VIRAL HEPATITIS Part 1

FECAL-BORNE HEPATITIS

General Goal: To know the major causes of this disease, how they are transmitted, and the major manifestations of the disease.

Specific Educational Objectives: The student should be able to:

1. describe the common causes of fecal-borne hepatitis and how they are transmitted.

3. describe the major manifestations of this disease. Know what human cells the viruses replicate in.

4. diagnose Hepatitis A via serological testing (acute vs. past infection).

4. describe how you can prevent Hepatitis A infections.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, G.S. Kobayashi and M.A. Pfaller, 3rd Edition. pp. 523-526, 535.

Mosby's Color Atlas and Text of Infectious Diseases by Christopher P. Conlon and David R. Snydman. pp. 112-120.

Lecture: Dr. Neal R. Chamberlain

References: 

ETIOLOGY

Hepatitis E (HEV), discovered 1990 (alpha-like super group)

Both are single-stranded RNA, unenveloped viruses. 

Natural hosts for HAV, HEV: Only humans and lower primates.

143,000 cases/year of HAV hepatitis. When children are infected they usually don't have any symptoms. Most individuals are infected as children.

Distribution: of HAV and HEV is worldwide. HEV is not presently endemic in the U.S.. Epidemics have been reported in India, Pakistan, Nepal, Burma, North Africa, Mexico).

Transmission: relies on ingestion of fecal-contaminated water or food, i.e., a fecal-oral route. Since a carrier state has not been identified, the virus is maintained by serial transmission from subclinically infected individuals to susceptible ones, with sporadic outbreaks due to eating shellfish harvested from fecal-contaminated water. Infected individuals shed virus up to 10 days before symptoms begin or before antibodies to the virus are present in the serum. 90% of children and 25-50% of adults shed virus and are asymptomatic. Daycares are good places for HAV infections to spread.

Incidence: The highest incidence of HAV infection is among children 5-9 years of age and young adults 25-35 years of age; HEV infects mostly young and middle-aged adults.

The incidence of disease is more prevalent in crowded living conditions and in areas of low socioeconomic development; >90% of the population in underdeveloped countries have experienced HAV infection, vs. to <50% of the population in developed countries.

The major risk of serious clinical disease in the U.S. is for adults traveling to third world countries.

Portal: After ingestion, the rigid polio-like capsid withstands the harsh conditions in the stomach and intestines.

Viremia: HAV replicates in the oropharynx and epithelial lining of the intestines, where it initiates a transient viremia and infects the liver.

Replication: HAV binds to and replicates primarily within liver parenchymal cells, but gastric and small intestine mucosa, kidney, and bones may also be involved.

Virus shedding: Virus is released into the bile and eventually the stools (also true for HEV). Virus may be shed for 10 days before clinical symptoms appear.

HAV-infected liver: Although most infections are subclinical, lymphoid infiltration, Kupffer cell proliferation, and necrosis of the parenchyma cells can occur. Immunological role in pathology: Antibody-antigen complexes and complement fixation contribute to inflammation and tissue damage.

Self-limited disease: All HAV infections are acute, being self-limited by the induction of IgM and IgG, which confers long-lasting immunity.

Incubation: 14-45 days. May develop a distaste for cigarettes.

Children: 84-94% are asymptomatic

Adults: 5-25% are asymptomatic; 66% have jaundice (Fig)

Initial symptoms: fever (102° F or less) in early stages of disease malaise, fatigue headache anorexia nausea vomiting pain in the right upper quadrant, hepatosplenomegaly

Classic symptoms: Cholestasis: Dark urine, clay-colored stools followed in 1-5 days by clinical jaundice The liver is enlarged and tender. Liver damage produces increased blood levels of:

• Aspartate transaminase (AST=SGOT)
• Alanine aminotransferase (ALT = SGPT)
• Bilirubin

Malaise

Liver enlargement

Elevated liver enzymes

High titer of anti-HAV IgM (only one serotype) in the serum during the acute phase of the illness (hepatitis panel).

HEV is serologically unrelated.

Supportive therapy and rest.

HAV: low mortality (0.1-0.2%)

HEV: Mortality rate 10 times HAV (1-2%). Especially high mortality (20%) during pregnancy

The following information is from the CDC:

"Hepatitis A vaccine or immune globulin (IG) is recommended for all susceptible persons traveling to or working in countries with intermediate or high rates of HAV infection. Vaccination of children 2 years of age and older, adolescents and adults at the age-appropriate dose is preferred for those who plan to travel repeatedly or reside for long periods in intermediate or high risk areas. Immune globulin is recommended for travelers < 2 years of age. Immune globulin is recommended for persons 2 years of age and older who desire only short term protection.

Two hepatitis A vaccines are licensed for use in the United States, HAVRIX® (manufactured by SmithKline Beecham Biologicals), and VAQTA® (manufactured by Merck Co., Inc.). Both are inactivated (killed) vaccines. The vaccine should be administered by intramuscular injection into the deltoid muscle. It is licensed in adult and pediatric formulations, with different dosages and administration schedules. Travelers can be considered to be protected four weeks after receiving the initial vaccine dose. Persons who travel to intermediate or high risk areas less than 4 weeks after the initial dose of vaccine should also be given IG (0.02 ml/kg of body weight), but at a different injection site. The vaccine series must be completed for long-term protection. Estimates derived by modeling techniques suggest that vaccine may provide protective antibody against hepatitis A for at least 20 years.

For travelers who plan to use IG, a single dose of IG (0.02 ml/kg of body weight) is recommended if travel is for less than 3 months. For prolonged travel or residence in developing countries a higher dosage of IG should be used (0.06 ml/kg of body weight) and should be repeated every 5 months. Immune globulin produced in developing countries may not meet the standards for purity required in most developed countries. Persons needing repeat doses overseas should use products that meet U.S. license requirements."

Immunoglobulin given within two weeks of infection lessens the severity of symptoms or prevents symptoms. ISG is of no value once symptoms have appeared.