HEPATITIS

Dr. Amany A. Ghazy

Hepatitis
v Hepatitis" means inflammation of the liver. v It is injury to the liver characterized by the presence of inflammatory cells in the liver tissue. v It can be caused by:
Toxins (aflatoxins) certain drugs, heavy alcohol use, bacterial and viral infections.

Viral Hepatitis
v It is liver inflammation due to a viral infection. v Viral hepatitis may be acute (recent infection, relatively rapid onset) or chronic forms. v Common viruses cause hepatitis include:
Hepatitis A,B,C,D,E viruses (> 95% of viral cause), Herpes simplex, Cytomegalovirus, Epstein-Barr virus, adenoviruses.

Viral Hepatitis - Historical Perspectives

Infectious Viral hepatitis Serum

A
NANB

Enterically E transmitted

B D
F, G,

Parenteral C y transmitte d

Types of Viral Hepatitis

A
Type of virus prevalence ssRNA

B
dsDNA

C
ssRNA

D
ssRNA

E
ssRNA

Very high

High (0.5-10%) yes

Highest up to 20% yes

law yes

rare no

Chronic infection Oncogenicity & HCC

no

no

yes

yes

yes

rare

Types of Viral zepatitis

A
Source of virus Route of transmission fulmination feces

E
feces

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

fecal-oral

fecal-oral

may occur pre/postexposure immunization

Yes, especially pregnant females ensure safe drinking water

Prevention

pre/postexposure immunization

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

Hepatitis A virus (HAV)

v Hepatitis A is acute liver disease caused by HAV, lasting from a few weeks to several months. It does not lead to chronic infection. v Most common. v Type of virus: RNA virus. v Mode of transmission: (feco-oral route)
Close personal contact (household contact, child day care centers) Contaminated food, water (e.g., infected food handlers, raw shellfish) Not transmitted by Trans-placental route

Prevalence

Hepatitis A virus (HAV)

v Causes of liver damage:
Localized areas of necrosis are frequently observed. accumulation of macrophages near Later degenerating hepatocytes.

v Clinical Manifestations:
Incubation period 2 6 weeks Malaise, Anorexia Nausea, vomitting, liver tenderness Onset of Jaundice Recovery in 4-6 weeks Mortality 0.1 1 %

Hepatitis A Infection
Typical Serological Course
Sympt oms Titer ALT Total antiHAV

Fecal HAV

IgM anti-HAV

Months after exposure

1 2

2 4

Hepatitis A virus (HAV)

v 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.

v Treatment:
No specific antiviral drug is available Treatment is symptomatic (should get plenty of rest and eat a nutritious diet). Also ensure not to spread HAV by washing their hands after using the toilet and before preparing food.

Hepatitis B virus (HBV)

v Hepatitis B is a liver disease caused by HBV. v 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 cirrhosis or liver cancer (HCC).

v It is the Most Important Infectious Disease because:

There are more than 350 million carriers 25% of them will develop chronic active hepatitis. It attributes to 1 million deaths a years, world wide.

Hepatitis B virus (HBV)

v HBV has many important Ag:
Surface component of HBV called as surface antigen (HBs Ag). HBc Ag. HBe Ag.

Pathogenesis (LIFE CYCLE)

Prevalence

Modes of Transmission
v Contact with infected blood, semen& other body fluids via:
Sexual: heterosexual or homosexuals. Parenteral: IVDA, tattoo or body piercing with dirty needles. Perinatal: Mothers who are HBeAg positive ..

v High Risk Individuals:

Health care providers (Physicians, surgeons, technicians) Addicts, Sexual workers. Babies of infected mothers (high prevalence populations). Patients undergoing Dialysis

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

Clinical Features

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Symptoms HBeAg anti-HBe
Total anti-HBc

Titre
HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 Weeks after

52

100

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

Acute (6 months) Chronic (Years) HBeA g HBsAg Total antiHBc anti-HBe

Titr e

IgM anti-HBc

0 4 8 1 1 2 2 2 3 3 5 6 0 after 6 2Weeks4 8 2Exposure 2

Yea rs

Diagnosis
v Serological tests used for the diagnosis of HBV infection:
HBsAg: used as a general marker of infection. HBsAb: used to document recovery or immunity to HBV infection. anti-HBc IgM: marker of acute infection. anti-HBcIgG: past or chronic infection. HBeAg: indicates active replication of virus (infectiveness). HBV-DNA: indicates active replication of virus, more accurate than
HBeAg. Used mainly for monitoring response to therapy.

Treatment
v Supportive treatment. v Recombinant Interferon alfa therpay is beneficial in HBV and HCV v Antiviral drugs:
Lamivudine: most patients will respond favorably. But, relapse on cessation of treatment or drug resistance. Adefovir: less resistance but more expensive and toxic

v Successful response to treatment result in disappearance of HBsAg & HBV-DNA.

MCQ
v In hepatitis B infected patients, the most important
indicator of active virus replication and risk of transmissibility is:
HBsAg HBeAg HBcAg HBsAb

Hepatitis C virus (HCV)

v HCV also known as Non A or Non B virus. v HCV infections are seen only in humans. v The virus has single stranded RNA genome surrounded by an enveloped carrying glycoprotein spikes.

Prevalence

Pathogenesis
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Mode of Transmission
v Blood transfusions v Transplantation of organs from infected donor. v Percutaneous:
injectable drug abusers Therapeutic (contaminated equipment, unsafe injections) Occupational (needle stick)

v Sexual transmission ?

Less important

v Vertical transmission is possible.

Clinical features
v short, mild, flu-like illness. v Nausea, vomiting & diarrhoea. v loss of appetite & weight loss. v jaundice seen in 5% of patients (yellow skin, eyes &urine) . v itchy skin. v About 50 80% patients progress to chronic hepatitis v May progress to Cirrhosis, or Hepatocellular carcinoma

Hepatitis C Virus Infection

Typical Serologic Course
Sympt oms Titr e
antiHCV

ALT

3 4 Mont hs

Norma l 5 6 1

2 3 Years

Time after Exposure

Laboratory Diagnosis
v HCV antibody: used to diagnose HCV infection.
Not useful in acute phase as it appears 4 weeks after infection.

v HCV-RNA: detected by PCR and branched DNA.

used to diagnose HCV infection in acute phase. However, its main use is in monitoring the response to antiviral therapy.

v Prognostic Tests:
Genotyping: genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon therapy. Viral Load: high viral load means poor prognosis.

HCV Treatment
v Combination of antiviral drugs (-interferon & ribavirin)
The antiviral drugs may cause significant side effects as
headaches , flu-like symptoms, nausea ,tiredness, body aches ,Depression ,skin rashes

v Effective in about 50% of cases v No vaccine

v It is a defective RNA virus need to be

surrounded by outer coat (HBsAg).
So it needs HBV to cause infection.

Hepatitis D virus (HDV) (Delta agent)

v Modes of Transmission:
Percutanous: injecting drug use. Permucosal exposures. sexual contact.

Prevalence

Clinical Features
v Coinfection: severe acute disease. low risk of chronic infection. v Superinfection: usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis.

HBV - HDV Coinfection

Typical Serologic Course
Sympto ms ALT Elevated
IgM antiHDV HDV RNA HBsAg Total antiHDV antiHBs

Titre

Time after

HBV - HDV Superinfection Typical Serologic

Course Jaund
ice Sympto ms ALT

Titre

Total antiHDV

HDV RNA HBsAg IgM antiHDV

Time after Exposure

Hepatitis E virus (HEV)

v Un-enveloped RNA virus. v Most outbreaks are associated with faecally contaminated drinking water. v Minimal person-to-person transmission. v It causes swelling of the liver, but no longterm damage.

Prevalence

Hepatitis E Virus Infection

Typical Serologic Course
Sympt oms ALT
IgG anti-HEV

Titer
Virus in stool

IgM anti-HEV

Weeks after

1 0

1 1

1 2

1 3

Hepatitis G virus
v A new virus recently identified in Humans. v Not grown in culture lines v RNA genome. v HGV RNA was found in acute, chronic, fulminant
hepatitis & patients with multiple transfusions

v It resembles HCV In all other aspects

Preventive & Control measures for Hepatitis v Immunization: (for infants & high risk persons) Viruses
Hepatitis A vaccination is recommended for all children starting
at age 1 year & travellers to endemic countries (2 injections, protection starts 4 weeks after injection and lasts for 10 - 20 years).

Hepatitis B vaccination, 3 injections are given over 3-6 months,

immunity for at least 5 years.

v Preventive Measures for HAV & HEV (water &food hygiene):

Wash hands well after using any washroom. Eat only freshly cooked foods. Drink only commercially bottled water or boiled water in endemic places where sanitation & water supply are questionable.

Other preventive measures

v Preventive Measures for HBV, HCV & HDV:

Cover open wounds, don't share razors, manicure tools or needles. Practice safe sex. Don't allow yourself to be pierced with non-sterile equipment. Screening of blood, organ, tissue donors.

Blood screening is Mandatory

v Screening of blood donors,
blood and body fluid precautions is mandatory in majority of Countries.
Click to edit Master text styles Second level Third level Fourth level Fifth level

MCQ
v Acute phase HCV infection can be diagnosed by:
HCsAg HCV-RNA HCV antibody HCeAg HBcAg