2. DEFINITION
Chronic hepatitis means ongoing
inflammation of the liver persisting for more
than six months that is detectable by
biochemical and histologic means.
4. 3.Drug-induced hepatitis
4.Metabolic disorders associated with chronic
liver disease
Wilson disease
Nonalcoholic steatohepatitis
α1-Antitrypsin deficiency
Tyrosinemia
Niemann-Pick disease type 2
Glycogen storage disease type iv
Cystic fibrosis
Galactosemia
Bile acid biosynthetic abnormalities
5.
6. Clinical presentation
Can present with acute decompensation
Asymptomatic
Signs of chronic liver disease/failure
7.
8. Hepatitis B
Chronic hepatitis : HBsAg positivity for >6 mo
Risk : >90% infected <1yr , 30% children &
2% of adults infected will become chronic
carriers.
Three phases of this chronic infection include
1. Immunotolerant phase - active viral
replication and minimal liver damage.HBsAg &
HBeAg are positive and anti Hbe is negative.
HBV DNA load is high. ALT normal
9. 2. Immuno active phase- host tries to resolve
infection HBsAg & HBeAg are positive and anti
Hbe is negative.
HBV DNA load is low. ALT high & with flares
3. Inactive carrier phase- HBsAg & anti Hbe are
positive and HBeAg is negative.
HBV DNA load is very low. ALT normal.
Sometimes may lead to resolution with HBsAg
being negative and Anti HBs positive.
10. Symptomatic Infection
Chronic Infection
Age at Infection
Chronic Infection (%)
SymptomaticInfection(%)
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
0
20
40
60
80
100100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
ChronicInfection(%)
11. Sexual - sex workers and homosexuals are
particular at risk.
Parenteral - IVDA, Health Workers are at
increased risk.
Perinatal - Mothers who are HBeAg positive
are much more likely to transmit to their
offspring than those who are not. Perinatal
transmission is the main means of
transmission in high prevalence populations.
Hepatitis B Virus
Modes of Transmission
Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936–962.
12. Diagnostic Interpretations of Hepatitis B
markers
HBsAg Non infectious component
of viral coat
Indicator of disease. If > 6
months: chronic HBV
Anti-HBs Antibody response to HBsAg Indicates recovery and/or
immunity
HBeAg Antigen that correlates with
replication and infectivity
High level of infectivity and
replication
Anti-HBe Antibody response to HBeAg Decreasing level of
replication
Remission/resolution
Anti-HBc IgM Non protective antibody to
the HBcAg
Recent HBV infection
Anti-HBc IgG As above Remote exposure to HBV
HBV DNA Replictative genetic
material of HBV; infectious
agent
Viral replication and
continues infection
13. Diagnostic Interpretations of Hepatitis B
markers
HBsAg Non infectious component
of viral coat
Indicator of disease. If > 6
months: chronic HBV
Anti-HBs Antibody response to HBsAg Indicates recovery and/or
immunity
HBeAg Antigen that correlates with
replication and infectivity
High level of infectivity and
replication
Anti-HBe Antibody response to HBeAg Decreasing level of
replication
Remission/resolution
Anti-HBc IgM Non protective antibody to
the HBcAg
Recent HBV infection
Anti-HBc IgG As above Acute or remote exposure
to HBV
HBV DNA Replictative genetic
material of HBV; infectious
agent
Viral replication and
continues infection
14. Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with
Recovery Typical SerologicCourse
Weeks after Exposure
Titre
15. IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after
Titre
Progression to Chronic Hepatitis B Virus
Infection Typical Serologic Course
17. 17
Possible Outcomes of HBV Infection
Acute hepatitis B infection
Chronic HBV infection
3-5% of adult-
acquired infections
95% of infant-
acquired infections
Cirrhosis
Chronic hepatitis
12-25% in 5 years
Liver failureHepatocellular
carcinoma
Liver transplant
6-15% in 5 years 20-23% in 5 years
DeathDeath
18. Treatment
Only useful for immunoactive phase as it will
reduce risk of hepatic cancer and cirrhosis
Treatment for children is only by :
Interferon(IF alpha 2b,peg IF) AND lamivudine
after thorough investigations and classification
of stage of disease.
Adefovir ,entecavir and tenofovir are used in
older children(>12 years)
19. Chronic hepatitis C
Prevalence low in children
Risk of perinatal transmission:5%
Increases to 20% if mother coinfected with HIV
Poses 85 % risk of developing chronicity but
no good evidence in children
20. Mostly asymptomatic with fluctuating /normal
transaminases levels
Slow progression to fibrosis/cirrhosis/CLD
Associated with extrahepatic manifestations
21. Natural History of Hepatitis C
Exposure
No infection
Acute
Chronic
Spontaneous
clearance
(early)
•Cirrhosis
(20-40%)
•HCC
(1-4%/year)
<75%
>20%
22. Diagnosis: HCV RNA and genotype , liver
biopsy
Treatment:
PEG INTERFERON ALPHA 2b and
RIBAVIRIN
(in > 3yrs of age) for 2 year duration
23. Autoimmune liver disease
Autoimmune liver disease is a clinical
constellation that suggests an immune-
mediated process characterized by :
hypergammaglobulinemia,
circulating autoimmune antibodies,
necro inflammatory histology &
responsive to immunosuppressive therapy .
They include autoimmune hepatitis,
autoimmune sclerosing cholangitis & de
novo hepatitis.
24. Pathophysiology
Triggering factors : molecular mimicry,
infections, drugs, environment (toxins) in a
genetically susceptible host
Inflammatory cells invades the surrounding
parenchyma.
HLA DR3, DR4, and DR7 isoforms confer
susceptibility to autoimmune hepatitis
25.
26. Clinical manifestations
Acute viral hepatitis like picture(40%) can
progress to ALF esp in Type 2
Insidious onset of liver disease with fatigue,
relapsing or prolonged jaundice.
Chronic liver disease and its complications
Extrahepatic manifestations: arthritis,
vasculitis, nephritis, throiditis, anemia, rash
27. Management
Diagnosis is done by:
elevated transaminases, positive auto
antibodies , raised gammaglobulins and IgG
levels, liver biopsy, absence of known etiology
and response to immunosuppressive drugs.
Steroids, Azathioprine are first line drugs
Cyclosporine and mycophenolate mofetil are
second line drugs
Liver transplantation as and when required.
28. Drug induced liver disease
Drugs commonly used in children that can
cause chronic liver injury include isoniazid,
methyldopa, pemoline, nitrofurantoin,
dantrolene, minocycline, pemoline, and the
sulfonamides.
Anti tubercular and anticonvulsant drugs are
major causes
Can be chemical hepatotoxicity/idiosyncratic
heapatotoxicity
29. They can mimic any form of liver
disease(acute &chronic hepatitis, ALF, portal
hypertension)
Good history taking and high index of
suspicion is required
Treatment is by withdrawal of drug and
supportive care
30. Metabolic causes
Can account for 15-20% of liver diseases in
India
Most common is Wilsons disease.
Most symptoms are due o hepatocyte injury or
secondary to hypoglycemia or
hyperammonemia
Treatment is cause specific.
31. Wilsons disease
a/k/a hepatolenticular degeneration
Toxic accumulation of copper in
liver,brain,cornea and other tissues
Due to abnormal gene, ATP 7B in
chromosome 13
32. Clinical features
Various forms of hepatic disease:
Asymptomatic hepatomegaly
subacute/chronic hepatitis
Acute hepatic failure with/without hemolytic
anemia
Others: neuropsychiatric disease, KF
Ring,sunflower cataract , coombs negative
hemolytic anemia, arthritis, pancreatitis,
nephrolithiasis, cardiomyopathy
,endocrinopathies
35. Nonalcoholic steatohepatitis
Usually associated with obesity and insulin
resistance
Most children are asymptomatic
May have vague abdominal pain.
o/e: hepatomegaly , features of insulin
resistance like striae, acanthosis nigricans
obesity and hepatomegaly.
It can progress to cirrhosis.
36. Diagnosis is usually clinicopathological
correlation . Other causes to be excluded
Treatment is by weight reduction and dietary
modifications.
Ursodeoxycholic acid and vitamin E have
promising results