VIRAL HEPATITIS

Clinical Features

Hepatitis due to all these viruses presents clinically in a very similar fashion, especially during the acute phase of the illness. Thus a specific diagnosis can only be made in the laboratory.
The majority of infections are totally asymptomatic, but common clinical features include: anorexia, nausea, vomiting, right upper quadrant pain and raised liver enzymes AST and ALT.
Jaundice is the hall mark of infection, but tends to develop late.
Anicteric cases are also very common.

ENTERICALLY TRANSMITTED HEPATITIS: A and E

PARENTERALLY TRANSMITTED HEPATITIS B , C , D and G

Clinical Features
Incubation period 3-5 weeks (mean 28 days)
Milder disease than Hepatitis B; asymptomatic infections are very common, especially in children.
Adults, especially pregnant women, may develop more severe disease.
Although convalescence may be prolonged, there is no chronic form of the disease.

Complications:
Fulminant hepatitis is rare: 0.1% of cases

Pathogenesis
Virus enters via the gut; replicates in the alimentary tract and spreads to infect the liver, where it multiplies in hepatocytes.
Viraemia is transient. Virus is excreted in the stools for two weeks preceding the onset of symptoms.

Epidemiology
World-wide distribution; endemic in most countries. The incidence in first world countries is declining. There is an especially high incidence in developing countries and rural areas.
In rural areas of South Africa , the seroprevalence is 100%.

Transmission - Enteric
Large numbers of virus particles are excreted in stools, before the onset of symptoms.

1) Case-to-case, via faecal-oral route.

Outbreaks in creches are very common.

2) Contamination of food or water with sewage

Infected food handlers

Shell fish grown in sewage-polluted water

Diagnosis
Virus cannot be cultured in vitro from clinical material, and diagnosis is made on the presence of HAV-specific IgM in the patient's blood.

Prevention
1) Passive immunisation -

Normal immunoglobulin given to:

Travellers to third world countries

Household contacts of acute cases

2) Active Immunization
Inactivated cell culture-derived vaccine has recently become available; not in general use

Calicivirus
spherical, non enveloped, 27-34 nm particles containing a ssRNA genome.

Clinical Features
Incubation period 30-40 days
Acute, self limiting hepatitis, no chronic carrier state
Age: predominantly young adults, 15-40 years

Complications
Fulminant hepatitis in pregnant women. Mortality rate is high (up to 40%).

Pathogenesis
Similar to hepatitis A; virus replicates in the gut initially, before invading the liver, and virus is shed in the stool prior to the onset of symptoms.
Viraemia is transient. A large inoculum of virus is needed to establish infection.

Epidemiology
Little is known yet. The incidence of infection appears to be low in first world countries.

1) Large outbreaks have been described in India, Mexico and North Africa where the source of infection is usually gross faecal contamination of drinking water supplies.
2) Case-to-case transmission to household contacts appears to be uncommon. This suggests that a large inoculum is needed to establish infection.

The incidence of infection in South Africa is unknown.

Diagnosis
No routine laboratory tests are available as yet. Virus cannot be cultured in vitro.

1) Calicivirus-like particles in the stool, by electron microscopy
2) Specific IgM in serum
3) PCR HEV-specific sequences in stool

Hepadna virus
42nm Virions (also known as "Dane particles") contain a circular dsDNA genome

HBV Antigens

HBsAg = surface (coat) protein

produced in excess as small spheres and tubules

HBcAg = inner core protein

HBeAg = secreted protein; function unknown

You can view a diagram and electron micrographs of the virus structure.

Clinical Features
Incubation period 2 - 5 months
Insidious onset of symptoms. Tends to cause a more severe disease than Hepatitis A.
Asymptomatic infections occur frequently.

Pathogenesis
Infection is parenterally transmitted. The virus replicates in the liver and virus particles, as well as excess viral surface protein, are shed in large amounts into the blood. Viraemia is prolonged and the blood of infected individuals is highly infectious.

Complications
1) Persistant infection:-
Following acute infection, approximately 5% of infected individuals fail to eliminate the virus completely and become persistantly infected.

Those who are at particular risk include:

babies, young children

immunocompromised patients

males > females

The virus persists in the hepatocytes and on-going liver damage occurs because of the host immune response against the infected liver cells.

Chronic infection may take one of two forms:
Chronic persistent Hepatitis - the virus persists, but there is minimal liver damage
Chronic Active Hepatitis - There is aggressive destruction of liver tissue and rapid progression to cirrhosis or liver failure.

2) Patients who become persistently infected are at risk of developing hepatocellular carcinoma (HCC)..
HBV is thought to play a role in the development of this malignancy because:

a) 80% of patients with HCC are carriers of hepatitis B.

b) Virus DNA can be identified in hepatocellular carcinoma cells.

c) Virus DNA can integrate into the host chromosome.

3) Fulminant Hepatitis
Rare; accounts for 1% of infections.

Epidemiology

Prevalence of disease in Africa
World-wide there are 450 million persistant carriers of hepatitis B, 50 million of which are in Africa. Carriage rates vary markedly in different areas. In South Africa, infection is much more common in rural communities than in the cities. Hepatitis B is parenterally transmitted

1) Blood:

• Blood transfusions, serum products,
• sharing of needles, razors
• Tattooing, acupuncture
• Renal dialysis
• Organ donation

    2) Sexual intercourse

3) Horizontal transmission in children, families, 'close personal contact'.
This is the major mode of transmission in South Africa where the majority of individuals become infected at between three and nine years of age.
Horizontal transmission also occurs in children's institutions and mental homes.

4) Vertical transmission - perinatal transmission from a carrier mother to her baby

• transplacental (rare)
• during delivery
• post natal , ??breast feeding , ??close contact

( This is the major mode of transmission in South East Asia)

A. Acute infection with resolution

Viral antigens:
1) Surface antigen (HBsAg) is secreted in excess into the blood as 22 nm spheres and tubules. Its presence in serum indicates that virus replication is occurring in the liver
2) 'e' antigen (HBeAg) secreted protein is shed in small amounts into the blood. Its presence in serum indicates that a high level of viral replication is occurring in the liver
3) core antigen (HBcAg) core protein is not found in blood

Antibody response:
1) Surface antibody (anti-HBs) becomes detectable late in convalescence, and indicates immunity following infection. It remains detectable for life and is not found in chronic carriers (see below).
2) e antibody (anti-HBe) becomes detectable as viral replication falls. It indicates low infectivity in a carrier.
3) Core IgM rises early in infection and indicates recent infection
4) Core IgG rises soon after IgM, and remains present for life in both chronic carriers as well as those who clear the infection. Its presence indicates exposure to HBV.

Prevention

1) Active Immunization

Two types of vaccine are available:

Serum derived - prepared from HBsAg purified from the serum of HBV carriers

Recombinant HBsAg - made by genetic engineering in yeasts

Both vaccines are equally safe and effective. The administration of three doses induces protective levels of antibodies in 95% of vaccine recipients.
Universal immunization of infants was introduced in April 1995. Infants receive 3 doses at 6, 10 and 14 weeks of age.

Vaccine should be administered to people at high risk of infection with HBV:

1) Health care workers

2) Sexual partners of chronic carriers

3) Infants of HBV carrier mothers

2) Passive Antibody
Hepatitis B immune globulin should be administered to non immune individuals following single episode exposure to HBV-infected blood.
For example: needlestick injuries

Virology

Putative Togavirus related to the Flavi and Pesti viruses.
Thus probably enveloped.
Has a ssRNA genome
Does not grow in cell culture, but can infect Chimpanzees

Clinical Features

Incubation period 6-8 weeks
Causes a milder form of acute hepatitis than does hepatitis B
But 50% individuals develop chronic infection, following exposure.

Complications
1) Chronic liver disease
2) Hepatocellular carcinoma

Epidemiology

Incidence endemic world-wide; high incidence in Japan, Italy and Spain
In South Africa, 1% blood donors have antibodies

Transmission

• Blood transfusions, blood products
• organ donation
• Intravenous drug abusers
• community acquired: mechanism unclear. ?Vertical transmission
• ?sexual intercourse

Diagnosis

1) Serology
Reliable serological tests have only recently become available.
HCV-specific IgG indicates exposure, not infectivity

2) PCR detects viral genome in patient's serum

Clinial Features
Increased severity of liver disease in Hepatitis B carriers.

Virology
virus particle 36 nm in diameter
encapsulated with HBsAg, derived from HBV
delta antigen is associated with virus particles
ssRNA genome

Epidemiology
Identified in intra-venous drug abusers in Italy. Incidence in South Africa is unknown.

A virus originally cloned from the serum of a surgeon with non-A, non-B, non-C hepatitis, has been called Hepatitis G virus. It was implicated as a cause of parenterally transmitted hepatitis, but is no longer believed to be a major agent of liver disease. It has been classified as a Flavivirus and is distantly related to HCV.