Serum Guanase Activity in Hepatitis C Virus Infection

Abstract

Guanase (guanine aminohydrolase, EC 3.5.4.3), catalyses the hydrolytic deamination of guanine. The reaction is important because of its potential to infuence intracellular guanine nucleotide pools: guanine is directly salvagable to GMP, whereas its product xanthine is not (see Figure 1). Amongst human tissues, liver contains the highest guanase activity; activity is also detectable in brain and kidney [1, 2]. In most assays, guanase activity in other tissues and in normal plasma and serum is close to or below the detection limit [3–5]. Gross increases in serum guanase are considered a specific indication of hepatocellular damage and have been shown to have prognostic and diagnostic value in a variety of clinical situations [2–9]. However, routine guanase measurement is not widely available due to lack of sufficiently facile and accurate assays. We have developed a sensitive assay for guanase using reversed-phase ion-pair HPLC. Using this assay, we found that guanase activity in normal sera was lognormally distributed about a geometric mean of 0.85 units/litre, with no significant gender difference. When sera submitted to us for testing by polymerase chain reaction (PCR) for suspected active hepatitis C virus (HCV) infection were screened in parallel for guanase activity, increases above the 95% percentile of the normal range were found to be predictive of HCV positivity. In two separate groups of patients being treated with interferon-alpha for chronic HCV infection, guanase activity was elevated before treatment and decreased significantly during treatment. We conclude that serum guanase activity is a useful surrogate marker for HCV infection and that serial measurements may have prognostic value.