Man With Elevated ALT and History of Blood Transfusion

A 43-year-old fireman comes to your office after a routine blood test revealed that his serum alanine transferase (ALT) level was elevated to approximately twice the normal value. The level was confirmed by repeated testing.

HISTORY

The patient is otherwise healthy and is physically fit. He denies having rashes or arthritis symptoms. He has sustained job-related trauma several times; in 1988, he required blood transfusions for multiple traumatic injuries. He does not smoke but occasionally drinks beer.

PHYSICAL EXAMINATION
Vital signs, heart, and lungs are normal. There is no evidence of scleral icterus, adenopathy, abdominal masses, enlargement of the liver or spleen, ascites, arthritis, rash, or spider angiomata.

LABORATORY FINDINGS

Hemogram and routine chemistry panel are normal. Bilirubin level is 1.2 mg/dL; aspartate aminotransferase level, 75 U/L; and ALT level, 200 U/L. INR is 1. Initial enzyme immunoassay reveals hepatitis C virus (HCV) infection.

Which of the following is the most appropriate next step?

A. Monitor the patient clinically and with biannual ALT measurements; initiate therapy when the level rises to 4 times the normal value.
B. Initiate therapy with peginterferon and ribavirin.
C. Evaluate the patient for elective liver transplantation.
D. Order a polymerase chain reaction test to assess viral load and genotype.
E. Order a liver biopsy to evaluate and stage HCV-related liver disease.

(Answer on next page)

ANSWER: Order a liver biopsy to evaluate and stage HCV-related liver disease.

This patient has well-documented HCV infection. The blood transfusion he received before 1990 placed him at high risk for the disease. (In fact, until recently, blood transfusion before 1990 was the major risk factor in developing countries.) His presentation-no obvious symptoms for a prolonged period after infection-is typical.

The elevated ALT level is a clinical clue that liver disease is present. Finally, the enzyme immunoassay was positive for HCV infection. Because the patient has a significant risk factor, confirmation by recombinant immunoblot assay is not necessary. Reserve confirmatory testing for patients without risk factors or without clinical or laboratory evidence of liver disease.

The issue here is, What is the best initial evaluation for an asymptomatic patient with newly diagnosed HCV infection who has an elevated ALT level? There has been an explosion in methods of characterizing HCV infection and measuring viral load. Assays based on molecular detection of HCV RNA can quantitate the presence and degree of viremia. The results of such assays are relevant to the outcome of and response to anti-HCV therapy, but they do not always correlate with either the extent of liver damage or the likelihood of disease progression. Viral genotyping can be performed in conjunction with viral load studies and can aid in selecting therapy and predicting outcome.

However, the need for therapy has not yet been determined in this patient. Thus, these studies (choice D) are not the best option at this time. Although ALT measurement is an excellent, inexpensive study for identifying liver disease, levels fluctuate greatly in patients with HCV infection. Consequently, this study cannot rule out active infection, assess progression of liver disease, or indicate success of therapy.¹

At a time when so many more effective means of measuring disease activity (quantification of viral load, liver biopsy) and of treating disease (antiviral therapy, liver transplantation) are available, few if any authorities would monitor a newly diagnosed patient only with ALT levels. Thus, choice A is not appropriate. The "gold standard" for determining viral activity and degree of liver damage remains biopsy. Tissue sampling is also the only reliable means of establishing a prognosis and determining the likelihood of HCV-related progression of liver disease.²

Liver biopsy can detect the degree and extent of active inflammation, as well as the presence of bridging fibrosis and cirrhosis.

Therefore, liver biopsy (choice E) is currently recommended for initial assessment of patients with chronic HCV infection.^2-4 There are currently insufficient data to make a decision about therapy for this patient. He has no severe immune complex findings (ie, mixed cryoglobulins with vasculitis, arthritis, and rash), which on their own can be an indication for therapy.

Treatment with interferon/ribavirin regimens (choice B) is usually reserved for patients with documented HCV titers, persistently elevated ALT levels, and a liver biopsy that shows significant necrosis and inflammation and/or fibrosis.

Hepatitis C is now the most common indication for liver transplantation (choice C), but the procedure is indicated for patients with decompensated cirrhosis. This patient has no clinical stigmata for cirrhosis, let alone decompensated liver failure. Although transplantation may be an option in the future, it is not at this time.