Viral HepatitisViral 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 ObjectivesEducational ObjectivesOutline the epidemiology of viral hepatitisList causative agents for viral hepatitisRecognize 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 Why Bother With Viral Hepatitis for a Dentist?Hepatitis for a Dentist?

Dentists can get it…if 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

Source ofvirus

feces blood/blood-derived

body fluids

blood/blood-derived

body fluids

blood/blood-derived

body fluids

feces

Route oftransmission

fecal-oral percutaneouspermucosal

percutaneouspermucosal

percutaneouspermucosal

fecal-oral

Chronicinfection

no yes yes yes no

Prevention pre/post-exposure

immunization

pre/post-exposure

immunization

blood donorscreening;

risk behaviormodification

pre/post-exposure

immunization;risk behaviormodification

ensure safedrinking

water

Type of HepatitisA B C D E

Clinical Manifestations of Acute Clinical Manifestations of Acute HepatitisHepatitis

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-LABAcute 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 Stigmata of Chronic Liver DiseaseDisease

Spider AgiomatasPalmar erythemaClubbing of fingersDupuytren contracturesGynecomasita (male) or breast atrophy

(female)Testicular atrophy

Incubation period: Average 25 daysRange 15-50 days

Jaundice by <6 yrs, <10%age group: 6-14 yrs, 40%-50%

>14 yrs, 70%-80% Complications: Fulminant hepatitis (0.1 %)

Prolonged Cholestasis? Autoimmune hepatitis

Chronic sequelae: None

Hepatitis A

Clinical Features

FecalHAV

Symptoms

0 1 2 3 4 5 6 12

24

Hepatitis A Infection

Total anti-HAV

Titre ALT

IgM anti-HAV

Months after exposure

Typical Serological Course

Total anti-HAV

IgM anti-HAV

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 A

Vaccination StrategiesEpidemiologic Considerations

Incubation period: Average 60-90 daysRange 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%

5 yrs: 2%-10% Premature mortality from

chronic liver disease: 15%-25%

Hepatitis B

Clinical Features

Extrahepatic Manifestations of Extrahepatic Manifestations of Hepatitis BHepatitis B

Acute infection– Arthralgias– Papular acrodrmatitis (Gianotti-Crosti

syndrome)

Chronic infection– Glomerulonephritis– Arthrlalgias– Polyarteritis nodosa (PAN)

Papular acrodermatitis

PAN

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 RecoveryTypical Serological Course

Weeks after Exposure

Titre

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 Exposure

Titre

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

Total anti-HBc

IgM anti-HBc

HBsAg

Symptomatic Infection

Chronic Infection

Age at Infection

Chronic Infection (%)

Sym

pto

matic In

fection

(%)

Birth 1-6 months 7-12 months 1-4 years Older Childrenand Adults

0

20

40

60

80

100100

80

60

40

20

0

Outcome of Hepatitis B Virus Infection

by Age at Infection

Ch

ron

ic In

fect

ion

(%

)

High ModerateLow/Not

Detectable

blood semen urineserum vaginal fluid feces

wound exudates saliva sweat

tearsbreastmilk

Concentration of Hepatitis B Virus in Various Body Fluids

Sexual – promiscous heterosexuals 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

Hepatitis B Serological ScenariosHepatitis 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

PreventionPrevention

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

hypervariableregion

capsid envelope

protein

protease/helicase

RNA-dependent

RNA polymerase

c22

5’

core E1 E2 NS2 NS3

33c

NS4

c-100

NS5

3’

Hepatitis C Virus

6 different genotypes

Incubation period: Average 6-7 wks

Range 2-26 wks

Clinical illness (jaundice): 20-30%

Chronic hepatitis: 75-85%

Persistent infection: 85-100%

Immunity: No protective antibody

response identified

Hepatitis C Clinical Features

Extrahepatic Manifestations of Extrahepatic Manifestations of Hepatitis CHepatitis C

Mixed cryoglobulinemia– Vasculitis– non-deforming arthritis– membranous glomerulonepgritis

Porphyria cutanea Sjogren-like syndrome

Porphyria cutanea tarda

Symptoms

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4

Hepatitis C Virus InfectionTypical Serologic Course

Titre

Months Years

Time after Exposure

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

Risk Factors Associated with Transmission of HCV

Laboratory DiagnosisLaboratory 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.

Screening of blood, organ, tissue donors

High-risk behavior modification

Blood and body fluid precautions

Prevention of Hepatitis C

HBsAg

RNA

antigen

Hepatitis D (Delta) Virus

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: None identified

Hepatitis E

Clinical Features

Symptoms

ALT IgG anti-HEV

IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 10

11

12

13

Hepatitis E Virus InfectionTypical Serologic

Course

Titer

Weeks after Exposure

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

Hepatitis E

Epidemiologic Features

Viral Hepatitis Serological DiagnosisViral Hepatitis Serological DiagnosisOrganism Acute Chronic Recovered/latent Vaccinated

HAV •Anti-HAV IgM •NA •Anti-HAV IgG •Anti-HAV IgG

HBV •Anti-HBc IgM•HBeAG•HBV DNA

•Anti-HBc IgG•HBsAg•HBeAg or HBeAb

•Anti-HBc IgG•Anti-HBs

•Anti-HBs

HCV •All tests possibly negative•Anti-HCV Ab•HCV RNA

•Anti-HCV Ab•HCV RNA

•Anti-HCV Ab •NA

HDV •Anti-HDV IgM•HD Ag

•Anti-HDV•HDV Ag•HBsAg

•Anti-HDV •NA

Thank You !and……get vaccinated!!