and urinary output (Foley) strict I&O • Laboratory Testing every 4-6hr electrolytes, BUN, creatinine, CBC, platelets, PT, PTT, ALT, AST, T. bilirubin, Alk Phos, Albumin
- 31. Management (2) • Maintaingastric pH above 5 - protonix IV • Preparation for endotracheal intubation • Prepare to initiate monitoring intracranial pressure • Enteral feeding tubes for grade 3 or 4 coma
- 32. Cerebral Edema Cerebral PerfusionPressure Mean Arterial Pressure – ICP = Cerebral Perfusion Pressure (CPP) Ideal ICP<20-25mm Hg Ideal CPP>50-60mm Hg Imazaki, et al When CPP<40 for 2 hrs. 0 of 7 patients recovered When CPP>50 6 of 8 patients recovered Improved ICP first sign of spontaneous recovery
- 33. Management (3) Cerebral Edema& Intracranial Hypertension (Most serious complications of ALF) Clinical signs of elevated ICP (Intracranial Pressure) -sluggish pupillary response -increased limb-muscle tone -none Monitoring ICP -usually reserved for grade 3 or 4 coma -awaiting OLT
- 34. Management (4) Cerebral Edema- General Measures -quiet environment -elevate head 10°-20° -avoid sedation (use restraints) -avoid Valsalva-like maneuvers -mental status assessments q1-2h -mannitol if signs of impending uncal herniation (0.5mg/kg, lolus q4-8h) when ICP<30-40mm -assisted ventilation (in all grade 3 and 4)
- 35. Multiple Organ Failure Hepaticdamage increased risk of infection Failure of clearance Endotoxemia Gut leak MOF Activation of macrophages Tissue Circulating Release of Hypoxia changes cytokines TNF, IL-1, IL-6 Williams, Sem Liver Dis, Vol 16, No.4, 1996
- 36. Management (5) Hemodynamic Complicationsinclude: Hypotension, tachycardia, vascular volume decrease with capillary leak and vasodilation •Volume expansion (central line) •FFP or 4.5% albumin, 10% dextrose •Maintain pulmonary capillary wedge pressure 12mm-14mm Hg •Minimize salt solutions (ascites, interstitial accumulation) •Inotropic/pressor support(epi, norepi, dopamine), but not vasopressin.
- 37. Management (6) Coagulopathy/Bleeding Diathesis •FFP or platelets given in presence of bleeding • Conventional treatment of GI bleeding • DIC thrombocytopenia Metabolic Complications • Prevent hypoglycemia • Phosphate and magnesium levels monitored - replace early • Enteral feeding, 60gm protein/24 hrs • No role for high branched-chain AA • Monitor for lactic acidosis secondary to tissue hypoxia, sepsis
- 38. Role of CardiacIndex (CI = cardiac output/body surface area) • ALF associated with high CI • Presence of low CI (<4.5L/min) is bad prognostic sign Look for - blood loss, pneumothorax lactic acidosis, cardiac tamponade
- 39. Management (7) Renal Failure -In 42% to 82% of ALF poor prognostic sign - Rising creatinine and oliguria - Metabolites of acetaminophen are nephrotoxic leading to acute renal failure similar to ATN and loss of phosphate -HRS
- 40. Additional Complications • ARDS •Sepsis - Severe complement deficiency - Decreased PMN motility - Decreased Kupffer cell function and removal of endotoxins - Increased levels of TNF and IL-6
- 41. Prognostic Factors • Dependenton Etiology • Younger patients do better (<40 and >10) • Presence of cerebral edema • Delay between jaundice and HE of more than 3 weeks - poorer prognosis • MOF - poor prognosis
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- 43. Temporary Measures • Hemodialysis- no proven benefit on survival • Charcoal hemoperfusion - no proven benefit • Resins (Cation or anion - exchange) - not proven • Extracoporeal liver perfusions - may be bridge to OLT • Hepatocyte transplants (peritoneum) - uncertain • Capillary hollow-fiber system - unproven, ?bridge
- 44. OUTCOME RESULTS U.S.ALF STUDY GROUP 308 Patients Spontaneous Survivors n=132 (43%) Transplanted N=89 (29%) Died before Transplantation n=87 (28%)
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- 46. Approach to SuspectedALF • Etiology and Pathogenesis • Evaluation and Diagnosis • Complications • Management • Prognosis • Current and future treatment approaches