Hepatitis (D, E and G) Virus

Epidemiology of HCV infection

• Globally, HCV has infected an estimated 130 million people, most of who are chronically infected.
• HCV- infected people serve as a reservoir for transmission to others and are a risk for developing chronic liver cirrhosis and primary hepatocellular carcinoma (HCC).
• It has been estimated that HCV accounts for 27% cirrhosis and 25% of HCC worldwide.
• HCV infection has likely been endemic in many populations.

Hepatitis D virus

• HDV is an infection that causes the liver to become inflamed.
• This swelling can cause long-term liver problems, including liver scarring and cancer i.e. Cause of acute and severe chronic liver damage.
• Acute hepatitis D occurs suddenly and causes more severe symptoms.
• The condition is caused by the hepatitis D virus (HDV).
• If the infection lasts for six months of longer, the condition is known as chronic hepatitis D. The long-term version of the infection develops gradually over time.
• Hepatitis D virus (HDV) is an unusual, single-stranded virus.
• It is the delta agent of a defective virus, which shows similarities with plant viroids.
• It is a very small virus about 35nm in diameter.
• The single-stranded RNA genome (17kb) is covalently closed circular, which appears a rod –like structure due to a large amount of base pairing.
• It consists of delta antigen surrounded by an outer coat of HBsAg.
• It requires the help of HBV for its replication.
• HBV synthesizes the envelope containing HBsAg that surrounds the HBV genome.
• 3 types of HBsAg: HBsAg-L, HBsAg-M, and HBsAg- S.
• The RNA genome of HDV encodes a single protein, hepatitis delta antigen (HD Ag).
• HDV does not encode any envelope proteins.
• As chronic hepatitis D progresses, the chances of complications increase. Many people with the condition eventually develop cirrhosis or severe scarring of the liver.

Transmission

• HDV is transmitted via similar to HBV i.e.

1. Percutaneous exposure
2. Injecting drug use
3. Per mucosal exposure
4. Sexual contact
5. Perinatal infection is infrequent

Clinical features

• Hepatitis D infection is limited to infection with HBV.
• HDV together with HBV can cause acute co-infection or HDV can superinfect a chronic HBV carrier.
• If a person is immune to HBV, he/she is also immune to hepatitis D.
• Co- infection is severe acute disease and there is a low risk of chronic infection.
• Superinfection usually develops chronic infection. There is high risk of severe chronic liver disease

Prevention of HDV infection

Co- infection and superinfection should but prevented through health education, reducing risk behavior among persons with chronic HBV infection.

Treatment

Interferon

• Considered for patients with chronic active hepatitis
• Response rate is around 50%

Ribavirin

• Less effective than interferon
• Ribavirin in combination with interferon is more effective than interferon did.

Prevention

• Screening of blood donors, tissue donors
• High-risk behavior modification
• Blood and body fluids prevention
• No vaccine available

Hepatitis E virus (HEV)

Family: Calciviridae

• Hepatitis E virus (HEV), the cause of enterically-transmitted non-A, non-B hepatitis, is another non-enveloped, single-stranded RNA virus.
• This virus shares many biophysical and biochemical features with caliciviruses.
• The most similar genome to HEV is found in a plant virus, and there are similarities in the functional domains to rubella virus.
• Hepatitis E virus is an important cause of large epidemics of acute hepatitis in the subcontinent of India, Central and Southeast Asia, the Middle East, parts of Africa and elsewhere.
• This virus is responsible for high mortality (15–20%), during pregnancy.

• It is a calcivirus like a virus
• Non-enveloped with an icosahedral capsid, having size 32-34nm in diameter.
• Contains positive- sense single-stranded RNA genome, about 706kb in size.
• Very labile and sensitive
• Does not replicate in tissue culture.
• Human is natural hosts.

Transmission

• Most outbreaks are associated with fecally contaminated water.
• Large epidemics have occurred in the Indian subcontinent, USSR, China, Africa, and Mexico.
• A low Seroprevalence of HEV (<2%) has been found in healthy populations
• The source of infection for this person is unknown
• Low chance of person to person transmission

Clinical features

• Incubation period 15-60 days (in average 40 days)
• Case fatality rate (CFR) 1-3% however in pregnant women 15-25%.
• Illness or severity increases with age.
• Chronic sequelae of HEV infection has not been identified

Prevention

• Avoid drinking water of unknown purity
• Uncooked shellfish, fruit, and vegetables should be washed with potable water.
• Immunoglobulin has been prepared, however, it does not prevent infection. No vaccine available.

Hepatitis G virus (HGV)

• It is flavirius and is closely related to HCV.
• It is associated with few cases of acute or chronic non-A, non-B, non- C, non-D and non-E hepatitis.
• HGV is common in human blood; therefore it may not be the significant causes of hepatitis in human.

The GB hepatitis viruses

• The GB hepatitis viruses (GBV-A, GBV-B, and GBV-C).
• GBV-A does not replicate in the liver whereas GBV-B causes hepatitis
• A series of studies including phylogenetic analysis of genomic sequences showed that GBV-A, B, and C are not genotypes of hepatitis C virus and that GBV-A and GBV-C are closely related.
• The GB hepatitis viruses were cloned recently and preliminary genomic characterization.
• The three GB viruses and HCV share only limited overall amino acid sequence identity.
• Diagnostic reagents were prepared with recombinant antigens, and limited testing was carried out in groups of patients, blood donors and patients with non-A, B, C, D, E hepatitis, intravenous drug addicts and other populations with a high incidence of viral hepatitis.

REFERENCE

Cheesbrough, M.Medical Laboratory Manual for Tropical Countries. Vol 2. ELBS London, 2007.

Tille, P.Diagnostic Microbiology.13th. Elsevier, 2014.

D Grenwood, Slack RCB, and Peutherer J.Medical Microbiology.Dunclude Livingstone: ELBS, 2001.