Virology

1. Virology HEPEATITIS C VIRUS GROUP B PRESENTATION I nur 13th march 2013

2. NAMES • BUCYEBUCYE Jean Pierre ug 12114191 • DUFATANYE Darius ug 12113300 • Duhuzekarera grace ug 12114360 • DUSHIMIMANA VESTINE UG 12113636 • GASANA JOEL UG 12215261 • HABANABASHAKA DESIRE UG 12113937 • HABIMANA CELESTIN UG 12114166 • HABINEZA BLAISE UG 12113381 • HAFASHIMANA EMMANUEL UG 12113174 • HABUMUFASHA JEAN PIERRE UG 12113102 • HAKIZIMANA THEONESTE UG 12113709 • HABIMANA jean UG 12113748 • Musabirema jean boscoug 12114321

3. The hepatitis C virus (HCV) is discovered in 1989, • Is a member of the Flaviviridae family • and it is a major cause of hepatitis (acute and chronic) and cirrhosis the world over. • According to the Centers for Disease Control and Prevention, 21% of all acute viral • hepatitis in the United States may be attributed to hepatitis C viral infection. • Infection with hepatitis C almost always results in chronic infection. 67% of all cases develop chronic liver disease with accompanying elevation of liver enzymes. Hepatitis C viral infection is also thought to be a major contributing factor to hepatocellular Carcinoma I.Introduction…1 II nur 13th march 2013

4. I.Introduction…2 HCV is transmitted by: • Inject street drugs or share a needle with someone who has hepatitis C • Have been on long-term kidney dialysis • Have regular contact with blood at work (such as a health care worker) • Have unprotected sexual contact with a person who has hepatitis C • Were born to a mother who had hepatitis C • Received a tattoo or acupuncture with needles that were not disinfected properly after being used on another person (risk is very low with practitioners who have a tattoo license or permit or an acupuncture license) • Received an organ transplant from a donor who has hepatitis C • Share personal items such as toothbrushes and razors with someone who has hepatitis C (less common) • Received a blood transfusion (rare in the U.S.) • Briefly HCV is a bloodborne so it is transmitted mainly by blood . III nur 13th march 2013

5. II.Epidemiology • Approximately 3% (170 million) of the world’s population has been infected with HCV. • For most countries, the prevalence of HCV infection is <3%. The prevalence is higher (up to 15%) in some countries in Africa and Asia and highest (>15%) in Egypt (Map below). • The most frequent mode of transmission in the United States is through sharing drug-injecting equipment among people who inject drugs. Travelers’ risk for contracting HCV infection is generally low • The principal activities that can result in blood exposure are the following: • Intravenous drug abuse (54%) • Multiple sex partners (36%) • Having had surgery within the last 6 month (16%) • Multiple contacts with an HCV-infected person (10%) • Employment in medical or dental fields (1.5%) • Needle stick injury (10%) and Unknown (32%) IV nur 13th march 2013

6. II.Epidemiology..2 V nur 13th march 2013

7. III.Pathogenesis • It is a small, enveloped, single-stranded RNA virus with a 9.6-kilobase (kb) genome that codes for a single polyprotein with one open reading frame, which is subsequently processed into functional proteins (Fig below ). • Pathogenesis of hcv can be divide into 2 : 1 -according to its genome 2-immunopathology • 1.According to its genome • We review, briefly, the genomic structure of HCV because this has a bearing on the pathogenesis of hepatitis C • The 5′ end of the genome encodes a highly conserved nucleocapsid core protein, followed by envelope proteins E1 and E2. • Two hypervariable regions (HVR 1 and 2) are present in the E2 sequence. A protein, p7, is believed to function as an ion channel. Toward the 3′ end are six less conserved nonstructural proteins: NS2, NS3, NS4A, NS4B, NS5A, and NS5B VI nur 13th march 2013

8. NS5B is the viral RNA-dependent RNA polymerase. The 3′ sequences of both the positive- and negative-strand RNAs contribute cis-acting functions that are essential for viral replication. • The secondary structure and protein-binding properties of these highly conserved nontranslated regions are thought to promote HCV RNA synthesis and genome stability through the binding of various host and viral proteins. • FIGURE Diagrammatic representation of the hepatitis C viral (HCV) genomic structure. HCV is a (+) strand RNA virus containing two untranslated regions at the 5′ and the 3′ ends. The virus encodes a single polypeptide that is processed into multiple viral proteins. The potential function of each individual protein is highlighted. VII 13th march 2013

9. Because of the poor fidelity of the HCV RNA polymerase (NS5B), the virus is inherently unstable, giving rise to multiple genotypes and subtypes • Indeed, within any given patient HCV circulates as a population of divergent but closely related variants known as quasispecies • Over time, dozens of quasispecies can be detected within one individual and mapped as derivative strains of the original HCV strain that infected the patient • The E2 protein of the envelope is the target of many anti-HCV antibodies but is also the most variable region of the entire viral genome, enabling emergent virus strains to escape from neutralizing antibodies. This genomic instability and antigenic variability have seriously hampered efforts to develop an HCV vaccine • A characteristic feature of HCV infection, therefore, is repeated bouts of hepatic damage, the result of reactivation of a preexisting infection or emergence of an endogenous, newly mutated strain. VIII nur 13th march 2013

10. The incubation period for HCV hepatitis ranges from 2 to 26 weeks, with a mean between 6 and 12 weeks • In about 85% of individuals, the clinical course of the acute infection is asymptomatic and easily missed. • HCV RNA is detectable in blood for 1 to 3 weeks, coincident with elevations in serum transaminases • In symptomatic acute HCV infection, anti-HCV antibodies are detected in only 50% to 70% of patients; in the remaining patients, the anti-HCV antibodies emerge after 3 to 6 weeks. The clinical course of acute HCV hepatitis is milder than that of HBV; rare cases may be severe and indistinguishable from HAV or HBV hepatitis. Strong immune responses involving CD4+ and CD8+ T cells are associated with self-limited HCV infections, but it is not known why only a small minority of individuals are capable of clearing HCV infection. IX nur

11. Persistent infection and chronic hepatitis are the hallmarks of HCV infection, despite the generally asymptomatic nature of the acute illness. This occurs in 80% to 85% of cases. Cirrhosis may develop over 5 to 20 years after acute infection in 20% to 30% of patients with persistent infection. The mechanisms that lead to the chronicity of HCV infection are not well understood, but it is clear that the virus has developed multiple strategies to evade host antiviral immunity HCV is able to actively inhibit the interferon (IFN)-mediated cellular antiviral response at multiple steps, including Toll-like receptor signaling in response to viral RNA recognition and signaling downstream of IFN receptors that confers on cells an anti-viral state. 2.immunopathology • Mechanisms involved in the persistence of HCVinfection • The quality of the cellular immuneresponse is crucial for the elimination or the persistence of HCV infection. X nur 13th march 2013

12. CD4+ T cells and their cytokines with inflammatory and regulatory activities seem to play an important role in the immunopathogenesis of chronic HCV infectionCD4+ T cell responses are polarized into type 1 and type 2 helper T cell (Thl and Th2) responses.The Thl cells secrete interleukin 2 (IL-2) and interferon gamma, which are important stimuli for the development of the host antiviral immune responses, including cytotoxic T-lymphocyte (CTL) generation and NK-cell activation. The Th2 cells produce IL-4 and IL-lo, which enhance antibody production and downregulate the Thl response. It is hypothesized that the imbalance between the Thl and the Th2 responses is implicated in disease progression and the inability to clear infection.Patients with acute HCV infection who clear the virus and have a self-limited acute hepatitis develop a strong Thl response, but a weak or absent Th2 response. Conversely, patients who develop a chronic infection show a predominant Th2 response, but a weak Th 1 response (4). These observations suggest that the effect of Thl cytokines is crucial for protection against HCV infection, whereas a preferential production of Th2 cytokines may have an inhibitory effect on the patient’s immune system and therefore favors persistent HCV infectionThe primary causes of these different early immune responses in acute HCV infection are not known. XI nur 13th march 2013

13. Mechanisms involved in liver lesions HCV is not directly cytopathic. The hepatitic process appears to result from the immune recognition and destruction of infected hepatocytes (4). Persistent HCV infection in the liver is continuously triggering an active T cell response, which is probably the main mechanism responsible for the liver lesions . Studies of the intrahepatic immune processes implicated in the pathogenesis of chronic hepatitis C are limited. However, HCV specific helper and cytotoxic T cells able to recognize structural and non structural HCV proteins (especially core and NS4 proteins) have been detected within the liver infiltrates The predominant production of Thl cytokines is believed to play a role in enhancing necro-inflammatory lesions (4,15). This continuous necro-inflammatory process, inefficient for clearing viral infection, is probably the main cause of the fibrogenesis mechanisms responsible for the progression of the liver disease However, necro-inflammatory lesions and progression of fibrosis are not always well correlated, which suggests the role of cofactors. XII nur 13th march 2013

14. CLINICAL PRESENTATION Most people with acute have few, if any, symptoms and are not even aware they are infected. If there are symptoms, they may include: .Dark urine .Fatigue .Jaundice .Loss of appetite. .Abdominal pain .Nausea or vomiting Symptoms of acute hepatitis C, if they appear at all, generally appear 6 to 12 weeks after exposure to the virus. Even if they don't show symptoms, some people with chronic hepatitis C may develop serious liver disease that is not apparent at first. In the United States, chronic hepatitis C infection is the leading cause of cirrhosis (severe liver disease) and liver cancer, both of which can be fatal. XIII nur 13th march 2013

15. DIAGNOSIS Two major types of tests are available: IgG assays for anti-HCV and nucleic acid amplification testing to detect HCV RNA in blood (viremia). Assays for IgM, to detect early or acute infection, are not available. Approximately 80% of people who seroconvert to anti-HCV, indicative of acute infection, will progress to chronic infection and persistently detectable viremia. False-negative antibody test results, while rare, may occur early in the course of acute infection, usually in the first 15 weeks after exposure and infection. TREATMENT Treatment for hepatitis C is rapidly evolving. In general, “sustained viral response” (considered a cure) is now achieved in 50% of patients taking pegylated interferon and ribavirin for 24–48 weeks. New oral agents added to a regimen of interferon and ribavirin are increasing cure rates to 85%–90% on initial treatment attempts; these may be approved and available by the time of printing this publication. XIV nur 13th march 2013

16. PREVENTIVE MEASURES FOR TRAVELERS No vaccine is available, and immune globulin does not provide protection. When seeking medical or dental care, travelers should be alert to the use of medical, surgical, and dental equipment that has not been adequately sterilized or disinfected, reuse of contaminated equipment, and unsafe injecting practices (such as reuse of disposable needles and syringes). HCV and other bloodborne pathogens can be transmitted if tools are not sterile or the clinician does not follow other proper infection-control procedures (washing hands, using latex gloves, and cleaning and disinfecting surfaces and instruments). There are still a few areas of the world, such as parts of sub-Saharan Africa, where blood donors may not be screened for HCV. Travelers should be advised to consider the health risks if they are thinking about getting a tattoo or body piercing in areas where adequate sterilization or disinfection procedures might not be available or practiced. XV nur 13th march 2013

17. Reference: -PATHOLOGIC BASIS OF DISEASES 8th Edition -Journal of Hepatology ISSN 0169-S/85 by Nathalie Boyer and Patrick Marcellin - www.pubmed.com XVI nur 13th march 2013