Hepatitis C infection update

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Hepatitis C infection update

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Hepatitis C infection update

  1. 1. Hepatitis C Infection an update Dr.T.V.Rao MD4/17/2012 1
  2. 2. Hepatitis C virus (HCV) Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States; approximately 3.2 million persons are chronically infected. Although HCV is not efficiently transmitted sexually, persons at risk for infection through injection drug use might seek care in STD treatment facilities, HIV counselling and testing facilities.4/17/2012 2
  3. 3. What is Hepatitis C InfectionInfection with Hepatitis C causes 1 Chronic hepatitis 2 Cirrhosis 3 Hepatocellular Carcinoma4/17/2012 3
  4. 4. 4/17/2012 4
  5. 5. 4/17/2012 5
  6. 6. HCV - Virology Family – Flaviviridae Genus – Hepacivirus A small ( 50 nm ) virus ss RNA virus, positive senstive RNA sequence analysis into at least six major genotypes (Clades) There are 1004/17/2012 6
  7. 7. Genome - HCV Clades differ from each other by 25-30% at the nucleotide level: The genome is 9.4kb in size and encodes a core protein The expression of cDNA clones of HCV in yeast led to the development of serological tests for antibodies to HCV HCV displays genomic diversity. The genomic diversity is not correlated to difference in clinical disease4/17/2012 7
  8. 8. Why Hepatitis C is an important Disease WHO estimates 170 million ( 3 % ) world population is infected with HCV. Highest in Egypt. Lowest in Sweden. In USA 2.7 to 3.4 million people infected. In USA there is a decline since 1990. Those born between 1940 and 1965 had highest incidence reaching a peak between the age of 20 to 35 years In USA 25,000 persons die of cirrhosis and chronic liver disease4/17/2012 8
  9. 9. How Hepatitis C is transmitted Blood transfusions Drug absue – Injections Tattooing Contamination of Medical equipment.4/17/2012 9
  10. 10. HCV Mother to Child transmission Vertical transmission occurs in 3 -10% Mother with higher HCV viral loads or co infection with HIV transmit in higher rates. No risk of transmission is associated with breast feeding.4/17/2012 10
  11. 11. Transmission of Infection in Spouses Sexual transmission of HCV can occur, with much lower frequency than that of HIV, and HBV Long term partners of HCV infected patients have higher rates of infection than the general population. May be associated with shared use of Razors and tooth brushes. Dr.T.V.Rao MD4/17/2012 11
  12. 12. CDC on Spouse Transmission CDC on the basis of current evidence does not recommend use of barrier precautions among the heterosexual monogamous couples, to prevent4/17/2012 HCV transmission. 12
  13. 13. Higher incidence of HCV Infections Increased prevalence in Sexually transmitted diseases. HIV co infection. Injecting drug use. High risk sexual practices.Dr.T.V.Rao MD4/17/2012 13
  14. 14. Health care devices and HCV WHO calculates that unsafe health care devices account for 2.3 million new HCV infections per year, and 200 000 HCV related premature deaths, mostly in Developing countries The re-use of injection equipments without sterilization contributes to major spread. WHO estimates that about 40% of injection related equipment is reused in Devloping countries.4/17/2012 14
  15. 15. HCV and Blood Transfusions Blood transfusions from unscreened donors and unsafe therapeutic procedures are major modes of transmission in Developing countries. Paid donors are grave risk Dr.T.V.Rao MD4/17/2012 15
  16. 16. Trends of Change in Transmission Education among the drug abusers, blood donor screening needle exchange programmes have remarkably reduced the incidence. Sexual, and Perinatal transmission has gained importance. Dr.T.V.Rao MD4/17/2012 16
  17. 17. Needle Stick Injuries A CDC report suggested risk of HCV transmission is about six times higher per needle stick exposure than is the risk with HIV infection ( 1.8% vs 0.35 ) Dr.T.V.Rao MD4/17/2012 17
  18. 18. Onset of Infection in HCV The average incubation period for HCV is 6-7 days The period for exposure to seroconversion is 8-9 weeks. About 90% of the infected are anti HCV positive in 5 months Dr.T.V.Rao MD4/17/2012 18
  19. 19. How Virus C replicates in Hepatocytes Depends on cellular factors and shared by viral proteins. Replicates with viral and host proteins Multiplication rate is very high a Trillion particles are produced every day.4/17/2012 19
  20. 20. Pathology of HCV infection Virus causes inflammation of Liver Microscopically spotted parenchymal cell degeneration Necrosis of Hepatocytes Causes diffuse lobular inflammatory reaction Disruption of liver cell cords Accumulation of Macrophages near degenerating Hepatocytes. Dr.T.V.Rao MD4/17/2012 20
  21. 21. Pathology Both Hepatitis B and C are cytopathogenic Cellular damage is immune mediated Both HBV and HBC have significant roles in in the development of Hepatocellular carcinoma Carcinoma may appear 15 – 60 years after the beginning of infection.4/17/2012 21
  22. 22. Viral clearance from Hepatocytes Virus clears either spontaneously or by treatment May lead to cure, even fibrosis is regresses Normalization of enzymes liver enzymes on clearance of virus4/17/2012 22
  23. 23. Clinical course of Hepatitis C Infection Acute HCV infection is asymptomatic in most patients. Natural history and chronicity rate varies much between the population groups. Persistence of virus has been defined as detectable HCV RNA for more than 6 months from the time of presumed infection4/17/2012 23
  24. 24. Progress of HCV infections4/17/2012 24
  25. 25. How Acute Infection Manifests Symptomatic infection in only 15 % of the infected Spontaneous clearance is higher in patients present with symptomatic than an asymptomatic acute HCV infections Major studies suggest that chronicity rates might depend on the mode of infection, and the age at which patient acquire infection.4/17/2012 25
  26. 26. Acute manifestations Only 10-20% of all acutely infected patients develop Jaundice, Higher incidence of Jaundice is in injecting drug users Fatigue,myalgia,low grade fever. Right upper quadrant pain,nausea or vomiting Dr.T.V.Rao MD4/17/2012 26
  27. 27. Other clinical Manifestations Influenza like illness Dark colored urine Clay colored stool Jaundice is more indicative of disease4/17/2012 27
  28. 28. Progress of events in HCV Infection4/17/2012 28
  29. 29. Bio Chemical marker Concentration of Alanine aminotransferase greater than ten times the upper limit of normal are uncommon. Even few cases symptomatic HCV infection have reported increase up to 20 times The presence of jaundice might be an indicator of an effective host immune response, leads to spontaneous viral clearance.4/17/2012 29
  30. 30. Diagnosis of HCV Infection No definitive pathological test to diagnose acute HCV infection. Diagnosis is supported by, Identifiable exposure to HCV Recent seroconversion Marked increased concentration of liver enzymes4/17/2012 30
  31. 31. Serology in Diagnosis Detection of antibodies against HCV immunoassay is unreliable to identify acute infections Antibodies may be absent in acute stage The appearance of antibodies against HCV could be delayed in as many as 30% of patients at the onset of symptoms, particularly in Immunosuppressed. IgM antibodies against HCV have not proven useful in diagnosis of acute HCV infections, as their concentration remain fairly constant in both acute and chronic infections. Dr.T.V.Rao MD4/17/2012 31
  32. 32. RNA estimation in HCV infections HCV RNA levels could fluctuate ( may be undetectable ) up to a year after the infection, necessitatin g serial measurements of HCV RNA for a period of 1 year. As many as 10% of acutely infected patients might eventually lose serological markers.4/17/2012 32
  33. 33. Sensitive methods of Diagnosis of HCV infection Qualitative and quantitative methods of detection of HCV RNA by 1 Reverse transcriptase RT- PCR, 2 Branched DNA (bDNA) 3 Transcription mediated amplification (TMA )4/17/2012 33
  34. 34. CDC guidelines for testing HCV infection.Testing for antibodiesMeasuring Analine aminotransferase concentrationTesting for HCV RNA by PCR at 4 -6 weeks after exposure and again for antibodies against HCV and analine aminotransferase concentration at 4- 6 months4/17/2012 34
  35. 35. Prevention and Control There is no vaccine for HCV infection Control measures focus on prevention activities that reduce risks for contracting HCV Major guidelines are 1 Screening and testing blood,plasma,organ, tissue,and semen donors.4/17/2012 35
  36. 36. Counseling and Educative measures Counseling of persons with high drug or sexual practices Implementation of infection control practices in health care and other settings. Professional and Public education4/17/2012 36
  37. 37. Treatment in HCV Optimum timing of treatment is critical to avoid unnecessary treatment of those who will clear the infection spontaneously The evidence suggests that it is prudent to wait for at least 12 weeks before initiating antiviral treatment in patients with acute Hepatitis C, especially when they present with symptomatic hepatitis C Physicians select the regimes depending on the clinical experience and to suit the circumstances.4/17/2012 37
  38. 38. Treatment Regimen With advent of newer pegylated Interferons and use has improved efficacy in patients with chronic HCV infection, clinicians now use pegylated interferon as first line therpay,high sustained Virological response rates have been reported.4/17/2012 38
  39. 39. New Improvements in HCV Treatment HCV treatment improved again in 2001 with FDA approval of pegylated interferon. Attaching the polyethylene glycol (PEG) molecule to interferon (a process called pegylation) keeps the drug in the bloodstream longer and makes it more effective against HCV.4/17/2012 39
  40. 40. Pegylated Interferons replaces… Replacing standard interferon with pegylated interferon has significantly improved response to HCV treatment and requires a dosing regimen of only one injection per week . Currently, therapy with pegylated interferon plus ribavirin is the standard treatment of HCV in HIV-positive people and the only FDA-approved treatment for coinfection.4/17/2012 40
  41. 41. Preventive strategies in HCV Infection As there is no effective vaccine ,preventive aspects should carry priority on Universal screening of Blood and Blood products Sterilization of medical and dental equipment. Mandatory used of disposable needles, avoidance of unnecessary injections or surgical procedures. Health workers, and public should be educated about the risk of infection from unsafe practices. Dr.T.V.Rao MD4/17/2012 41
  42. 42. Created by Dr.T.V.Rao MD for Medical and HealthWorkers in the Developing World Email doctortvrao@gmail.com4/17/2012 42

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