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Viral Hepatitis

Khaled Jadallah, MD Assistant Professor of Medicine Gastroenterology, Hepatology, & Nutrition

Knowing is not enough; we must apply. Willing is not enough; we must do. (Goethe)

Educational Objectives

Outline the epidemiology of viral hepatitis List causative agents for viral hepatitis Recognize the clinical features of acute and chronic viral hepatitis and their complications Interpret serologic tests to accurately diagnose the specific cause of viral hepatitis Identify appropriate candidates for vaccination against HAV and HBV

Why Bother With Viral Hepatitis for a Dentist?


Dentists can get itif not properly protected Dentists can involuntarily transmit it to patients (improper sterilization techniques of tools) Dental patients with chronic hepatitis complicated by coagulopathy can have uncontrollable bleeding

Type of Hepatitis
A
Source of virus feces

E
feces

blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids percutaneous percutaneous percutaneous permucosal permucosal permucosal

Route of transmission

fecal-oral

fecal-oral

Chronic infection
Prevention

no

yes

yes

yes

no

pre/postexposure immunization

pre/postexposure immunization

blood donor pre/postscreening; exposure risk behavior immunization; modification risk behavior modification

ensure safe drinking water

Clinical Manifestations of Acute Hepatitis

Acute HAV mostly symptomatic, especially in adults Acute HEV is most symptomatic and severe in pregnant women Acute HCV is least symptomatic Acute HBV can present with a serum sickness-like picture (fever, arthritis, urticaria, angioedema) Generally, symptoms improve after jaundice appears Symptoms are non specific-the viral syndrome (fever, malaise, anorexia, RUQ pain, diarrhea, pruritis)

Acute Hepatitis-LAB

Markedly elevated levels of AST/ALT (more than 500 U/L) typically occurs in acute hepatocellular injury (viral, drug-induced, ischemic) Modest elevations (less than 300 U/L) may be seen in a variety of conditions
chronic hepatitis infiltrative diseases biliary obstruction

acute alcoholic hepatitis

Bilirubin and AP may or may not be elevated WBC count may show leucopenia

Stigmata of Chronic Liver Disease

Spider Agiomatas Palmar erythema Clubbing of fingers Dupuytren contractures Gynecomasita (male) or breast atrophy (female) Testicular atrophy

Hepatitis A
Clinical Features

Incubation period: Jaundice by age group: Complications: Chronic sequelae:

Average 25 days Range 15-50 days <6 yrs, <10% 6-14 yrs, 40%-50% >14 yrs, 70%-80% Fulminant hepatitis (0.1 %) Prolonged Cholestasis ? Autoimmune hepatitis None

Hepatitis A Infection
Typical Serological Course
Symptoms

Total anti-HAV

Total anti-HAV

Titre

ALT

Fecal HAV

IgM anti-HAV
IgM anti-HAV

Months after exposure

1 2

2 4

Hepatitis A Vaccination Strategies


Epidemiologic Considerations

Many cases occur in community-wide outbreaks No risk factor identified for most cases Highest attack rates in 5-14 year olds Children serve as reservoir of infection Persons at increased risk of infection Travelers Homosexual men Injecting drug users

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

Extrahepatic Manifestations of Hepatitis B

Acute infection
Arthralgias Papular acrodrmatitis (Gianotti-Crosti

syndrome)

Chronic infection
Glomerulonephritis

Arthrlalgias
Polyarteritis nodosa (PAN)

Papular acrodermatitis

PAN

Acute Hepatitis B Virus Infection with Recovery


Typical Serological Course
Symptoms HBeAg anti-HBe

Total anti-HBc

Titre
HBsAg IgM anti-HBc anti-HBs

12 16 20 24 28 32 36

52

100

Weeks after Exposure

Progression to Chronic Hepatitis B Virus Infection


Typical Serologic Course
Acute (6 months) HBeAg HBsAg Total anti-HBc Chronic (Years) anti-HBe HBsAg Total anti-HBc

Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36

52

Years

Weeks after Exposure

Outcome of Hepatitis B Virus Infection by Age at Infection 100


Chronic Infection (%)

100 80

80

Symptomatic Infection (%)

60

Chronic Infection
Chronic Infection (%)

60

40

40

20

20

Symptomatic Infection
0 Birth 1-6 months 7-12 months 1-4 years 0 Older Children and Adults

Age at Infection

Concentration of Hepatitis B Virus in Various Body Fluids


High
blood serum wound exudates

Moderate
semen vaginal fluid saliva

Low/Not Detectable urine feces sweat tears breastmilk

Hepatitis B Virus Modes of Transmission


Sexual promiscous heterosexuals homosexuals are particular at risk and

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 Serological Scenarios


HBsAG + + HBcAb (IgG) + HBsAb Interpretation Acute infection (+ HBc IgM Ab) 3 possibilities: 1. Acute infection 2. Chronic infection (high ALT) 3. Carrier (normal ALT) 2 possibilities: 1. Remote infection 2. Immunized

2 possibilities: 1. Window disease 2. Remote infection


Acute on chronic infection

Prevention

Vaccination - Vaccine can be given to those who are at increased risk of HBV infection such as
health care workers neonates as universal vaccination in many countries. 3 doses are

given (at 0,1,and 6 months)

Hepatitis B Immunoglobulin - efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive Other measures - screening of blood donors, blood and body fluid precautions

Hepatitis C Virus
6 different genotypes
capsid envelope protein c22 protease/helicase 33c c-100 RNA- RNA polymerase dependent

5
core E1 E2 NS2 NS3 NS4 NS5

hypervariable region

Hepatitis C
Clinical Features
Incubation period: Clinical illness (jaundice): Chronic hepatitis: Persistent infection: Average 6-7 wks Range 2-26 wks 20-30% 75-85% 85-100%

Immunity:

No protective antibody response identified

Extrahepatic Manifestations of Hepatitis C


Mixed

cryoglobulinemia

Vasculitis

non-deforming arthritis
membranous glomerulonepgritis Porphyria

cutanea Sjogren-like syndrome

Porphyria cutanea tarda

Hepatitis C Virus Infection


Typical Serologic Course
Symptoms

antiHCV

Titre

ALT

Normal 0 1 1 2 3 2 3 4 5 6 Years Months Time after Exposure 4

Risk Factors Associated with Transmission of HCV


Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment)

Accidental injuries with needles/sharps


Sexual/household exposure to anti-HCV-positive contact

Multiple sex partners


Birth to HCV-infected mother

Laboratory Diagnosis

HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.

HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

Prevention of Hepatitis C
Screening of blood, organ, tissue donors
High-risk behavior modification Blood and body fluid precautions

Hepatitis D (Delta) Virus


antigen HBsAg

RNA

Hepatitis E
Clinical Features

Incubation period:
Case-fatality rate:

Illness severity: Chronic sequelae:

Average 40 days Range 15-60 days Overall, 1%-3% Pregnant women, 15%-25% Increased with age
None identified

Hepatitis E Virus Infection


Typical Serologic Course
Symptoms

ALT

IgG anti-HEV

Titer
Virus in stool

IgM anti-HEV

1 0

1 1

1 2

1 3

Weeks after Exposure

Hepatitis E
Epidemiologic Features

Most outbreaks associated with faecally contaminated drinking water Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico Minimal person-to-person transmission

Viral Hepatitis Serological Diagnosis


Organism HAV HBV Acute
Anti-HAV IgM

Chronic
NA

Recovered/latent Vaccinated
Anti-HAV IgG Anti-HAV

IgG
Anti-HBc HBeAG HBV DNA

IgM

Anti-HBc HBsAg HBeAg

IgG

Anti-HBc Anti-HBs

IgG

Anti-HBs

or

HBeAb HCV
All

tests possibly negative Anti-HCV Ab HCV RNA


Anti-HDV IgM HD Ag

Anti-HCV Ab HCV RNA

Anti-HCV Ab

NA

HDV

Anti-HDV HDV Ag HBsAg

Anti-HDV

NA

Thank You !
andget vaccinated!!