Biochemistry of Hepatitis A

Biochemistry of Hepatitis A (Biochemical Tests)

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Last Updated on August 10, 2020 by Sagar Aryal

What is Hepatitis A Virus?

  • Hepatitis A virus (HAV) is a cause of acute liver inflammation or hepatitis. It can cause relapsing signs and symptoms but not a chronic infection.
  • The virus is a 27-nm-diameter non-enveloped RNA virus. It belongs to the family Picornaviridae and the genus Hepatovirus.
  • Viral transmission occurs in a fecal-oral fashion. The genome is positive-strand RNA, 7474 nucleotides long, 7.5 kb in length that encodes a polyprotein with structural and nonstructural components.
  • Viral replication and assembly occur in the hepatocyte cytoplasm of humans and non-human primates, the virus’ exclusive natural hosts. The virus is then secreted into the bile and serum.
  • In order to establish infections, picornaviruses are optimized to invade target cells, replicate large numbers of progeny virions, and spread these progeny to initiate new rounds of infection in neighboring cells.
  • However, host organisms possess systemic, as well as cell-based, defense mechanisms to limit virus spread and to remove the virus at last.
Biochemistry of Hepatitis A
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Biochemistry

The innate cell-based responses to viral infections, which include the interferon (IFN) system and apoptosis of infected cells, are designed to act fast at the sites of infection.

Induction of IFN synthesis in infected cells can curtail the spread of infection by inducing an antiviral state in neighboring cells, whereas induction of apoptosis can interrupt the infection cascade by entailing the death of the infected cells without virus release.

In particular, viruses that establish persistent infections have to cope with cellular antiviral responses. Without the involvement of the cellular immune system, HAV replication results in persistent infections.

In summary, the results presented here show three new qualities of HAV, by which the virus interacts with host cells to establish persistent infections.

  • HAV inhibits dsRNA-induced IFN expression.
  • HAV inhibits dsRNA-induced apoptosis.
  • HAV is able to downregulate its own replication.

Diagnosis

Cases of hepatitis A are not clinically distinguishable from other types of acute viral hepatitis. Specific diagnosis is made by the detection of HAV-specific Immunoglobulin G (IgM) antibodies in the blood.

Additional tests include reverse transcriptase-polymerase chain reaction (RT-PCR) to detect the hepatitis A virus RNA, and may require specialized laboratory facilities.

Biochemical Tests

There are several laboratory tests that may be performed in cases of known or suspected hepatitis. They include:

Alanine aminotransferase (ALT) 

  • an enzyme found mainly in the liver. When the liver is damaged, ALT is released into the blood, usually, before more obvious signs of liver damage occur, such as jaundice.
  • This makes ALT a useful test for early detection of liver damage. Results are often compared to those of the AST test to help determine the cause of liver injury.

Aspartate aminotransferase (AST)

  • Also, an enzyme found in the liver and a few other organs, particularly the heart and other muscles. The test is most useful in detecting liver damage due to hepatitis and may be elevated more than ALT with exposure to drugs toxic to the liver, cirrhosis, or alcoholism.
  • AST, however, is not specific for the liver and may be increased in conditions affecting other parts of the body. Results are often compared to those of the ALT.

Alkaline phosphatase (ALP)

  • An enzyme related to the bile ducts but also found in other tissues throughout the body. The ALP test is often increased when bile ducts are blocked but may also be increased with bone disorders.

Bilirubin

  • A waste product made from the breakdown of old blood cells that are ultimately processed by the liver so that it can be eliminated from the body.
  • Bilirubin is a yellow compound that can accumulate when the liver is damaged, causing jaundice and dark urine.

Albumin

  • The main protein made by the liver. Since albumin is produced by the liver, its level can decrease with loss of liver function; however, this typically occurs only when the liver has been severely affected.
  • Many other conditions also affect albumin levels.

Total protein

  • Albumin and all other proteins in blood; may be decreased with severe liver disease.

Prothrombin time (PT)

  • This test may be ordered for a person with hepatitis or suspected hepatitis. Proteins used in the formation of a blood clot (coagulation factors) are mostly produced by the liver, and a prolonged PT may indicate the severity of liver damage.

Gamma-glutamyl transpeptidase (GGT)

  • An enzyme found in the liver that is very sensitive to changes in liver function.
  • The GGT test helps to differentiate between the causes of an elevated ALP; if GGT is increased, then the elevated ALP is due to liver, not the bone disease.

Lactate dehydrogenase (LD)

  • An enzyme released with cell damage; found in cells throughout the body.

Alpha-Fetoprotein (AFP)

  • Associated with regeneration or proliferation of liver cells.

Reference

  1. Adhami, T., & Hannouneh, I. (2014). Hepatitis A. Cleveland Clinic Center for Continuing Education: Disease Management.
  2. Der, S. D., Yang, Y. L., Weissmann, C., & Williams, B. R. (1997). A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis. Proceedings of the National Academy of Sciences94(7), 3279-3283.
  3. Jacobs, B. L., & Langland, J. O. (1996). When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. Virology219(2), 339-349.
  4. Goodbourn, S., Didcock, L., & Randall, R. E. (2000). Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. Journal of General Virology81(10), 2341-2364.
  5. Lee, S. B., & Esteban, M. (1994). The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. Virology199(2), 491-496.
  6. Díaz-Guerra, M., Rivas, C., & Esteban, M. (1997). Activation of the IFN-inducible enzyme RNase L causes apoptosis of animal cells. Virology236(2), 354-363.

Internet Sources

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  • 4% – https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-A/
  • 3% – https://loinc.org/51913-2/
  • 3% – https://labtestsonline.org/tests/albumin
  • 2% – https://www.sciencedirect.com/topics/medicine-and-dentistry/bile-secretion
  • 2% – http://abmedlab.com/laboratory-services/hepatitis-panel/
  • 1% – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312766/
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  • 1% – https://www.labcorp.com/help/patient-test-info/alkaline-phosphatase-alp
  • 1% – https://quizlet.com/134019680/blood-coagulation-1-flash-cards/
  • 1% – https://labtestsonline.org/tests/gamma-glutamyl-transferase-ggt
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