(PFIC-3), due to mutations in the ABCB4 gene on chromosome 7q21. The encoded protein, MDR3, is a canalicular transport protein that is responsible for flipping phosphatidylcholine
from the internal to the external hemileaflet of the canalicular membrane. In patients with this disorder, the absence of secreted phosphatidylcholine in bile leaves the apical surfaces of the
biliary tree epithelia subject to the full detergent action of secreted bile salts, with resultant toxic destruction of these epithelia and release of GGT into the circulation.
Children with severe cholestasis but with absence of elevated serum GGT and absence of pruritus may also have inherited defects in bile acid synthesis. The most common condition is a
deficiency of 3b-hydroxysteroid dehydrogenase, an enzyme located early in the pathway for bile acid synthesis from cholesterol.
Infectious Disorders
Inflammatory disorders of the liver dominate the clinical practice of hepatology. This is due in part to the fact that virtually any insult to the liver can kill hepatocytes and recruit
inflammatory cells, but also because inflammatory diseases are frequently long-term chronic conditions that must be managed medically. Among inflammatory disorders, infection is by far
the most frequent. The liver is almost inevitably involved in blood-borne infections, whether systemic or arising within the abdomen. The foremost hepatic infections are viral in origin.
Other infections in which the hepatic lesion is prominent include miliary tuberculosis, malaria, staphylococcal bacteremia, the salmonelloses, candida, and amebiasis.
VIRAL HEPATITIS
Unless otherwise specified, the term "viral hepatitis" is reserved for infection of the liver caused by a group of viruses having a particular affinity for the liver ( Table 18-6 ). [14] [15]
Systemic viral infections that can involve the liver include (1) infectious mononucleosis (Epstein-Barr virus), which may cause a mild hepatitis during the acute phase; (2) cytomegalovirus,
particularly in the newborn or immunosuppressed patient; and (3) yellow fever, which has been a major and serious cause of hepatitis in tropical countries. Infrequently, in children and
immunosuppressed patients, the liver is affected in the course of rubella, adenovirus, herpesvirus, or enterovirus infections. Hepatotropic viruses cause overlapping patterns of disease.
Each hepatotropic virus and the disease conditions it causes will be introduced before a general discussion of hepatitis.
Hepatitis A Virus
Hepatitis A virus (HAV), the scourge of military campaigns since antiquity, is a benign, self-limited disease with an incubation period of 2 to 6 weeks.[16] HAV does not cause chronic
hepatitis or a carrier state and only rarely causes fulminant hepatitis, so the fatality rate associated with HAV is about 0.1%. The outcome of HAV infection may be more severe if it is
superimposed on chronic hepatitis due to Hepatitis B virus (HBV), Hepatitis C virus (HCV), or alcohol. HAV occurs throughout the world and is endemic in countries with substandard
hygiene and sanitation, so populations there may have detectable anti-HAV by the age of 10 years. Clinical disease tends to be mild or asymptomatic and rare after childhood. In developed
countries, the prevalence of seropositivity increases gradually with age, reaching 50% by age 50 years in the United States. In this population, acute HAV tends to be a sporadic febrile
illness. Overall, HAV accounts for about 25% of clinically evident acute hepatitis worldwide and an estimated 270,000 new cases per year in the United States.[4]
HAV is a small, nonenveloped, single-stranded RNA picornavirus that occupies its own genus, Hepatovirus. Ultrastructurally, HAV is an icosahedral capsid 27 nm in diameter. HAV
TABLE 18-6-- The Hepatitis Viruses
Hepatitis A Virus Hepatitis B Virus Hepatitis C Virus Hepatitis D Virus Hepatitis E Virus Hepatitis G Virus *
*At present, hepatitis G virus is not considered pathogenic.
is spread by ingestion of contaminated water and foods and is shed in the stool for 2 to 3 weeks before and 1 week after the onset of jaundice. Thus, close personal contact with an infected
individual or fecal-oral contamination during this period accounts for most cases and explains the outbreaks in institutional settings such as schools and nurseries and the waterborne
epidemics in places where people live in overcrowded, unsanitary conditions. HAV is not shed in any significant quantities in saliva, urine, or semen. In developed countries, sporadic
infections may be contracted by the consumption of raw or steamed shellfish (oysters, mussels, clams), which concentrate the virus from seawater contaminated with human sewage.
Infected workers in the food industry may also be the source of outbreaks. Outbreaks of the disease in September and November, 2003, in the United States involved more than 600
infected persons and caused at least three deaths. Consumption of raw green onions contaminated with HAV was the most likely cause of these outbreaks. Because HAV viremia is
transient, blood-borne transmission of HAV occurs only rarely; therefore, donated blood is not specifically screened for this virus.