Papers

Normal aminotransferase concentrations in patients with antibodies to hepatitis C virus

BMJ 1994; 308 doi: http://dx.doi.org/10.1136/bmj.308.6930.697 (Published 12 March 1994) Cite this as: BMJ 1994;308:697
  1. S Bruno,
  2. S Rossi,
  3. M L Petroni,
  4. E Villa,
  5. M Zuin,
  6. M Podda
  1. Department of Internal Medicine, S Paulo Institute of Biomedical Sciences, University of Milan, 20142 Milan, Italy
  2. Department of Gastroenterology, University of Modena, Modena, Italy
  1. Correspondence to: Dr Bruno.
  • Accepted 8 November 1993

Two studies have recently reported normal aminotransferase concentrations in patients with antibodies to hepatitis C virus and histologically proved chronic liver disease.1,2 These studies, however, disagreed about the predictive values of concentrations of hepatitis C virus RNA in detecting liver disease.

Tests for hepatitis C virus are now included in screening tests for blood donors and in health check ups in Italy, and the number of patients with antibodies to hepatitis C virus and normal aminotransferase concentrations referred to outpatient clinics is rising sharply. We conducted a study to determine the prevalence of histological liver disease in these patients and its relation to serum hepatitis C virus RNA.

Patients, methods, and results

During April 1991 to March 1992, 22 patients presented to our liver clinic with antibodies to hepatitis C virus (detected by enzyme linked immunoassay (ELISA 2)), normal aminotransferase concentrations, and no biochemical or ultrasonographic evidence of liver disease. Of these patients, eight had relatives with chronic liver disease due to hepatitis C virus, three were blood donors, one was a nurse in a dialysis unit, and 10 had had a test for hepatitis C virus as part of general health screening. Nineteen patients (eight men, median age 55 (range 22 to 69) years) agreed to participate in the study.

We measured patients' serum alanine aminotransferase concentrations monthly for at least six months (median 12 (range 7-28) months). The records of five patients showed that they had previously had aminotransferase concentrations above the upper limit of normal (45 IU/l) and they were excluded. A further six patients were excluded because of indeterminate results in the second generation recombinant immunoblot assay (RIBA-2, Ortho, Raritan, New Jersey). In the remaining eight patients we tested for hepatitis C virus RNA by the polymerase chain rection using primers from the 5' UT region.

After a median follow up of 14 (range 7-28) months the eight patients had persistently normal aminotransferase concentrations. All gave informed consent for a percutaneous liver biopsy and the biopsy specimens were blindly evaluated by a pathologist. Chronic liver disease was found in seven patients (table). A test for serum hepatitis C virus RNA done at the time of the biopsy gave positive results in all patients.

Test results in patients with antibodies to hepatitis C virus

View this table:

Comment

Patients with hepatocellular damage have been thought always to have raised serum aminotransferase concentrations. Our results show, however, that chronic liver disease is also likely in patients with antibodies to hepatitis C virus who have normal aminotransferase concentrations and no biochemical or ultrasonographic signs of liver disease.

Unlike an earlier study,1 we found that tests for hepatitis C virus RNA in the serum were no better than cheaper conventional tests in identifying patients with liver disease. Monthly measurement of serum aminotransferase concentrations to detect flare ups of disease was also unhelpful. Thus liver disease can be diagnosed only by biopsy.

None of our patients had advanced disease and since the risk of complications is low in patients without cirrhosis3 we believe that at present liver biopsy is justified for diagnosis alone. Large scale prospective studies are needed to determine the rate of progression of liver disease in these patients.

References

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View Abstract