questions 6

Hepatitis B

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Topic updated on 07/15/17 7:07am

Snapshot
  • A patient presents to the ED with bright yellow discoloration of his skin.  He states that this started yesterday and has been getting progressively worse.  Upon obtaining further history you learn that this patient has recently lost 10 pounds over the past month and has had urine that he believes is darker.  The patient is currently sexually active with women and does not use protection.  On physical exam you note the patient has prominent scleral icterus.
Introduction
  • Classification
    • enveloped DNA hepadnavirus
  • Pathogenesis
    • transmission
      • parenteral (contact with bodily fluids)
        • healthcare workers are at particular risk
      • sex
      • mother-to-fetus 
        • perinatal infection
          • both transplacental infection and infection during birth are possible
          • 20% chance if mother is HBeAg negative, 95% chance if mother is HBeAg positive
          • higher risk of infection if mother became infected in 3rd trimester
          • vertical HBV transmission can cause hepatocellular carcinoma at age 20-40
    • reservoir
      • all human body fluids
        • long incubation period (3 months)
      • some people are asymptomatic carriers (see below)
    • molecular biology
      • 2 phases of damage
        • proliferative
          • viral antigens expressed on hepatocyte surface
          • host CD8+ T cells destroy infected hepatocytes
            • note that the virus does not have a cytopathic effect - the host immune system (CD8+ T cells) does the damage!
        • integrative
          • HBV DNA integrated into host genome 
          • risk of HCC remains even after host mounts successful antibody response to virus
      • immune complex deposition (HBsAg and antibodies)
        • leads to arthritis, skin damage, and renal insufficiency
      • carries a DNA-dependent DNA polymerase within the virion
        • the only hepatitis virus with this characteristic
        • replicates via a positive, single-stranded RNA template intermediate
Diseases
  • Acute hepatitis
    • long asymptomatic incubation period (6-8 weeks)
  • Fulminant hepatitis
    • severe acute hepatitis
    • rapid hepatic destruction
  • Chronic hepatitis
    • can take one of 4 forms
      • asymptomatic carrier
        • antibodies never develop yet liver is never injured
        • can transmit the virus to others!
      • chronic-persistent hepatitis
      • chronic active hepatitis
        • acute hepatitis that persists longer than 6-12 months
      • co-infection with HDV
  • Primary hepatocellular carcinoma
    • HBV DNA is incorporated into host hepatocyte DNA, triggering malignant growth
      • causes liver cell hyperplasia via HBx protein that interferes with p53
  • Cirrhosis
    • permanent liver scarring and nodular fibrosis Cirrhosis - Histology demonstrating nodules and fibrosis
  • Mortality is 1-2%
  • Most common outcome is acute hepatitis that completely resolves (>95%)
Laboratory
  • The intact virus is large (42 nm) and called a Dane particle
    • "B is Big like a great Dane"
  • Diagnostic tests of HBV infection
    • the surface antigen describes whether the patient is diseased or immune
      • HBsAg
        • the surface antigen of the virus
        • having this antigen means the patient has the disease (chronic, acute, or asymptomatic carrier)
        • precedes onset of symptoms and elevation of liver enzymes
      • Anti-HBsAg
        • presence of this antibody indicates that patient is immune and/or cured
        • NO active disease present
    • the core antigen tells us how long the infection has been present
      • HBcAg
        • the antigen of the core of the virus (HBsAg removed)
        • antibodies are not protective but yield information about the state of infection
        • positive antibodies seen during the "window period" (a period of active infection)
      • IgM anti-HBcAg
        • new infection is present
        • most specific marker for diagnosis of acute HBV infection because it persists during the window period
      • IgG anti-HBcAg
        • old infection is present
    • the soluble component of the core antigen tells us how infective the patient is
      • HBeAg
        • a soluble component of the viral core
        • presence connotes high infectivity  
          • ↑ "e" = ↑ "enfectivity"
      • Anti-HBeAg
        • presence connotes low infectivity
 
Acute Infection
Chronic Carrier
Window Period
Complete Recovery
Immunized
HBs
+
+
-
-
-
Anti-HBs
-
-
-
+
+
Anti-HBc
+ (IgM)
+ (IgG)
+
+ (IgG)
-
  • Characteristics
    • DNA 
      • double-stranded circular
    • enveloped
    • icosahedral capsid
  • Histology
    • hepatocytes have granular, eosinophilic appearance
      • "ground glass" appearance due to deposition of HBsAg in cytoplasm
    • ballooning degeneration, hepatocyte necrosis, portal inflammation are also seen
Treatment
  • Prevention
    • vaccine given to all infants (birth, 1-2 mo, 6-18 mo), adolescents, high-risk population (e.g., healthcare workers, IV drug users), individuals with other risk factors for liver disease (HCV infection) 
      • recombinant vaccine
      • contains HBsAg (antigen only without DNA or capsid)
      • also recommended for household contacts of HBV patients
    • blood screened for virus
    • infants born to infected mothers also get passive immunization with hepatitis B immune globulin at birth
  • Drugs
    • IFN
      • flu-like side effects
    • nucleoside analogs (e.g., lamivudine)
    • adefovir, tenofovir, entecavir, telbivudine
    • note that relapse is possible with all available treatment options


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