Presented By Eman El-KhateebClinical pharmacy instructorFaculty of PharmacyTanta University

What Is HepatitisWhat Is Hepatitis??

Dr.T.V.Rao MD 2

Hepatitis means inflammation of the liver Hepat (liver) + itis (inflammation)= Hepatitis

Viral hepatitis means there is a specific virus that is causing your liver to inflame (swell or become larger than normal)

HepatitisHepatitisInflammation of the liverInflammation of the liver

Dr.T.V.Rao MD 3

Can have many causes drugs toxins alcohol viral infections (A, B, C, D, E) other infections (parasites, bacteria)

physical damage

Viral HepatitisViral Hepatitis

Dr.T.V.Rao MD 4

55 typestypes::A: fecal-oral transmission

B: sexual fluids & blood to blood

C: blood to bloodD: travels with BE: fecal–oral transmission

VaccinePreventable

Adapted from Corneil, 2003

AA“ Infectious”

“ Serum”

Viral hepatitis

Entericallytransmitted

ParenteralytransmittedF, G, TTV

? other

EE

OthersOthers

BB DD CC

Viral Hepatitis - Historical Perspectives

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

Hepatitis A

Hepatitis A is an acute liver disease caused by the hepatitis A virus (HAV), lasting from a few weeks to several months. It does not lead to chronic infection.

Picornavirus (RNA)

Humans are only natural host

Stable at low pH Inactivated by

high temperature, formalin, chlorine

Hepatitis A Virus

Dr.T.V.Rao MD 9

Close personal contact

(e.g., household contact, child day care centers)

Contaminated food, water(e.g., infected food handlers, raw shellfish)

Blood exposure (rare)(e.g., injecting drug use, transfusion)Not transmitted by Transplacental route

Hepatitis A Virus Transmission

Clinical Manifestations

Incubation period 2 – 6 weeks May be asymptomatic Overt illness in 5% Present as two stages, 1 Preicteric 2 Icteric

Clinical features

Malaise, arthralgia Anorexia Nausea, omitting liver tenderness Onset of Jaundice Recovery in 4-6 weeks Mortality 0.1 – 1 %

Complications: Fulminant hepatitis (Cs)

Cholestatic hepatitis (Cs)

Relapsing hepatitis

Chronic sequelae: None

Hepatitis A - Clinical Complications

Laboratory Diagnosis

Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA.

Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.

Cell culture – difficult and take up to 4 weeks, not routinely performed

Direct Detection – EM, RT-PCR of faeces. Can detect illness earlier than serology but rarely performed.

FecalHAV

Symptoms

0 1 2 3 4 5 6 12 24

Hepatitis A Infection

Total anti-HAV

Titer ALT

IgM anti-HAV

Months after exposure

Typical Serological Course

Treatment No specific antiviral drug is available Treatment is symptomatic (Diet,

rest, fluid balance, avoiding hepatotoxic drugs)

Lab tests Fluminant Hepatitis Protection (hygiene, hand

washing, water purity and avoiding uncooked food)

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

Post-exposure prophylaxis Specific passive prophylaxis by

pooled normal human immunoglobulin given directly before exposure or in early incubation period can prevent or attenuate clinical illness.

Vaccination for HAV Hepatitis A vaccination is

recommended for all children starting at age 2 year, travellers to certain countries, and others at risk.

A safe and effective formalin inactivated HAV vaccine.

A full course containing two intramuscular injections of the vaccine (6-12 M in between)

Protection starts after 4 weeks after injection and lasts for 5-8years

Hepatitis A Vaccines

Dr.T.V.Rao MD 20

Inactivated whole virus HAVRIX (GlaxoSmithKline) VAQTA (Merck Vaccine Division) Pediatric and adult formulations Licensed for persons >2 years

Epidemiology

A major communicable disease in the Devloping world. (Infectious)

Well cooked food and sanitary water supply will protect the individual living

Community hygiene is important in schools, hostels and jails, as overcrowding and poor sanitation favour the spread

Dr.T.V.Rao MD 22

Most Important Infectious Disease

There are more than 350 million carriers

25% of them will develop chronic active hepatitis.

World wide 1 million deaths a years are attributed to HBV related liver disease and Hepatocellular Carcinoma

Hepatitis B

Hepatitis B is a liver disease caused by the hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead to liver disease or liver cancer.

HBV – Surface antigens

Enveloped proteins on surface of virions and surplus 22 nm diameter spherical and filamentous particles constitute the B surface antigens

HBs Ag consists two major polypeptides and is glycolated

Structure of hepatitis b virus

Dr.T.V.Rao MD 26

HBV Structure & Antigens Dane Dane

particleparticle

HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr)HBcAg = inner core protein (a single serotype) HBeAg = secreted protein; function unknownDr.T.V.Rao MD 27

What are the clinical symptoms of Hepatitis B??

Spectrum of Chronic Hepatitis B Diseases

1Chronic Persistent Hepatitis - asymptomatic

2. Chronic Active Hepatitis - symptomatic exacerbations of hepatitis

3. Cirrhosis of Liver

4. Hepatocellular Carcinoma

Acute infection HBsAg positive, HbeAg

positive and anti-HBcAg IgM Rarely, IgM anti-HBc only

marker Usually seen in acute

fulminate Hep B Chronic infection

HBsAg positive and anti-HBcAg IgG

Previous Infection HBsAg negative anti-HBs positive IgG anti-HBc positive

Hbv – serology interpretation

HEPATITIS B MARKERS: HBsAg:Present in acute or chronic

infection. HBsAb:Present in recovery or

immunization. Anti -HB Core: May be “Total”

(IgG&IgM) or IgM. Lifelong marker of past and active infection in either acute or chronic.

HBeAg:Acute infection, and extremely infectious.

Dr.T.V.Rao MD 31

PRACTICE!!!!!!!!!!!!!!! HBsAg N. HBcAB (TOTAL) N. HBsAB N. HAV-IGM N. HCV N.

NO evidence of viral hepatitis viruses.

Dr.T.V.Rao MD 32

Solving the problems

HBsAG N. HBcAB (TOTAL) P. HBsAB P. HAV-IGM N. HCV N. PAST INFECTION.

Dr.T.V.Rao MD 33

Immunized for HBV infection

HBsAg N. HBcAB (total) N. HBsAB P. HAV-IGM N. HCV N.

Dr.T.V.Rao MD 34

Practice..……

Dr.T.V.Rao MD 35

HBsAg P HBcAB (Total) P HBsAB N HAV-IGM N HCV N MAY BE ACUTE OR CHRONIC. Order Hep. B Core IgM and biopsy to clarify.

Recent injury & the IgM will be positive , If Acute.

Co infection with HBV, HAV, and HCV

HBsAg P HBcAB (TOTAL) P HBsAB N HAV-IGM P HCV P

Dr.T.V.Rao MD 36

Past infection with recovery, and then re-infection that has become chronic, this is very

rare but does happen.

HBsAG P HBcAB (total) P HBsAB P HAV-IGM N HCV N .

Dr.T.V.Rao MD 37

Diagnosis A battery of serological tests are used for the diagnosis of

acute and chronic hepatitis B infection. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to

HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore

infectiveness. (Critical outcome for chronic pts) HBV-DNA - indicates active replication of virus, more

accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

High ModerateLow/Not

Detectable

blood semen urineserum vaginal fluid feces

wound exudates saliva sweattears

breastmilk

Concentration of Hepatitis B Virus in Various Body Fluids

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

Treatment Patients with Hepatitis needs

supportive treatment Recombinant Interferon alfa therpay

is beneficial in HBV and HCV

Treatment Interferon - for HBsAg +ve carriers with chronic active hepatitis.

Response rate is 30 to 40%. alpha-interferon 2b (original) alpha-interferon 2a (newer, claims to be more efficacious and

efficient)

Lamivudine - a nucleoside analogue reverse transcriptase inhibitor.

Adefovir – less likely to develop resistance than Lamivudine and may be used to treat Lamivudine resistance HBV. However more expensive and toxic

Entecavir – most powerful antiviral known, similar to Adefovir Successful response to treatment will result in the disappearance of

HBsAg, HBV-DNA.

Vaccination Genetically Engineered

Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.

Blood screening is Mandatory

Other measures - screening of blood donors,

blood and body fluid precautions

is mandatory in majority of

Countreis

Hepatitis B Immunoglobulin Hepatitis B Immunoglobulin - HBIG may be

used to protect persons who are exposed to hepatitis B. It is particular 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

Hand washing Minimal health precaution to Medical and Paramedical staff

ImmunoglobulinImmunoglobulin VaccineVaccine

HAV Post exposure during the incubation period (2-6 weeks) Or directly before exposure

• Inactivated virus•Before exposure by 2 weeks (preferably 4 weeks) • Immunized for 5-8 years • 2 years or older

HBV • Post exposure within 48 hours • For neonates of infected mother

• Recombinant vaccine- HBsAg•Before exposure • Can be taken routinely in neonates