alpha-Glutathione S-transferase as a marker of hepatocellular damage in chronic hepatitis C virus infection.

alpha-Glutathione S-transferase (alpha GST) may be a good serologic marker of hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosolic concentration, and short half-life. To determine the clinical utility of alpha GST in patients with chronic hepatitis C virus (HCV) infection, serum alpha GST levels were measured in 96 patients with chronic HCV infection, of whom 47 subsequently underwent interferon-alpha therapy. Patients were simultaneously evaluated with conventional liver biochemistry, serum HCV RNA levels, and liver histology. Different methods of serum collection did not affect alpha GST values, indicating that this was a stable serum marker. In 93% of patients with chronic HCV infection, alpha GST was elevated and showed an excellent correlation with serum aminotransferases. Histologic analysis revealed a correlation of alpha GST with both lobular inflammation and bile duct lesions. There was no correlation between serum alpha GST levels and the demographic features, mode of transmission, virologic, other histologic parameters, or subsequent response to interferon-alpha. During serial monitoring in patients undergoing interferon-alpha therapy, elevation of serum alpha GST correlated with biochemical relapse and in some patients virologic relapse in the presence of normal liver biochemistry. alpha GST was persistently elevated in all nonresponders. Four of six of those patients who responded completely followed by early relapse had elevated alpha GST intermittently or continuously during therapy despite normalization of serum aminotransferases. Two of five of those with a complete and sustained response had elevated alpha GST during treatment and follow-up, and both were also seropositive for HCV RNA during follow-up. These data demonstrate that alpha GST is a stable marker, has similar diagnostic utility as serum aminotransferases, and may have a role in the monitoring of patients undergoing interferon-alpha therapy.