A 35-year-old Asian man with jaundice and markedly high aminotransferase levels
WHAT IS CAUSING HIS ACUTE HEPATITIS?
3. On the basis of the new data, which of the following statements about the cause of acute hepatitis in this patient is the most accurate?
- Herpetic hepatitis is the most likely cause, given his positive test for immunoglobulin M (IgM) against herpes simplex virus
- Hepatitis C cannot be excluded with the available data
- Negative HBV e antigen does not exclude the diagnosis of acute exacerbation of HBV infection
- Hepatocellular carcinoma is the likely diagnosis, given the elevated alpha fetoprotein level
The third answer above is correct: a negative test for hepatitis B e antigen does not exclude the diagnosis of acute exacerbation of HBV infection
Herpetic hepatitis. Although not common, hepatitis due to herpes simplex virus infection should be considered in the differential diagnosis of any patient presenting with severe acute hepatitis, particularly when fever is present. Common features of herpetic hepatitis on presentation include high fever, leukopenia, markedly elevated aminotransferases, and mild cholestasis. Vesicular rash occurs in only less than half of cases of herpetic hepatitis.10
Serologic testing is of limited value because it has high rates of false-positive and false-negative results. The diagnosis can be confirmed only by viral polymerase chain reaction testing or by identifying herpes simplex viral inclusions in the liver biopsy.
However, the death rate is high in this disease, and since herpetic hepatitis is one of the few treatable causes of acute liver failure, parenteral acyclovir (Zovirax) should be considered empirically in patients presenting with acute liver failure. Our patient was started on acyclovir when his tests for IgM against herpes simplex virus came back positive.
Hepatitis C. Antibodies against hepatitis C virus do not develop immediately after this virus is contracted; they may take up to 12 weeks to develop after exposure. For this reason, about 30% to 50% of patients with acute hepatitis C virus infection are negative for these antibodies initially. In those patients, hepatitis C virus RNA in the blood is the most sensitive test to detect acute hepatitis C virus infection.
Our patient has neither antibodies against hepatitis C virus nor hepatitis C virus RNA by polymerase chain reaction testing, which rules out hepatitis C virus infection.
Disappearance of e antigen in HBV infection. The disappearance of HBV e antigen is usually associated with a decrease in serum HBV DNA and remission of liver disease. However, some patients continue to have active liver disease and high levels of HBV DNA despite e antigen seroconversion. This is due to a stop codon mutation in the precore region of the viral genome that decreases or prevents production of HBV e antigen.4 In other words, even though HBV e antigen is a good marker of HBV replication in general, a subgroup of patients with chronic HBV infection are negative for e antigen but still have a high rate of viral replication as evidenced by high serum HBV DNA levels.
Patients with perinatally acquired chronic HBV infection most often have immune-tolerant chronic HBV infection. Among those patients (mostly Asian),5,7 the virus is spontaneously cleared at a rate of approximately 2% to 3% per year,8 most often during the second and third decades of age.
Transition from the immune-tolerant phase to the immune clearance phase is frequently associated with mild transient worsening of the liver function profile.9,11,12 However, in a small percentage of patients, hepatic decompensation and even (rarely) death from hepatic failure may occur secondary to a sudden activation of the immune system as it attempts to clear the virus. This may result in an increase in immune-mediated lysis of infected hepatocytes.
Hepatocellular carcinoma. Exacerbation of hepatitis B may be associated with an elevation of alpha fetoprotein, which may falsely raise concerns about the possibility of hepatocellular carcinoma. However, our patient had abdominal imaging with both ultrasonography and computed tomography, which showed no evidence of hepatocellular carcinoma.
Comment. The most likely cause of the patient’s acute liver failure is an acute exacerbation of hepatitis B. However, herpetic hepatitis should be ruled out by testing for herpes simplex virus by polymerase chain reaction, performing a liver biopsy, or both.
Case continues: His condition worsens
A transjugular liver biopsy shows changes associated with chronic hepatitis B, severe acute hepatitis with extensive confluent and submassive hepatic necrosis, and no intracellular viral inclusions. Subsequently, acyclovir is stopped.
On the 6th hospital day, he develops progressive metabolic acidosis and hypotension, with worsening hypoxemia. A chest radiograph is obtained to look for pneumonia, but it is indeterminate; computed tomography of the chest without contrast medium is likewise unremarkable. Duplex ultrasonography of the four extremities is negative for venous thrombosis.
The patient becomes more lethargic and difficult to arouse. He is transferred to the intensive care unit and intubated. His prothrombin and partial thromboplastin times continue to rise, the prothrombin time reaching values of more than 50 seconds. In addition, progressive renal insufficiency develops.
