1

Name : Muhammad Hisyam Bin Kamarulzaman

Title : Fulminant Hepatitis
DEFINITION
Fulminant Hepatitis is a clinical syndrome where there will be a rapidly progressive loss
of hepatic function due to viral infection or other cause of inflammatory destruction of liver
tissues. It may be characterized by the rapid development of triggered apoptosis or by massive
necrosis of the liver cell resulting in severe hepatocellular dysfunction, specifically coagulopathy
and mental status changes known as encephalopathy. It may occurs suddenly in a patient without
any history of liver disease or previously stable liver disease. The onset of Fulminant Hepatitis
occurs within 8 weeks after the onset of first hepatic symptoms.
PATHOGENESIS
Aetiologically, 40% of Fulminant Hepatitis is caused by acute viral hepatitis such as
HAV, HBV, HCV, HDV and HEV. Other viruses that can cause are less common, such as
Epstein - Barr virus, HSV, cytomegalovirus, varicella and many other more. For all aetiologies,
the incidence are higher in females simply because females are generally responded more to
immunological challenge compared to that in males.
HAV is a RNA virus that causes the liver damage by both direct killing of the
hepatocytes and by the host immune response to infected hepatocytes. It is infected via fecal-oral
route. Meanwhile, HBV is a DNA virus that is transmitted sexually or via infected blood or other
bodily fluids. HBV does not kill the cell but rather causing the immune system to attack the
infected hepatocytes after recognizing the viral antigens on the surface of the cell. Excessive
immune response thus causes the fulminant hepatic failure. HCV on the other hands, is a RNA
virus generally transmitted by blood or bodily fluids, causes hepatic infection similar to HBV but
with greater progression to become chronic. HDV is a RNA virus that requires helper function of
HBV, it infected either as co-infection which occurs simultaneously with HBV or superinfection
in the chronic HBV. HEV has a common characteristic as HAV but can cause fulminant hepatic
failure in pregnant women.


2

During the incubation period (HAV 15-50 day; average 28 days/ HBV 45-160 days;
average 120 days/ HCV 14-180 days; average 45 days), intense viral replication leads to the
appearance of viral component (first antigens, later antibodies) in the urine, stool and bodily
fluids. Liver cell death and an associated inflammatory response occur afterward, following by
the changes in liver function test and clinical features in liver disease. Hepatocellular necrosis
starts in the centrizonal distribution and progressing towards portal tracts.
CLINICAL FEATURES
The clinical features of Fulminant Hepatitis includes encephalopathy, the condition in
which when the liver fails, nitrogenous waste such as ammonia builds up in the blood stream and
are circulated until it reaches the brain. To clear up the waste, astrocytes in the brain will convert
glutamate into glutamine, excessive glutamine will cause the osmotic imbalance and a shift of
fluid into these cells, hence causing cerebral oedema. There are 4 grades in hepatic
encephalopathy:-
Grades Explanation
I Altered mood or sleep disturbance (e.g. reversed sleep pattern)
II Increasing drowsiness, confusion, slurred speech
III Stupor, incoherence, restlessness, significant confusion
IV Coma
Table 1. Grading in hepatic encephalopathy
Note that too much of ammonia in blood can also be detected in breath, a condition
known as Foetor Hepaticus (breath of the death/smells like pear drops).
Another significant clinical feature in Fulminant Hepatitis is the impaired synthesis of
many coagulation factors and inhibitors, known as coagulopathy. Due to the massive necrosis of
hepatocelluler, the liver can no longer produces almost all coagulation factors and some
inhibitors of coagulation and fibrinolysis. As the result, there will be a prolongation in
prothrombine time and bleeding time, making it easier for the patient to bleed and bruising.
Hence, both tests can be used to monitor the severity of hepatic failure.


3

As the function of the liver fails to work, unconjugated bilirubin in the blood serum (also
known as indirect bilirubin) which are not water-soluble are unable to be conjugated with
glucoronic acid to form a water-soluble bilirubin (also known as direct bilirubin). The increase of
indirect bilirubin in the blood serum (>41.75 mol/L/>2.5 mg/dL) will be manifested as
jaundice, a condition of yellow pigmentation of the skin, sclera and mucosa.
Sometimes, Fulminant Hepatitis can be presented in a patient as constructional apraxia. It
is a neurological disorder where the patient has inability to perform tasks or movements,
eventhough they understand and willing to do the order. As an example, the patient is unable to
draw a 5-pointed star. Asterixis can also be detected, the condition in which the patient has a
flapping tremor when the wrists are dorso-flextioned with finger spreading.
DIAGNOSIS
To diagnose Fulminant Hepatitis, patients history taking must be done completely,
which includes the complaints of sign and symptoms in the prodromal phase, presented as flu-
like fever, 1-2 weeks before jaundice occur. Symptoms of severe liver failure include confusion,
extreme irritability, altered consciousness (usually leading to unconsciousness or coma), blood-
clotting defects, and build up of fluid in the abdominal cavity, arms, and legs. Fever can be mild
in Fulminant Hepatitis from HAV and HEV, but can be very high from HBV. Patient may also
complaint of dark urine colour and clay-colour stool due to indirect hyperbilirubinemia.
Testing for Prothrombine Time (PT) is important to evaluate the severity of the liver
damage, prolonged PT signify intensive hepatocellulat necrosis. Based on the evidence from the
laboratorial test, serum AST and ALT (formerly known as SGOT and SGPT) will be increased,
followed by the increase in bilirubin level. When jaundice appears, it shows that serum bilirubin
may have been exceeded >41.75 mol/L or >2.5 mg/dL, typically ranging 83-340 mmol/L or 5-
20 mg/dL. In Fulminanat Hepatits, there will be mild increased in the level of serum bilirubin,
AST and ALT with prolonged PT. Neutropenia and lymphopenia occurs in a short period, then
followed by lymphocytosis.




4

MANAGEMENT
No medication can reverse Fulminant Hepatitis. People who have the disease need to be
hospitalized in an intensive care unit (ICU) so they can be cared for until their condition becomes
more stable. For some people, a liver transplant is the only lifesaving option. People younger
than age 40 who have Fulminanat Hepatitis are more likely to recover than older adults or people
who have chronic liver disease. Below are the criteria for Liver Transplantation based on Kings
College Hospital.
Paracetamol Liver Failure Non-Paracetamol Liver Failure
Arterial pH <7.3, 24 H after ingestion PT > 100 s
Or all of the following Or 3 out of 5 of the following
1) PT > 100 s
2) Creatinine > 300 mol/L
3) Grade III or IV encephalopathy

1) Drug-induced liver failure
2) Age <10 or >40 years old
3)1 week from first jaundice of encephalopathy
4) PT > 50 s
5) Bilurubin >300 mol/L
Table 2. Kings College Hospital Criteria for Liver Transplantation
Usually, patient with Fulminant Hepatitis will be admitted in the ICU. Endotracheal
intubation is always recommended to protect the airways. Nasogastric tube is often inserted to
avoid aspiration and to remove blood from stomach due to coagulopathy. Catheter is inserted to
monitor fluid status and to assess urine output hourly. Vital signs and pupils must also be
monitored hourly, while body weight must be checked daily.
For laboratorium investigation, Full Blood Count (FBC), ureum and creatinine, liver
function test and prothrombine test are also important to see the progression of liver damage. To
avoid hypoglycaemia, infuse 10% Dextrose IV, 1L/ 12 hours and monitor the blood level every
1-4 hours. Some patient comes with malnutrition, diet rich in carbohydrates and protein
delivered calories are preferably given oral as good nutrition lower the risk of mortality.


5

If bleeding occurs, gives vitamin K IV (10 mg/ day) for 3 days together with platelets.
Fresh frozen plasma (FFP) is required under certain condition. To treat infection, give
Ceftriaxone 1-2 g/ day IV unless the sensitivities are known. Avoid Gentamicin as it could
increase the risk of renal failure. If blood sugar fall below 2mmol/L or 36 mg/dL, or
symptomatically presented as hypoglycaemia, give 50 mL of 50% glucose IV. To treat
encephalopathy, avoid sedatives but only use lorazepam if seizure occurs. Give lactulose 30-50
mL/ 8 hours PO to lower down the number of nitrogen-forming bowel organism while cerebral
oedema is treated with 20% mannitol IV and hyperventilation.
REFERENCES
1. Longmore M, Wilkinson I.B, Davidson E.H, Foulkes A, Mafi A.R. Liver failure. Oxford
handbook of clinical medicine. 8
th
ed. Oxford university press. China.2012. Page 258 9.
2. McPhee S.J, Hammer G.D. Liver disease. Pathophysiology of disease. An introduction of
medicine. Chapter 14. 6
th
ed. McGraw-Hill companies. China. 2010. Page 391 8.
3. Dienstag J.L. Acute Viral Hepatitis. Harrison principle of internal medicine. Chapter 304
(14); vol 2. 18
th
ed. McGraw-Hill companies. USA. 2012. Page 2537 56
4. Daniel C. Fulminant Hepatitis. Updated June 24, 2008 from http://hepatitis.about.com on
April 23, 2013.