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The Liver Slide 4: 20/07/1430 HCV 4 What does the liver do? Stores vitamins, sugars, fats and other nutrients from the food that we eat Builds chemicals that our body needs to stay healthy Breaks down harmful substances, like alcohol and other toxic (poisonous) chemicals Removes waste products from our blood Makes sure that our body has just the right amount of other chemicals that it needs Viral Hepatitis : 20/07/1430 HCV 5 Viral Hepatitis Hepatitis [liver inflammation] is a disease that affects the liver. It is often caused by viruses such as: hepatitis A virus (HAV) hepatitis B virus (HBV) hepatitis C virus (HCV) Also D and E. What is hepatitis? Types of Viral Hepatitis : 20/07/1430 HCV 6 Types of Viral Hepatitis Source: Center for Disease Control and Prevention (CDC) Slide 7: 20/07/1430 HCV 7 Almost it is estimated that globally over 200 million people are infected with HCV. One of the problems in recognizing this epidemic is that it is a "silent” epidemic. Hepatitis C Slide 8: 20/07/1430 HCV 8 That is to say, most people who are infected do not know they are infected and have not reached the stage of the infection when clinical symptoms of liver failure begin to show. Veterans seem to have a higher rate of hepatitis C virus infection than others . THE GLOBAL HEPATITIS C VIRUS EPIDEMIC : 20/07/1430 HCV 9 THE GLOBAL HEPATITIS C VIRUS EPIDEMIC Egypt has the largest epidemic of hepatitis C in the world. : 20/07/1430 HCV 10 Egypt has the largest epidemic of hepatitis C in the world. Important Facts !!!!! HCV epidemic in Egypt is unique in the world and well documented in the international medical scientific literature.. Many publications suggest that over 15% of the people in Egypt are infected. This is ten times greater than any other country in the world. The prevalence of HCV in Western countries is less than 2%. Slide 11: 20/07/1430 HCV 11 The prevalence of HCV varies throughout the Egyptian country. The northern Nile Delta appears to have the highest prevalence, ~28%. The much smaller population of Upper Egypt, in the south, seems to have the lowest HCV prevalence, ~ 6%. Slide 12: 20/07/1430 HCV 12 Figure : It represents the prevalence in age groups of blood donors. Persons over 25 years old show a prevalence of 14% or higher of HCV. : 20/07/1430 HCV 13 Figure : It represents the prevalence in age groups of blood donors. Persons over 25 years old show a prevalence of 14% or higher of HCV. How Is the Hepatitis C Virus Spread? : 20/07/1430 HCV 14 How Is the Hepatitis C Virus Spread? The hepatitis C virus is spread through contact with the blood of an infected person. Some of the ways that people have been infected include having had a blood transfusion or organ transplant . a clotting factor problem, and being given a blood product . used a contaminated needle to inject drugs like heroin or cocaine, even if it was only once, many years ago been on long-term kidney dialysis How Is the Hepatitis C Virus Spread? : 20/07/1430 HCV 15 How Is the Hepatitis C Virus Spread? The hepatitis C virus is spread through contact with the blood of an infected person. Some of the ways that people have been infected include having been a health care worker and having had contact with blood in the workplace, especially through needle stick injuries been born to a woman who had hepatitis C when she gave birth to you Slide 16: 20/07/1430 HCV 16 People who work with disposable needles such as health workers, body piercers and tattoos should be very careful and make sure that their equipment is sterile. Special care should be taken when disposing needles or other 'sharps'. Slide 17: 20/07/1430 HCV 17 Sexual transmission of HCV is probably rare. Nevertheless, everyone should always take precautions to prevent sexually transmitted infections. Slide 18: 20/07/1430 HCV 18 Funny Carelessness Latrogenic Infections : 20/07/1430 HCV 19 Latrogenic Infections It plays an Important role in HCV transmission and prevention in Egypt, it results in many new HCV infections. It occurs non-intentionally from medical or dental procedures. For example, injections with HCV contaminated needles or syringes from trained or untrained medical or dental workers can transmit infection. Sometimes these workers have not been correctly trained, or are careless, or have not received any training at all. How Can I Decide If I Am at Risk for Hepatitis C? : 20/07/1430 HCV 20 How Can I Decide If I Am at Risk for Hepatitis C? you wish to be tested, or you are a veteran you had a blood transfusion you have injected drugs (past or present) you have unexplained liver disease you have unexplained/abnormal ALT levels you have a history of drinking alcohol excessively How Can I Decide If I Am at Risk for Hepatitis C? : 20/07/1430 HCV 21 How Can I Decide If I Am at Risk for Hepatitis C? your skin or mucous membranes have been exposed to another person's blood you have had multiple sexual partners you were on hemodialysis you have tattoos or repeated body piercings you have a history of snorting cocaine What Are Some Ways in Which the Hepatitis C Virus Is NOT Spread? : 20/07/1430 HCV 22 What Are Some Ways in Which the Hepatitis C Virus Is NOT Spread? The hepatitis C virus is not spread by holding someone’s hand hugging or kissing someone being coughed or sneezed on sharing eating utensils or food eating food or drinking water donating blood What Are the Symptoms of Hepatitis C? : 20/07/1430 HCV 23 What Are the Symptoms of Hepatitis C? Symptoms of hepatitis C are usually very mild. You may not have any symptoms at all. Even though hepatitis C might not make you feel sick, it is still a serious illness. In most cases, hepatitis C never goes away. Over time, it can cause other problems, including cirrhosis and liver cancer. What Is Cirrhosis? : 20/07/1430 HCV 24 What Is Cirrhosis? Cirrhosis, (pronounced "sir-o-sis"), is a medical term that means “scarring of the liver." When you have cirrhosis, large parts of your liver are damaged. Because it has been damaged, your liver may not work as well as it should. Cirrhosis can be very dangerous if it is not treated properly. Can I Get a Vaccine Against Hepatitis C? : 20/07/1430 HCV 25 Can I Get a Vaccine Against Hepatitis C? There is no a vaccine that will keep you from getting hepatitis C. There are vaccines that can keep you from getting other kinds of hepatitis, such as A and B. How Can I Prevent Myself from Getting or Spreading the HCV? : 20/07/1430 HCV 26 How Can I Prevent Myself from Getting or Spreading the HCV? Don’t inject drugsIf you can’t stop, use a clean needle every time, and never share your needle or works with anyone else. Practice safe sexUse a latex barrier, such as a rubber (condom), to prevent the spread of other sexually transmitted diseases. Slide 27: 20/07/1430 HCV 27 If you are a health care worker, observe standard precautionsHandle needles and other sharps safely. Don’t share personal items that might have blood on themDon’t share items such as razors, toothbrushes, or personal medical supplies. Talk with your health care provider about hepatitis C A Model for HCV Structure : 20/07/1430 HCV 28 A Model for HCV Structure Slide 29: 20/07/1430 HCV 29 The viral genome of HCV is RNA, very small, does not generate a cDNA and has been sequenced as shown before. Due to the structure of the viral genome, it is genetically very unstable and mutates rapidly. This means that the virus can quickly become resistant to anti-viral agents making treatment more difficult. In addition, with rapid mutation making an effective vaccine will also be a challenge. Pathogenetic mechanisms involved in hepatitis C virus-induced liver diseases : 20/07/1430 HCV 30 Pathogenetic mechanisms involved in hepatitis C virus-induced liver diseases The pathogenetic mechanisms for liver damage in acute hepatitis C are not clear, but a host immune cellular response may be involved. In chronic hepatitis C, strong evidence that host cellular immune response is involved in the control of viral replication and contributes to hepatocellular damage. Slide 31: 20/07/1430 HCV 31 As hepatitis C virus infection persists, continuous liver damage and regeneration, together with enhanced fibrogenesis , may eventually lead to cirrhosis in a proportion of patients. Transplant patients on high-dose immunosuppression may have high-level intrahepatic hepatitis C viral expression, and, in this setting, the virus may induce direct cytopathic liver damage Slide 32: 20/07/1430 HCV 32 Chronic hepatitis C (CHC) may become the main problem for the national public health bodies in many countries in the forthcoming 10 to 20 years . The wide spread of this form of hepatitis may lead to a 60% increase in the number of patients with hepatic cirrhosis, a 68% increase in the incidence of cancer (hepatocarcinoma), a 28% increase in the number of hepatic decompensation, and a twofold increase in fatal outcome from liver disorders. Slide 33: 20/07/1430 HCV 33 Slide 34: 20/07/1430 HCV 34 (a) cytoplasmic release and uncoating (b) IRES-mediated translation and polyprotein processing (c); RNA replication (d) packaging and assembly (e) virion maturation and release Virus binding and internalization Slide 35: 20/07/1430 HCV 35 The topology of HCV structural and non-structural proteins at the endoplasmic reticulum membrane is shown schematically. HCV RNA replication occurs in a specific membrane alteration, the membranous web. Note that IRES-mediated translation and polyprotein processing, as well as membranous web formation and RNA replication, which are illustrated here as separate steps for simplicity, might occur in a tightly coupled fashion. IRES, internal ribosome entry site. Hepatocellular Morphology in HCV infected Liver : 20/07/1430 HCV 36 Hepatocellular Morphology in HCV infected Liver Medicines to Treat Hepatitis C ? : 20/07/1430 HCV 37 Medicines to Treat Hepatitis C ? There are treatments for hepatitis C. However, these treatments are not right for everyone. Treatments for hepatitis C that have been approved by the Food and Drug Administration (FDA) include interferon by itself(called interferon monotherapy) interferon combined with ribavirin(called combination therapy) long-acting interferon(called pegylated interferon) A- Conventional Chemical Therapy : 20/07/1430 HCV 38 A- Conventional Chemical Therapy The main drug reliably proved to be effective in the treatment of hepatitis C is interferon-alpha (IF- ). It was the basis of all effective schemes developed for the treatment of HCV since HCV discovery. The mechanism of drug action is still insufficiently studied. It is believed that it prevents the infection of new cells, reducing the viral load in the blood serum. Slide 39: 20/07/1430 HCV 39 At present, the scheme adopted for monotherapy with IF- is generally as follows: a single dose of IF- (3000000 MU) is administered subcutaneously or intramuscularly three times a week over a period of 12 months. Stable positive effect of the treatment amounts to 15 – 20%. Slide 40: 20/07/1430 HCV 40 In recent years, therapists mostly employed combined schemes. The optimum treatment combines IF- with ribavirin, for which a certain synergism in the drug action is observed. Ribavirin is a guanosine analog exhibits a broad spectrum of activity in vitro with respect to DNA- and RNA-genomic viruses, including those of the Flaviviridae family. Slide 41: 20/07/1430 HCV 41 However, with respect to hepatitis C, ribavirin proved to be therapeutically effective only in combination with IF-. Ribavirin suppresses HCV replication and inhibits the activity of antiinflammatory cytokines. Conventionally, patients with primary CHC diagnosis are administered IF- with ribavirin for 6 months (in cases of low level of viremia). In cases of CHC with a high viremia level, the same treatment is conducted for 12 months. Recent advances in IF therapy : 20/07/1430 HCV 42 Recent advances in IF therapy In recent years, the IF- treatment efficacy was increased by means of pegilation ( a method based on attaching polyethylene glycol) (PEG) chains to IF- molecules). Pegilated interferon (PEG interferon) offers a number of advantages over the usual interferon : Slide 43: 20/07/1430 HCV 43 Pegasis is more stable with respect to enzymes capable of hydrolyzing IF, exhibits increased biological activity at a reduced immunogenicity, and is characterized by a lower rate of systemic clearance and by a significantly (almost tenfold) longer half-elimination time as compared to the usual IF-. B- Herbal therapeutic trials : 20/07/1430 HCV 44 B- Herbal therapeutic trials A number of herbal products claim to be beneficial for the liver, and hepatitis C patients who do not respond to conventional drug therapy, cannot tolerate its side effects, or simply want to support their body’s fight against the disease may try these products. Many patients reported using many different herbal products, but silymarin (milk thistle, (scientific name Silybum marianum) ) was by far the most common. Slide 45: 20/07/1430 HCV 45 Other supplements are also being studied for HCV as: Ginseng has shown some beneficial effects on the liver in laboratory studies but has not yet shown effects in people. Thymus extract is sometimes marketed for the treatment of hepatitis C, but there is currently no research to support their use for this purpose. Slide 46: 20/07/1430 HCV 46 People with chronic liver disease sometimes use licorice root or its extract glycyrrhizin. It was reported that glycyrrhizin administered intravenously for hepatitis C , suggests that glycyrrhizin may have beneficial effects against hepatitis C. Preliminary studies conducted primarily outside the United States have examined the potential of the following herbal products for treating chronic hepatitis C: lactoferrin, TJ-108 (a mixture of herbs used in Japanese Kampo medicine), schisandra, and oxymatrine (an extract from the sophora root). More research is needed before the safety and effectiveness of these products can be fully evaluated. Important advice : If You Have HCV and Thinking to Use an Herbal Supplement : 20/07/1430 HCV 47 Important advice : If You Have HCV and Thinking to Use an Herbal Supplement Do not replace proven conventional treatments for hepatitis C with complementary alternative medicine (CAM) treatments that are unproven. Be aware that some herbal products may damage the liver. For example, the herbs kava and comfrey have been linked to serious liver damage. Slide 48: 20/07/1430 HCV 48 Also be aware that the label on a supplement bottle may not accurately reflect what is inside. Tell your health care providers about any complementary and alternative practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care. If you are pregnant or nursing a child, or if you are considering Slide 49: 20/07/1430 HCV 49 Feb 2009 Thank You You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.