Hepatitis c virus in blood transfusion

HCV INFECTION POST TRANSFUSION

1. HCV IN TRANSFUSION DR SUJAY BHOWMIK RESIDENT DEPT OF IMUUNOHEMATOLOGY & BLOOD TRANSFUSION , AFMC ,PUNE

2. Contents

3. HISTORY OF HCV 1975 Researchers identified a type of hepatitis didn’t test positive for HAV & HBV 1989 HCV isolated from the serum by Choo et al 1991 (FDA) approves interferon alfa-2B (Intron A), the first interferon drug for the treatment of HCV 1992 Testing of the Blood for HCV begins 1998 FDA Approves combination of Interferon and Ribavirin

4. HISTORY OF HCV 2001 Pegylated Interferon boosts effectiveness of Interferon therapy 2002 Mandatory screening for HCV was introduced in India 2010 Rapid Antibody Test improves HCV detection 2013 New Direct-Acting Anti- Virals are approved

5. The hepatitis viruses

6. Epidemiology Globally estimated 71 million people living with chronic hepatitis C 399,000 were estimated to have died from HCV-related liver disease in 2017. Most affected regions are Eastern Mediterranean and European Regions , with prevalence of 2.3% and 1.5% respectively. Prevalence of HCV infection in other regions varies from 0.5% to 1.0%.   Source:(WHO), 2018  

7. Global distribution - HCV genotypes HCV virus classified into 6 recognized genotypes O n the basis of the sequence of amino acids in the HCV HCV genotype 1 is the most prevalent worldwide ( 46.2% ) Genotype 3 is the next most prevalent globally ( 30.1% ) Genotyping is used for assessment course of infection , treatment duration and response .

8. Prevalence of HCV genotype Hepatology. 2014 Jul 28. doi: 10.1002/hep.27259. India, majority HCV genot ype 3 ( green)

9. Indian Scenario HCV prevalence estimated between 0.5% and 1.5% (15-18 million) Higher in the north-eastern part, tribal populations and Punjab. Lower in the western and eastern parts of the country Genotype 3 is the most common HCV genotype in India ( 54–80% of cases), followed by genotype 1 Genotype 1 has been reported more commonly from southern India

10. BURDEN OF DISEASE Hepatitis C is the most common cause of chronic liver disease and cirrhosis Worldwide 27% of cirrhosis and 25% of liver cancer is due to hepatitis C Leading cause of liver transplantation HCV prevalence exceeds 5 times HIV prevalence N o prophylactic vaccine or Specific immunoglobulin Effective antiviral treatment exist, which is disease prophylaxis as well

11. STRUCTURE AND GENETICS

12. Structure of the Hepatitis C virus HCV virus is enveloped , spherical, 55-65 nm in diameter Family- Flaviviridae , Genus - Hepacivirus Single-stranded RNA as genetic material A lipid envelope (E) containing glycoproteins (E1 and E2) , core of capsid proteins

13. GENOME 9600 nucleotides , composed of a long open reading frame (ORF) flanked by untranslated regions (UTR's) at both the ends Viral RNA forms 3 structural and 7 non-structural proteins Structural proteins ( core, E1, E2 ) help in forming structure of the virus non-structural proteins (NS1,NS2, NS3, NS4A, NS4B, NS5A, NS5B) The non structural proteins are important for performing viral functions

14. HCV RNA structure

15. PATHOGENESIS HCV has high propensity for establishing chronic infection . Chronically infected people generated approximately 10 12  viral particles every day. Remarkable replicative rate with highly error prone polymerase activity results in genetic diversity Existence of various quasispecies within infected individual. CD8+ and CD4+ T cell responses are higher in individuals who control the infection. Chronic infections occur when unable to mount HCV-specific T cell responses Impairment of Natural Killer (NK) in chronic infections

16. transmission of HCV Injection/I.V drug abuse (60%) S e x ual tran s mission(15%) Transfusion of blood and blood products (1-10%) Occupational exposure to blood (2- 4% ) Mother to baby (1%) Unknown (10%) HCV spread in India mainly through unsafe blood transfusion and injection reuse

17. Transmission by transfusion 1988, 90% of posttransfusion hepatitis were due to HCV Volunteer blood donors significantly reduced the risk of posttransfusion hepatitis to 10%. Screening reduced transmission to a rate of 1 per million transfusions . New cases due to infected people donating blood in the window period Recent studies report prevalence of <1.0% by blood transfusion.

18. Routes of transmission of HCV: Contaminated sharps/needles

19. Signs and Symptoms of HCV Most patients are asymptomatic or very mild non-specific symptoms Fatigue or tiredness may be prominent symptoms appear 6 to 7 weeks after infection Other symptoms include : mild fever muscle and joint pain nausea & vomiting loss of appetite abdominal pain diarrhea

20. Natural history of HCV

21. progress ION

22. Chronic hepatitis C Persistence of HCV RNA at least 6 months after the onset of acute infection. The risk of progression to chronic infection is influenced by various factors including: Age (more if infection occurs at age >25 years) Gender (males > females) Ethnicity ( Africans > Caucasians and Hispanic whites) Coinfection with HIV, HBV Concomitant alcohol consumption Comorbid conditions like cancer, immunosuppression, insulin resistance, nonalcoholic steatohepatitis, obesity, etc.

23. screening for Hepatitis C IV drug users Recipients of blood & blood products I nvasive procedur es Children born to mothers infected with HCV People with sexual partners ( HCV-infected ) People with HIV infection Prisoners People with tattoos or piercings Healthcare workers after needle sticks , sharps, or mucosal exposures Patients of Thalassemia Patients receiving long-term hemodialysis Unexplained long term liver disease and hepatitis including high liver enzymes

24. Diagnosis of HCV Virological diagnosis of HCV infection is based on two categories of tests : Indirect tests : serologic assays detecting specific antibody to HCV (anti-HCV) 2. Direct tests : assays that detect, quantify or characterize components of HCV viral particles ( HCV RNA and core antigen) Tests play a key role in the diagnosis , therapeutic decision-making, and assessment of response to therapy

25. WHO RECOMMENDATIONS To minimize the risk of HCV through transfusion: Screening should be performed using a highly sensitive and specific HCV antibody immunoassay or a combination HCV antigen-antibody immunoassay (EIA/CLIA). The assay should be capable of detecting genotypes specific to the country or region. Screening using a highly sensitive and specific HCV antibody rapid assay may be performed in laboratories with small throughput, in remote areas or emergency situations

26. INDIRECT tests   Seroconversion occurs on an average at 6-8 weeks after the onset of infection. In patients with spontaneously resolving infection, antibodies may persist throughout life, decrease slightly , gradually disappear after several years. Antibodies persists indefinitely in patients who develop chronic infection Antibodies may become undetectable in hemodialysis patients or in cases of profound immunosuppression.

27. ACUTE & CHRONIC HCV

28. ANTI HCV ELISA Four generations of ELISAs have been developed : 1989, First generation assays, which incorporated the recombinant c100-3 epitope from the NS4 region 1992, Second generation assays, which additionally incorporated epitopes c22-3 and c33c from the HCV core and NS3 regions. 1995 , Third generation assays contain reconfigured core and NS3 antigens and in addition a newly incorporated antigen from the NS5 region . 2012 , Fourth generation of tests is simultaneously detect HCV capsid antigen as well as antibodies to the core, NS3, NS4, and NS5 regions of the virus

29. ELISA Elisa Gen Core E1/E2/NSI NS2 NS3 NS4 NS5 Capsid 1st - - - - C100-3 - - 2nd C22-3 - - C33-C C200 HC-31 - - 3rd C22-P - - C33-C C100-3 5-1-1P NS-5 - 4th C22-P - - C33-C C100-3 5-1-1P NS-5 CAPSID Ag

30. Reduction in window period

31. NAT: Detection of HCV RNA NAT is considered the ‘gold standard’ for detecting active HCV replication. HCV NAT useful : Establishing diagnosis of acute HCV infection (RNA detectable as early as 1 week after exposure ) Confirmation as well as for follow-up of patients Viral load assessment for determining response during therapy.

32. NAT Qualitative NAT traditionally used as confirmatory tools for HCV diagnosis. These assays commonly utilize conventional RT-PCR or transcription-mediated amplification (TMA). Quantitative NAT include quantitative RT-PCR ( qRT -PCR) and branched deoxyribonucleic acid ( bDNA ) technology Due to greater sensitivity (99%) and specificity (98-99%) quantitative PCR has replaced qualitative PCR .

33. Treatment G oal of treatment : 1.N o HCV detected at least 12 weeks after complete treatment : sustained virologic response (SVR) 2. Prevent progression to cirrhosis, HCC, and decompensated liver disease Earlier weekly injections of I nterferons were administered with daily oral R ibavirin (antiviral drug) for as long as 6-12 months (40-70% cure rates)

34. Directly acting antivirals Directly acting antivirals or DAAs : Sofosbuvir D aclatasvir S ofosbuvir - L edipasvir S ofosbuvir - V elpatasvir ( fixed dose combination ) A chieve cure rates above 95% E ffective , safer and better-tolerated than the older therapies T reatment is shorter (usually 12 weeks)

35. Iatrogenic exposure and postexposure prophylaxis Transmission HCV to healthcare worker (HCW) due to : ( estimated incidence of 1.9% ) Poor disinfection practices Contaminated equipment ,improper cleaning , unsterilized equipment Medication administration ( through syringe reuse, etc.) Unsafe Blood sampling/ handling procedures

36. Post exposure prophylaxis Follow-up of personnel who sustain percutaneous or per mucosal exposure : Baseline testing for anti-HCV at source. Follow-up testing for anti-HCV and alanine aminotransferase (ALT) levels at 6 months and 1 year postexposure. Confirmation by NAT Education of workers about the risk and prevention of spread PEP is not recommended for HCV exposures

37. Thank you