Fulminant hepatic failure (fhf)

Short about Fulminant hepatic failure (fhf)

1. Fulminant Hepatic Failure (FHF) (Acute Liver Failure {ALF}) Dr / Reyad Alfaky

2. Definitions Fulminant hepatic failure Acute severe impairment of liver function associated with progressive mental changes in patients who have had liver disease for less than 8 weeks.

3. Definitions Fulminant Hepatic Failure biochemical evidence of acute liver injury (usually <8 wk duration) no evidence of chronic liver disease; and hepatic-based coagulopathy defined as : prothrombin time (PT) >15 sec or international normalized ratio (INR) >1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy, or biochemical ;acute liver injury (usually <8  wk ) no evidence of chronic liver disease; and PT >20 sec or INR >2 regardless of the presence of clinical hepatic encephalopathy. OR

4. Definitions Late-onset hepatic failure development of the hepatic encephalopathy occurs 8-24 wk from the first sign of liver disease in patients with pre-existing liver disease

5. subfulminant ” or “ subacute ” liver failure Rapid deterioration of liver function with the development of HE within six months

6. Definitions Chronic hepatocellular failure The combination of jaundice, and/or ascites and/or encephalopathy, in varying degrees, persistent or fluctuant, caused by chronic liver disease.

7. Definitions Acute on chronic hepatocellular failure Acute decompensation in clinical state produced in patients with chronic liver disease by precipitants such as sepsis, hemorrhage, surgery, or sedatives.

8. “Recurrent” liver failure Conditions associated with recurrent PALF include metabolic disease, particularly fatty acid oxidation defects, and re-exposure to an unsuspected drug or herbal remedy

9. epid The estimated frequency of acute liver failure (ALF) in all age groups in the United States is about 17 cases per 100,000 population per year, but the frequency in children is unknown. PALF accounts for 10 to 15 percent of pediatric liver transplants performed in the United States annually.

10. Etiology of FHF CAUSES OF PEDIATRIC ACUTE LIVER FAILURE : categorized as infectious, immunologic, metabolic, and toxin or drug-related

11. Etiology of FHF The etiology of pediatric acute liver failure (PALF) is identified in approximately 55 percent of cases, indeterminate cause in 45 percent Indeterminate cases are likely composed of a number separate conditions including immune dysregulation, with the latter condition having a variety of manifestations.

12. Categories of idiopathic pediatric acute liver failure

13. Etiology of FHF Idiopathic form of FHF : It accounts for 40-50% of cases in children. The disease occurs sporadically and usually without the risk factors Viral hepatitis HAV: In endemic areas, HAV constitutes up to 40% of all cases of pediatric acute liver failure. Autoimmune hepatitis 5% of cases

14. Etiology of FHF Toxins, Drugs, and Chemicals Hepatic ischemia and hypoxia Acute extensive infiltration of hepatocytes with microdroplets of fat ; hemophagocytic lymphohistocytosis Metabolic disorders Hepatotoxic herbal or dietary supplements

15. Metabolic diseases lead to acute liver failure in children * Mitochondrial disease includes fatty acid oxidation defects, respiratory chain defects, and mitochondrial DNA depletion or damage.

16. PATHOGENESIS Neurotoxic substances False neurotransmitters Multifactorial causes Massive destruction of hepatocytes

17. NEUROTOXIC SUBSTANCES Ammonia Mercaptans fatty acids benzodiazepine like-compounds gammaaminobutyric acid=GABA

18. FALSE NEUROTRANSMITTERS Impaired capacity of the liver to remove aromatic aminoacids promotes the synthesis of serotonin and false neurotransmitters as octopamine (inhibitory neurotransmitters) at the expense of true ones as dopamine and norepinephrine (excitatory neurotransmitters) —> encephalopathy and coma.

19. MULTIFACTORIAL CAUSES Factor may contribute to its pathogenesis. Hypoglycemia Hypoperfusion Anoxia Electrolyte Disturbances Brain Edema

20. PATHOLOGY Liver pathology Massive necrosis of the hepatocytes Mixed inflammatory cell infiltrate is usually present Brain pathology: Brain edema

21. CLINICAL MANIFESTATIONS Patients should be closely observed for hepatic encephalopathy, which is initially characterized by minor disturbances of consciousness or motor function. Irritability, poor feeding, and a change in sleep rhythm may be the only findings in infants; asterixis may be demonstrable in older children. Patients are often somnolent, confused, or combative on arousal and can eventually become responsive only to painful stimuli. Patients can rapidly progress to deeper stages of coma in which extensor responses and decerebrate and decorticate posturing appear. Respirations are usually increased early, but respiratory failure can occur in stage IV coma

22. STAGES OF HEPATIC ENCEPHALOPATHY I II III IV Symptoms Periods of lethargy, euphoria; reversal of day-night sleeping; may be alert Drowsiness, inappropriate behavior, agitation, wide mood swings, disorientation Stupor but arousable , confused, incoherent speech Coma IVa : responds to noxious stimuli IVb : no response Signs Trouble drawing figures, performing mental tasks Asterixis , fetor hepaticus , incontinence Asterixis , hyperreflexia , extensor reflexes, rigidity Areflexia , no asterixis , flaccidity Electroencephalogram Normal Generalized slowing q waves Markedly abnormal, triphasic waves Markedly abnormal bilateral slowing, d waves, electric-cortical silence

23. Assessment of Encephalopathy for Young Children: Birth to Age 3 Years   Clinical Asterixis / Reflexes Neurologic Signs Electroencephalographic (h nges Early (l and II) Inconsolable crying Sleep reversal Inattention to task Unreliable/ normal or hyperreflexic UntestaMe Normal or abnormal gener alized slowing/tnphasic waves Mid (III) Somnolence Stupor Combativeness Unreliable/ hypereflexic Most likely untestable Abnormal, generalized slow­ing, triphasic waves Late (IV) Comatose Arouses with painful stimuli ( IVa ) No response ( IVb ) Absent Decerebrate or Abnormal, very slow, activity

24. approach to the child with acute liver failure should include the following: initial stabilization establishment of an accurate diagnosis provision of intense, comprehensive medical supportive therapy anticipation, prevention, and timely treatment of complications. early referral to a liver transplant center, prior to the onset of complications of multiorgan failure, to assess both for indications and contraindications to liver transplantation.

25. INITIAL STABILIZATION/THERAPY Assure the airway is patent and ventilation is adequate. Maintain vital signs within normal limits; IV fluid administration if indication

26. DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE Assess liver function Determined etiology Monitor and detect complication

27. DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE General work-up Alanine aminotransferase , aspartate aminotransferase , gamma glutamyl transpeptidase , alkaline phosphatase , total and conjugated bilirubin , prothrombin time (INR), PTT, CBC, serum electrolytes, blood urea, creatinine , blood and urine cultures, blood group, chest X-ray, serum alphafetoprotein , lactate, lactate dehydrogenase , blood ammonia, arterial blood gas, and urine for reducing substances.

28. Specific work-up Infectious IgM anti- hepatitis A virus, IgM anti - hepatitis E virus, hepatitis B virus surface antigen, IgM anti-hepatitis B core antibody, cytomegalovirus PCR, IgM varicella zoster virus, IgM Epsteinbarr virus, HIV 1 and 2 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE

29. DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE Specific work-up Wilson disease Serum ceruloplasmin 24 hour urinary copper estimation, KF ring. Clue to etiology: alkaline phosphatase / bilirubin ratio <4.0 AST/ ALT ratio > 2.2 ± evidence of Coombs negative hemolysis

30. DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE Specific work-up Autoimmune Coombs test, antinuclear antibody (> 1:40), liver kidney microsomal antibody, smooth muscle antibody (>1:20), Immunoglobulin G levels

31. DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE Specific work-up Hemophagocytosis Serum triglyceride Cholesterol ferritin bone marrow biopsy Drug overdose Acetaminophen drug levels valproate drug levels

32. <3 months of age Herpes blood PCR (or other testing: HSV IgM , viral culture of blood or CSF, CSF PCR) Enterovirus blood PCR (or other testing) Lactate, pyruvate (mitochondrial screen) Plasma acylcarnitine profile (fatty acid oxidation defects) Ferritin (screen for gestational alloimmune liver disease [neonatal hemachromatosis ]) Serum amino acid profile (urea cycle and metabolic) Echocardiogram: Cardiac dysfunction Abdominal ultrasound with Doppler (vascular and anatomic) Confirm newborn screening results ( galactosemia and tyrosinemia ) Confirm maternal hepatitis B serology 3 months to 4 years HBsAg , HAV IgM , EBV VCA IgM or EBV PCR Lactate, pyruvate (mitochondrial screen) Autoimmune markers: ANA, ASMA, ALKM, IgG Drug history, acetaminophen level Plasma acylcarnitine profile (fatty acid oxidation defects) Serum amino acids Abdominal ultrasound with Doppler (vascular and anatomic) 5 years to 18 years HBsAg, HAV IgM, EBV (EBV VCA IgM or PCR) Autoimmune markers: ANA, ASMA, ALKM, IgG Ceruloplasmin Drug history, acetaminophen level Lactate, pyruvate (screen for mitochondrial disorders) Plasma acylcarnitine profile (Fatty acid oxidation defects) Serum amino acids Abdominal ultrasound with Doppler (vascular and anatomic) Age-specific diagnostic priorities for children with acute liver failure

33. Additional diagnostic screening tests to consider, directed by history and clinical course Infectious causes Blood culture Viral PCR in blood for adenovirus, enterovirus , EBV, HHV-6, parvovirus Nasal wash for influenza (infections) Hepatitis E antibody Serologic tests for celiac disease ( eg , tissue transglutaminase )  Soluble IL2R, ferritin in older patients, triglycerides ( hemophagocytic lymphohistiocytosis ) Echocardiogram (cardiac) MRI for tissue iron (gestational alloimmune liver disease [neonatal hemochromatosis ]) Urine succinyl acetone ( tyrosinemia ) Urine orotic acid (urea cycle defects) Urine organic acids (metabolic) Liver copper, Wilson gene mutation analysis (Wilson) Liver biopsy for histology, culture, electron microscopy Age-specific diagnostic priorities for children with acute liver failure

34. MANAGEMENT Evaluate the cause of pediatric acute liver failure (PALF), guided by the patient’s age and prioritizing the diagnosis of treatable disorders Monitor the function of each organ system Identify and treat complications Provide medical support to maximize health and survival

35. Complications of acute liver failure Metabolic Hypoglycemia Hypophosphatemia Hypokalemia Hyponatremia Acid–Base Disturbance Respiratory alkalosis Metabolic acidosis Gastrointestinal Bleeding—ulcers, gastritis Pancreatitis Hematologic Aplastic anemia Coagulopathy Disseminated intravascular coagulopathy Infections Sepsis Spontaneous bacterial peritonitis Ascites Neurologic Encephalopathy Cerebral edema Seizures Intracranial hemorrhage Multiorgan Dysfunction Pancreatitis Pulmonary edema/hemorrhage Shock Acute tubular necrosis Hepatorenal syndrome Respiratory failure

36. MANAGEMENT Care setting should be cared for in a pediatric intensive care unit close serial observation with surveillance for potential life-threatening complications. Enteric isolation procedures must be enforced blood specimens should be labeled as potentially infectious. All medical personnel should consider wearing protective gowns, gloves, and masks when dealing with a child in acute liver failure.

37. Management of Fulminant Hepatic Failure No sedation except for procedures Minimal handling Enteric precautions until infection ruled out Monitor Fluid balance Maintain circulating volume with colloid/FFP Coagulation support only if required Drugs Nutrition

38. Management of Fulminant Hepatic Failure Drugs: Vitamin K H2 antagonist Antacids Lactulose N- acetylcysteine for acetaminophen toxicity Broad-spectrum antibiotics Antifungals

39. Management of Fulminant Hepatic Failure Monitor: Heart and respiratory rate Arterial BP, CVP Core/toe temperature Neurological observations Gastric pH (>4) Blood glucose (>4 mmol /L) Acid-base Electrolytes PT, PTT

40. MANAGEMENT every 4 hours vital signs, including blood pressure every 4 hours, more frequently in an unstable child continuous oxygen saturation monitoring every 12 hourly neurological observations/coma grading, Electrolyte,arterial blood gases, blood sugar every 12 hourly (more frequently in an unstable child); prothrombin time should be monitored 12 hourly till patient stabilizes or decision to perform a transplant is taken daily daily measurements of liver span and prescription review liver function tests, blood urea, serum creatinine, calcium and phosphate at least twice weekly. Surveillance of blood and urine cultures should be done during the course of illness.

41. MANAGEMENT Coma grade It should be monitored to detect any progression. Avoid sedatives, antiemetics , hepatotoxic drugs, and corticosteroids.

42. MANAGEMENT No therapy is known to reverse hepatocyte injury or to promote hepatic regeneration

43. MANAGEMENT identified and corrected. precipitate encephalopathy Gastrointestinal hemorrhage, infection, constipation, sedatives, electrolyte imbalance, and hypovolemia

44. MANAGEMENT Intensive care unit Progression beyond stage I indicates transfer to an intensive care unit Placement of arterial and central venous and urinary catheters. Continuous pulse, blood pressure, and ECG monitoring.

45. MANAGEMENT Intensive care unit Endotracheal intubation may be required to prevent aspiration, to reduce cerebral edema by hyperventilation, and to facilitate pulmonary toilet. Mechanical ventilation and supplemental oxygen are often necessary in advanced coma.

46. MANAGEMENT CARDIOPULMONARY Excessive fluid administration contributes to pulmonary edema and should be avoided. For patients who develop pulmonary edema, careful fluid restriction and discrete use of diuretics may be needed in some instances, but should be used with caution because these interventions can reduce organ perfusion and precipitate renal failure. Central venous pressure monitoring may assist in assessing volume needs for the child Ionotropic support may be needed to maintain perfusion of vital organs.

47. Management of Fulminant Hepatic Failure Fluid balance: 85% maintenance Dextrose 10%-50% (provide 6-10 mg/kg/min) Sodium (0.5-1 mmol /L) Potassium (2-4 mmol /L

48. MANAGEMENT Fluids : However, as a general rule, restricted for most patients with PALF. Total daily fluid intake (including medications and blood products) should initially be restricted to between 85 to 95 percent of the maintenance fluid requirement.

49. MANAGEMENT Fluids At the same time, the serum glucose should be maintained between 90 and 110 mg/ dL . Adjustment in fluid rates is based upon the clinical conditions

50. Management of Fulminant Hepatic Failure Nutrition: Initial protein intake should not exceed 1 g/kg/day Nutrition support should be maintained to avoid a catabolic state. PN if ventilated

51. MANAGEMENT NUTRITION We suggest the following parameters for PN in patients with pediatric acute liver failure (PALF): Total fluid input including PN, blood products, and medications should generally be limited to between 85 to 95 percent of the maintenance fluid requirement to avoid excessive hydration

52. MANAGEMENT NUTRITION We suggest the following parameters for PN in patients with pediatric acute liver failure (PALF): Protein input should generally be no more than 1 g/kg/day , but this may need to be reduced to 0.5 mg/kg/day for patients with elevated serum ammonia levels

53. MANAGEMENT NUTRITION We suggest the following parameters for PN in patients with pediatric acute liver failure (PALF): Trace metals (trace elements) should generally be eliminated or reduced . This is because copper and manganese are metabolized in the liver. Moreover, chromium, molybdenum, and selenium should be eliminated or reduced if renal disease is also present.

54. MANAGEMENT METABOLIC Metabolic abnormalities often seen in patients with acute liver failure (ALF) include : Hypoglycemia – caused by impaired hepatic gluconeogenesis and depleted glycogen stores. treated with continuous infusion of glucose Glucose infusion rates of 10 to 15 mg/kg/minute may be required to achieve stable serum glucose levels.

55. MANAGEMENT METABOLIC Hypokalemia – caused by dilution from volume overload ascites, or renal wasting.

56. MANAGEMENT METABOLIC Hypophosphatemia – Serum phosphorus should be monitored frequently, as hypophosphatemia can be profound. the mechanism is unknown, hypophosphatemia is presumed to result from increased needs due to active liver cell regeneration. Hyperphosphatemia, often associated with renal insufficiency, is considered a poor prognostic sign    

57. MANAGEMENT Acid-base balance Respiratory alkalosis due to hyperventilation requires no action. Respiratory acidosis due to cerebral or respiratory infection requires tracheal intubation , paralysis, and mechanical ventilation. Metabolic acidosis requires correction with sodium bicarbonate .

58. MANAGEMENT METABOLIC Acid-base disturbances – metabolic acidosis from hepatic necrosis Shock increased anaerobic metabolism inborn errors of metabolism.  

59. MANAGEMENT HEMATOLOGIC ; Coagulopathy The prothrombin time (PT) and international normalization ratio (INR) are used to assess the severity of liver injury in the setting of acute liver failure (ALF) because these tests reflect hepatic production of clotting factors, particularly factors V and VII, which have the shortest half-lives.

60. MANAGEMENT HEMATOLOGIC ; Coagulopathy This is because ALF reduces both procoagulant proteins ( eg , factor V, VII, X, and fibrinogen) and anticoagulant proteins. A single dose of vitamin K should be administered once to initially assess response of the coagulation profile. However , daily administration of vitamin K is unnecessary

61. MANAGEMENT HEMATOLOGIC ; Coagulopathy Efforts to “correct” the PT/INR with plasma or other procoagulation products such as recombinant Factor VII should be avoided . Correction of the PT/INR should be limited to patients with active bleeding or in anticipation of an invasive surgical procedure.

62. MANAGEMENT Bleeding tendency Coagulopathy can be treated by fresh frozen plasma and parenteral vitamin K administration. Recombinant factor Vlla has been used for transient correction of coagulopathy refractory to other measures.

63. MANAGEMENT Bleeding tendency Prophylactic use of antacids, or H2 receptor blockers, or both should be considered because of high risk of GIT bleeding.

64. MANAGEMENT HEMATOLOGIC : Aplastic anemia Bone marrow failure, characterized by a spectrum of features ranging from mild pancytopenia to aplastic anemia occurs in a significant minority of children with ALF Treatment includes immunomodulatory medications that include steroids, cyclosporine A, and antilymphocyte or antithymocyte globulin, as well as hematopoietic stem cell transplant.

65. MANAGEMENT Renal failure Causes include Dehydration acute tubular necrosis functional renal failure ( hepatorenal syndrome) →→→ prerenal or renal uremia..

66. MANAGEMENT Renal failure renal doses” of dopamine may help to maintain renal perfusion. Renal replacement therapy with hemofiltration or dialysis may be necessary in some cases, but only liver transplantation (LT) can reverse HRS

67. MANAGEMENT Infection The patients have increased susceptibility of bacterial and fungal infection possibly due to low serum complement and defective opsonization . Septicemia, peritonitis, pneumonia, and UTI may occur. The child should be nursed in protective isolation. White blood cell count, blood cultures (aerobic, anaerobic, and fungal), urine culture, and chest Xray should be done. Broad-spectrum antibiotics (not hepatotoxic ) can be started if Fever, ascites , or clinical deterioration until the results of cultures are available.

68. INFECTION Infection Sepsis is the most frequent severe infection, with the most frequently implicated organisms being gram-positive ( Staphylococcus aureus, S epidermidis , and streptococcus) organisms, presumably of skin origin. Occasionally gram-negative bacteria or fungal infections are observed.

69. MANAGEMENT GASTROINTESTINAL ; Ascites Ascites develops in some but not all patients with acute liver failure (ALF). Precipitating factors include hypoalbuminemia, excessive fluid administration, and infection.

70. MANAGEMENT GASTROINTESTINAL ; Ascites The primary treatment is moderate fluid restriction. Diuretics should be reserved for patients with respiratory compromise or generalized fluid overload. Overly aggressive diuresis may precipitate hepatorenal syndrome.

71. MANAGEMENT GASTROINTESTINAL ; Bleeding Gastrointestinal bleeding is surprisingly infrequent, given the degree of coagulopathy . This is probably because of a balanced reduction in the procoagulant and anticoagulant proteins

72. MANAGEMENT GASTROINTESTINAL ; Bleeding Prophylactic use of acid-reducing agents is often initiated when the patient is admitted, but their usefulness is difficult to assess. Causes for bleeding include gastric erosions or ulcers due to nonsteroidal anti-inflammatory drugs (NSAIDs), or idiopathic gastroduodenal ulceration.

73. MANAGEMENT GASTROINTESTINAL ;Bleeding Infection can precipitate bleeding in this vulnerable population, so blood cultures and initiation of antibiotics should also be considered when bleeding develops. Administration of platelets, blood, and plasma is necessary if bleeding is hemodynamically significant.  

74. MANAGEMENT GASTROINTESTINAL ;Pancreatitis Biochemical and clinical pancreatitis is increasingly recognized as a condition associated with multisystem failure in critically ill children. patients who develop pancreatitis in the setting of acute liver failure, glucose and fluid management may become even more challenging.  

75. MANAGEMENT Encephalopathy determined by serial clinical evaluations of Behavior Cognition neurological examination, and, occasionally, electroencephalogram (EEG) While neurologic morbidity remains a major determinant of outcome following pediatric ALF

76. MANAGEMENT Encephalopathy Hepatic encephalopathy is not always clinically apparent in infants and young children. other causes of an altered mental status such as Sepsis Hypotension electrolyte disturbances Hypoglycemia anxiety, or “intensive care unit (ICU) psychosis” is difficult for all age groups.

77. Precipitate Encephalopathy Gastrointestinal hemorrhage, infection, constipation, sedatives, electrolyte imbalance, hypoglycemia, and hypovolemia

78. MANAGEMENT OF ENCEPHALOPATHY Flumazenil, a benzodiazepine antagonist, may reverse early hepatic encephalopathy. Morphine or other opiates used in small doses can relieve pain associated with monitoring and catheter placement

79. MANAGEMENT Enteric production of ammonia and nitrogenous toxins can be managed by The gut should be purged with several enemas. Protein intake should be restricted or eliminated. GIT hemorrhage should be prevented or rapidly stopped. Lactulose: It can be given orally or by nasogastric tube (10-50 mL every 2-4 hr) sufficient to cause diarrhea or given as retention enema (diluted 1:3) every 6 hr.

80. MANAGEMENT Bowel “decontamination” with rifaximin or neomycin metronidazole

81. MANAGEMENT Cerebral edema Cerebral edema is a life threatening complication of ALF It may lead to ischemic and hypoxic brain injury, or brainstem herniation and death commonly in those with advanced hepatic encephalopathy (stage III or IV) and can progress rapidly

82. MANAGEMENT Cerebral edema Monitoring of intracranial pressure by observing the progression or the regression of the mental changes (clinical) and by subdural transducer. Corticosteroid therapy has shown a worsened outcome in controlled trials.

83. MANAGEMENT Cerebral edema Oxygen saturation above 95 percent Head elevation of 20° to 30° Total daily fluid between 85 and 90 percent of maintenance Diastolic pressure >40 mmHg initial restriction of protein intake to no more than 1 g/kg/day, minimizing excess stimulation, treating suspected sepsis, and, if possible,

84. MANAGEMENT ENCEPHALOPATHY For patients with progressive HE, we suggest medical therapy with lactulose , Bowel “decontamination” with rifaximin or neomycin can be used as a second-tier treatment, but ototoxicity and nephrotoxicity are potential risks when neomycin is used metronidazole

85. MANAGEMENT Cerebral edema include hypertonic saline to maintain serum sodium between 145 and 150 mEq /L, and mannitol keeping serum osmolarity less than 320 mOsm /L to create a more favorable osmotic gradient to extract water from the brain. Hypothermia has been used in adults with acute liver failure with some success, but has not been studied in children

86. MANAGEMENT seizures Children with ALF may experience generalized or focal seizures, or nonconvulsive (electrographic) seizures (NCS). treatment begins with phenytoin refractory to phenytoin , therapeutic options may include midazolam infusion, phenobarbital , levetiracetam , or topiramate .

87. TREATMENT OPTIONS FOR ACUTE LIVER FAILURE intravenous NAC as treatment in children with acute liver failure not resulting from acetaminophen toxicity will hopefully bridge to transplantation, experimental treatment strategies have included growth hormone, plasmapheresis, antioxidants, and other cytoprotective agents, along with temporary “ bioartificial ” liver support.

88. MANAGEMENT Liver dialysis with an albumin-containing dialysate and biologic liver support Devices involving perfusion of the patient's blood through a cartridge containing liver cell lines or porcine hepatocytes can remove some toxins, improve serum biochemical abnormalities, and in some cases, improve neurologic function.

89. MANAGEMENT Liver transplantation may offer the best possibility of survival, but it is usually precluded by donor availability. Reduced-size allograft and living donor transplantation are important advances. Partial auxiliary orthotopic or heterotopic liver transplantation is successful in some cases that allowed regeneration of the native liver and eventual withdrawal of immunosuppression . Liver transplantation should not be done in patients with liver failure (progressive neurologic deterioration continues post transplant)

90. Fulminant hepatic failure: etiology and indications for liver transplantation Acetaminophen-induced disease     • Arterial pH <7.3 (independent of the grade of encephalopathy) OR     • Grade III or IV encephalopathy  and     • Prothrombin time >100 s  and     • Serum creatinine >3.4 mg/dL (301 μ mol/l) All other causes of fulminant hepatic failure Prothrombin time >100 s (independent of the grade of encephalopathy) OR Any  three  of the following variables (independent of the grade of encephalopathy) 1. Age <10 years or >40 years 2. Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions 3. Duration of jaundice before onset of encephalopathy >7 days 4. Prothrombin time >50 s 5. Serum bilirubin >18 mg/dl (308 μmol/l)

91. MANAGEMENT Immunosuppressive therapy It may be effective in fulminant autoimmune hepatitis

92. MANAGEMENT The antiviral drug pleconaril : It is the treatment of choice for fulminant enteroviral hepatitis in the neonate.

93. ACETAMINOPHEN POISONING

94. INITIAL STABILIZATION/THERAPY Maintain vital signs within normal limits; IV fluid administration is usually indicated Assess the serum acetaminophen concentration at least 4 hr post-ingestion

95. INITIAL STABILIZATION/THERAPY First Line IV NAC is indicated in a single acute ingestion of acetaminophen when the acetaminophen concentration ≥4 hr post-ingestion is above the treatment line It is ideal to start NAC within 8 hr of ingestion in order to prevent significant hepatoxicity and mortality Second Line Consider activated charcoal

96. INITIAL STABILIZATION/THERAPY NAC IV dosing (21-hr NAC protocol): 150 mg/kg over 60 min, then 50 mg/kg over 4 hr , then 100 mg/kg over 16 hr It is usually mixed with 5% dextrose NAC oral dosing: 140 mg/kg PO loading dose followed by 70 mg/kg PO q4h for 72 hr.

97. Efficacy of treatments of hepatic encephalopathy Ammonia hypothesis Decrease in ammoniagenic substrates Enemas with lactulose Restriction of dietary protein intake Inhibition of ammonia production Antibiotics Neomycin Rifaximin Metronidazole Vancomycin Disaccharides Lactulose Lactitol Lactose in lactase deficiency Modification of colonic flora Lactobacillus SF 68

98. Efficacy of treatments of hepatic encephalopathy Fluids 85% maintenance Dextrose 10%-50% (provide 6-10 mg/kg/min) Sodium (0.5-1 mmol /L) Potassium (2-4 mmol /L Infection Renal failure GASTROINTESTINAL Cerebral edema Liver dialysis with Metabolic ammonia removal Ornithine-aspartate Benzoate

99. Efficacy of treatments of hepatic encephalopathy Metabolic ammonia removal Ornithine-aspartate Benzoate False neurotransmitter hypothesis Branched chain amino acid supplementation Modified amino acid solutions (FO80 type) "COMA" solutions Dietary BCAA supplementation Increased dopamine L-DOPA, bromocriptine GABA hypothesis Flumazenil Other Zinc

100. PROGNOSIS The mortality rate may reach 80-90% in the absence of liver transplantation

101. PROGNOSIS Children with hepatic failure might fare somewhat better than adults, but overall mortality with supportive care alone exceeds 70%. The prognosis varies considerably with the cause of liver failure and stage of hepatic encephalopathy.

102. PROGNOSIS According to the etiology: Survival rate of 50 -60% occurs in cases of FHF due to HAV or HBV infection and acetaminophen overdose but it is only 10-20% of cases due to idiopathic form of FHF or an acute onset of Wilson disease.

103. PROGNOSIS In patients who progress to stage IV coma ,the prognosis is extremely poor. Brainstem herniation is the most common cause of death. Major complications such as sepsis, severe hemorrhage, or renal failure increase the mortality. The prognosis is particularly poor in patients with liver necrosis and multiorgan failure. Age <1 yr, stage 4 encephalopathy, an INR >4, and the need for dialysis before transplantation have been associated with increased mortality.

104. PROGNOSIS The overall mortality exceeds 70%. Death is usually attributable to cerebral edema with or without herniation, massive hemorrhage of the upper intestinal tract from stress injury, sepsis multisystem organ failure. The mortality rate is highest in patients <1 yr of age.

105. PROGNOSIS Causes of death: neurological (67%) GIT hemorrhage (13%) bacterial infection (13%) hemodynamic complication ( hypovolemia , arrhythmia) progressive respiratory and renal failure (other patients).

106. PROGNOSIS According to the stage of hepatic encephalopathy: Extremely poor prognosis in cases with stage IV coma. According to laboratory data: Poor prognosis with a prothrombin time more than 50 sec serum bilirubin more than 17.5 mg%. Pretransplantation serum bilirubin concentration or the height of hepatic enzymes is not predictive of posttransplantation survival. plasma ammonia concentration >200 µ mol /L is associated with a 5-fold increased risk of death.

107. PROGNOSIS According to presence or absence of complications: Poor prognosis with severe hemorrhage Sepsis renal failure aplastic anemia (a fatal complication of idiopathic form of FHF). Liver transplantation: It will lead to -75% survival rate in the 6 mo post liver transplantation.

108. Admission Criteria of hepatitis fulminant hepatitis indicated by Biochemical evidence coagulopathy evidence encephalopathy require hospital admission. Persistent vomiting, dehydration, and electrolyte abnormalities High fever 39.5c Comorbidity