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  • 1. Hepatitis B, C & D Viruses Dr. Masood Ahmad
  • 2. Viral hepatitis B
  • 3. Etiology  Hepatitis B virus (HBV)  HBV is a kind of hepadnavirus Three particles in serum:  spherical particles and tubular particles with a diameter of 20 nm, composed of HBsAg large particles with a diameter of 42 nm, named Dane particle. It consists of an outer protein shell (envelope, contain HBsAg) and an inner body ( core, contain HBcAg, HBeAg, HBV-DNA and DNAP )
  • 4. Hepatitis B Virus
  • 5. pathology       Three antigen-antibody system HBsAg-- anti-HBs system: HBsAg appears 1-2 weeks (late up to 11-12 weeks) after exposure, persists for 1-6 weeks( even 5 months) in acute hepatitis B. In chronic patients or carrier, HBsAg persist many years HBsAg is the marker of infectivity HBsAg can be found in blood and secretions: saliva, urine, semen, tears, sweat and breast milk Anti-HBs appear after HBsAg disappear several weeks (or months) anti-HBs is protective antibody, can persist for many years
  • 6. pathology HBcAg—anti-HBc system  HBcAg can be found in the nuclei of liver cells, no free HBcAg in serum  HBcAg is the marker of replication of HBV  The stage called window phase  Anti-HBc IgM is a marker of acute infection and acute attack of chronic infection of HBV. Anti-HBc IgG is the marker of past infection, high titer means low level replication of HBV
  • 7. pathology HBeAg—anti-HBe system    HBeAg is a soluable antigen HBeAg is a reliable indicator of active replication of HBV Anti-HBe is a marker of reduced infectivity. If exist long may be a marker of integration of HBV into liver cell
  • 8. Pathogenesis  Hepatitis B:   HBV invades into the human body by skin and mucosa, Via blood flow enters the liver and other organs such as pancreas, bile ducts, vessels, WBC, bone marrow, glomerular basement membrane HBcAg,HBsAg,HBeAg and HLA-Ⅰ appear on the liver cells infected with are recognized by CTL simultaneously and lead to the cytolysis of liver cells
  • 9. Pathogenesis  Helper T cell are activated by the receptor of HLAon its surface combing with HBsAg, HBcAg and HLA- antigen on the B cells promote B cell to release anti-HBs and clear HBV  The representation of HBcAg on the liver cells may cause cytopathy
  • 10. Hepatitis B - Clinical Features  Incubation period:  Clinical illness (jaundice):  Acute case-fatality rate:  Chronic infection:  Premature mortality from chronic liver disease: Average 60-90 days Range 45-180 days <5 yrs, <10% 5 yrs, 30%-50% 0.5%-1% <5 yrs, 30%-90% 5 yrs, 2%-10% 15%-25%
  • 11. Spectrum of Chronic Hepatitis B Diseases 1.Chronic Persistent Hepatitis 2.Chronic Active Hepatitis exacerbations of hepatitis 3.Cirrhosis of Liver 4.Hepatocellular Carcinoma asymptomatic - symptomatic
  • 12. Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg anti-HBe Total anti-HBc Titre 0 4 anti-HBs IgM anti-HBc HBsAg 8 12 16 20 24 28 32 36 Weeks after Exposure 52 100
  • 13. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc 0 4 8 12 16 20 24 28 32 36 Weeks after 52 Years
  • 14. Outcome of Hepatitis B Virus Infection by Age at Infection 100 100 80 ) % ( c no h C no t cef nI i r i 60 40 Chronic Infection 60 40 Chronic Infection (%) 20 20 Symptomatic Infection 0 Birth 1-6 months 7-12 months Age at Infection 1-4 years 0 Older Children and Adults Symptomatic Infection (%) 80
  • 15. Global Patterns of Chronic HBV Infection  High (>8%): 45% of global population  lifetime risk of infection >60%  early childhood infections common  Intermediate (2%-7%): 43% of global population  lifetime risk of infection 20%-60%  infections occur in all age groups  Low (<2%): 12% of global population  lifetime risk of infection <20%  most infections occur in adult risk groups
  • 16. Concentration of Hepatitis B Virus in Various Body Fluids High Moderate blood serum wound exudates semen vaginal fluid saliva Low/Not Detectable urine feces sweat tears breast milk
  • 17. Hepatitis B Virus Modes of Transmission  Sexual - sex workers and homosexuals are particular at risk.  Parenteral - IVDA, Health Workers are at increased risk.  Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.
  • 18. .        Diagnosis HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.
  • 19. Treatment      In acute hepatitis B the treatment is basically symptomatic Rest Ant emetics to control vomiting Plenty of fluids and carbohydrates Hepatotropic agents
  • 20. Treatment  Chronic Hepatitis B  Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%. Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance. Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.  
  • 21. Prevention  Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.  Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive.  Other measures - screening of blood donors, blood and body fluid precautions.
  • 22. Hepatitis C Virus
  • 23.         Hepatitis C virus (HCV) HCV is a member of flavivirus family. HCV genome is a single stranded positive-sense RNA and contains 9.4kb HCV genome may be divided into many types and subtypes. Resistance Antigen-antibody system The concentration of HCV in blood is low, HCV Ag has not be detected, anti-HCV is the indicator of infection and the marker of infectivity HCV-RNA HCV-RNA may be detected from blood or liver tissue, it’s the direct evidence of infectivity
  • 24. Hepatitis C - Clinical Features Incubation period: Average 6-7 wks Range 2-26 wks Clinical illness (jaundice): 30-40% (20-30%) Chronic hepatitis: 70% Persistent infection: Immunity: 85-100% No protective antibody response identified
  • 25. Chronic Hepatitis C Infection  The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.  All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.
  • 26. Hepatitis C Virus Infection Typical Serologic Course antiHCV Symptoms Titr e ALT Normal 0 1 2 3 4 5 6 Mont hsTime after Exposure 1 2 3 Years 4
  • 27. Risk Factors Associated with Transmission of HCV  Transfusion or transplant from infected donor  Injecting drug use  Hemodialysis (yrs on treatment)  Accidental injuries with needles/sharps  Sexual/household exposure to anti-HCV-positive contact  Multiple sex partners  Birth to HCV-infected mother
  • 28. Laboratory Diagnosis  HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.  HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
  • 29. Treatment  Acute infection  Chronic infection  Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. However addition of  Ribavirin – Improves the response rate to almost 70%.
  • 30. Treatment    Different genotypes of HCV have been identified and have been named as genotype 1 to 8 and there are still many which presently are untypeable. Many different types of interferons are also available including conventional, pegylated, and consensus interferon. Genotype 2 & 3(common subtypes in Pakistan) respond well to conventional interferon
  • 31. Prevention of Hepatitis C  Screening of blood, organ, tissue donors  High-risk behavior modification  Blood and body fluid precautions
  • 32.  Hepatitis D (Delta) Virus
  • 33.         Hepatitis D virus (HDV) HDV (Delta hepatitis virus) is a kind of defective virus HDV is found in the nuclei of infected hepatocytes and replicate HDV genome is a circular single strand RNA and contains 1.7kb The replication of HDV depends on HBV or other hepadnavirus, coated by HBsAg in blood HDV has one antigen-antibody system No free HDAg is detected in blood, it’s in the nuclei of hepatocytes; anti-HDV can be detected by RIA or ELISA in serum HBV and HDV co-infection or superinfection may make the disease exacerbation and may lead to fulminant hepatitis HDV RNA may be detected from liver cells, blood or humor.
  • 34. Hepatitis D (Delta) Virus HBsAg δ antigen RNA
  • 35. Hepatitis D - Clinical Features  Co-infection – severe acute disease. – low risk of chronic infection.  Super-infection – usually develop chronic HBV infection. – high risk of severe chronic liver disease. – may present as an acute hepatitis.
  • 36. Hepatitis D Virus Modes of Transmission  Percutaneous exposures  injecting drug use  Per mucosal exposures  sex contact
  • 37. HBV - HDV Coinfection Course Typical Serologic Symptoms ALT Elevated Titre IgM anti-HDV anti-HBs HDV RNA HBsAg Total antiHDV Time after Exposure
  • 38. HBV - HDV Typical Serologic Superinfection Course Jaundice Symptoms Titre Total anti-HDV ALT HDV RNA HBsAg IgM anti-HDV Time after
  • 39. Hepatitis D - Prevention  HBV-HDV Co-infection Pre or post-exposure prophylaxis to prevent HBV infection.  HBV-HDV Super-infection Education to reduce risk behaviors among persons with chronic HBV infection.
  • 40. Thanks