Fulminant hepatitis is a severe clinical syndrome of liver dysfunction characterized by coagulopathy and encephalopathy, developing within 26 weeks in patients without pre-existing liver disease. Key causes include viral hepatitis, drug toxicity, metabolic disorders, and vascular issues, leading to non-specific symptoms, jaundice, and complications like hepatic encephalopathy and renal failure. Management focuses on treating complications and specific causes, with liver transplantation being a critical option in severe cases.

1. Fulminant Hepatitis
(Acute liver cell failure)
By,
Kerollos Motwade
Demonstrator of Internal Medicine,
Faculty of Medicine - Assiut University.

2. Def.:
It is the clinical syndrome of liver dysfunction, coagulapathy
and encephalopathy which develops within
26 weeks of onset of symptoms in patients without pre-
existing liver disease.
Triad
of diagnosis

3. Disease duration of greater than 28 weeks before the onset of
encephalopathy is categorized as chronic liver disease.

4. Etiology

5. Viral Hepatitis
-HAV
-HBV
It may occur due to
Acute Hepatitis B
Reactivation of viral replication in inactive carriers either
spontaneously or after chemotherapy or immunosuppressive therapy.
Delta superinfection
-HEV
The susceptible groups: *Chronic liver disease patients
*Pregnant women.
±HCV
-Herpes simplex 1 and 2
-Varicella zoster virus

6. Paracetamol toxicity
Paracetamol is a dose-related toxin.
Paracetamol is usually undetectable at the time of presentation, and
etiology often has to be based on clinical presentation, history and
typical laboratory results.
POD characterized by extreme elevations of serum aminotransferase
(usually >10,000 IU/L) and relatively low bilirubin levels.
Metabolic acidosis, elevated serum lactate, hypoglycemia and acute
kidney injury (AKI) can occur in early stages of clinical evolution.

7. Idiosyncratic drug
reaction
Cases are subacute with moderately elevated aminotransferases and
high bilirubin levels.
The most frequent drugs are anti-tuberculosis medications, NSAIDs,
anaesthetic agents and anti-seizure medications.
Herbal remedies, especially those containing green tea extract, have
been implicated in acute liver failure.

9. Vascular causes
These include
Low cardiac output states “ Shock Liver”= “Hypoxic hepatitis”
N.B. The absence of a documented episode of hypotension or hypoxia
does not exclude this condition.
Acute Budd-Chiari syndrome

10. Other Etiologies
These include
Acute fatty liver of pregnancy
Eclampsia
Massive infiltration of the liver with tumor as in lymphoma and
breast cancer
Wilson’s disease

11. Clinical Picture

12. Non - specific symptoms such as nausea, vomiting and malaise.
Jaundice and signs of hepatic encephalopathy, evolving relatively
quickly.
Impairs synthesis of clotting factors and glucose leading to coagulopathy
and hypoglycaemia.
Metabolic acidosis; lactic acidosis.
Ascites, oedema & renal failure are more likely in patients with a more
gradual onset of hepatic insufficiency.

13. Investigations

14. Laboratory

17. Abdominal imaging
&
liver biopsies
Abdominal U/S
…to assess for vasculature patency and mass lesions.
CT scanning
…it will show a reduction in liver size
Liver biopsy
…if diagnosis can’t be reached
with non-invasive techniques

18. Brain CT
Non - contrast computed tomography of the brain may help rule out
other pathology, such as haemorrhage.
N.B. The yield of such studies is low and may not justify the risk of
moving a critically ill patient

19. Complications & Management

20. Treatment has focused on the management of complications except for
a few etiology specific therapies.

21. Hepatic Encephalopathy
Lactulose ; it has shown no benefit
*It may increase aspiration risk
*It may cause bowel distension
Rifaximine ; there is not enough evidence to recommend non -
absorbable antibiotics in acute liver failure
l- ornithine l- aspartate ; it treats encephalopathy by increasing
muscle metabolism of ammonia but a recent randomized controlled trial
showed no benefit in acute liver failure
These may complicate transplanation

22. Progression of encephalopathy is often
triggered by infection and
empiric antibiotics
should be administered to these patients

23. Cerebral oedema
&
Intracranial hypertension
Acute liver failure is uniquely associated with cerebral oedema, which
can lead to an increase in intracerebral pressure.
This is uncommon in patients with stage 1 or 2 encephalopathy. But
develops in the majority with stage 4.

24. Clinically , increased intracranial pressure is suggested by :
Systolic hypertension (sustained or intermittent)
Increased muscle tone and myoclonus
Extension and hyperpronation of the arms and extension of the legs
(decerebrate posturing).
Dysconjugate eye movements
Brainstem herniation

25. Limiting stimulation.
Elevating the head to 30 degrees.
Correction of acidosis and electrolytes.
Prophylactic infusion of hypertonic saline to keep serum sodium 145 –
155 mmol/L in patients with severe encephalopathy.
A bolus of intravenous mannitol (0.25 – 1 g/kg, 20% solution)
Pentobarbital can be used to induce a barbiturate coma
N.B. Corticosteroids are not effective in controlling cerebral oedema or
improving survival in acute liver failure.
Management…

26. Coagulapthy
The resulting coagulopathy predisposes to bleeding.
This is a potential cause of death; it may be spontaneous, from the
mucous membranes, the gastrointestinal tract or into the brain or after
invasive procedures.
The prothrombin time and its associated INR is a widely used guide to
prognosis.

27. Management..
Vitamin K
Fresh frozen plasma
Cryoprecipitate
Platelets transfusion if < 50,000/mm³ + active bleeding
Prophylactic blood products are NOT advised, as they do not decrease
the risk of bleeding, result in volume overload and obscure the trend of
INR as a prognostic value.

28. Metabolic derangements
3rd generation
Cephalosporins
Or
Fluoroquinolones
±
Vancomycin
Antifungals
Hepatorenal syndrome
Acute tubular necrosis
Direct drug nephrotoxicity
H2 blocker infusion

29. Crystalloids
Salt-free Albumin
Norepinephrine
Corticosteroids
Daily Chest X-ray
Intrapulmonary arterio-venous shunting
Adult respiratory distress syndrome
N.B. Hyperamylasaemia in 12% of acute liver failure pts, only 9% of whom had pancreatitis!
Acute haemorrhagic /necrotizing pancreatitis

30. Paracetamol hepatotoxicity
Doses exceeding 10 g/day are usually needed but severe hepatic injury
can occasionally occur with as little as 4 g/day in susceptible patients.
N.B. Even if history is negative, aminotransferases over 3500 IU/L with
low bilirubin levels are usually indicative of paracetamol toxicity
When to give NAC ?
it is most effective when given within 10 h of paracetamol overdose,
NAC may be of benefit 48 h or more after ingestion
It should be administered even if acute liver failure has developed

31. Oral dose
140 mg/kg
followed by
70 mg/kg every 4 h
for 17 doses
Intravenous dose
150 mg/kg in 5% dextrose over 15
min
then
50 mg/kg over 4 h
followed by
100 mg/kg over 16 h

32. Autoimmune hepatitis
Fulminant liver failure is an uncommon presentation of autoimmune
hepatitis.
N.B. Autoantibodies may be absent.
Liver biopsy may be required for definitive diagnosis.
Patients are treated with prednisone or prednisolone 60 mg/day

33. Pregnancy – related causes
Acute liver failure may occur in the setting of
Acute fatty liver of pregnancy
 Severe pre – eclampsia / eclampsia
HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome
Prompt Deliveryof the fetus
results in recovery.

34. Wilson’s disease
The usual therapies of penicillamine or trientine are ineffective in
acute liver failure and are not recommended.
Fulminant Wilson ’ s disease is 100% fatal without
liver transplantation
CRRT, plasmapheresis or plasma exchange can be initiated to remove
copper and alleviate renal tubular damage until a graft becomes
available.

35. Hepatitis B
Although randomised controlled trials are lacking, several cohort
studies indicate that the early antiviral therapy – in case of severe acute
hepatitis B- with highly potent NAs can prevent progression to acute
liver failure and subsequently liver transplantation or mortality.
This effect, however, is not seen if antiviral therapy is initiated late in
the course of severe acute hepatitis B in patients with already
manifested acute liver failure and advanced hepatic encephalopathy.
Data supports the use of Tenofovir fumarate, Entecavir or even
Lamivudine.

36. Liver Transplantation