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General aspects and definitions of hepatitis B

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General aspects and definitions of hepatitis B

  1. 1. Outcomes HBV str Serology Acute vs Patterns Interpretn Phases General Points on Hepatitis B Virus Infection
  2. 2. Introduction and generalities on viral hepatitis Outcomes HBV str Serology Acute vs Patterns Interpretn Phases Learning Outcomes At the end of this module, participants are expected to: • Be able to define the common terminologies used regarding hepatitis B virus and outcome of infection • Differentiate acute from chronic infection • Explain the clinical significance of the serological markers of hepatitis B virus
  3. 3. Introduction and generalities on viral hepatitis Outcomes HBV str Image from Microbiology Info.com • HBsAg, HBV surface antigen is on surface of virus. • There is nucleocapsid core within the viral particle. • HBcAg, HBV core antigen is on surface of nucleocapsid • HBV DNA is in the inside of nucleocapsid • HBeAg, HBV envelope antigen, is located between HBV surface and core • DNA Polymerase – enzyme that helps in the replication of the HBV Structure of Hepatitis B virus Serology Acute vs Patterns Interpretn Phases
  4. 4. Introduction and generalities on viral hepatitis Outcomes HBV str Serology HBV DNA (Viral load) | Quantitative or qualitative Antigens Antibodies HBsAg Hepatitis B surface Antigen Anti-HBs HBcAg Hepatitis B core Antigen (absent in blood) IgM anti-HBc IgG anti-HBc HBeAg Hepatitis B e Antigen Anti-HBe Types of Serological Markers for HBV Acute vs Patterns Interpretn Phases
  5. 5. Outcomes HBV str Serology Acute vs Patterns Interpretn Phases *Breakwell et al, 2017 Marker Clinical significance HBsAg Appears in blood in acute stage of infection and persists in chronic infection – Its an alternative to HBV DNA to monitor response to treatment IgM Anti-HBc IgM subclass of anti-HBc – this is a serological marker of acute infection. Disappears in chronic infection (in the presence of HBsAg) HBeAg Indicates high viral load as well as high infectivity (HBV patients in Africa have low prevalence of this antigen*) Anti-HBe Indicates decreasing viral load. But may be absent in some mutant forms of HBV infection Anti-HBs Indicates recovery from hepatitis B infection (in the presence of Anti-HBc IgG) or immunity from vaccination Clinical Significance of Serological Markers for HBV
  6. 6. Introduction and generalities on viral hepatitis Outcomes HBV str Serology Acute vs Acute 6 months Chronic Acute versus chronic HBV • The terms, acute and chronic as it refers to HBV infection refers to a timeline rather than severity • Acute means infection lasting less than 6 months • Chronic means infection lasting beyond 6 months Patterns Interpretn Phases
  7. 7. Introduction and generalities on viral hepatitis Outcomes HBV str Serology Acute vs Patterns Pattern of serological markers in acute HBV infection Patterns Pattern of serological markers in acute HBV infection Interpretn Phases • The 1st serological marker to appear in blood is HBsAg, followed by HBeAg and then anti-HB core • Anti-HB core is like a scar that does not disappear, even when one achieves HBsAg clearance
  8. 8. Introduction and generalities on viral hepatitis Outcomes HBV str Serology Acute vs Patterns Pattern of serological markers in chronic HBV infection Interpretn Phases
  9. 9. Introduction and generalities on viral hepatitis Outcomes HBV str Serology Acute vs Patterns Interpretn Phases Interpretation of serological markers in HBV infection HBsAg Anti-HBc IgG Anti-HBc IgM Anti-HBs Interpretation - - - - Never exposed (susceptible) - + - + Past infection, cleared; natural immunity acquired - + - - Past infection, cleared; natural immunity has waned over time - - - + Immunity due to vaccination - - + + Recent infection, recovered; immunity achieved + - + - Acute ongoing infection + + - - Chronic ongoing infection
  10. 10. Introduction and generalities on viral hepatitis Outcomes HBV str Serology Acute vs Patterns Interpretn Phases Phases of HBV infection by immune response
  11. 11. Phases of HBV infection by immune response • These phases provide a summary of the natural course of HBV infection • The phases are not necessarily sequential • Strictly, there are 4 phases • Next, we shall describe the events of the phases in terms of clinical and laboratory parameters 1 e tolerance otolerant stently normal ve | HBeAb –ve ry high mal or mild 2 ance se ermittently ve an in immune lammatory 3 rrier state mal +ve (but upto d 4 ns 5 e
  12. 12. Phases of HBV infection by immune response • These phases provide a summary of the natural course of HBV infection • The phases are not necessarily sequential • Strictly, there are 4 phases • Next, we shall describe the events of the phases in terms of clinical and laboratory parameters 1 Phase 1: Immune tolerance • Alternative term is immunotolerant • Liver enzyme, ALT is persistently normal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is very high • Liver histology – either normal or mild inflammatory changes 2 ance se ermittently ve an in immune lammatory 3 rrier state mal +ve (but upto d 4 ns 5 e
  13. 13. Phases of HBV infection by immune response • These phases provide a summary of the natural course of HBV infection • The phases are not necessarily sequential • Strictly, there are 4 phases • Next, we shall describe the events of the phases in terms of clinical and laboratory parameters 1 Phase 1: Immune tolerance • Alternative term is immunotolerant • Liver enzyme, ALT is persistently normal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is very high • Liver histology – either normal or mild inflammatory changes 2 Phase 2: Immune clearance • Alternative term is immune reactive phase • Liver enzyme, ALT is persistently or intermittently abnormal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is high, but less than in immune tolerant phase • Liver histology – moderate or severe inflammatory changes 3 rrier state mal +ve (but upto d 4 ns 5 e
  14. 14. Phases of HBV infection by immune response • These phases provide a summary of the natural course of HBV infection • The phases are not necessarily sequential • Strictly, there are 4 phases • Next, we shall describe the events of the phases in terms of clinical and laboratory parameters 1 Phase 1: Immune tolerance • Alternative term is immunotolerant • Liver enzyme, ALT is persistently normal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is very high • Liver histology – either normal or mild inflammatory changes 2 Phase 2: Immune clearance • Alternative term is immune reactive phase • Liver enzyme, ALT is persistently or intermittently abnormal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is high, but less than in immune tolerant phase • Liver histology – moderate or severe inflammatory changes 3 Phase 3: Immune control • Alternative term is inactive HBsAg carrier state • Liver enzyme, ALT is persistently normal • Serology shows HBeAg -ve | HBeAb +ve • HBV DNA (viral load) is <2,000 IU/mL (but upto 20,000 IU/mL) • Liver histology – either normal or mild inflammatory changes 4 ns 5 e
  15. 15. Phases of HBV infection by immune response • These phases provide a summary of the natural course of HBV infection • The phases are not necessarily sequential • Strictly, there are 4 phases • Next, we shall describe the events of the phases in terms of clinical and laboratory parameters 1 Phase 1: Immune tolerance • Alternative term is immunotolerant • Liver enzyme, ALT is persistently normal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is very high • Liver histology – either normal or mild inflammatory changes 2 Phase 2: Immune clearance • Alternative term is immune reactive phase • Liver enzyme, ALT is persistently or intermittently abnormal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is high, but less than in immune tolerant phase • Liver histology – moderate or severe inflammatory changes 3 Phase 3: Immune control • Alternative term is inactive HBsAg carrier state • Liver enzyme, ALT is persistently normal • Serology shows HBeAg -ve | HBeAb +ve • HBV DNA (viral load) is <2000IU/mL (but upto 20000IU/mL) • Liver histology – either normal or mild inflammatory changes 4 Phase 4: Immune escape • Alternative term is HBeAg negative chronic hepatitis B or reactivation (relapse) • Liver enzyme, ALT is persistently or intermittently abnormal • Serology shows HBeAg -ve | HBeAb +ve • HBV DNA (viral load) is >2,000 IU/mL (fluctuates) • Liver histology – Moderate to severe inflammation and fibrosis +/- cirrhosis • Predominance of HBV with precure mutations 5 e
  16. 16. Phases of HBV infection by immune response • These phases provide a summary of the natural course of HBV infection • The phases are not necessarily sequential • Strictly, there are 4 phases • Next, we shall describe the events of the phases in terms of clinical and laboratory parameters 1 Phase 1: Immune tolerance • Alternative term is immunotolerant • Liver enzyme, ALT is persistently normal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is very high • Liver histology – either normal or mild inflammatory changes 2 Phase 2: Immune clearance • Alternative term is immune reactive phase • Liver enzyme, ALT is persistently or intermittently abnormal • Serology shows HBeAg +ve | HBeAb –ve • HBV DNA (viral load) is high, but less than in immune tolerant phase • Liver histology – moderate or severe inflammatory changes 3 Phase 3: Immune control • Alternative term is inactive HBsAg carrier state • Liver enzyme, ALT is persistently normal • Serology shows HBeAg -ve | HBeAb +ve • HBV DNA (viral load) is <2000IU/mL (but upto 20000IU/mL) • Liver histology – either normal or mild inflammatory changes 4 Phase 4: Immune escape • Alternative term is HBeAg negative chronic hepatitis B or reactivation (relapse) • Liver enzyme, ALT is persistently or intermittently abnormal • Serology shows HBeAg -ve | HBeAb +ve • HBV DNA (viral load) is >2000IU/mL(fluctuates) • Liver histology – Moderate to severe inflammation and fibrosis +/- cirrhosis • Predominance of HBV with precure mutations 5 Additional Phase: HBsAg negative phase • Alternative name is resolved hepatitis B • Loss of HBsAg • HBV DNA may remain detectable in the liver, but not in the serum • Some patients with HBsAg loss may still have detectable HBV DNA in the serum (occult HBV) • The latter are vulnerable to HBV reactivation following immunosuppression
  17. 17. Transmission of Hepatitis B Virus Horizontal transmission This by far the commonest mode of transmission in Africa Occurs in family members and between child to child Unsafe Blood transfusion This was particularly the case before screening for Infections prior to transfusion was commenced Vertical transmission From mother to child at: Time of delivery (labour or shortly after- perinatal) Or Rarely in 2nd or third trimester of pregnancy
  18. 18. Transmission of Hepatitis B Virus Blood and blood products contact This includes needle stick injuries and contacts with blood spills Unhealthy medical practice Razors, inadequate sterilization, dental and surgical procedures Intravenous drug use This is not very commonly reported in Africans, but may be contributing to adult acute infection cases
  19. 19. Transmission of Hepatitis B Virus Non medical risks Manicures, tattoos, sharing toothbrushes, traditional surgical -scarification practice -hair and barbing salons Unprotected sexual contact Most infections in Africans occur in childhood For most adults with infections, only a small proportion may have acquired HBV via hetero or homo sexual routes
  20. 20. Groups at high risk of Hepatitis B Virus infection Listen to this video first! YouTube Video on Routes of transmission of HBV Opens a new window!
  21. 21. Birth before 1985 (people who have ever received unsafe blood or blood product) Children born to HBV positive mothers These are less likely to clear the virus and thus become chronic carriers – hence birth dose HBV vaccine is paramount for prevention
  22. 22. Pregnant women Health care workers exposed to biological fluids Especially if they are engaged in exposure-prone procedures Risk to baby if mum has high HBV DNA, or is HBeAg +ve
  23. 23. Individuals infected with HIV or HCV Inmates of correctional facilities – (prisoners) Due to weakened immune systems These tend to have risky behaviours and or live in suboptimal conditions
  24. 24. Persons who have ever injected drugs Persons requiring immunosuppressive therapy These persons tend to share needles in an unsafe way and thus promote transmission of HBV Immune systems are weakened and chance of reversion of occult HBV is high
  25. 25. Sex workers Men having sex with men History of multiple sexual partners or STIs Patients undergoing renal dialysis These individuals are dependent on blood and blood products and hence prone to infection
  26. 26. Cirrhosis • Defined as an advanced stage of liver disease characterized by o extensive liver fibrosis o nodularity of the liver o alteration of liver architecture o disrupted blood flow to the liver
  27. 27. Decompensated cirrhosis o Clinical complications of cirrhosis including: o Jaundice • Ascites • spontaneous bacterial peritonitis • oesophageal varices • hepatic encephalopathy • sepsis and renal failure
  28. 28. More definitions • Persistently abnormal LFTs • Three ALT determinations above the upper limit of normal, made at unspecified intervals during 6 to 12-month period or predetermined intervals during a 12-month period • HBeAg seroconversion: Loss of HBeAg and seroconversion to anti-HBe • HBsAg seroconversion: Loss of HBsAg and development of anti-HBs • HBeAg reversion: Reappearance of HBeAg in a person who was previously HBeAg negative • Presence of anti-HBc indicates: • If HBsAg –ve: prior exposure to HBV • If HBsAg +ve: current HBV infection
  29. 29. What you have learned in this module • Commonly used terminologies about hepatitis B, including serology and phases of infection • Structure of hepatitis B virus and explanations about the various proteins • Although described in phases, the course of hepatitis B infection is non-linear • Patients fluctuate between immune tolerant phases through to immune clearance and reversal • Modes of transmission of HBV and groups at high risk were also defined • Transmission of HBV in African is often horizontal, meaning that most infections occur before the age of 5. • Unsafe blood transfusion and use of unsterile equipment are also important • HBV infection can lead to cirrhosis and its decompensation
  30. 30. General Points on Hepatitis B Virus Infection This ends the trial modules – Consider purchasing the Liver Course for a complete set of modules You have done well to have completed this module:

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