5. VIRAL HEPATITIS GENERAL CONSIDERATION
     Hepatitis A is a viral infection of the liver that may occur sporadically or in epidemics. The liver involvement is part of a generalized infection but dominates the clinical picture. Although transmission of the virus may occur by contaminated needles, it is usually by the fecal-oral route. The excretion of hepatitis A virus (HAV) as determined by immune electron microscopy of stool occurs up to 2 weeks prior to illness. HAV is rarely demonstrated in feces after the third week of illness. There is no known carrier state with HAV. Blood and stools are infectious during the incubation period (2 to 6 weeks) and early illness until peak transaminase levels are achieved. Although theoretically possible, the short duration of viremia makes
posttransfusion hepatitis unlikely. In fact, posttransfusion hepatitis due to HAV has not been documented. Although the mortality rate with hepititis A is low, it may cause fulminant disease. The mortality rate (as with hepatitis B) appears to be age-related. Marmoset monkeys and chimpanzees appear to be the only susceptible
animals; livers of infected marmoset monkeys have revealed the 27-nm particles.
      An unequivocal diagnosis of HAV is established by demonstrating the hepatitis A virus antigen (HAAg) in the stool or the IgM antibody to hepatitis A in serum.
The absence of HAAg in the stool does not rule out HAV infection.
      Antibodies to type A hepatitis appear early in the course of the illness and tend to persist in the serum. Immune electron microscopy and radioimmunoassay detect
both IgM and IgG antibodies and are positive soon after the onset of the illness. Immune adherence hemagglutination reflects an IgG response and is positive later in the course of the disease. Peak titers of IgG antibodies occur after 1 month of disease and may persist for years. Peak titers of IgG antibodies occur during the first week of clinical disease and disappear within an 8-week period; therefore measurement of these antibodies is an excellent test for demonstrating acute hepatitis A infection. The presence of anti-HAV activity indicates: (1) previous exposure to HAV; (2) nonin fectivity; and (3) immunity to recurring HAV infection. It does not imply previous clinically apparent hepatitis, nor does it establish a relationship to ongoing liver disease unless seroconversion has been demonstrated.
     The viral agent of hepatitis A is a small 27-nm RNA virus that belongs to the
picornavirus group, which also includes poliomyelitis virus and coxsackie-virus. The agent is inactivated by ultraviolet light, by heating to 100 degrees centigrade for 5 minutes, and by exposure to 1:4000 formalin solution.
     Hepatitis B is a viral infection of the liver usually transmitted by inoculation of infected blood or blood products. However, the antigen has been found in most body secretions, and it is known that the disease can be spread by oral or sexual contact. Hepatitis B virus (HBA) is highly prevalent in homosexuals and intravenous drugs abusers. Other group at high risk include patients and staff at hemodialysis centers, physicians, dentists, nurses and personnel working in clinical and pathologic laboratories. Approximately 5-10% of infected individuals become carriers, providing a substantial reservoir of infection. 40-70% of infants born to HBsAg-positive mothers will develop antigens to hepatitis B in the bloodstream. Fecal-oral transmission of virus B has also been documented. The incubation period of hepatitis B is 6 weeks to 6 months. Clinical features of hepatitis A and B are similar; however, the onset in hepatitis B tends to be more insidious.
     Hepatitis B virus is pleomorphic and occurs in spherical and tubular forms of different sizes. The largest of these, the Dane particle, is thought to be the complete infectious virus. The 42-nm Dane particle is composed of a core (27-rim particle) found in the nucleus of infected liver cells, and a double-shelled surface particle found in the cytoplasm. The other particles form an excess coating of the virus and contain no nucleic acid.
     There are 3 distinct antigen-antibody systems that relate to HBV infection. In addition, DNA polymerase activity can be measured as a sensitive index of viral
replication and infectivity.
     The surface antigen (HBsAg) is the antigen routinely measured in blood. HBsAg
is unaffected by repeated freezing and thawing or by heating at 56 degrees centigrade overnight or at 60 degrees centigrade for l hour. It is inactivated by heating between 85 and 100 degrees centigrade for 15 to 30 minutes. HBsAg can exist in serum as 3 antigenically identical forms: (1) the outer coat of the intact Dane particle; (2) a spherical 22-nm particle; and (3) elongated tubular particles, The spherical and tubular particles do not contain nucleic acid and are not infectious. Four major antigenic subtypes of HBAg have been recognized. Subtyping of HBsAg if primarily of epidemiologic importance. The presence of GBsAg is the first manifestation of HBV infection occurring before biochemical evidence of liver disease. HBsAg persists throughout the clinical illness, persistence of HBsAg is usually associated with clinical and laboratory evidence of chronic hepatitis. The presence of HBsAg establishes infection with HBV and implies infectivity. Specific antibody to HBsAg (anti-HBs) occurs in most individuals after clearance of HBsAg. Anti-HBs is usually delayed after clearance of HBsAg. During this serologic gap, infectivity has been demonstrated. Development of anti-HBs signals recovery from HBV, noninfectivity, and protection from HBV infection.
      Disruption of the Dane particle releases an antigenically distinct inner core structure (HBcAg). Antibodies against core antigen (anti-HBC) localize the core
antigen primarily to the nucleus of infected human and primate liver cells. The core
particles are not found in the serum. Core particles may be present in liver tissue in the