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Approach to Acute liver Failure

Approach to Acute liver Failure. Bader Alenezi, MD Chairman of Internal Medicine Jahra Hospital Consultant Gastroenterolgy & Hepatology. Outlines . Definition Acute Liver failure common causes of ALF Acetaminophen toxicity Diagnosis and Initial Evaluation ALF

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Approach to Acute liver Failure

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  1. Approach to Acute liver Failure Bader Alenezi, MD Chairman of Internal Medicine Jahra Hospital Consultant Gastroenterolgy & Hepatology

  2. Outlines • Definition Acute Liver failure • common causes of ALF • Acetaminophen toxicity • Diagnosis and Initial Evaluation ALF • Manage complications of ALF • Identify prognostic criteria • Future therapy in ALF

  3. Acute liver Failure (ALF) • Rare • Represent the most sever form of liver injury • Hard to treat • Difficult to study

  4. Acute liver Failure • Fulminant hepatitis • Fulminant hepatic failure • Subfulminant liver failure • Subacute hepatic necrosis • Subacute liver failure • Hyperacute liver failure

  5. ALF: Definition • The original term “fulminant hepatic failure” • “a severe liver injury, potentially reversible in nature and with onset of hepatic encephalopathy within 8 weeks of the first symptoms in the absence of pre-existing liver disease,” • Trey C , Davidson CS. The management of fulminant hepatic failure. Prog Liver Dis 1970;3:282-98

  6. ALF: Definition • The most widely accepted definition of ALF: • Coagulation abnormality, usually an INR >1.5, and any degree of mental alteration (encephalopathy) without preexisting cirrhosis and with an illness of <26 weeks duration. • AASLD Position Paper: The Management of Acute Liver Failure: Update 2011 • William M. Lee, MD, Anne M. Larson, MD, and R. Todd Stravitz, MD

  7. 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)

  8. ALF: Causes • 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

  9. U.S. ALF STUDY GROUP 2002 (308 Patients, 73% Women)

  10. ALF: Causes • ALF in developed world << developing world • developing world viral infections (hepatitis A, B, and E) are the predominant causes. • Western world drug-induced liver injury is the most common cause of acute liver failure

  11. ALF CAUSES: Viruses • Globally, hepatitis A and E infections are probably responsible for the majority of cases of ALF • ALF may occur after hepatitis B infection, Asian and Mediterranean countries. • Reactivation of HBV without established chronic liver disease treatment-induced immunosuppression during or after therapy for cancer • Antiviral prophylaxis before the initiation of chemotherapy, immunotherapy, or glucocorticoid therapy are effective in prevention

  12. ALF CAUSES: Other Viruses • rare viral causes of acute liver failure : • Herpes simplex virus • CMV • Epstein–Barr virus • Parvoviruses • Ichai P, Samuel D. Etiology and prog- nosis of fulminant hepatitis in adults. Liver Transpl 2008;14:Suppl 2:S67-S79.

  13. Drug-Induced Liver Injury (DILI)

  14. Drug-Induced Liver Injury (DILI) • DILI is responsible for approximately 50% of cases of ALF in United States • Can be dose- dependent and predictable, as exemplified by acetaminophen-induced hepatotoxicity • Or may be idiosyncratic, unpredictable, and independent of dose • idiosyncratic drug hepatotoxicity usually within the first 6 months after drug initiation. • A potentially hepatotoxic medication used continually 1 to 2 years is unlikely to cause de novo liver damage. • Certain herbal preparations, weight loss agents and other nutritional supplements  need complete medication history. • OstapowiczG,et al. Ann Intern Med 2002 .

  15. Acetaminophen Hepatotoxicity • Dose-related • Dose leading to ALF exceed 10 gm/day (>150 mg/kg) • Doses as low as 3-4 gm/day rarely causes ALF • Very high aminotransferase levels • Serum levels exceeding 3,500 IU/L are highly correlated with acetaminophen poisoning • low or absent levels do not rule out hepatotoxicity (remote ingestion or over several days)

  16. Rumack-Matthew Nomogram • Used to interpret plasma acetaminophen values to assess hepatotoxicity risk after a single, acute ingestion • Nomogram tracking begins 4 hours after ingestion (time when acetaminophen absorption is likely to be complete) and ends 24 hours after ingestion • About 60% of patients with values above the "probable" line develop hepatotoxicity

  17. Rumack-Matthew Nomogram • The standard acetaminophen toxicity nomogrammay aid in determining the likelihood of serious liver damage • cannot be used if: • 1- multiple doses over time • 2- when the time of ingestion is unknown • 3- When altered metabolism occurs such as in the alcoholic or fasting patient Larson AM. Acetaminophen hepatotoxicity. Clin Liver Dis. 2007;11: 525-48. Lee WM. Drug-Induced Hepatotoxicity. N Engl J Med 2003;349: 474-485.

  18. Treatment of Acetaminophen Hepatotoxicity • Activated charcoal for gastrointestinal decontamination best if given within 1hr of ingestion may be of benefit as long as 3 to 4 hours after ingestion. • Administration of activated charcoal (standard dose 1 gm/kg orally) just prior to administration of N-acetylcysteine does not reduce the effect of N-acetylcysteine. • Sato RL,et al Efficacy of superactivated charcoal administration late (3 hours) after acetaminophen overdose. Am J Emerg Med 2003;21:189-191.

  19. Treatment: N-acetylcysteine (NAC) • N-acetylcysteine(NAC), the antidote for acetaminophen poisoning effective and • NAC should be given as early as possible • NAC is nearly 100% hepato protective when it is given within 8 hours • but may still be of value 48 hours or more after ingestion

  20. N-acetylcysteine (NAC) • NAC orally (140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth q 4 h x 17 doses) • Oral administration has largely been replaced by intravenous administration (loading dose is 150 mg/kg in 5% dextrose over 15 minutes; maintenance dose is 50 mg/kg given over 4 hours followed by 100 mg/kg administered over 16 hours or 6 mg/kg/hr)

  21. N-acetylcysteine (NAC) • Use of the IV formulation of NAC is preferred in the following situations: • Altered mental status • GI bleeding and/or obstruction • A history of caustic ingestion • Potential fetal acetaminophen toxicity in a pregnant woman • Inability to tolerate oral NAC because of emesis refractory to proper use of antiemetics

  22. Wilson disease • uncommon cause of ALF (2% to 3% of cases in the U.S. • Early identification is critical because the fulminant presentation of Wilson disease is considered to be uniformly fatal without transplantation • young patients with Coombs negative hemolytic anemia with serum bilirubin levels >20 mg/dL • Kayser-Fleischer rings are present in about 50% of patients

  23. Wilson disease • Serum ceruloplasminis typically low, but may be normal in up to 15% of cases and is reduced in ~50% of other forms of ALF. • High plasma and urinary copper levels as well as hepatic copper measurement will confirm the diagnosis. • Very low serum alkaline phosphatase or uric acid levels • A high bilirubin to alkaline phosphatase ratio (>2.0) is a rapid, reliable indicator of Wilson disease

  24. Wilson disease • Rx: • penicillamine is not recommended in ALF due to risk of hypersensitivity • recovery is very rare absent transplantation. • Patients must be promptly considered for liver transplantation • (AASLD recommendation 2011)

  25. Autoimmune Hepatitis • unrecognized preexisting chronic disease and yet still be considered as having ALF. • AIH patients that develop ALF represent the most severe form of the disease. • Autoantibodies absent (up to 30% of cases) • Liver biopsy should be considered if autoimmune hepatitis is suspected and autoantibodies are negative • Recommended to receive corticosteroid therapy

  26. ALF in Pregnancy • Acute Fatty Liver of Pregnancy/HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelets) Syndrome • Near the end of pregnancy will develop rapidly progressive hepatocyte failure. • Increased fetal or maternal mortality. • Triad of jaundice, coagulopathy, and low platelets • Hypoglycemia and Features of pre-eclampsia are common • Transplantation may need to be considered if hepatic failure does not resolve quickly following delivery

  27. Budd-Chiari Syndrome • Acute hepatic vein thrombosis • Abdominal pain, ascites and striking hepatomegaly • Diagnosis confirmed with hepatic imaging studies (computed tomography, Doppler ultrasonography, venography, magnetic resonance venography) • Prognosis is poor • Liver transplantation is indicated, provided underlying malignancy is excluded

  28. Budd-Chiari Syndrome

  29. Ischemic Hepatitis and ALF • Liver cell necrosis - massive • Cardiac tamponade • Acute heart failure • Pulmonary embolus • Hepatic artery thrombosis

  30. 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

  31. Diagnosis and Initial Evaluation ALF • In all patients with clinical or laboratory of acute hepatitis PT and careful evaluation for subtle alterations in mentation should done • If PT is prolonged by ~4-6 seconds or more (INR >1.5) and there is any evidence of altered sensorium, the diagnosis of ALF is established and hospital admission is mandatory. • Transfer to intensive care unit (ICU) and contact with a transplant center if indicated

  32. Diagnosis and Initial Evaluation ALF • Physical Exam: • Determine presence or absence of pre-existing liver disease • Hepatic tenderness • Hepatic decompensation

  33. Diagnosis and Initial Evaluation ALF • HISTORY: • Family members with liver disease? • Recent cold sores • Onset of jaundice • Work environment- toxic agents • Hobbies • Herbal products/dietary supplements

  34. Initial Laboratory Analysis • Prothrombintime/INR • Chemistries • Liver enzymes • Arterial blood gas • Acetaminophen level Toxicology screen • Viral hepatitis serologies(anti-HAV IgM, HBsAg, anti-HBcIgM, anti-HEV, anti-HCV, HCV RNA , HSV1 IgM, VZV)

  35. Initial Laboratory Analysis • Ceruloplasmin level • Pregnancy test (females) Ammonia (arterial if possible) • Autoimmune Markers (ANA, ASMA, Immunoglobulin levels ) • Liver Biopsy reserved for diagnostic dilemma (Transjugular approach)

  36. Liver biopsy in ALF

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

  38. Cerebral Edema • There is increasing evidence that ammonia plays an important role in the pathogenesis of cerebral edema/ ICH • arterial ammonia level >200 ug/dLcerebral herniation; rarely if <75 ug/dL • Degree of encephalopathy correlates w/ cerebral edema • Grade I-II: rare • Grade III: 25-35% risk risk • Grade IV: 65-75% risk • Uncal herniation • Compromises cerebral blood flow  hypoxic brain injury

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

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

  41. Cerebral Edema/Intracranial Hypertension • Grade I/II Encephalopathy Consider transfer to liver transplant facility and listing for transplantation • Brain CT: rule out other • Avoid stimulation; avoid sedation if possible Antibiotics: surveillance and treatment of infection required; prophylaxis possibly helpful • Lactulose, possibly helpful

  42. Grade III/IV Encephalopathy • Intubate trachea • Elevate head of bed • Consider placement of ICP monitoring device • Immediate treatment of seizures required; prophylaxis of unclear value • Mannitol: use for severe elevation of ICP or first clinical signs of herniation • Hypertonic saline to raise serum sodium to 145-155 mmol/L • Hyperventilation: effects short-lived; may use for impending herniation

  43. Infection • Surveillance for and prompt antimicrobial treatment of infection required • Antibiotic prophylaxis possibly helpful but not proven • Prophylactic antibiotics and antifungals have not been shown to improve overall outcomes in ALF

  44. Coagulopathy • Vitamin K: give at least one dose • FFP: give only for invasive procedures or active bleeding • Platelets: give only for invasive procedures or active bleeding • Recombinant activated factor VII: possibly effective for invasive procedures • Prophylaxis for stress ulceration: give H2 blocker or PPI

  45. Hemodynamics/Renal Failure • Volume replacement • Pressorsupport (dopamine, epinephrine, norepinephrine) as needed to maintain adequate mean arterial pressure • Avoid nephrotoxic agents • Continuous modes of hemodialysis if needed • Vasopressin recommended in hypotension refractory to volume resuscitation and norepinephrine

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