Hepatitis Viruses

This section includes viruses whose primary site of infection is the liver. They belong to different families. There are other viruses which cause hepatitis as part of their clinical syndromes e.g. Yellow Fever Virus, Epstein Barr Virus, VZV etc. but they are not included in this section.

Hepatitis A Virus

It actually is Enterovirus 72. So, it will be non enveloped, single stranded RNA with icosahedral nucleocapsid. It is transmitted by the feco-oral route and causes infectious hepatitis. Outbreaks in schools, summer camps etc have been caused by HAV contaminated food or water. Cytotoxic T cell mediated immune response against infected hepatocytes is responsible for cell damage as the virus is not directly cytopathic.

Clinical features: Incubation period is 2-6 weeks. There is an anicteric stage where jaundice has not yet set in, characterised by fever, loss of appetite, nausea, vomiting and RUQ pain. This is followed by the icteric stage characterized by jaundice, yellowing of skin and eyes, dark urine and pale feces.

Laboratory diagnosis of HAV infections: Detection of IgM can be done by ELISA. Direct visualisation in stool samples can be done by electron microscopy and immunofluorescence.

Hepatitis B Virus

It belongs to the family Hepadnaviridae.

Morphology: It is partially double stranded, enveloped, icosahedral DNA virus. The envelope has a surface antigen called HBsAg or Australia antigen. Inside the envelope is the nucleocapsid antigen called core antigen or HbcAg. Inside the core particle, the viral polymerase directs the synthesis of minus strand DNA from the RNA template. It then degrades the RNA pregenome and generates the plus strand DNA from the minus strand template. A third detectable antigen is HBeAg. It is not part of the virion structure but is secreted by the virus. Remember that HBeAg is NOT a part of the viral envelope. HBcAg and HBeAg are alternate translation products of the same core gene. HbeAg causes immune tolerance and helps the infection to persist.

A complete virion is called a Dane particle. Under electron microscope three types of particles are seen in sera from hepatitis B patients - spherical, tubular or filamentous forms (which are HBsAg) and Dane particles.

Pathogenesis: Transmission is mainly parenteral, via blood, needlesticks, sexual transmission, perinatal and intravenous drug addicts. It is a highly infectious virus. Immune attack by cytotoxic T cells against infected cells displaying viral antigens causes inflammation and cell necrosis. Resulting antigen antibody complexes cause arthralgias, urticaria, glomerulonephritis, vasculitis and cryoglobulinemia. Few people become chronic carriers after the initial infection. Carrier state has been associated with the development of hepatocellular carcinoma. Integration of Hepatitis B DNA with the cellular DNA and chronic inflammation from hepatitis are thought to cause carcinoma. Chronic carrier state is more common when infection is acquired in infancy with 90% of infants become chronic carriers. Antibody to HBsAg is protective while anti HBc antibody is not protective. HBeAg is determinant of high transmissibility. Super carriers are positive for HBeAg and HBsAg while simple carriers are positive for HBsAg and negative for HBeAg. Super carriers are highly infectious.

Clinical features: The infection can be asymptomatic or lead to acute hepatitis, chronic active or chronic persistent hepatitis, carrier state or hepatocellular carcinoma. Acute hepatitis presents as fever, jaundice and abdominal RUQ pain, anorexia with an incubation period of 2-6 months. Rash, arthritis and arthralgia, polyarteritis nodosa and glomerulonephritis may be seen.

Laboratory diagnosis of HBV infections: Both HBV antigens and antibodies are useful in diagnosis. Interpretation is commonly tested and may be confusing for students. Remember a few rules as follows:

1. In acute infection IgM antibodies will be seen while in chronic infection it will be IgG.
2. HBeAg positive means the patient will be highly infectious.
3. Following anti-HbV vaccination ,only antibody detected will be Anti HBs. No other antigen or antibody will be detected.
4. Anti HBc is the first antibody to appear and will stay positive forever. It will be IgM early in the disease and IgG in later stages. Remember that this antibody does not confer protection.
5. In the window period, HBsAg cannot be detected.
6. In carrier state, HBsAg will be positive for more than 6 months.
7. HBV DNA can be detected by PCR anytime after infection has happened and only disappears when the patient recovers.

Different stages of Hepatitis B

Hepatitis C Virus

It belongs to the family Flaviviridae. It is an enveloped, single stranded RNA virus. It shows considerable genetic diversity having 6 genotypes and multiple subgenotypes. It results from a high rate of mutation in the genes coding for the envelope glycoproteins. Infection spreads like HBV. Blood and blood products are the main source of infection. Chronic carrier state , chronic hepatitis , cirrhosis and hepatocellular carcinoma can occur.

Clinical features: Following an incubation period of 5-12 weeks there is jaundice, anorexia, fever etc. It is asymptomatic in most patients. Autoimmune effects like arthralgia, vasculitis, essential mixed cryoglobulinemia and membranoproliferative glomerulonephritis may be seen. It may precipitate Hashimoto’s thyroiditis.

Laboratory diagnosis of HCV infections: Viral antigen can be detected by immunofluorescence. Antibodies are detected by ELISA or chemiluminescence assay and have to be confirmed by recombinant immunoblot assay (RIBA). Immunochromatography based rapid assays are available. HCV RNA can be detected by RT-PCR and DNA amplification methods.

Hepatitis D Virus

It used to be considered as a defective virus as it could not complete its replicative cycle on it’s own. It needs HBV for envelope proteins which are used for packing of progeny virions. Now it is considered a satellite Hepatitis B Virus. The genome consists of single stranded RNA. Hepatitis D is transmitted through percutaneous or mucosal contact with infectious blood and can be acquired either as a coinfection with HBV or as a superinfection in people with HBV infection. Incubation period is 2-12 weeks. It potentiates hepatitis caused by HBV and the patient’s clinical condition may deteriorate further leading to fulminant hepatitis. Laboratory diagnosis is by detection of Delta antigen (which is a nucleoprotein) by direct immunofluorescence of hepatocytes or by immunoperoxidase staining on liver biopsy . HDV RNA can be detected by hybridization with radiolabelled probes. ELISA or RIA can be used for antibody detection.

Hepatitis E Virus

It belongs to the family Caliciviridae and is a non enveloped, single stranded RNA virus with icosahedral capsid. It is transmitted by the feco-oral route. Incubation period is 2-8 weeks. Clinically it presents as a mild hepatitis. In pregnant women it causes fulminant hepatitis with hepatic failure and death. Demonstration of the virus by electron microscopy, antibodies by ELISA and Western Blot and HEV RNA by PCR can be used for diagnosis.