A 35-year-old Asian man with jaundice and markedly high aminotransferase levels
WHAT IS THE LEAST LIKELY DIAGNOSIS?
2. Which one of the following is the least likely diagnosis in this patient?
- Reactivation of hepatitis B
- Drug-associated liver injury
- Acute viral hepatitis
- Acute alcoholic hepatitis
- Ischemic hepatitis
The degree and pattern of liver function abnormalities in our patient reflect hepatocellular injury rather than cholestatic liver disease, because his aminotransferase levels are elevated much higher than his alkaline phosphatase level (Table 1). Bilirubin elevation does not help differentiate the two conditions.
The degree and pattern of aminotransferase elevations are also helpful in narrowing the differential diagnosis. Serum aminotransferase levels of more than 1,000 U/L are mainly seen in patients with ischemic, viral, and toxininduced liver injury. Other rare causes of such high levels include Budd-Chiari syndrome, Wilson disease, and autoimmune hepatitis.
Ischemic hepatitis. Our patient has mild hypotension, but it does not seem to have been severe enough or of long enough duration to have caused ischemic hepatitis.
Drug-associated liver injury. Hepatotoxicity associated with drugs (most commonly acetaminophen [Tylenol]), herbal therapy, or mushroom poisoning should be considered in any patient whose aminotransferase levels are this high. However, our patient denies taking any medications (prescribed or over-the-counter), herbal remedies, or illicit drugs.
Acute viral hepatitis can certainly explain the patient’s clinical picture. Infection with hepatitis A virus, hepatitis D virus, hepatitis E virus, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses types 1 and 2, and varicella zoster virus have all been implicated in severe acute hepatitis. Although hepatitis E virus infection is more common in developing countries, it has been reported in the United States.6 It is unlikely that acute hepatitis C virus infection is producing this degree of elevation in aminotransferase levels.
Reactivation of the patient’s chronic HBV infection can also account for his clinical presentation.
Acute alcoholic hepatitis should be suspected clinically if a patient has a history of heavy alcohol use and clinical and laboratory findings that are compatible with the diagnosis. However, the absolute values of serum aspartate aminotransferase and alanine aminotransferase in acute alcoholic hepatitis are almost always less than 500 IU/L (and typically less than 300 IU/L). Our patient’s values are much higher, and he says he does not drink very much. Although people sometimes underestimate their alcohol intake, alcoholic hepatitis is the least likely diagnosis in our patient.
Case continues: The patient is hospitalized
The patient is admitted with a diagnosis of acute hepatitis. Given his history of chronic hepatitis B, he is empirically started on lamivudine (Epivir-HBV).
- Antinuclear antibody negative
- Autoimmune liver disease panel negative
- Serum ceruloplasmin 30 mg/dL (normal range 15–60)
- Alpha fetoprotein 35.1 μg/L (< 10).
Abdominal ultrasonography is performed and reveals a small stone in the gallbladder with no evidence of biliary dilatation; otherwise, the gallbladder appears normal. Doppler ultrasonography shows the liver vessels to be patent; the liver is normal in appearance. The abdomen and pelvis appear to be normal on computed tomography without intravenous contrast.
On the third hospital day, the patient’s blood test results are:
- Aspartate aminotransferase 199 U/L (normal range 7–40)
- Alanine aminotransferase 735 U/L (0–45)
- Total bilirubin 22.9 mg/dL (0–1.5)
- International normalized ratio 6.0 (0.77–1.17)
- White blood cell count 5.1 × 109/L (4–11)
- Hemoglobin 11.7 g/dL (12–16)
- Platelet count 166 × 109/L (150–400)
- Blood and urine cultures negative.
