Dr Theresa, Dr Bhanu Vikraman Pillai (paediatric gastro), Dr C Jayakumar, Amrita Institute of Medical Sciences, Kochi
Five year old male referred from out side hospital with the complaints of fever abdominal pain and lethargy of 3days durations and abnormal liver enzymes . He also had several episodes of non projectile non bilious vomiting and watery stools over 3 days duration.
Labs SGOT of 9229 and SGPT of 7845, PT-INR: 56.9/5.5 and APTT: 52.2, ALP:211 .
He is the 2nd child of non-consanguineous marriage. His perinatal history, development and immunisation history were normal
At admission, the child was irritable with stable vitals.Pallor and icterus were present. Abdomen examination showed hepatomegaly with liver palpable 2cm below the right subcostal margin
CNS examination showed hyperreflexia, GCS-13/15. Other systems were within normal limit.
Initial labs: CBC: TC-9.84K/Ul, N:65%, L:24.5%, Hb:8.1g/dl
LFT: Total bilirubin:2.96mg/dl, direct bilirubin: 2.40mg/dl, SGOT:5631.8IU/L, SGPT:5079IU/L, ALP:172.0IU/L
RFT: Serum urea:17.2mg/dl, serum creatinine:0.32mg/dl
Serum electrolytes: normal, Ammonia:120.8
PT- NCD. Repeat PT-INR: 71.8/14/7/5.29
APTT-45.8/30.5
LDH:1665.0U/L, serum Ferritin: 29124ng/ml
Paracetamol toxicity level did was 88.6mcg/ml
Considering the outside reports showing significant derangement of liver functions and coagulation, he was admitted with a provisional diagnosis of acute liver failure with grade 2 encephalopathy and hypoglycaemia He was given a fluid bolus, IV Piptaz, IV N- Acetyl cysteine infusion, laxatives and neuroprotective measures including medicines for raised ICP measures
Related lab parameters all corelating with acute inflammatory response with hepatic encephalopathy
Clinical condition worsened after admission Sensorium started progressively falling and he was intubated
CT brain was done to rule out any bleed and herniation and CT abdomen was done to look for evidence of chronic liver disease.
In view of such a fulminant presentation, preparations were made for a possible liver transplant and clinical workup of recipient was started
In view of significantly deranged coagulation, nephrology team was consulted for a possible need for CRRT, which was started and continued for 3 days.
For the etiological workup, hepatotropic viruses sent were negative. Of the non hepatotropic viruses, parainfluenza virus was positive from the respiratory viral panel and dengue IgM was positive , but PCR was negative. Leptospira was negative. ANA and autoimmune hepatitis panel were negative. Blood and urine culture were negative. Ceruloplasmin to rule out Wilsons was normal.
Serum paracetamol level were sent and was high.
Urine for toxicology sent was negative.
He responded well to CRRT and other supportive treatment. Coagulation profile, serum ammonia gradually improved and sensorium started getting better. He was later extubated and continued on IV NAC and symptomatic management. As culture were sterile and CRP was falling in absence of further fever spikes , IV antibiotics were stopped . He was gradually started on oral feeds which he tolerated well. IV NAC was tapered and stopped after 5 days. He was noticed to have relative bradycardia for which ECG was taken which showed right bundle branch block and prolonged QTc.
2D echo did was normal. During hospital stay he had an episode of seizure for few minutes but EEG taken was normal. He didn’t have any further episodes. During his ward stay his liver enzymes progressively improved and PT-INR continued to remain normal. Oral intake was completely established and was hemodynamically stable with daily improving liver function tests. Hence discharged.
Possible diagnosis
Acetaminophen poisoning even though the is no history of suicidal or homicidal poisoning
Or it could be due to Dengue infection (IgM was positive
DISCUSSION: FULMINANT HEPATIC FAILURE:
Also known as acute liver failure is defined as acute sever impairment of liver function associated with progressive mental changes in patients who have had liver disease for less than 8 weeks
EPIDEMOLOGY: The estimated frequency 17 cases per 100,ooo population per year, but the frequency in children is unknown. Pediatirc acute liver failure accounts for 10-15 percent of pediatric liver transplants performed in the United states annually.
Etiology: Idipathic: in 40-50% cases
Infective: Viral: Hepatitis , adenovirus, enterovirus, EBV, CMV, Parvovirus B 19, Herpes simplex, Varicella Zoster
Bacterial: Enteric fever, Weil’s disease, Septicemia
Protozoal: Falciparum malaria
Drugs: Acetaminophen overdose is the most common cause of acute hepatic failure in children and adolescents.
Isoniazid, Sodium Valporate, Phenytoin, Salicylates, Halothane , herbal medictaions
Metabolic causes: Wilsons’s disease, Hemochromatosis, Galactosemia, Alpha 1 ant- trypsin deficiency
Circulatory causes: Budd-chiari syndrome, Myocarditis, Acute circulatory failure
Miscellaneous: Reye’s syndrome, Graft vs host reactions
CLINICAL FEATURES: 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, abdominal pain, foetor hepaticus, confusion, neuropsychiatric changes, bleeding manifestations, altered sensorium, coma
INVESTIGATIONS:
1)For liver cell injury: Serum bilirubin- both direct and indirect will be increased
ALT and AST are normal or increased or even decreased. The enzymes are decreased if the liver cell necrosis is severe
2)Investigations for etiological factors: CBC, Viral markers, blood and urine culture, serum paracetamol levels and other drug levels for drug toxicity, Autoantibodies like LKM, ANA and SMA. Urine and serum screening tests for metabolic disorders. Blood ammonia level is elevated in reye’ssyndrome. Serum ceruloplasmin level to rule out Wilson’s. Blood urea levels will be decreased in urea cycle disorders.
3)Investigations for complications: ABG, blood sugar levels, serum lactate levels, RFT, serum elctrolytes ,coagulationprofile, Imaging like USG abdomen, CT/MRI brain for cerebral edema and to rule out other causes of altered sensorium.
MANAGEMENT:
Children with fulminant hepatic failure should be admitted in ICU with continuous monitoring of vitals . Maintain a normal fluid balance and avoid fluid overload. Correction of hypoglycemia should be done and maintain normal urine output.
Coagulopathy can be treated with parenteral vitamin K, Fresh frozen plasma and cryoprecipitate. Prophylactic use of broad spectrum antibiotics and antifungals. Maintain a platelet count of more than 50,000. Gut sterilisation with antibiotics such as ampicillin/neomycin. Fat soluble vitamin supplementation. Prophylactic use of proton pump inhibitors because of high risk of GI bleeding. In complicate cases, endotracheal intubation may be required to prevent aspiration, to reduce cerebral edema hyperventilation and to facilitate pulmonary toilet. Mechanical ventilation and supplemental oxygen are often necessary in advanced coma.
Sedatives should be avoided unless needed in the intubated patient because these agents can aggravate or precipitate encephalopathy. Patients should me monitored closely for sepsis, pneumonia and UTI. Liver dialysis with an albumin containing dialysate and biologic liver support devices that involve perfusion of the patients blood through a catridgecontaining liver cell lines or porcine hepatocytes can remove some toxins , improve serum biochemical abnormalities.
Orthotopic/auxiallry orthotopic liver transplantation can be life saving in patients who reach advanced stages of hepatic coma.
Specific treatment: Paracetamol poisoning- N Acteylcysteine
Hepatitis B- antiviral agents
Herpes simplex- acyclovir
Autoimmune hepatitis- steroids, azathioprine
Enteric encephalopathy- IV Ceftriaxone
Wilsons disease:
D-pecillamine, zinc
PROGNOSIS: Age<1 year
Depending on etiological factor
Stage 4 encephalopathy
INR>4
Plasma ammonia concentration > 200micro nol/L
Sepsis and bleeding
Carry home message
Paracetamol poisoning must be strongly suspected in all cases of acute Liver cell failure