Case 47

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 22/04/2025

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CASE 47

ED is a 33-year-old man with a history of “globe-trotting” since the age of 18 and who has recently returned from a 4-month trip to Indonesia. He had declined all vaccinations before travel, with the exception of those (e.g., for yellow fever) demanded by the immigration authorities of the countries he wished to visit. Three weeks after his return his family noticed he was quite “yellow” about the face, and he felt listless and nauseated. His family physician ordered a variety of blood tests. Results of these show a picture of acute hepatitis, negative serology for hepatitis C or hepatitis A(E), but positive results for hepatitis B. You ask the laboratory for more detailed information on the immunoglobulin isotypes of the anti–hepatitis B antibodies. Why?

QUESTIONS FOR GROUP DISCUSSION

1. Obviously we can be wise with hindsight here and agree that ED should have received the standard hepatitis B vaccine at some time before he became naturally exposed. The big question now is whether he is a carrier of hepatitis B (infected a long time ago) or whether this is a new infection. Explain why testing for particular anti–hepatitis B isotypes would help you to determine this.

2. Draw a schematic of hepatitis B virus and show the following antigens: surface antigen HBsAg, core antigen HBcAg, and HBeAg, from which the HBcAg is derived.

3. During the course of hepatitis B infection, antibodies are generated that are specific for the antigens listed in question 2. Detection of antibodies to these various antigens plays an important role in determining the stage of infection. Explain why anti-HBs antibodies will not be detected until after the disappearance of HBsAg in serum, even though it is believed that these antibodies are produced early in the infection.

4. Study Figure 39-1. Discuss the role of anti-HBc IgM antibodies in the diagnosis of hepatitis B. How would you interpret a report in which the patient has anti-HBc IgG antibodies? Why would you not use anti-HBe antibody titers to diagnose an early infection?

5. Discuss how you would assess recurrent/novel infection with hepatitis B.

6. Discuss antiviral therapy for hepatitis B and hepatitis C.

7. The best treatment is avoidance (if possible) or immunization (for hepatitis B [not yet available for hepatitis C]).

RECOMMENDED APPROACH

Implications/Analysis of Family History

There is no evidence to indicate the susceptibility to hepatitis B infection had a genetic component. However, spontaneous recovery from hepatitis B infection versus persistent infection may in fact have a genetic basis in that it has been shown that some human leukocyte antigen (HLA) class II alleles confer protection against chronic infection.

Implications/Analysis of Clinical History

ED was listless and nauseated. As well, he was quite “yellow” about the face. These are typical symptoms of hepatitis A and hepatitis B infection. Clinical symptoms may also include rashes, joint pains, arthritis, and abdominal pain. Individuals infected with hepatitis C often have just a mild illness or no clinical symptoms. Obviously we can be wise with hindsight here and agree that ED should have received the standard hepatitis B vaccine at some time before he became naturally exposed. The big question now is whether he is a carrier of hepatitis B (infected a long time ago) or whether this is a new infection.

Implications/Analysis of Laboratory Tests

A number of automated tests (Abbott Laboratories) are available. In general, these are modified enzyme-linked immunosorbent assays (ELISAs) that permit large numbers of samples to be processed in a short time period. In essence, the patient’s serum is allowed to react with immobilized antibody in a reaction vessel, and then (after several washings to remove unbound antibody) some indicator system is added to detect and quantify the signal. Results of ED’s tests showed a picture of acute hepatitis: negative serology for hepatitis C and hepatitis A(E) but positive results for hepatitis B. On request for antibody isotype information, you are told that both IgM and IgG anti-HBc antibodies were present, indicating that this is a new infection. Antibody tests to HBsAg and HBeAg were negative.

Additional Laboratory Tests

To further assess the stage of hepatitis B infection, tests were requested for the hepatitis antigens HBsAg and HBeAg. When testing for hepatitis B antigens, the same general procedure and principle is used as that described earlier for anti–hepatitis B antibodies, except that the patient’s serum is allowed to react with immobilized antigen. Results were positive for HBsAg and HBeAg. (There are no commercially available tests for HBcAg.)

DIAGNOSIS

ED was diagnosed with acute hepatitis B infection. Based on the fact that he is positive for HBsAg and HBeAg and is seropositive for anti-HBc IgM antibodies, we know that this is a recent infection. HBeAg is released into the bloodstream when hepatitis B virus is actively replicating, and so these patients are highly infectious. The incubation period for hepatitis B ranges from 45 to 160 days, suggesting that ED was infected long before he returned home.

Discrepancy?

As you think about this apparent discrepancy in the data you realize that the anti-HBs antibodies are binding to HBsAg to form complexes (and HBeAg with anti-HBe antibodies). HBsAg detected in serum represents intact virion antigen as well as shed particles that consist primarily of aggregated HBsAg. In the face of high antigen in plasma and low antibody titers, immune complexes form so that the antibodies to these two antigens cannot be detected. These antigen-antibody complexes may precipitate in the joints and skin to cause joint pain, arthritis, and a rash (type III hypersensitivity reaction). Consequently, the negative result for anti-HBs antibody and anti-HBe antibody (see earlier) were false negatives.

THERAPY

HBV-infected persons should be evaluated by their doctor for liver disease. ED should be monitored for liver disease. Drugs licensed for the treatment of chronic hepatitis B infection include lamivudine and adefovir dipivoxil. Both of these drugs are nucleoside reverse transcriptase inhibitors that block (DNA polymerase) and in doing so stop the replication of the virus. Both of these drugs are used for HIV therapy.

Interferon Alfa

A more recent development in antiviral drug therapy is interferon alfa (IFNα), which is administered by intramuscular or subcutaneous injection. IFNα is a cytokine secreted by virally infected cells during a normal immune response. When this cytokine is secreted, it binds to cognate receptors on neighboring cells, functioning in a paracrine fashion. Receptor-ligand interaction activates a signaling cascade that leads to the production of 2′5′-oligoadenylate synthetase, an enzyme whose activation triggers processes that result in the inhibition of viral replication. Additionally, IFNα leads to the upregulation of cell surface expression of members of the class I major histocompatibility complex, which enhances target cell recognition by cytotoxic T cells.

HEPATITIS B AND IMMUNIZATION

Hepatitis B infects the parenchymal cells of the liver, although it is also found in body fluids, including saliva, semen, breast milk, and blood. Transmission is by direct contact with these fluids. Consequently, health care workers are at risk for acquiring hepatitis B infection. Other individuals who are at high risk for infection are those who have unprotected sex with infected partners, as well as those who are intravenous drug users. Infected mothers can transmit the virus to neonates.

The hepatitis B vaccine (HBsAg) is a recombinant protein (Engerix B and Recombivax). Typically, the schedule of vaccination consists of three doses of vaccine administered intramuscularly on a 0-, 1-, and 6-month schedule. Slight modifications of this schedule are possible, depending on the commercial source of the vaccine. Accelerated schedules are possible if someone is traveling before the recommended immunization schedule can be completed; however, this is not approved by the U.S. Food and Drug Administration.

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