Chronic Hepatitis 3.10.14.1.pptx

Dr. Ghulam Mustafa
MBBS; MCPS;FCPS (peds)
Associate Professor
Fellow Pediatric Pulmonology & Intensive Care (Sg)

A Long History of Human Misery
400 B.C.
“epidemic
jaundice”
1947
infectious
hepatitis
“Hepatitis A”
Serum
hepatitis
“Hepatitis B”
1973
Hepatitis A
identified by
electron
microscopy
1989
He
patitis C
cloned
1990
Hepatitis E
cloned
Hippocrates

Clinical Terms
• inflammation of liver; presence of
inflammatory cells in organ tissue
Hepatitis:
• symptoms last less than 6 months
Acute Viral
Hepatitis:
• Massive hepatic necrosis with impaired
consciousness within 8 wks of onset of
illness.
Acute Hepatic
Failure:
• severe impairment of hepatic functions or
severe necrosis of hepatocytes in the
absence of preexisting liver disease
Fulminant
Hepatitis:
• Inflammation of liver for at least 6 months
Chronic
Hepatitis:

Hepatitis B Perinatal Transmission*
 If mother positive for HBsAg and HBeAg
 70%-90% of infants infected
 90% of infected infants become chronic
carriers
 If positive for HBsAg only
 20% of infants infected
 90% of infected infants become chronic
carriers
*in the absence of postexposure prophylaxis

Acute hepatitis B
Acute Hepatitis B
Virus
clear
6 Months
Virus first enters the
body
Healthy
90%

Acute hepatitis B
Acute Hepatitis B
Virus
clear
6 Months
Virus first enters the
body Healthy
90%
Protected from hep B for
life
“Immune”

6 Months
Acute hepatitis B
Chronic Hepatitis B= Carrier
Virus
not
clear
Time of
Infection
Healthy
90%

Risk of Developing Chronic
Hepatitis B by Age at Infection
Healthy
90%
Carrier
90%
Healthy
50%
Carrier
50%
Adults
Infants
children

Can my baby die from hepatitis B?
• Most babies do not die from hepatitis B.
carriers
If babies get all 3 shots, +
a shot called H-BIG,
they have a 95% chance of being safe from hepatitis B for life.
• 9/of 10 babies born to
infected mothers will end
up being hepatitis B
carriers for the rest of
their lives,

Pathogenesis of Hepatocellular
Carcinoma
Primary
Hepatocellular
Carcinoma

HBsAg Prevalence
8% - High
<2% - Low
Geographic Distribution of Chronic Hepatitis B
Source: CDC and Prevention
Endemic
Non Endemic

Transfusion and
transplant recipients
Individuals with
multiple
sexual partners
Healthcare
workers
Hepatitis B: who is at risk?

Relative Transmission Efficiency of
Bloodborne Viral Infections
+++ ++++ ++
+++ + ++
++++ + ++
+++ +/– +/–
HBV HCV HIV
Injection-drug use
Sexual
Perinatal
Occupational
Hepatitis B is 100 times
More infectious than Aids

Hepatitis B:
A world-wide public health problem
• More than 2 billion exposed people
• Currently 350 million HBV carriers
• Over 1 million infected die each year
• Three quarters of the world’s 5.2 billion people
live in endemic regions
• Established cause of chronic hepatitis and
cirrhosis
• Human carcinogen - cause of up to 80% of
hepatocellular carcinomas

• High (8%): 45% of global population
– lifetime risk of infection >60%
– early childhood infections common
• Intermediate (2%-7%): 43% of global population
– lifetime risk of infection 20%-60%
– infections occur in all age groups
• Low (<2%): 12% of global population
– lifetime risk of infection <20%
– most infections occur in adult risk groups
Global Patterns of Chronic HBV Infection

Hepatitis B Epidemiology
• Reservoir Human. Endemic
• Transmission Bloodborne
Sub clinical cases transmit
• Communicability 1-2 months before
and after onset of
symptoms
Chronic carriers

• Incubation period Average 60-90 days
Range 45-180 days
• Clinical Illness (jaundice) <5 yrs, <10%
>5 yrs, 30%-50%
• Acute case-fatality rate 0.5%-1%
• Chronic Infection <5 yrs, 30%-90%
>5yrs, 2%-10%
• Premature mortality 15%-25%
from chronic liver disease
Hepatitis B—Clinical Features

 Fulminant hepatitis
 Hospitalization
 Cirrhosis
 Hepatocellular carcinoma
 Death
Hepatitis B Complications

Risk of Developing Chronic
Hepatitis B by Age at Infection
0
20
40
60
80
100
Infant 1-5 years >5 years
%

Possible Outcomes of
Hepatitis B Infection
Possible Outcomes of
Hepatitis B Infection
Recovery
Chronic
HBV
infection
Fulminant
hepatitis
HBsAg
carrier
Reactivation
Cirrhosis
HCC
Chronic hepatitis B
HBeAg positive
Chronic hepatitis B
HBeAg positive
HDV
superinfection
Chronic hepatitis B
HBeAg positive
Acute
HBV
infection

Estimated Number of Persons with Chronic
Bloodborne Virus Infections 1998
Region Population (millions)
(millions) HIV HCV HBV
Africa 749 22.7 22.5 59.3
Asia 3,585 7.3 107.5 286.8
Latin America 504 1.7 15.1 10.3
Europe 729 0.8 21.8 10.9
Oceania 30 0.0 0.9 2.4
North America 305 0.9 9.1 1.9
Total 5,902 33.4 176.9 371.6
Chronic infections

Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBs
HBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titer

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
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Weeks after Exposure

Age at Acquisition of Acute
and Chronic HBV Infection
United States, 1989 Estimates
Adults 83% Adults 59%
(4%) Perinatal (24%)
(4%) Children (12%)
(1 –10 years)
(8%) Adolescents (6%)
Acute HBV Infections Chronic HBV Infections

Source: CDC Viral Hepatitis Surveillance Program
Age Group (Years)
Rate of Reported Hepatitis B by Age Group
United States, 1990

Pediatric Deaths Due to
Vaccine Preventable Diseases (VPD)
(aged < 12 years)
Varicella 1
Pneumococcal Disease 3
H. Influenza Disease 6
Measles l0
Hepatitis B 25**
* Pre-vaccine era
** Most HBV deaths are deferred until 15-30 years from time of perinatal/childhood exposure
Estimated Annual VPD Deaths in Wisconsin*

Concentration of Hepatitis B Virus
in Various Body Fluids
High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk

Blood transfusion
0%
Other* 15%
Unknown 32%
Hemodialysis 0%
Multiple sex partners
17%
Injection drug use
14%
Men who have
sex with men 6%
Sexual contact with
hepatitis B patient
13%
Medical
Employee 1%
Household contact of
hepatitis B patient
2%
Risk Factors Associated with
Reported Hepatitis B, 1990-2000, United
States
Source: NNDSS/VHSP
*Other: Surgery, dental surgery, acupuncture, tattoo, other percutaneous injury

Relative Transmission Efficiency of
Bloodborne Viral Infections
+++ ++++ ++
+++ + ++
++++ + ++
+++ +/– +/–
HBV HCV HIV
Injection-drug use
Sexual
Perinatal
Occupational

Interpretation of Diagnostic Tests
for Hepatitis B
Acute Past Exposures Previous
Test Hepatitis B (Immunity) Immunization
HBsAg + – –
anti-HBs – + +
HBeAg + – –
anti-HBe – +/ – –
anti-HBc + + –
IgM anti-HBc + – –
HBV DNA* + – –
ALT Elevated Normal Normal
*By conventional assay. A lower level of viremia may be detected by other more sensitive tests such as
PCR.Shetty K et al Practical Gastroenterology 1998;22:39-47.

Chronic Chronic Healthy
Test Hepatitis B Precore Carrier
HBsAg + + +
anti-HBs – – –
HBeAg + – –
anti-HBe – + +
anti-HBc + + +
IgM anti-HBc – – –
HBV DNA* +/ – +/ – –
ALT Elevated Elevated Normal
Interpretation of Diagnostic Tests
for Hepatitis B (cont.)
*By conventional assay. A lower level of viremia may be detected by other more sensitive tests such as PCR.
Shetty K et al Practical Gastroenterology 1998;22:39-47.

Chronic Hepatitis 3.10.14.1.pptx

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