Acute liver failure MBBSPPT.COM

DEFINITION Acute liver failure (ALF) is not a diagnosis but a clinical syndrome evidence of liver dysfunction within 8 weeks of onset of symptoms/liver disease uncorrectable coagulopathy with INR >1.5 in patients with hepatic encephalopathy or INR> 2.0 in patients without encephalopathy No evidence of chronic liver disease either at presentation or in the past.

Adult Vs pediatric liver failure Etiology: infective & metabolic cause Clinical picture : encephalopathy is difficulty to diagnose Etiology : drugs predominant cause Clinical picture : encephalopathy essential criteria

Grades of hepatic encephalopathy

Etiology of ALF in India Acute viral hepatitis ( most common-60-95%) hepatitis A 10-54%;hepatitis E 3-27%; hepatitis B 8-17%; and multiple viruses 11-30%- commonest being hepatitis A+E. Acute liver failure secondary to hepatitis B usually presents at about 12 weeks of age. Drugs (6-8%) Indeterminate (13-20%)

Etiology of acute liver failure Neonate/infant up to 6 months Infection: septicaemia, hepatitis B, adenovirus, echovirus,Coxsackie B. Metabolic: neonatal haemochromatosis, tyrosinaemia typeI, mitochondrial disorders, fatty acid oxidation defects. Poisoning: paracetamol. Familial haemophagocytic syndrome.

Etiology Children >6 months Viral hepatitis: hepatitis A/B/E/non-A-G, Epstein-Barrvirus, parvovirus B19. Autoimmune type I or II. Drug induced: paracetamol overdose, sodium valproate,carbamazepine, isoniazid,halothane. Metabolic: Wilson’s disease( most common >3yr), Reys syndrome

Clinical Presentation Clinical presentation depends on the etiology of FHF. Usually acute. Can be prolonged to 10 weeks if due to metabolic liver disease. The extent of jaundice is variable in the early stages, but all children have coagulopathy.

Clinical Presentation Encephalopathy is particularly difficult to diagnose in neonates. Vomiting and poor feeding are early signs Irritability and reversal of day/night sleep patterns indicates more established hepatic encephalopathy. Older children: aggressive behavior or seizures.

Clinical Presentation Hypoglycemia is present in 40% of patients with ALF. Due to increased plasma insulin levels secondary to reduced hepatic uptake, and reduced glycogen stores gluconeogenesis.

SYMPTOMS Fever Vomiting /poor feeding Easy brusibility Jaundice Altered sensorium, irritability, inattention, altered sleep rhythm Developmental delay Seizure

SIGNS Trouble drawing figures Poorly performed mental tasks Asterexix in older children Incontinence Fetor hepaticus Hyperreflexia ( stage II &III) Areflexia , decortications &decerebration/faccidity, extensor plantar (stage IV)

DIAGNOSTIC WORK-UP General work-up ALT, AST, GTT,ALK total and conjugated bilirubin, PT(INR), PTTK, hemogram, serum electrolytes, blood urea, creatinine, blood and urine cultures, blood group, chest X-ray, serum AFP, lactate, LDH, blood ammonia,ABG, and urine for reducing substances

Specific work-up Infectious IgM anti- hep A, IgM anti - hep E, HbsAg, IgM anti- hepatitis B core antibody, cytomegalovirus PCR, IgM VZV, IgM EBV, HIV 1 and 2 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

Specific work-up Autoimmune Coombs test, antinuclear antibody (> 1:40), liver kidney microsomal antibody, smooth muscle antibody (>1:20), Immunoglobulin G levels Drug overdose Acetaminophen, valproate drug levels

Management of ALF Key Components: Prevent complications such as encephalopathy and cerebral edema, sepsis, gastrointestinal bleeding, renal failure, electrolyte imbalance and multiorgan failure. To assess prognosis and consider liver transplantation.

MANAGEMENT Transport ( HE I &II ) Management in the Intensive Care Unit Fluid balance: 75% maintenance. Volume resuscitation if necessary Vasopressor for saline unresponsive shock Glucose based solution ( minimum GIR 4-6 mg/kg/mt) should be used Sedation should be avoided

How frequently clinical &biochemical parameters should be monitored vital signs every 4 hours continuous oxygen saturation monitoring neurological observations/coma grading, electrolyte , ABG, blood sugar every 12 hourly ; PT should be monitored 12 hourly daily measurements of liver span liver function tests, blood urea, serum creatinine, calcium and phosphate at least twice weekly. Surveillance of blood and urine cultures

Management of Electrolyte disturbances Hyponatremia, hypokalemia, hypocalcemia, hypophosphatemia and hypomagnesemia and hypoglycemia are commonly observed Intravenous fluids should be tailored in accordance to electrolyte, sugar and renal status of the patient.

Supportive management NAC therapy for all ALF prophylactic administration of PPI L-ornithine L-aspartate, lactulose and other non-absorbable antibiotics have not been found to be beneficial lactulose is administered in grades I-II HE

Management of raised ICT Infection and cerebral edema remain the leading causes of death. Routine invasive ICP monitoring is not recommended Hypertonic saline Vs mannitol Routine hyperventilation is not recommended Hypothermia, routine phenobarbitone and steroids are not indicated

Management of coagulopathy Prophylactic use of FFP and platelet transfusion is not recommended Clinical significant bleeding is indication of FFP transfusion Vit k 5-10mg single dose is indicated in all patients of ALF INR > 7 is another indication Platelet transfusion is given at a threshold value of 10000-20000 or bleeding with platelet count < 50000/cumm

SEPSIS IN ALF Staph , strepto and gram-ve organism are the predominat organism Candida is responsible for 30% cases Routine preventive antibiotics not recommended Indications of emperical antibiotics surveillance cultures reveal significant isolates, progression of, or advanced stage (III/IV) HE, refractory hypotension, renal failure, presence of SIRS components (temperature >38°C or <36°C, white blood count >12,000or <4,000/mm3, tachycardia)

Acute kidney injury in ALF Causes Pre renal ( hypovolumia, hepato renal syndrome ) Renal ( ATN ) Indications of Renal replacement therapy persistent hyperkalemia (>7 mEq/L), uremic encephalopathy, fluid overload (pulmonary edema,severe hypertension), severe metabolic acidosis, Hyponatremia (120 mEq/L or symptomatic) or Hypernatremia.

Nutrition Use of BCAA in ALF and HE is controversial Protein restriction is not recommended in HE High calorie diet If metabolic cause is suspected then stop nutrition for 24 h

Liver transplantation Indications INR> 4 Factor V < 25% Contraindications uncontrollable and untreatable sepsis, Severe cardiopulmonary disease, multi-organ failure, Extrahepatic malignancy, mitochondrial disease, HE grade IV encephalopathy

Prognosis Mortality is 70% without LT Poor prognostic factors elevated serum bilirubin and prothrombin time, young age high arterial ammonia and high WBC count, low alanine aminotransferase, and presence of encephalopathy drug-induced ALF (non- acetaminophen), hepatitis B, and indeterminate cases (25% spontaneous survival).

Prognosis The prognosis is better with hepatitis A, acetaminophen overdose ischemia (approximately 60% spontaneous survival)

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