acute viral hepatitis and fulminant hepatic failure

1. DR. KAMRUN NAHAR
CHILD SPECIALIST
DHAKA

2. Hepatitis means inflammation of the liver.
Liver is a vital organ that processes nutrients, filters
the blood, and fights infections.
When the liver is inflamed or damaged, its function
can be affected.

3. Hepatotropic virus
Other organism responsible
for acute hepatitis:
Bacteria:
Leptospira,Treponema pallidum
M.Tuberculosis, Brucella, E. coli
Protozoa:
- Toxoplasma gondi, Amoeba,
Malaria
Helminths:
- Echinococcus granulosus (
hydatid disease)
- Schistosoma mansoni
Drugs:
- valproate, carbamazepine,
Paracetamol, isoniazid,
rifampicin, halothane,
chlorpromazine
Toxins:
Carbon tetracholoride, phosphorus
Auto immune hepatis – rare
Measles, varicella, herpes simplex 1&2, flavi viruses

4. Hematogenous spread
- typically spread through contact with food or water that has been contaminated
by an infected person’s stool. Also by eating undercooked pork, shellfish. (HEV)
Acute viral hepatitisA and E are usually self-limiting diseases. Hepatitis B, C, and D
viruses can cause acute and chronic, or long-lasting, infections.
Chronic hepatitis can lead to cirrhosis, liver failure, and liver cancer .
Early diagnosis and treatment can prevent chances of developing these complications.

5. ACUTEVIRAL
HEPATITIS
Acute viral
hepatitis is a short-
term, viral
infection.
Chronic viral
hepatitis is a
longer-lasting, and
generally life-long,
viral infection
lasting at least six
months.

6. Acute Chronic
Etiological
factor
1. Acute viral hepatitis (e.g. HAV,
HEV)
2. Toxic hepatitis – drugs,
chemicals
3. Acute metabolic hepatitis
4. Ischemic hepatitis
1. Viral hepatitis (HCV, HBV)
2. Alcohol hepatitis
3. Drugs (acetaminophen, α-
methyldopa, etc)
4. Non alcoholic fatty liver disease
5. Auto immune hepatitis
6. Hereditary α1-antitrypsin
deficiency
Acute viral hepatitis : is characterized by inflammation of liver which results damage to
hepatocytes with subsequent cell death (necrosis).
Chronic hepatitis: is defined as continuing hepatic inflammation which may lead
to liver damage like cirrhosis, liver failure, and liver cancer persisting beyond 6 months
period. Early diagnosis and treatment can prevent chances of developing these
complications.

7.  Hepatotrophic viruses, after reaching liver, causes injury to hepatocytes.
- Direct cytopathic injury by A,C,D &E
- Immune mediated injury by B & C
 Extend of injury variable, ranging from mild injury to hepato-cellular
necrosis with loss of parenchymal architecture as occurs in fulminant
hepatic failure.
 With recovery, liver morphology returns to normal within 3 months of
acute infection.
 However, in HBV,HCV, the inflammatory cells settle in periportal areas
and lead to progressive fibrosis and scarring.
 Abnormal bile flow at the canalicular and cellular level because of
hepatocytes damage and inflammatory mediators that lead to
cholestasis

8.  There for main clinicopathological consequences are –
a. Hepatocytopathy –
- characterized by e.g. ALT, AST
b. Cholestasis –
- elevated serum conjugated (direct) bilirubin, alkaline
phosphatase, 5-nucleotidase, γ-glutamyl transpeptidase
c. Synthetic dysfunction – most important marker of liver injury
- low serum albumin with prolonged PT, high INR
d. Metabolic disturbances –
e.g. low blood glucose, high ammonia, lactic acidosis
e. Hepatic encephalopathy –

10.  Asymptomatic
 Anicteric – no jaundice, but may suffer from anorexia, nausea,
vomiting and influenza like symptoms.
 Clinical presentation: occurs in 3 phases-
Phases Features
Prodromal phase
by 1-2 wks
non-specific symptoms like malaise, anorexia,
nausea, vomiting, fever, headache, myalgia,
arthralgia etc.
Icteric phase Yellow sclera, tender hepatomegaly with right
hypochondriac or epigastric pain. Stool often
turn pale and urine becomes high colored.
Recovery phase Constitutional symptoms disappear but mild
hepatomegaly and biochemical abnormalities
persists.

12.  Counseling
 Supportive treatment: Choice of Rx, these includes-
 Rest – restrict outdoor activities
 Diet – normal, high calorie diet. (traditional low fat, high
carbohydrate diet has no benefical effect)
 Vomiting- antiemetics + IV fluid (if required)
 Vitamin K- if PT is high (>15 sec), INR >1.5. [ normal INR <1.2]
 Purgatives: gut sterilizers or lactulose – no benefit in
uncomplicated case
 Specific treatment: no specific Rx for HAV, HEV.
Anti viral available for HCV, HBV
AHMolla

13.  All children with acute viral hepatitis do not require hospitalization. In
majority it is a self limiting disease with complete recovery, full
restoration of liver function and clearance of virus occurs.
 Certain warning signs-symptoms necessitate more monitoring:
1. Persistent fever
2. Persistent anorexia
3. Deepening jaundice
4. Bleeding tendency
5. Altered sensorium
6. GI bleed
7. Fluid retention-pedal oedema/ascites
8. Decreasing liver size
9. Prolonged PT
10. Increasing serum bilirubin, ALT, BUN
MR Khan

19. Virus replicates in GI tract and spread to liver hematogenously.
Hepatocytes are infected but mechanism of cell damage is unclear.
CytotoxicT-cells may damage the hepatocytes infected with virus.
If infection is cleared damage will be repaired and there is no chronic infection

20.  Immune response IgM is detected at the appearance of jaundice, Peaks at 2 -3 weeks,
disappears in 3 -4 months.
 HAV IgMAb to is important in diagnosis of HAV.
 1 -3 weeks after the Ig. M appears IgG is seen. IgG provides life long immunity

22. Spontaneous recovery is the rule in 2 -3 weeks time
Mostly asymptomatic (maybe solely detected
on basis of Ig. G Ab)
HAV Ag - by ELISA, not routinely done

23. HAVVACCINE
Efficacy: 100% after 2nd dose and protection for 10 years
at 6-12 months interval
No antiviral therapy

28.  Hepatitis B e antigen (HBeAg) – present in inner
portion of virus and serve as a marker of active
viral replication

31.  Worldwide, particularly prevalent in the oriental countries- including
India.
 These areas have high incidence of hepatocellular carcinoma-
hepatoma.
 HBV is a tumor associated virus Immunization against HBV in
Taiwan has decreased the incidence of hepatoma.
 HBV vaccine: first vaccine against human cancer

32. Very small amount of blood necessary for transmission. Eg.
Needle stick injury

38.  Immune mediated hepatocyte injury,
 Progressive hepatocyte damage, fibrosis & scarring
 Consequences are – chronic hepatitis, cirrohosis, end stage liver
disease and HCC.
Clinical features:
• Most acute cases are aymptomatic
• Acute manifestations are similar to those caused by other viruses
• Jaundice present in 25% cases
• Rate of Acute liver failure, coagulopathy, encephalopathy is
higher than the other hepatotropic virus
• Severity increases when associated with HDV.
• May have extra- hepatic manifestations like e.g. arthralgia,
urticaria

39. NATURAL HISTORY OF HBV

51. MONOVALENTVACCINE
 HBVaccine given at birth
 Dose:
o Child – 0. 5 ml/dose (10
mcg of purified HBs. Ag)
o Adult - 1 ml/dose (20 mcg
of purified HBs.Ag)
 Route: intramuscular
 Site: >2 yrs: Deltoid
<2 yrs: antero lateral
aspect of thigh

PENTAVALENTVACCINE
 In combination with other
vaccine use in EPI schedule
(DPT, Hib and Hepatitis B)
 Dose: 0. 5 ml/dose
 Route: Intramuscularly on
lateral aspect of thigh
Duration of protection:
Immunologic memory remains intact for
at least 20-30 years

52. Infants Born to Mothers who Have Hepatitis B:
Rx:
1. Hepatitis BVaccine (as schedule below)
2. Hepatitis Immunoglobulin
These medications should be given immediately
after birth in delivery room or within first 12-24
hours of life*.

53. 4-Dose CombinationVaccine Series for Infants (Pentavelent or Hexavalent)
Duration of protection:
Immunologic memory remains intact for
at least 20-30 years

54.  If recovery- life long immunity after natural
infection because humoral Ab against HBs. Ag.
Antibody to HBc. Ag is not protective.

55.  Hepatic complications:
1. Fulminant hepatitis or
2. Cirrhosis or
3. Hepato-cellular carcinoma
 Extra-hepatic complications:
- during prodromal phase, serum sickness like syndrome
(arthritis, rash, angioedema, proteinuria) in 5 -10% patients due to
Immune complex deposition.

61. * For persons who might have been exposed to HCV within past 6 months, testing for HCV RNA or follow-up testing for
HCV antibody is recommended. For persons who are immunocompromised, testing for HCV RNA can be considered.
** To differentiate past, resolved HCV infection from biologic false positivity for HCV antibody, testing with another HCV
antibody assay can be considered. Repeat HCV RNA testing if the person tested is suspected to have had HCV exposure
within the past 6 months or has clinical evidence of HCV disease, or if there is concern regarding the handling or storage of
the test specimen. Source: CDC. Testing for HCV infection: An update of guidance for clinicians and laboratorians. MMWR 2013;62(18).

82. It is a clinical syndrome in children characterized by –
 Biochemical evidence of acute liver injury (usually of <8 wks
duration)
 No evidence of chronic liver failure
 Presence of Hepatic based coagulopathy.
Fulminant hepatic failure (FHF) is usually defined as the severe
impairment of hepatic functions or severe necrosis of hepatocytes in
the absence of preexisting liver disease.
Hepatic based coagulopathy is defined as
- PT >15 sec or INR >1.5 not corrected by vitamin K1 in the
presence of hepatic encephalopathy or
- PT >20 sec or INR >2 regardless of the presence of clinical
hepatic encephalopathy

83. Unlike in adults, encephalopathy may be absent, late,
or apparent in children only at the terminal stages.
Thus, the emphasis in children is placed on presence
of significant coagulopathy in absence of sepsis or DIC
that is not correctable by administration of parenteral
vitamin K within 8 hours.

84. 1. Acute Viral hepatitis (A, B, C, D or E)
- HBV the most common cause of FHF in endemic areas.
2. Idiopathic (50%)
3. Drug induced – 20%
(e.g. acetaminophen (paracetamol), INH, Na-valproate, halothane, IV tetracycline,
methanol, salicylate)
4. Auto immune hepatitis
5. Other viruses
– EBV, CMV, paramyxovirus, VZV, herpes-virus types 1, 2 &6; parvovirus; and adenovirus.
6. Metabolic Disorders: varies with age,
-- In neonates, inborn errors of metabolism (including tyrosinemia, hereditary fructose
intolerance, galactosemia) and neonatal hemochromatosis, are the major causes .
-- In older children & adolescents, Wilson disease is the most common .
7. Circulatory Conditions: uncommon , include congestive heart failure, cardiomyopathy,
sepsis, shock, cyanotic heart disease, obstructive aorta, vascular occlusions, myocarditis,
and severe asphyxia.
8. Others e.g. Hypoxic-ischemic injury to hepatocytes from any cause eg. Hodgkin
Lymphoma , leukemic infiltration

85.  FHF usually begins with exposure of a susceptible person to an agent capable of
producing severe hepatic injury, although the exact etiology remains unidentified
in many cases of FHF.
 May be the effect of accumulation of neurotoxic or neuroactive
substances as a consequence of HCF. Like false neurotransmitters,
ammonia, increased gamma-aminobutyric acid receptor activity, and increased
circulating levels of endogenous benzodiazepine-like substances. Decreased
hepatic clearance of these neurotoxins and increased absorption may contribute
to the encephalopathy.
 Virus may cause damage to hepatocytes either by direct cytotoxic
effect or as a result of hyperimmune response to viral antigens.
 Hepatotoxic metabolites produced by hepatotoxic drugs, may
cause injury to hepatocytes.

86.  GIT bleeding
 Hypokalemia
 Drugs- e.g. sedatives, diuretics
 Uraemia
 High protein diet
 Paracentesis
 Hypovolemia
 Hypoglycemia
 Sepsis
 Constipation

87. Patient may present with-
 Rapid development of –
- Deepening of jaundice
- Bleeding ; commonly haematemesis,
malena, but may have hematuria or ICH.
- Confusion and progressive coma.
 Asymptomatic at the onset, but
later on become suddenly ill (during
2nd wk) and presents with –
- Fever
- Anorexia
- Vomiting
- Jaundice
- Abdominal pain

88.  Physical examination:
• Tender hepatomegaly, which
may have progressive
shrinking, often with worsening
hepatic function.
• Resp rate: tachyponoea;resp.
failure occur only in stage 4.

89.  Hepatic encephalopathy is defined as a spectrum
of neuropsychiatric abnormalities in patients with
liver dysfunction, after exclusion of brain disease.
o Characterized by personality changes, intellectual
impairment, and a depressed level of consciousness.
o When liver doesn’t work properly, toxins build up in blood
then travel to brain and affect brain function.
o Treatments can rid toxins and reverse this temporary
condition.

90.  Based on C/F & relevant investigations -
Investigations Results
S bilirubin, SGPT, SGOT Raised
PT Prolonged (INR >2.0)
Often not improved with Inj vit K
S Alkaline phosphatase Raised
Blood ammonia Raised
Blood glucose, albumin Low
CBC & PBF May show anemia, leukocytosis and
thrombocytopenia
Blood urea, serum creatinine,
BUN
Altered, BUN often low
S. electrolytes Hypokalemia
Hyponatremia
ABG Metabolic acidosis or Respiratory acidosis
S Ca,Mg,Phosphate May be altered

91. Counseling
Supportive – PICU care ---Provide ABC
1. Nutritional support – IV fluid
2. Diet – normal carbohydrate with restricted fat and protein
3. Restrict fluid – give 75% of daily requirement
4. Correction of –
a. Hyovolemia – with normal saline
b. Hypoglycemia - inf 10%DA – 2 ml/kg
c. Dyslelectrolytemia, hypocalcemia, hypophosphataemia, hypomagnesemia – appropiately
[ Supplements – calcium, magnesium, phosphorus (parenteral route) ]
5. Correction of coagulopathy – vit K (for 3 days) + FFP
- whole blood/platelet transfusion – if need
6. Anti-ulcerant: Omeprazole (to prevent GI bleeding)
7. Antibiotics: non-hepatotoxic broad spectrum drugs like Cefotaxime (preferable),ampicillin,
gentamycin
8. Neomycin (oral) / metronidazole – to reduce enteric bacteria
9. Mannitol (IV) – to reduce cerebral oedema &ICP.
10. Identify and treat precipitating factors
11. Avoid any sedative
12. Empty bowel of nitrogen containing material, blood by NG tube suction, lactulose (oral or enema)

92. Specific Rx: –
Orthotropic liver transplantation
Orthotopic liver
transplantation (OLT)
involves the
substitution/removal of a
diseased native liver with a
normal liver (or part of
liver) from donor
(deceased or living); and at
the same anatomic region
as the original liver
The first human liver
transplantation was
performed in US in 1963

93.  Children with FHF who have –
1. Severe coagulopathy,
2. Prolonged duration of illness prior to onset of encephalopathy, and
3. Lower SGPT on admission
- are more likely to require liver transplantation.
Indications for liver transplantation: for adults and children
- Acute or chronic liver disease that cannot be treated medically or with alternative
forms of surgery.
- The most common indications are:
1. Cirrhosis (viral, alcohol-related, cryptogenic),
2. Cholestatic liver disease,
3. Metabolic liver disease,
4. Acute liver failure,
5. Liver tumors, and other forms of liver disease.

94.  ALF in children is a potentially
devastating disease.
 Mortality rate 80-90% .
 Prognostic criteria: include
1. Patient’s age,
2. Etiology of liver disease,
3. Degree and onset of encephalopathy,
4. S. bilirubin, PT or INR, s. creatinine,
factorV level, and arterial pH level.
Poor prognostic facts:
a. Presence of jaundice for at least 1 week before
onset of encephalopathy.
b. Illness lasting >8 weeks before onset of
encephalopathy have a higher chance of
developing portal hypertensive manifestations
such as renal failure.
c. Illness lasting <4 weeks before disease chance
of Increased incidence of cerebral edema.
d. Hemorrhagic diathesis and systemic collapse
indicate a poor prognosis.
e. Maximum INR reached during the course of
illness is a sensitive predictor of outcome. With
INR of ≥4, mortality rate 86%; with INR of <4, it
is as low as 27%.