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H EPATITUS V IRUSES

H EPATITUS V IRUSES. M aryam A fifi Osy Ndubaku Lani Kwon. Case Studies: Patient A.

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H EPATITUS V IRUSES

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  1. HEPATITUS VIRUSES Maryam Afifi Osy Ndubaku Lani Kwon

  2. Case Studies: Patient A • A 55-year-old man was admitted to the hospital with fatigue, nausea, and abdominal discomfort. He had a slight fever, his urine was dark yellow, and his abdomen was distended and tender. He had returned from a trip to Thailand within the previous month.

  3. Case Studies: Patient B • A 28-year-old woman was admitted to the hospital complaining of vomiting, abdominal discomfort, nausea, anorexia, dark urine and jaundice. She admitted that she was a former heroin addict and that she had shared needles. In addition, she was three months pregnant.

  4. Case Studies: Patient C • A 65-year-old man was admitted with jaundice, nausea, and vomiting six months after undergoing coronary artery bypass grafting.

  5. What is hepatitis? • Hepatitis is inflammation of the liver. • Cirrhosis is scaring of the liver. Healthy Liver Liver Cirrhosis http://peer.tamu.edu/curriculum_modules/Properties/Module_5/Lesson_four/L4_topic6.htm http://www.stanford.edu/group/virus/hepadna/2004tansilvis/Patient%20Ed.htm

  6. What factors may cause inflammation? http://hepatite-c.webhealth.com/wiki/Viral_Hepatitis

  7. Why is the liver important? • Organ responsible for multiple metabolic functions • Bile production and excretion • Excretion of bilirubin, cholesterol, hormones, and drugs • Metabolism of fats, proteins, and carbohydrates • Enzyme activation • Storage of glycogen, vitamins, and minerals • Synthesis of plasma proteins, such as albumin, and clotting factors • Blood detoxification and purification http://www.best-vitamin-supplements-guide.com/symptoms-liver-disease-health.html

  8. Types of Hepatitis HEPATITIS VIRALNON-VIRAL Hepatitis A Drug/Toxin Induced Hepatitis B Alcoholic Consumption HepatitisC Autoimmune Disorders Hepatitis D Hereditary Conditions Hepatitis E

  9. Common Symptoms • Mild • Moderate • Severe • Note: A patient may only experience fatigue, or no symptoms at all.

  10. Common Symptoms in Severe Hepatitis • Jaundice (yellowing of the skin & the whites of the eyes) • Muscle Aches • Headaches • Joint Pain (due to circulating immune complexes) • Fever • Diminished Appetite • Nausea • Vomiting • Diarrhea • Abdominal Pain • Dark “tea-colored” urine • Pale “clay-colored” stools • Edema (large amount of fluid collect in the abdomen beneath the skin) • Bleeding easily (decrease in levels of coagulation factors made by liver)

  11. Initial Diagnosis • Using the patient's medical history • drug and medication use • alcohol consumption • family history • exposure to toxins • past surgeries • past travels • sexual history • Invasive diagnostic approach • palpate the liver area to look for signs of swelling or tenderness • perform laboratory tests • order a liver biopsy

  12. Hepatitis A Virus (HAV) • Overview • Family Picornaviridae • Has a worldwide distribution and is endemic in most countries • HAV has an incubation period of 3 to 5 weeks • Enters the body via the gut  • Replicates in the digestive tract  • Spreads to infect the liver, where it multiplies • Only acute HAV • Symptoms often go unrecognized • However, some symptoms may be more severe • fever, tiredness, loss of appetite, nausea, abdominal discomfort, dark urine, and jaundice

  13. Laboratory Testing of HAV • A blood test showing the presence of IgM anti-HAV in serum confirms the diagnosis of acute hepatitis A infection.

  14. HAV • Means of Viral Acquisition: • Transmission through fecal-oral contact • Acquired by drinking water or eating foods that have been contaminated with fecal matter from an infected individual • Unprotected sex with an infected individual • Individuals at Risk: • International travelers • Sexually active homosexual men • Individuals with blood-clotting factors disease • Injecting and non-injecting drug users • Patients awaiting liver transplants • Chronic liver disease suffers • Individuals w/ risky occupations (i.e., laboratory researchers, animal handlers, daycare personnel) • Children living in areas of frequent Hepatitis A outbreaks

  15. HAV • Prevention: • Washing hands well with soap & water (1) before preparing foods (2) after changing diapers or (3) using the restroom • Short-term prevention is available from immune globulin • Treatment: • Hepatitis A vaccine • Immunity begins about four weeks after the first dose and lasts for at least 20 years • No infectious reoccurrence once immunity is developed • 99% of those infected recover on there own

  16. Classification of Hepatitis B Virus (HBV) • Family Hepadnaviridae • Classified into 8 genotypes of HBV designated A to H and are distributed in distinct geographical regions • Genotypes A and G have been divided into sub-genotypes identified by the Arabic numerals 1 and 2 • Genotype A  India, Burundi, Cameroon & Norway • Genotype B  China, East Asia, Societe Island & Vietnam • Genotype C  China & Bangladesh • Genotype D  Iran, Tunisia, North Africa, Sweden & Denmark • Genotype E  Senegal & Nigeria • Genotype F  Columbia, Venezuela & Spain • Genotype G  United States

  17. Structure of HBV • Genome is partially single-stranded circular nicked DNA • HBV is the only hepatitis causing virus that has DNA instead of RNA • HBcAg = core antigen • HBsAg = surface antigen in the outer capsid • HBeAg = antigen associated with the viral nucleocapsid http://www.ahealthyme.com/topic/printview

  18. Acute HBV • Symptoms don’t persist longer than 2 or 3 months • Usually asymptomatic or ‘flu-like’ symptoms • Jaundice: 20% of patients • Complete liver failure: ~ 0.1% of patients • Recovery normally takes 6 to 12 weeks after the onset of illness. • The mortality of acute HBV infection increases with age and with the presence of other disorders.

  19. Chronic HBV • HBV infection lasting longer than 6 months • 25% of HBV carriers develop liver disease which gets worse over time • Cirrhosis (scarring) of the liver occurs and is less able to carry out its normal functions • Enlarged liver • HBV DNA is integrated chromosomally in the hepatocytes. • Liver Cancer (hepatocellular carcinoma)

  20. Laboratory Testing of HBV • Serological Diagnosis: Enzyme-linked immunosorbent assays (ELISAs) and radioimmunoassays (RIAs) are used for the diagnosis of specific serological markers of HBV infection in both acute and chronic stages. • HBV core antibody test • Real-Time PCR amplification and detection of viral DNA or viral DNA polymerase are used in diagnosis of chronic HBV. • HBV DNA test

  21. Markers Used in HBV • IgG and IgM antibodies • HBsAg and HBeAg • HBcAg is present but undetectable due to the appearance of anti-HBc.

  22. Analysis of HBV • Acute – HBsAg (surface antigen) and Anti-HBc (core antibody IgM) • Anti-HBc appears early • Chronic – HBsAg (surface antigen) and HBeAg (nucleocapsid antigen) • HBeAg indicates viral replication • Note: If the surface antigen and/or DNA test is positive, the carrier is contagious.

  23. Diagnostic Testsfor HBV Modified from: http://www.doh.wa.gov/hsqa/fsl/Documents/LQA_Docs/Acute_hepatitis.pdf

  24. Acute vs. Chronic HBV http://virology-online.com/viruses/HepatitisB.htm

  25. HBV • Means of Viral Acquisition: • Sexual activity with an infected partner • Living with a chronically infected person • Infected mother to newborn during childbirth • Sharing needles with an infected person • Individuals at Risk: • People with multiple sexual partners • People diagnosed with a sexually transmitted disease • Injecting drug users • People living with others who are chronically infected • Newborns born to infected mothers • Children of immigrants from nations w/ a higher rate of hepatitis B • Health care and public safety workers that in contact w/ blood or bodily fluids • Hemodialysis patients • People not vaccinated for hepatitis B

  26. HBV • Prevention: • Receive the hepatitis B vaccine • Avoid contact with blood and other body fluids of infected individuals • Use latex condoms during every sexual encounter with every sexual partner • Don’t share items with an infected individual that might have their blood on it (i.e., toothbrush, razor, washcloth, or nail clippers) • Avoid getting tattoos because transmission may occur through unsterilized tattoo or piercing instruments. • Avoid sharing needles or syringes • If exposed to the virus, get a hepatitis B immune globulin injection within two weeks of exposure. • To prevent passing hepatitis to your infant, get a blood test for hepatitis B and receive appropriate injections if infected • If you are a health care or public safety worker, follow standard barrier precautions, safely handle all sharps and needles, and get the hepatitis vaccine.

  27. HBV • Treatment for Acute HBV: • Immunity typically occurs after infection or vaccination • Bed rest • Eat a healthy diet • Treatment for Chronic HBV: • Antiviral therapy  inhibit steps of viral genome replication • Viral polymerase inhibitors: lamivudine, adefovir dipivoxil, pegylated interferon alpha & entecavir • Reduce the risk of hepatocelluar carcinoma and viral load • May be curative • Problems • Emergence of HBV drug resistant mutants • Use combination of antiviral therapy • Certain genotypes are at higher risk for poor response to treatment • Genotyping prior to treatment

  28. Hepatitis C Virus (HCV) • Overview • Blood borne disease • Spread by blood to blood contact with infectious person • Leading cause of liver transplant in the United States

  29. HCV • Properties • Family Flaviviridae • Small Enveloped SS (-) strand RNA • Distinctly different genetically and clinically from HAV and HBV. http://www.rit.edu/~japfaa/infectious.html

  30. HCV • Replication • High rate • No proofreading by HCV RNA polymerase • Within hepatocytes in liver • Binds 2 receptors: CD81 & SR-class B1

  31. Acute HCV • Acute hepatitis C (First 6 months) • 60-70% infected are asymptomatic • 20-30% will clear the virus at this stage • Cleared from the body by the body's own natural defenses • Decreased appetite, fatigue, abdominal pain, jaundice, itching and flu-like symptoms.

  32. Chronic HCV • Chronic hepatitis C (After 6 months) • Can cause cirrhosis, liver failure and liver cancer • Those infected for 20 to 40 years are at higher risk of developing HCV-related liver cancer • Displays serve symptoms (mentioned earlier) • Hepatic encephalopathy

  33. Clinical Diagnosis of HCV • Acute phase diagnosis is challenging. • Chronic phase diagnosis on medical history, related symptoms, history of tattoos and piercing.

  34. Laboratory Testing of HCV • Serological blood tests used to detect antibodies and Virus • Anti-HCV test: Detect antibodies. • HCV-RNA test: Identifies virus in the blood. • Viral Load test: Measure viral RNA in particles in the blood • Viral genotyping: Determine the kind of virus present.

  35. HCV • Means of Viral Acquisition: • Transmission through blood contact • Individuals at Risk: • Injecting drug users • people who received clotting factors before 1987 are at the highest risk of hepatitis C • Patients on hemodialysis • Recipients of blood and/or organs prior to 1992 • People with undiagnosed liver problems • Infants born to infected mothers • Health care and public service employees • People with multiple sex partners • People having sex with infected partners are at a low risk of infection

  36. HCV • Prevention: • No vaccine is available • Avoid sharing of needles • Don’t share personal items that might have blood on them • Treatment: • Combination of pegylated interferon alpha (brand names Pegasys and PEG-Intron) and the antiviral drug Ribavirin • 24-48 weeks depending on genotype • Seek a medical evaluation for liver disease • Combination drug therapy is often used • Possible Hepatitis C vaccination in the near future. • Scientists are testing new vaccines on mice.

  37. Epidemiology of HCV • 170 million worldwide, 4 million in the United States • 35,000 to 185,000 new cases a year in the US • Co-infection rates with HIV are extremely high • 10,000 to 20,000 deaths a year

  38. www.thegicompany.com/graphics/ghepC.gif

  39. Final Diagnosis Patient A • Clinical Clues: • Fatigue, nausea, abdominal discomfort, slight fever, dark urine, abdomen distended and tender • Returned from a trip • Suggests food/water contamination • Oral-fecal contact • Final Diagnosis: • Hepatitis A

  40. Final Diagnosis Patient B • Clinical Clues: • Vomiting, abdominal discomfort, nausea, anorexia, dark urine, jaundice • chronic stage (HBV or HCV) • Former heroin addict (IDU) • May have been sexually active • Eliminates HCV • Pregnant • Newborn has a chance of being infected • Final Diagnosis: • Hepatitis B

  41. Final Diagnosis Patient C • Clinical Clues: • Jaundice, nausea, vomiting • Chronic stage (HBV or HCV) • Had surgery 6 months earlier • Suggests infection via blood transmission • Eliminates HBV • Final Diagnosis: • Hepatitis C

  42. References • About Hepatitis A. Outbreak 2005. <http://www.about-hepatitis.com>. • Arbor A. Antiviral-resistance HBV: Can we prevent this monster from growing? Journal of Clinical Virology 2006; S22. • Berger A., Preiser W. and Doerr H.W. The role of viral load determination for the management of immunodeficiency virus, hepatitis B virus and hepatitis C virus infection. Journal of Clinical Virology 2001; 23-30. • Buti M. Treatment of HBV resistance. Journal of Clinical Virology 2006; S22. • Campbell J, Hagan H, Latka M, Garfein R, Golub E, Coady M, Thomas D, Strathdee S (2006). "High prevalence of alcohol use among hepatitis C virus antibody positive injection drug users in three US cities.". Drug Alcohol Depend 81 (3): 259-65. PMID 16129567. • Christensen P.B., Krarup H.B., Niesters H.G.M., Norder H., Schaffalitzky de Muckadell O.B., Jeune B. and Georgsen J. Outbreak of Hepatitis B among injecting drug users in Denmark. Journal of Clinical Virology 2001; 22: 133-141. • Chiron Corporation Chiron Hepatitis C Research Honored with 2000 Lasker Award for Clinical Medical Research Press release, 18 September 2000. • Choo Q, Kuo G, Weiner A, Overby L, Bradley D, Houghton M (1989). "Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.". Science 244 (4902): 359-62. PMID 2523562.

  43. References • De Clercq E. Antiviral drugs in current clinical use. Journal of Clinical Virology 2004; 115-133. • Diagnosing and Treating Hepatitis. Hepatitis Foundation International 2003.<http://www.hepfi.org/living/liv_diagnosis.html>. • First Principles of Gastroentrology. AstraZeneca 2005. <http://www.gastroresource.com/GITextbook/en/Chapter14/14-5.htm>. • Gunson R.N., Shouval D., Roggendorf M., Zaaijer H., Nicholas H., Holzmann H., de Schryver A., Renders D., Connell J., Gerlich W.H., Marinho R.T., Tsantoulas D., Rigopoulou E., Rosenheim M., Valla D., Puro V., Struwe J., Tedder R., Aitken C., Alter M., Schalm S.W., Carmen W.F. and European Consensus Group. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of HBV and HCV from HCW to patients. Journal of Clinical Virology 2003; 213-230. • Hahn JA (2007). "Sex, Drugs, and Hepatitis C Virus". J Infect Dis 195: 1556–9. • Hochberger S., Althof D., Gallegos de Schrott R., Nachbaur N., Rock H. and Leying H. Fully automated quantitation of Hepatitis B virus (HBV) DNA in human plasma by the COBAS AmpliPrep/COBAS TaqMan System. Journal of Clinical Virology 2006; 373-380. • Houghton, M., Q.-L. Choo, and G. Kuo. NANBV Diagnostics and Vaccines. European Patent No. EP-0-3 18-216-A1. European Patent Office (filed 18 November 1988, published 31 May 1989).

  44. References • HBV ARUP Laboratories 2007. <http://www.arupconsult.com/Topics/InfectiousDz/Viruses/HBV.html>. • Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G, Dietrich M, Trautwein C, Manns MP (Nov 2001). "Treatment of acute hepatitis C with interferon alfa-2b". New England Journal of Medicine 345 (20): 1452-1457. PMID 11794193. • Johnson R, Gretch D, Yamabe H, Hart J, Bacchi C, Hartwell P, Couser W, Corey L, Wener M, Alpers C (1993). "Membranoproliferative glomerulonephritis associated with hepatitis C virus infection.". N Engl J Med 328 (7): 465-70. PMID 7678440. • Kuo G, Choo Q, Alter H, Gitnick G, Redeker A, Purcell R, Miyamura T, Dienstag J, Alter M, Stevens C (1989). "An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis.". Science 244 (4902): 362-4. PMID 2496467. • Lavanchy D. Worldwide epidemiology of HBV infection, disease burden and vaccine prevention. Journal of Clinical Virology 2005; S1-S3. • New Vaccine for Hepatitis C in Development. SpiritIndia.com 2007 <http://www.spiritindia.com/health-care-news-articles-1624.html>. • Niesters H.G.M., Pas S. and DeMan R.A. Detection of hepatitis B virus genotypes and mutants: current status. Journal of Clinical Virology 2005; 34: S4-S8.

  45. References • Pascual M, Perrin L, Giostra E, Schifferli J (1990). "Hepatitis C virus in patients with cryoglobulinemia type II.". J Infect Dis 162 (2): 569-70. PMID 2115556. • Prevention and treatment for Hepatitis A. Essortment 2002. <http://nyny.essortment.com/hepatitis_rjds.htm>. • Rodella A., Galli C., Terlenghi L., Perandin F., Bonfanti C. and Manca N. Quantitative analysis of HBsAg, IgM anti-HBc and anti-HBc avidity in acute and chronic hepatitis B. Journal of Clinical Virology 2006; 206-212. • Ruiz J, Molitor F, Plagenhoef J (2002). "Trends in hepatitis C and HIV infection among inmates entering prisons in California, 1994 versus 1999.". AIDS 16 (16): 2236-8. PMID 12409752. • Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, pp. 551–2. ISBN 0838585299. • Thompson S, Hernberger F, Wale E, Crofts N (1996). "Hepatitis C transmission through tattooing: a case report". Aust N Z J Public Health 20 (3): 317-8. PMID 8768424. • Tillmann H.L. Shall we treat acute hepatitis B infection? Journal of Clinical Virology 2006; S59-S60.

  46. References • Ulrich P, Romeo J, Lane P, Kelly I, Daniel L, Vyas G (1990). "Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase." (PDF & scanned pages). J Clin Invest 86 (5): 1609-14. PMID 2173725. • Villeneuve, J.P. The natural history of chronic hepatitis B virus infection. Journal of Clinical Virology 2005; S139-S142. • Viral Hepatitis A. CDC August 9, 2007. <http://www.cdc.gov/Ncidod/diseases/hepatitis/a/fact.htm>. • Viral Hepatitis B. CDC December 8, 2006. <http://www.cdc.gov/Ncidod/diseases/hepatitis/b/index.htm>. • Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB; for the Italian Association of the Study of Liver (A.I.S.F.) Commission on Extrahepatic Manifestations of HCV infection (2006). "Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach". Dig Liver Dis.: E-publication. PMID 16884964. • Zoulim F. Entecavir: A new treatment option for chronic hepatitis B. Journal of Clinical Virology 2006; 8-12.

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