Receiver operating characteristic analysis of serum chemical parameters as tests of liver transplant rejection and correlation with histology

Receiver operating characteristic (ROC) analysis was used to determine the strength of the serum chemical parameters alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, y-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, and the ratio of delta bilirubin to conjugated bilirubin as tests of acute cellular rejection in liver transplant patients. The study consisted of 70 liver biopsies performed between February 1989 and January 1992 on 37 transplant patients who were classified as showing either no rejection (35 biopsies) or moderate to severe rejection (35 biopsies); mild cellular rejection biopsies were not included in this study to highlight any differences between rejectors and nonrejectors. Corresponding serum values for liver enzymes, alkaline phosphatase, GGT, and bilirubin fractions were obtained on the morning of the biopsy. ROC analysis demonstrated that there is no single chemical parameter or combination thereof that can statistically or clinically distinguish patients with acute rejection from those with other etiologies of allograft dysfunction. We also assessed by regression analysis the correlation between histologic features in the biopsies and corresponding serum parameters. The degree of histologic cholestasis was compared with the same-day serum value for total bilirubin, alkaline phosphatase, and GGT. The degree of centrilobular necrosis and the number of apoptotic cells were compared with values for aspartate aminotransferase and alanine aminotransferase. There was no correlation between the se- rum values and histologic abnormalities. We conclude that serum chemistry values are not good tests for rejection or histologic abnormalities in the liver transplant population; liver biopsy should therefore be performed on a scheduled basis.