A 24-year-old man who works as a grocery clerk in a large city seeks medical help at the ER of the nearest city hospital. For several days, he has felt increasingly weak, nauseated, and feverish. Other symptoms include periodic vomiting, joint pain, and pain on the right side of the abdomen. He has no appetite because the thought of food makes him nauseous. He thought that he had just picked up a bad case of the "stomach flu" until, while shaving, he noticed that his eyeballs were yellow. As you take the patient's history, he admits that he has experimented with a variety of oral and injected drugs but denies being addicted. He has a stable job and a girlfriend with whom he is sexually active.

Question 1.1: What is your preliminary diagnosis?

The jaundice is indicative of liver damage and only a limited number of pathogens are commonly associated with infectious diseases of the liver. The most important of these are the hepatitis viruses, and the symptoms in this case are consistent with a viral hepatitis. The patient's history of injection drug use suggests a type of serum hepatitis rather than infectious hepatitis. The most frequently encountered forms of serum hepatitis are hepatitis B (caused by the hepatitis B virus; HBV) and hepatitis C (caused by the hepatitis C virus; HCV).

Question 1.2: What is the differential?

The differential includes diseases caused by all of the hepatitis viruses (HAV, HBV, HCV, etc.), as well as by other viruses that can produce systemic disease and hepatitis. In the latter category, the most frequently seen causative agents are yellow fever virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Depending on the circumstances, hepatitis can also be produced (less often) by rubella, rubeola, coxsackie B, adenovirus, or HSV. Non-viral etiologies for hepatitis include alcoholic hepatitis, drug-induced hepatitis (e.g., from use of isoniazid), and toxic hepatitis (e.g., from consumption of carbon tetrachloride or benzene).

Question 1.3: What tests should you perform?

It is impossible to identify the infectious agent with certainty based solely on the symptoms and the history. Therefore, hepatitis B serology (HBsAg, HBsAb, HBcAb, HBeAg, HBeAb) should be ordered on a serum specimen, along with tests for HAV- and HCV specific antibodies. The standard tests for liver function (e.g., ALT, AST, bilirubin, and alkaline phosphatase) should be ordered as well.

Test Results

The lab reports that antibodies to HAV and HCV were not detected in the serum. A surface antigen associated with HBV, called HBsAg, was detected in the serum, though antibodies directed against this antigen (HBsAb) were not detected. ALT, AST, bilirubin, and alkaline phosphatase were all elevated above the normal range. These results confirm a diagnosis of HBV infection.

Question 1.4: How did the patient become infected?

Hepatitis B, like other types of serum hepatitis, is transmitted by the exchange of blood or sexual fluids. Given that he has experimented with injection drugs, the patient was most likely infected when using a shared needle that contained blood from another infected individual. Infection during intercourse with his girlfriend is another possibility, if she is infected with HBV. She should be tested for HBV infection in any case because she might have been infected by him and might still be asymptomatic.

Question 1.5: What follow-up is required in this case?

Because the patient has HBsAg antigen in his serum, but does not have antibodies to this antigen (HBsAb), he may be entering the chronic phase of infection. Chronic patients typically have little or no freely circulating anti-HBs, but viral products such as HBsAg may be detectable in their serum for decades. The persistence of HBsAg in the serum for six months or more confirms the diagnosis of a chronic infection. The patient should be monitored for this because chronic infections can lead to cirrhosis and liver failure.

The patient's serum should also be tested for the presence of hepatitis delta virus (HDV) antibodies. HDV is found only in individuals who are infected with HBV because it can only replicate with the help of HBV. HDV co-infection is associated with increased risk of death from fulminant hepatitis during the acute phase of the disease and (more relevant to this patient) higher incidence rates for liver cirrhosis and hepatocellular carcinoma during the chronic phase. Even if the patient is negative for HDV, he should be warned that he will continue to be susceptible to a HDV superinfection.

Question 1.6: How can this disease be treated?

Unfortunately, the treatment options are limited if the patient does become chronically infected. Many patients respond favorably to administration of (-interferon (a natural antiviral cytokine) and their blood level of virus decreases. However, the benefit is transient for about 70% of the patients and viral levels rebound after treatment ceases. A number of new drugs (mostly nucleoside analogs) are being evaluated in clinical trials and it is possible that one or more of them will prove to be effective.

Question 1.7: What advice should the patient be given to avoid further transmission?

He should be made aware that he can and will infect others unless he uses condoms during intercourse and does not share needles. In addition, of course, he can no longer donate blood. If his girlfriend tests negative for the virus, she should immediately be vaccinated to prevent infection in the future.