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Chronic Hepatitis C with Normal Liver Enzyme Tests

Am Fam Physician. 2005 Feb 15;71(4):788.

About 2.7 million persons in the United States harbor hepatitis C virus in their blood. The majority of these persons remain asymptomatic for many years following the initial infection. About 20 percent of infected persons progress to cirrhosis during the first 20 years of infection. The risk of progression is higher in patients with elevated alanine transaminase (ALT) levels. Liver biopsy is the best way to stage hepatic fibrosis and damage. Treatment of hepatitis C infection involves the use of interferon and ribavirin combinations and is, at best, 50 percent effective. This treatment has multiple adverse effects and is costly. Because many patients with hepatitis C infection have normal ALT levels (about 20 percent of those infected with hepatitis C), it is possible that this group should be managed differently from patients with elevated liver enzyme levels. Ahmed and Keeffe reviewed the case of a 43-year-old woman with hepatitis C virus infection whose laboratory test results were normal.

A normal ALT level is defined as a test result within normal limits that remains so persistently over a six-month period with testing intervals of at least one month. Although some patients with normal liver enzymes have liver disease or even cirrhosis, the great majority of them have mild liver disease. Natural history studies of these patients are difficult because often they are not identified, and they have been excluded from many trials. The rate of progression to fibrosis and other evidence of histologic damage appear to be slower, although a few studies hint at rapid progression during flares of hepatitis C.

Most patients with hepatitis C and normal liver enzymes can be observed safely with the hope of better treatments to come in the future. Some of them will want to have treatment to eradicate viral infection, especially in light of evidence that patients with less liver damage have a better rate of response to treatment. The second National Institutes of Health (NIH) Consensus Development Conference on Hepatitis C recommended that these patients can be observed and not treated, but that this decision be made on an individual basis in consultation with the patient. Other factors, including viral genotype, viral load, the presence of hepatic fibrosis, and individual contraindications to treatment, should be considered.

According to results of a cost-effectiveness study, preemptive treatment of patients with hepatitis C using interferon plus ribavirin reduces the risk of future cirrhosis to 16 percent as opposed to 27 percent with no treatment and 18 percent with watchful waiting and biopsy every three years. Preemptive treatment also was found to be less costly than watchful waiting with multiple liver biopsies. Liver biopsy is helpful in patients with hepatitis C infection, but the yield is low because of the slow fibrosis rate. Currently, the decision to perform a liver biopsy should be made jointly by the clinician and the patient based on (1) the risk of finding advanced disease, (2) the high response to treatment of genotypes 2 or 3, (3) the risks of the procedure, and (4) the medical values of the patient.

The authors conclude with a recommended strategy that expectant management is appropriate for patients with mild liver disease proved by biopsy and in patients with normal ALT levels. Patients with biopsy-proven moderate or advanced disease should be treated regardless of liver enzyme results. However, because early treatment yields a better response, management decisions should be individualized.

Ahmed A, Keeffe EB. Chronic hepatitis C with normal aminotransferase levels. Gastroenterology. May 2004;126:1409–15.


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