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Introduction to Microbiology. Anas Abu - Humaidan M.D. Ph.D. Lecture 29. Viruses overview. The causes of hepatitis (inflammation of the liver) are varied and include infectious causes ( viruses , bacteria, and protozoa), as well as non-infectious causes (drugs and toxins like ethanol).
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Introduction to Microbiology Anas Abu-Humaidan M.D. Ph.D. Lecture 29
Viruses overview • The causes of hepatitis (inflammation of the liver) are varied and include infectious causes (viruses, bacteria, and protozoa), as well as non-infectious causes (drugs and toxins like ethanol). • The clinical symptoms and course of acute viral hepatitis can be similar, regardless of etiology • Hepatitis may be caused by at least five viruses belonging to different virus families • The following viruses associated with hepatitis will be discussed in this lecture: • hepatitis A virus (HAV) • hepatitis B virus (HBV) • hepatitis C virus (HCV) • hepatitis D virus (HDV) • hepatitis E virus (HEV)
Hepatitis A virus (HAV) • Belongs to the Picornaviridae. Naked with icosahedral capsid , single-stranded, positive-sense RNA virus. • The assembly of the progeny viruses takes place in the cytoplasm after the packaging of viral genomes into HAV capsid proteins. • Virions are released upon cell lysis. • The response to replication in the liver consists of lymphoid cell infiltration and necrosis of liver parenchymal cells.
Hepatitis A disease • The major mode of spread of HAV is person to person by fecal–oral exposure, and it occurs very frequently in nursing home settings and day care centers. • Outbreaks related to ingestion of contaminated food or water. • More than 90% of the adult population in many developing countries shows evidence of previous hepatitis A infection. • The risk of clinically evident disease is much higher in infected adults than in children.
Hepatitis A disease FIGURE 13–3. Sequence of appearance of viremia, virus in feces, alanine aminotransferase (ALT), symptoms, jaundice, and IgM and IgG antibodies in hepatitis A virus (HAV) infection. • Contagion is greatest 10 to 14 days before the symptoms appear • Detectable levels of IgG antibody to HAV persist indefinitely in serum, and patients with anti-HAV antibodies are immune to reinfection.
Hepatitis A disease • Manifests as Fever; anorexia (poor appetite); nausea; pain in the right upper abdominal quadrant; and, within several days, jaundice. • The infection-to-disease ratio is dependent on age; it may be as high as 20:1 in children and approximately 1:1 in older adults. • There is no specific treatment for patients with acute hepatitis A. Supportive measures include adequate nutrition and rest. • Almost all cases (99%) of HAV are self-limiting. • There is currently a vaccine for HAVwith almost 100% protection (like a natural infection)
Hepatitis B virus (HBV) • Belongs to the family Hepadnaviridae. is an enveloped partially double-stranded DNA virus. • Has the smallest genome size among DNA viruses. • Aggregates of HBsAg are often found in great abundance in serum during infection A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription.
Hepatitis B disease • The symptoms associated with acute hepatitis B are more severe and more prolonged than those of hepatitis A; however, asymptomatic infection occur (infection-to-disease ratio 3:1) • Acute hepatitis B is usually manifested by the gradual onset of fatigue, loss of appetite, nausea and pain, and fullness in the right upper abdominal quadrant. • One important difference between hepatitis A and hepatitis B is the development of chronic hepatitis, which occurs in approximately 10% of all patients with hepatitis B infection. • Chronic hepatitis may lead to cirrhosis, liver failure, or HCC in up to 25% of the patients. • There is no specific treatment recommended for acute hepatitis B. • Recombinant (HBsAg) vaccine recommended for all children and high-risk persons
Hepatitis B disease • Hepatitis B infection is found worldwide, with prevalence rates varying markedly among countries, but a total of approximately 400 million persons • Chronic carriers constitute the main reservoir of infection: in some countries, particularly in the Far East, up to 5% to 15% of all persons carry the virus. • The virus is spread vertically (during child birth), parenterally (needle stick injuries), and by sexual contact (especially in men who have sex with men).
Hepatitis B disease • Upon resolution of acute hepatitis B, HBsAg and HBeAg disappear from serum with the development of antibodies (anti-HBs and anti-HBe) against them. • Appearance of anti-HBssignals elimination of infection • The laboratory diagnosis of acute hepatitis B is best made by demonstrating the IgM antibody to HBcAg in serum • Past infection with hepatitis B is best determined by detecting IgG anti-HBc, or anti-HBs.
Hepatitis D virus (HDV) • Enveloped, Small, single-stranded (–) circular RNA virus • HDVrequires the presence of HBsAg (HBV surface antigen) for its transmission, and is thus found only in persons with acute or chronic HBV infection. • Simultaneous infection with both delta and hepatitis B may result in clinical hepatitis that is indistinguishable from acute hepatitis A or B, but usually the disease is more severe. • Diagnosis is by detection of antibodies to delta antigen
Hepatitis C virus (HCV) • Enveloped RNA virus of Flaviviridae family, positive sense, single-stranded RNA genome, • HCV is highly heterogeneous because the genome of HCV is highly mutable, which hinders the development of an HCV vaccine. • Similar to other positive-sense RNA viruses, HCV also replicates in the cytoplasm of the infected cell.
Hepatitis C disease • Similar to HBV, HCV is spread parenterally (blood transfusions, childbirth). • Screening of donor blood for antibody has reduced posttransfusionhepatitis by 80% to 90%. • The highest prevalence of HCV is in the Middle East, especially in Egypt.
Hepatitis C disease • After entering the blood, HCV moves to the main site of infection—the liver. • The immune response to HCV (antibodies, cytokines, cell infiltration) causes liver damage, and HCV can evade the immune system leading to chronic infection and liver damage. • The acute infection is usually asymptomatic or mild, but it results in a chronic carrier state in up to 85% of adult patients. • HCV-infected patients may develop cirrhosis of liver with increased risk of hepatocellular carcinoma (HCC). FIGURE 13–13. Inflammation in chronic hepatitis C virus (HCV) infection. Chronic inflammation of the portal area with a lymphoid aggregate in the center can be seen.
Hepatitis E virus (HEV) • Naked capsid, icosahedral, positivesense RNA virus • Hepatitis E spreads in a similar manner to that of hepatitis A. Twenty million HEV infections occur every year worldwide, mostly in developing countries. • Frequently subclinical, like hepatitis A HEV acute hepatitis indistinguishable from other acute hepatitis infections
Viruses overview Interferon and nucleoside and nucleotide analogs and inhibitors can be of benefit in chronic infection
Further reading: • Sherris Medical Microbiology, sixth edition • Chapter 13