Fulminant hepatic failure

CAIMS KARIMNAGAR

1. FULMINANT HEPATIC FAILURE

2. Fulminant hepatic failure is a clinical syndrome of coagulopathy and encephalopathy resulting from massive necrosis of hepatocytes or from severe functional impairment of hepatocytes. The disease evolves over a period of 8wks from the onset of precipitating illness. Synthetic, excretory, and detoxifying functions of the liver are all severely impaired.

3. The current criteria suggested by pediatric acute liver failure study group ( PALFSG) Biochemical evidence of acute liver injury (<8 wk duration) No evidence of chronic liver disease Hepatic-based coagulopathy defined as a 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 PT >20 sec or INR >2 regardless of the presence of clinical hepatic encephalopathy.

4. Previously asymptomatic children with chronic liver disease like wilsons disesase , galactosemia and other metabolic conditions can also present with fulminant hepatic failure for the first time.

5. ETIOLOGY: IDIOPATHIC: in 40-50% cases INFECTIVE VIRAL CAUSES Hepatitis a,b,c,d & e high risk of fulminant hepatic failure occurs in combined infections with the hepatitis B virus (HBV) and hepatitis D. EBV Adenovirus Enterovirus Cmv Parvovirus B19 Herpes simplex Varicella zoster

6. BACTERIAL Enteric fever Weil’s disease Septicemia PROTOZOAL Facliparum malaria

7. DRUGS: Acetaminophen overdose is the most common etiology of acute hepatic failure in children and adolescents Isoniazid Sodium valproate Phenytoin Salicylates Halothane Exposure to carbon tetrachloride, Amanita phalloides mushroom, herbal medication,methanol .

8. METABOLIC CAUSES: Wilsons disease Hemochromatosis Galactosemia Alpha 1 anti-trypsin deficiency Hereditary tyrosinemia Hereditary fructose intolerance Neonatal iron storage disease Defects in β-oxidation of fatty acids Deficiencies of mitochondrial electron transport

9. CIRCULATORY CAUSES Budd- chiari syndrome Myocarditis Acute circulatory failure Cyanotic heart disease IMMUNOLOGICAL CAUSES Auto immune hepatitis MISCELLANEOUS Reye’s syndrome Acute leukemia ( infiltration) Graft vs host disease Hyperthemia

10. CLINICAL PRESENTATION: Some children with fulminant hepatic failure may present with or without features of encephalopathy and some present only with coagulopathy in the absence of sepsis or DIC . SYMPTOMS: Jaundice A prodrome of flu-like illness may precede the onset of jaundice Fever Anorexia vomiting

11. Abdominal pain Foetor hepaticus Confusion Restlessness Neuropsychiatric changes Irritability poor feeding and disturbance in sleep pattern in infants Bleeding manifestations- hematemisis , hematochezia , melena. Altered sensorium coma

12. EVALUATION OF CHILD H/O fever H/O onset of jaundice Constitutional symptoms like vomitings H/O bleeding H/O decreased urine output H/O altered sensorium H/O i.v drug abuse

13. H/O herbal medication Similar illness in family or community H/O mushroom eating Past history of ATT, anticonvulsant therapy Developemental history : Failure to thrive Developemental delay Neuromuscular weakness

14. Family history of consanguinity , early infant death, liver disease. Per abdominal examination: liver size, tenderness, ascites CNS examination: level of consciousness, other causes of altered sensorium

15. INVESTIGATIONS Investigations for ascertaining liver cell injury Serum bilirubin-both direct and indirect are increased Hepatic enzymes do not correlate with the severity of fulminant hepatic failure. ALT and AST are normal or increased or even decreased. The enzymes are decreased if the liver cell necrosis is severe. Liver biopsy – autoimmune hepatitis, metastatic liver disease, lymphomas.

16. Investigations for aetiological factors CBP- WBC increased in infections Viral markers-hepatitis B (HBV-DNA, antibody to HBV, HBsAg , IgM core antigen), hepatitis A ( IgM anti-HAV), hepatitis C (anti-HCV, HCV-RNA) and hepatitis D (anti-HDV antibody) Blood culture and sensitivity

17. Serum paracetamol levels, other drug levels in poisonings Autoantibodies-LKM, ANA and SMA Urine/serum screening test for metabolic disorders Blood ammonia is elevated in Reye's syndrome Seum ceruloplasmin levels Blood urea levels decreased in urea cycle disorders

18. Investigations for complications: ABG- metabolic acidosis and respiratory alkalosis blood sugar levels Serum lactate levels RFT: Blood urea and Serum creatinine levels Serum electrolytes- hyponautremia , hyperkalemia . Prothrambin time elevated it doesnot respond to vit k administration. Imaging: ultrasound abdomen, CT/MRI brain for cerebral edema and to ruleout other causes of altered sensorium.

19. Management: supportive Children with fulminant hepatic failure should be admitted in icu with continuous monitoring of vital functions. Minimal handling of the child. Maintain a normal fluid balance. Avoid fluid overload. Correction hypoglycaemia. Maintain normal urine output.

20. Administration of calcium, phosphorus, magnesium, factor concentrate, magnesium and platelets. Coagulopathy can be treated with parenteral vitamin K, fresh frozen plasma, cryoprecipitate. Prophylactic use of broad spectrum antobiotics , antifungals

21. Maintain a platelet count of more than 50,000. Gut sterilisation-using antibiotics such as ampicillin/neomycin. Lactulose inhibits colonic organisms, decrease the intestinal transit time. Fat soluble vitamin supplementation. Diet with decreased protein, high calories, high carbohydrates and moderate fat should be given.

22. Prophylactic use of proton pump inhibitors because of the high risk of gastrointestinal bleeding. In complicated cases 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.

23. Sedatives should be avoided unless needed in the intubated patient because these agents can aggravate or precipitate encephalopathy. Patients should be monitored closely for sepsis, pneumonia, peritonitis, and urinary tract infections. Gastrointestinal hemorrhage , infection, constipation, sedatives, electrolyte imbalance, and hypovolemia can precipitate encephalopathy and should be identified and corrected.

24. liver dialysis with an albumin-containing dialysate, and biologic liver support devices that involve perfusion of the patient’s blood through a cartridge containing liver cell lines or porcine hepatocytes can remove some toxins, improve serum biochemical abnormalities. Orthotopic / auxillary orthotopic liver transplantation can be lifesaving in patients who reach advanced stages of hepatic coma.

25. Specific Paracetamol poisoning-N- acetylcysteine Hepatitis B -antiviral agents lamivudine,entecavir Herpes simplex- acyclovir Galactosaemia , fructosaemia , hereditary tyrosinaemia type I-dietary elimination. Autoimmune hepatitis-steroids, azathioprine

26. BZD antagonist like flumazenil in BZD over dosage Enteric encephalopathy- ceftriaxone Wilson’s disease- D- pencillamine,zinc Hemochromatosis- desferoxamine , deferiprone Leptospirosis- pencillins , doxycycline Malaria- anti malarials Amanita posoning - pencillins L-ornithine and L-aspartate preparation (LOLA) removes ammonia by conversion to urea through the urea cycle.

27. COMPLICATIONS: Infections Hepatic encephalopathy Cerebral edema Hepatorenal syndrome Hepatopulmonary syndrome Coagulopathy –GI bleeding Hypotension Electrolyte and acid base imbalance

28. POOR PROGNOSTIC FACTORS: Age < 1 yr Depending on etiological factor Stage 4 encephalopathy INR > 4 Plasma ammonia concentration > 200 micro mol / L Sepsis Severe bleeding

29. HEPATIC ENCEPHALOPATHY Hepatic encephalopathy is a complex neuropsychiatric syndrome characterised by disturbances in level of consciouness , behaviour and personality seen in patients with acute or chronic liver disease. Type A- seen in fulminant hepatic failure Type B- seen in portosystemic shunt cases Type C- seen in chronic liver disease

30. PATHOGENESIS: Accumulation of neurotoxins in brain Increased activity of the inhibitory GABA neurotransmission system Imbalance between aromatic and branched amino acids Action of cytokines and bacterial lipopolysaccharide on astrocytes

31. DIFFERENTIAL DIAGNOSIS Organic brain diseases Intracranial lesiom -intracranial bleeding Infections-meningitis, encephalitis Metabolic encephalopathy-hypoglycaemia, electrolyte imbalances, hypercarbia , an< Xlia , uraemia Toxic encephalopathy Postseizure encephalopathy Hyperammonaemia Alcohol intoxication

32. MANAGEMENT Same as above but may require ventilatory support.