This section covers viruses whose primary site of infection is the liver. These viruses belong to different families. Some other viruses can cause hepatitis as part of a broader clinical syndrome (e.g., Yellow fever virus, Epstein-Barr virus, VZV), but they are not included in this section.
HAV is also known as Enterovirus 72. As an enterovirus, it is a non-enveloped, single-stranded RNA virus with an icosahedral nucleocapsid. It is transmitted by the fecal-oral route and causes infectious hepatitis. Outbreaks in schools, summer camps, etc. have been linked to HAV-contaminated food or water.
Cell damage is mainly due to a cytotoxic T-cell-mediated immune response against infected hepatocytes, because the virus itself is not directly cytopathic.
Clinical features: Incubation period is 2-6 weeks. There is an anicteric stage (before jaundice) characterized 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 visualization in stool samples can be done by electron microscopy and immunofluorescence.
It belongs to the family Hepadnaviridae.
Morphology: HBV is a partially double-stranded, enveloped, icosahedral DNA virus.
A third detectable antigen is HBeAg. It is not part of the virion structure; it 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 persist.
A complete virion is called a Dane particle. Under electron microscopy, 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 transmission, and intravenous drug use. It is highly infectious. Inflammation and cell necrosis result from cytotoxic T-cell attack on infected cells displaying viral antigens. Antigen-antibody complexes can cause arthralgias, urticaria, glomerulonephritis, vasculitis, and cryoglobulinemia.
A few people become chronic carriers after the initial infection. The carrier state is associated with development of hepatocellular carcinoma. Integration of hepatitis B DNA with cellular DNA and chronic inflammation from hepatitis are thought to contribute to carcinoma.
Chronic carrier state is more common when infection is acquired in infancy; 90% of infants become chronic carriers.
Clinical features: Infection may be asymptomatic or may lead to acute hepatitis, chronic active or chronic persistent hepatitis, carrier state, or hepatocellular carcinoma. Acute hepatitis presents with fever, jaundice, and abdominal RUQ pain, along with anorexia. Incubation period is 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 can be confusing. Use the following rules:
| HBsAg | HBsAb | HBcAb | |
| Window Period | Negative | Negative | Positive |
| Acute Infection | Positive | Negative | Positive |
| Complete Recovery | Negative | Positive | Positive |
| Chronic Carrier | Positive | Negative | Positive |
It belongs to the family Flaviviridae. It is an enveloped, single-stranded RNA virus. It shows considerable genetic diversity, with 6 genotypes and multiple subgenotypes. This diversity results from a high mutation rate in 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: After an incubation period of 5-12 weeks, jaundice, anorexia, fever, etc. may occur, but infection is asymptomatic in most patients. Autoimmune effects such as 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.
HDV was previously considered a defective virus because it cannot complete its replicative cycle on its own. It requires HBV for envelope proteins, which are used to package progeny virions. It is now 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 (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.
It belongs to the family Caliciviridae and is a non-enveloped, single-stranded RNA virus with an icosahedral capsid. It is transmitted by the fecal-oral route. Incubation period is 2-8 weeks. Clinically, it presents as a mild hepatitis. In pregnant women, it can cause 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.
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