ACUTE VIRAL HEPATITIS
DEFINITION:
ACUTE INFLAMATION OF THE LIVER
CAUSED BY PRIMARLY
HEPATOTROPIC VIRUSES (A,B,C,D,E)
(WHO)
VIRAL HEPATITIS
HISTORICAL PERSPECTIVE
Enterically
“Infectious” A E transmitted
Viral “NANB”
hepatitis C
Parenterally
“Serum” B D transmitted
other
Viral Hepatitis Overview
Types of Viral Hepatitis
A B C D E
Source of feces blood/ blood/ blood/ feces
virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids
Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral
transmission permucosal permucosal permucosal
Chronic no yes yes yes No/yes
infection
Prevention pre- pre/post- blood donor pre/post- ensure safe
exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; Water
modification risk behavior immunization
modification
HEPATITIS A VIRUS
RNA Picornavirus
Single serotype worldwide
Acute disease and asymptomatic
infection
No chronic infection
Protective antibodies develop in
response to infection - confers lifelong
immunity
HEPATITIS A VIRUS TRANSMISSION
• Close personal contact
(e.g., household contact, sex
contact, child day-care centers)
• Contaminated food, water
(e.g., infected food handlers)
• Blood exposure (rare)
(e.g., injection drug use, rarely by
transfusion)
HEPATITIS A - CLINICAL
FEATURES
•Jaundice by <6 yrs <10%
age group: 6-14 yrs 40%-50%
>14 yrs 70%-80%
•Rare complications: Fulminant hepatitis(<0.1%)
Cholestatic hepatitis
Relapsing hepatitis
•Incubation period: Average 30 days
Range 15-50 days
•Chronic sequelae: None
EVENTS IN HEPATITIS A VIRUS INFECTION
Clinical illness
Infection ALT
IgM IgG
Response
Viremia
HAV in stool
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Week
HEPATITIS A VACCINES
Recommended Dosages of Hepatitis A Vaccines
Age Volume 2-Dose
Schedule
Vaccine (yrs) Dose (mL) (mos)
HAVRIX ® # 1-18 720 (EL.U.*) 0.5 0, 6-12
>18 1,440 1.0 0, 6-12
VAQTA ® ## 1-18 25 (U**) 0.5 0, 6-18
>18 50 1.0 0, 6-18
* EL.U. – Enzyme-linked immunosorbent assay (ELISA) units
** Units
# has 2-phenoxyethanol as a preservative
## has no preservative
Hepatitis B Virus
Concentration of HBV
in Various Body Fluids
Low/Not
High Moderate Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk
HBV Modes of Transmission
• Sexual
• Parenteral
• Perinatal
Hepatitis B – Clinical Features
Incubation period : Average 60-90 days
(range from 45-180 days)
Clinical illness: <5 yrs, <10%
(jaundice):>5 yrs, 30%-50%
Acute case-fatality rate: 0.5%-1%
Chronic infection: <5 yrs, 30%-90%
>5 yrs, 2%-10%
Premature mortality from
chronic liver disease: 15%-25%
Outcome of HBV Infection
Infection
Symptomatic
Asymptomatic
acute hepatitis B
Resolved Resolved Chronic
Chronic infection
Immune Immune infection
Cirrhosis Cirrhosis
Asymptomatic Asymptomatic
Liver cancer Liver cancer
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBsAg anti-HBs
0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36 52
Weeks after Exposure
Hepatitis B Vaccine
• Licensed in 1982; currently recombinant (in US)
• 3 dose series, typical schedule 0, 1-2, 4-6 months -
no maximum time between doses (no need to
repeat missed doses or restart)
• 2 dose series (adult dose) licensed by FDA for 11-
15 year olds (Merck)
• Protection ~30-50% dose 1; 75% - 2; 96% - 3;
lower in older, immunosuppressive illnesses (e.g.,
HIV, chronic liver diseases, diabetes), obese,
smokers
Hepatitis D (Delta) Virus
d antigen HBsAg
RNA
Hepatitis D - Clinical Features
• Coinfection
– severe acute disease
– low risk of chronic infection
• Superinfection
– usually develop chronic HDV infection
– high risk of severe chronic liver disease
Hepatitis D Virus
Modes of Transmission
• Percutanous exposures
–injecting drug use
• Permucosal exposures
–sex contact
HBV - HDV Coinfection
Typical Serologic Course
Symptoms
ALT Elevated
anti-HBs
Titer
IgM anti-HDV
HDV RNA
HBsAg
Total anti-HDV
Time after Exposure
HBV - HDV Superinfection
Typical Serologic Course
Jaundice
Symptoms
Total anti-HDV
ALT
Titer
HDV RNA
HBsAg
IgM anti-HDV
Time after Exposure
Hepatitis D - Prevention
• HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection
• HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection
Hepatitis C
Features of Hepatitis C Virus
Infection
• Incubation period: Average 6-7 weeks
• Range 2-26 weeks
• Acute illness (jaundice):Mild (<20%)
• Case fatality rate: Low
• Chronic infection: 60%-85%
• Chronic hepatitis: 10%-70%
• Cirrhosis:<5%-20%
• Mortality from CLD:1%-5%
Sources of Infection for
Persons With Hepatitis C
Injecting drug use 60% Sexual 15%
Transfusion 10%
(before screening)
Occupational 4%
Other 1%*
Unknown 10%
* Nosocomial; iatrogenic; perinatal
Serologic Pattern of Acute HCV Infection
with Recovery
anti-HCV
Symptoms +/-
HCV RNA
Titer
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure
Serologic Pattern of Acute HCV Infection with
Progression to Chronic Infection
anti-HCV
Symptoms +/-
HCV RNA
Titer
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure
Hepatitis E Virus
Hepatitis E - Clinical Features
• Incubation period: Average 40 days
Range 15-60 days
• Case-fatality rate: Overall, 1%-3%
Pregnant women, 15%-25%
• Illness severity: Increased with age
• Chronic sequelae: Identified in
immunocompromised person
Hepatitis E -
Epidemiologic Features
• Most outbreaks associated with
fecally contaminated drinking water
• Minimal person-to-person transmission
• Cases usually have history of travel
to HEV-endemic areas
Hepatitis E Virus Infection
Typical Serologic Course
Symptoms
ALT
IgG anti-HEV
IgM anti-HEV
Titer
Virus in stool
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Weeks after Exposure
Hepatitis E
Genotype 1 Genotype 2 Genoyipe 3 Genotype 4
W Europe, SAD
Location Africa Asia Mexico, W Africa China, Taiwan, Japan
China
Transmision Fecal-oral By woter fecal-oral Food Food
Adult (>40 yer) and
Risk group Young person Young person Young person
Immunocompromised
Zoonosis transmision No No Yes Yes
Chronic infection No No Yes No
Epidemic outbreaks Often rare rare rare
Geographic Distribution of Hepatitis E
Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC Hepatitis
Prevention and Control Measures for
Travelers to HEV-Endemic Regions
• Avoid drinking water (and beverages with ice) of
unknown purity, uncooked shellfish, and uncooked
fruit/vegetables not peeled or prepared by traveler
• Vaccine (China)
INFECTIOUS DISEASES VIII semester 2017 / 2018 19th Feb to 1th
June
Lecture 90 min....... 11.00 – 12.30, Practical 90 min...........12.30 – 14.00
Week 19-22 ( SEMINARS).........12.30 -13.00........Practical ..........13.00 – 14.15
WEEK DATE THEME TEACHER
19 14 MAR. Meaning of laboratory tests for diagnosis of sepsis and DOC DR BOJOVIĆ
SIRS (SE, fibrinogen, CRP, feritin, prokalcitonin, Fe,
D-dimer, etc)
Referents:Marko Tapuri, Toma Peic , FloraTerpsihori
20 21 MAR. Liver and hepatitis (when do we suspect, and what is PROF DR SIMONOVĆ
diagnostic approach)
Referents:Jovana Zivanovic38, Luka Novakovic, Lara
Letunica
21 28 MAR. Zoonoses (significance for settlers and travelers) PROF DR KORAĆ
Referents:Terzic Milan, Stefan Djurdjevic Zaim
22 4 APR. Intracranial infections (clinical picture, diagnosis, DOC DR POLUGA
differential diagnosis)
Referents:
Mijailovic Julija, Helena Stok Djordjevic Natalija
