H EPATITUS V IRUSES

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

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