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HEPATITUS VIRUSES Maryam Afifi Osy Ndubaku Lani Kwon 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. 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. Case Studies: Patient C A 65-year-old man was admitted with jaundice, nausea, and vomiting six months after undergoing coronary artery bypass grafting. What is hepatitis? Hepatitis is inflammation of the liver. Cirrhosis is scaring of the liver. Healthy Liver http://peer.tamu.edu/curriculum_modules/Properties/Mod ule_5/Lesson_four/L4_topic6.htm Liver Cirrhosis http://www.stanford.edu/group/virus/hepadna/2004tansilvi s/Patient%20Ed.htm What factors may cause inflammation? http://hepatite-c.webhealth.com/wiki/Viral_Hepatitis 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-supplementsguide.com/symptoms-liver-disease-health.html Types of Hepatitis HEPATITIS VIRAL Hepatitis Hepatitis Hepatitis Hepatitis Hepatitis NON-VIRAL A B C D E Drug/Toxin Induced Alcoholic Consumption Autoimmune Disorders Hereditary Conditions Common Symptoms Mild Moderate Severe Note: A patient may only experience fatigue, or no symptoms at all. 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) 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 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 Laboratory Testing of HAV A blood test showing the presence of IgM anti-HAV in serum confirms the diagnosis of acute hepatitis A infection. 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, Children living in areas of frequent Hepatitis A outbreaks animal handlers, daycare personnel) 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 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 Genotype Genotype Genotype Genotype Genotype Genotype A India, Burundi, Cameroon & Norway B China, East Asia, Societe Island & Vietnam C China & Bangladesh D Iran, Tunisia, North Africa, Sweden & Denmark E Senegal & Nigeria F Columbia, Venezuela & Spain G United States 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 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. 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) 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 Markers Used in HBV IgG and IgM antibodies HBsAg and HBeAg HBcAg is present but undetectable due to the appearance of anti-HBc. Analysis of HBV Acute – HBsAg (surface antigen) and Anti-HBc (core antibody IgM) Chronic – HBsAg (surface antigen) and HBeAg (nucleocapsid antigen) Anti-HBc appears early HBeAg indicates viral replication Note: If the surface antigen and/or DNA test is positive, the carrier is contagious. Diagnostic Tests for HBV Modified from: http://www.doh.wa.gov/hsqa/fsl/Documents/LQA_Docs/Acute_hepatitis.pdf Acute vs. Chronic HBV http://virology-online.com/viruses/HepatitisB.htm 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 Prevention: HBV 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. 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 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 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 HCV Replication High rate No proofreading by HCV RNA polymerase Within hepatocytes in liver Binds 2 receptors: CD81 & SR-class B1 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. 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 Clinical Diagnosis of HCV Acute phase diagnosis is challenging. Chronic phase diagnosis on medical history, related symptoms, history of tattoos and piercing. 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. 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 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. 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 www.thegicompany.com/graphics/ghepC.gif 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 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 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 References About Hepatitis A. 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