2. Viral hepatitis is a systemic disease primarily involving the liver. Most cases of acute viral hepatitis in children and adults are caused by one of the following agents: 1- Hepatitis A virus (HAV), the etiologic agent of viral hepatitis type A (infectious hepatitis); 2- Hepatitis B virus (HBV), which is associated with viral hepatitis B (serum hepatitis); 3- Hepatitis C virus (HCV), the agent of hepatitis C (common cause of post transfusion hepatitis); or 4- Hepatitis E virus (HEV), the agent of enterically transmitted hepatitis.

4. HAV is stable to treatment with 20% ether, acid (pH 1.0 for 2 hours), and heat (60°C for 1 hour), and its infectivity can be preserved for at least 1 month after being dried and stored at 25°C and 42% relative humidity or for years at –20°C. The virus is destroyed by autoclaving (121°C for 20 minutes), by boiling in water for 5 minutes, by dry heat (180°C for 1 hour), by ultraviolet irradiation (1 minute at 1.1 watts), by treatment with formalin (1:4000 for 3 days at 37°C), or by treatment with chlorine (10– 15 ppm for 30 minutes). Heating food to >85°C (185°F) for 1 minute and disinfecting surfaces with sodium hypochlorite (1:100 dilution of chlorine bleach) are necessary to inactivate HAV. The relative resistance of HAV to disinfection procedures emphasizes the need for extra precautions in dealing with hepatitis patients and their products.

8. Pathology Hepatitis is a general term meaning inflammation of the liver. Microscopically, there is spotty parenchymal cell degeneration, with necrosis of hepatocytes, a diffuse lobular inflammatory reaction, and disruption of liver cell cords. These parenchymal changes are accompanied by reticuloendothelial (Kupffer) cell hyperplasia, periportal infiltration by mononuclear cells, and cell degeneration. Localized areas of necrosis are frequently observed. Later in the course of the disease, there is an accumulation of macrophages near degenerating hepatocytes. The damaged hepatic tissue is usually restored in 8–12 weeks. Chronic carriers of HBsAg may or may not have demonstrable evidence of liver disease. Persistent (unresolved) viral hepatitis, a mild benign disease that may follow acute hepatitis B in 8–10% of adult patients, is characterized by sporadically abnormal aminotransferase values and hepatomegaly. Histologically, the lobular architecture is preserved, with portal inflammation, swollen and pale hepatocytes (cobblestone arrangement), and slight to absent fibrosis. This lesion is frequently observed in asymptomatic carriers, usually does not progress toward cirrhosis, and has a favorable prognosis.

9. Occasionally during acute viral hepatitis, more extensive damage may occur that prevents orderly liver cell regeneration. Such fulminant or massive hepatocellular necrosis is seen in 1–2% of jaundiced patients with hepatitis B. It is 10 times more common in those coinfected with HDV than in the absence of HDV. None of the hepatitis viruses are typically cytopathogenic, and it is believed that the cellular damage seen in hepatitis is immune-mediated. Both HBV and HCV have significant roles in the development of hepatocellular carcinoma that may appear many (15–60) years after establishment of chronic infection.

11. In viral hepatitis, onset of jaundice is often preceded by gastrointestinal symptoms such as nausea, vomiting, anorexia, and mild fever. Jaundice may appear within a few days of the prodromal period, but anicteric hepatitis is more common. Extrahepatic manifestations of viral hepatitis (primarily type B) include a transient serum sickness-like prodrome consisting of fever, skin rash, and polyarthritis; necrotizing vasculitis (polyarteritis nodosa); and glomerulonephritis. Extrahepatic manifestations are unusual with HAV infections. Uncomplicated viral hepatitis rarely continues for more than 10 weeks without improvement. Relapses occur in 5–20% of cases and are manifested by abnormalities in liver function with or without the recurrence of clinical symptoms. The onset of disease tends to occur abruptly with HAV (within 24 hours), in contrast to a more insidious onset with HBV and HCV. Complete recovery occurs in most hepatitis A cases; chronicity has not been observed. The disease is more severe in adults than in children, in whom it often goes unnoticed. Relapses of HAV infection can occur 1–4 months after initial symptoms have resolved.

12. Laboratory Features Hepatitis A The clinical, virologic, and serologic events following exposure to HAV are shown in Figure. Virus particles have been detected by immune electron microscopy in fecal extracts of hepatitis A patients. Virus appears early in the disease and disappears within 2 weeks following the onset of jaundice. HAV can be detected in the liver, stool, bile, and blood of naturally infected humans and experimentally infected non human primates by immunoassays, nucleic acid hybridization assays, or PCR. HAV is detected in the stool from about 2 weeks prior to the onset of jaundice up to 2 weeks after.

14. Anti-HAV appears in the IgM fraction during the acute phase, peaking about 2 weeks after elevation of liver enzymes (Table ). Anti-HAV IgM usually declines to nondetectable levels within 3–6 months. Anti-HAV IgG appears soon after the onset of disease and persists for decades. Thus, detection of IgM-specific anti-HAV in the blood of an acutely infected patient confirms the diagnosis of hepatitis A. ELISA is the method of choice for measuring HAV antibodies.

15. Hepatitis B Clinical and serologic events following exposure to HBV are depicted in Figure. DNA polymerase activity, HBV DNA, and HBeAg, which are representative of the viremic stage of hepatitis B, occur early in the incubation period, concurrently or shortly after the first appearance of HBsAg. High concentrations of HBV particles may be present in the blood (up to 10 10 particles/mL) during the initial phase of infection; communicability is highest at this time. HBsAg is usually detectable 2–6 weeks in advance of clinical and biochemical evidence of hepatitis and persists throughout the clinical course of the disease but typically disappears by the sixth month after exposure.