IM Board Review

A 35-year-old Asian man with jaundice and markedly high aminotransferase levels

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A 35-year-old man who was born in Vietnam presents to the emergency department of a local hospital because he has had jaundice for 5 days and fatigue, malaise, and anorexia for 2 weeks. He also has nausea and mild epigastric and right upper quadrant abdominal pain. He denies having fevers, chills, night sweats, vomiting, diarrhea, melena, hematochezia, or weight loss.

His medical history is remarkable only for perinatally acquired hepatitis B virus (HBV) infection, for which he never received antiviral therapy. He does not take any prescribed, over-the-counter, or herbal medications.

He lives in the Midwest region of the United States and works full-time as a physician in private practice. He is married and has two children.

He has not travelled recently. He has no pets at home and has not been exposed to any.

He has never smoked. He drinks alcohol socially but has never used recreational drugs.

In a laboratory evaluation performed a year ago for insurance purposes, his liver function tests—serum albumin, total bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels—were all normal. He was positive for HBV surface antigen and HBV e antigen and negative for antibodies against these antigens.

PHASES OF HBV INFECTION

1. Which of the following best describes the status of HBV infection in this patient before his current symptoms developed?

  • Resolved HBV infection
  • Chronic inactive HBV infection
  • Chronic active HBV infection
  • Immune-tolerant chronic HBV infection

The correct answer is immune-tolerant chronic HBV infection.

Resolved infection. In immunocompetent adults, most primary HBV infections are self-limited: people clear the virus and gain lasting immunity (defined as the loss of HBV surface antigen, the development of antibody against surface antigen, no detectable HBV DNA in the serum, and normal alanine and aspartate aminotransferase levels). However, a minority of primary HBV infections persist and become chronic.

Figure 1. Clinical course of hepatitis B virus infection. ALT = alanine aminotransferase; AST = aspartate aminotransferase; HBsAg = hepatitis B virus surface antigen; HBeAg = hepatitis B virus e antigen

The risk of an HBV infection becoming chronic is higher in immunocompromized patients and in infants and children. In 90% of infected newborns, the disease progresses to chronic infection, but it does so in only 10% of adults (Figure 1).

Chronic HBV infection is defined as the persistence of HBV surface antigen in the serum for at least 6 months. Patients with chronic HBV infection can be broadly classified as having either inactive disease (the inactive surface antigen carrier state) or chronic active hepatitis B (Figure 1).1–9

Chronic inactive HBV infection. Carriers of inactive HBV infection have low serum levels of HBV DNA (< 2,000 IU/mL), persistently normal aminotransferase levels, and no HBV e antigen; if a liver biopsy is performed, no significant hepatitis is found.

Chronic active HBV infection. Patients with chronic active HBV infection, in contrast, have high serum HBV DNA levels (> 20,000 IU/mL) and persistently or intermittently high aminotransferase levels; they do have HBV e antigen, and a liver biopsy shows moderate or severe necroinflammation.

A small group of patients with chronic active hepatitis B may be negative for e antigen but still have high aminotransferase levels, high HBV DNA levels, and continued necroinflammation in the liver.4 The virus in these patients has a mutation in its precore or core promoter gene that prevents the production of e antigen.

Patients with chronic active HBV infection (whether positive or negative for e antigen) are at a significantly greater risk of progressive liver injury and developing cirrhosis and hepatocellular carcinoma than are inactive carriers of HBV.

Immune-tolerant chronic HBV infection. Patients who acquired HBV at birth (eg, our patient) may have immune-tolerant HBV infection, which is characterized by significant HBV replication manifested by the presence of HBV e antigen and high levels of HBV DNA in the serum. However, these patients have no clinical or pathologic evidence of active liver disease (no symptoms, normal serum alanine aminotransferase levels, and minimal changes on liver biopsy).5 This was obviously the case in our patient, based on his history and laboratory results before his current symptoms developed.

Case continues: Liver function abnormalities

On physical examination, the patient’s temperature is 99.9°F (37.7°C), heart rate 106 per minute, blood pressure 98/54 mm Hg, respiratory rate 18 per minute, and oxygen saturation 100% while breathing ambient air. He is alert and oriented to time, place, and person.

He has icteric sclera, and his skin is jaundiced. His lymph nodes are not palpable. His cardiac examination is normal except for tachycardia. His lungs are clear to auscultation and percussion. He has mild epigastric and right upper quadrant abdominal tenderness with no peritoneal signs, hepatosplenomegaly, or masses.

He has no asterixis, and his complete neurologic examination is normal. His extremities are normal, with no edema.

His basic laboratory values on admission are listed in Table 1. His amylase and lipase levels are normal. A urine dipstick test is positive for bilirubin.

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