1 / 65

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

ringo
Télécharger la présentation

Approach to 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. 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

More Related