Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

U N I T 8

routinely in blood. It appears before onset of symptoms, peaks during overt disease, and then declines to unde- tectable levels in 3 to 6 months. Persistence beyond 6 months indicates continued viral replication, infectivity, and chronic hepatitis. HBeAg appears in the serum soon after HBsAg and signifies active viral replication. IgM anti-HBc becomes detectable shortly before the onset of symptoms, concurrent with the onset of an elevation in serum transaminases. Over the months, the IgM anti- body is replaced by IgG anti-HBc. Anti-HBe is detectable shortly after the disappearance of HBeAg and its appear- ance signals the onset of resolution of the acute illness. IgG anti-HBs, a specific antibody to HBsAg, occurs in most individuals after clearance of HBsAg. Development of anti-HBs signals recovery from HBV infection, non- infectivity, and protection from future HBV infection. Anti-HBs is the antibody present in persons who have been successfully immunized against HBV. The presence of viral DNA (HBV DNA) in the serum is the most reliable indicator of HBV infection. It is tran- siently present during the presymptomatic period and for a brief time during the acute illness. The presence of DNA polymerase, the enzyme used in viral replication, usually is transient but may persist for years in persons who are chronically infected. Hepatitis B can be prevented by vaccination and by the screening of donor blood, organs, and tissues. The vac- cine, which is prepared from purified HBsAg produced in yeast, induces a protective antibody response in 95% of vaccinated infants, children, and adolescents. 3 The CDC recommends vaccination of all children 0 to 18 years of age as a means of preventing HBV transmission. 12 The vaccine also is recommended for all unvaccinated adults who are at high risk for infection, international travelers to regions with high or intermediate levels of endemic HBV infection, persons with human immunodeficiency virus (HIV) infection, persons with chronic liver dis- ease, injection drug users, and all other persons seeking protection. 12 It is also recommended that all pregnant women be routinely tested for HBsAg during an early prenatal visit and that infants born to HBsAg-positive mothers receive appropriate doses of hepatitis B immune globulin (HBIG) and hepatitis B vaccine. 9 Hepatitis C. The hepatitis C virus, discovered in 1989, is a member of the Flaviviridae family. It is a small, envel- oped, single-stranded RNA virus. 3,4 The virus is geneti- cally unstable, giving rise to multiple genotypes and subtypes. This allows a divergent population of closely related variants to circulate in infected persons. 3 One of the HCV envelope proteins, the E2 protein, which is the target for anti-HCV antibodies, is the most vari- able region of the entire viral genome. It is likely that the wide diversity of genotypes contributes to the patho- genicity of the virus, allowing it to escape the actions of host immune mechanisms and antiviral medications, and to difficulties in developing a preventive vaccine. Hepatitis C is the most common cause of chronic hepatitis, cirrhosis, and hepatocellular cancer in the world. 3,4,13,14 Before 1990, the main route of transmission of HCV was through contaminated blood transfusions

or blood products. With implementation of HCV testing in blood banks, the current risk of HCV infection from blood transfusion is almost nonexistent in the United States and other developed countries. Currently, recre- ational injection drug use is the most common mode of HCV transmission in the United States. 13,14 Other risk factors include needlestick injuries in health care settings and birth to an HCV-infected mother. 13,14 In fact, the risk from needle sticks is much higher than for human immunodeficiency virus (HIV). 3 The incubation period for HCV infection ranges from 2 to 26 weeks (average, 6 to 12 weeks). 3 Children and adults who acquire the infection usually are asymp- tomatic or have nonspecific signs and symptoms such as fatigue, malaise, anorexia, and weight loss. A minor- ity of persons develop sufficient elevations in bilirubin to produce overt jaundice or the development of dark urine. Only a few persons who are newly infected with HCV will clear the infection, with the majority going on to develop chronic hepatitis. 13–15 Factors associated with spontaneous clearing of HCV infection appear to include younger age, female sex, and certain histo- compatibility genes. The most serious consequences of chronic HCV infection are progressive liver fibrosis leading to cirrhosis, and hepatocellular cancer. Both HCV RNA and anti-HCV antibody tests are available for detecting the presence of HCV infection (Fig. 30-9). Unlike hepatitis A and B, antibodies to HCV are not protective, but they serve as markers for the dis- ease. With anti-HCV antibody tests, infection often can be detected as early as 6 to 8 weeks after exposure, but false-negative results can occur in immunocompromised people and early in the course of the disease. Direct measurement of HCV RNA in the serum can detect the virus as early as 1 to 2 weeks after exposure with viral tests that use polymerase chain reaction (PCR) methods (see Chapter 14). Hepatitis D and E. Hepatitis D virus, or the delta hepa- titis agent, is a defective RNA virus that requires con- comitant infection with HBV for its own replication. 16

Symptoms

Exposure

Anti-HCV

ALT

HCV RNA

1 2 3 4 5 6

0 1 2 3 4 5 6

Months

Years

FIGURE 30-9. The sequence of serologic changes in chronic hepatitis C, with persistence of hepatitis C virus (HCV) RNA and exacerbations and remissions of clinical symptoms indicated by changes in serum alanine aminotransferase (ALT) levels.