Survival from hepatic transplantation. Relationship of protein synthesis to histological abnormalities in patient selection and postoperative management.
Forty-one patients, all in end stage hepatic failure, underwent 46 liver transplantations with a long-term survival rate of 63%. Six patients died of uncontrollable bleeding due to primary graft malfunction at or immediately after operation. Nine died early or late with overwhelming infection. In addition to clinical assessment, needle liver biopsy, central plasma clearance rate of amino acids (CPCR-AA), and routine "liver function tests" were employed to aid in selection of patients for transplantation and for guidance in postoperative management. Although liver biopsies usually afforded an exact diagnosis, neither they nor the routine liver function tests quantitated the extent to which hepatocyte function was impaired. CPCR-AA, which measures the rate of amino acid uptake by the liver and other central tissues for oxidation, gluconeogenesis, and protein synthesis was 91 +/- 9 ml/M2/min in the preoperative transplant group. This compares with a value of 97 +/- 16 in a previously studied series of cirrhotics who died following other forms of surgery and a CPCR-AA of 220 +/- 26 ml/m2/min in those who survived. In addition, the preoperative CPCR-AA was found to correlate with the in vitro hepatic protein synthetic rate of slices from the resected recipient liver (r = 0.72, p less than 0.02). After operation, serial hepatic needle biopsies were classified by histology into four grades of injury, ranging from normal liver transplant (Grade I) to mild hypoxic or rejection injury (Grade II), viral hepatitis (Grade III), and severe hypoxic or rejection injury (Grade IV). Significant relationships of the histological grades to ultimate mortality, CPCR-AA, and prothrombin times were found. CPCR-AA and prothrombin time correlate inversely (r = 0.57, p less than 0.001), further demonstrating the relationship of CPCR-AA to protein synthesis of clotting factors. These patterns of posttransplant response were delineated by serial CPCR-AA values. "Early" responders had values over 290 ml/M2/min and all survived. Twelve patients with delayed response were characterized by values of 150 +/- 12, rising to over 200 ml/M2/min after 2 weeks. Two who failed to increase CPCR-AA died. In six "poor" responders, CPCR-AA with Grade IV injury remained below 110 ml/M2/min. All died except for one whose CPCR-AA subsequently rose following retransplantation. It is concluded that percutaneous hepatic needle biopsies and CPCR-AA measurements in combination are of proven value, not only in understanding the nature of injury and functional impairment of the liver, but are also important as guides to selection of patients and for their posttransplant management.
D000596:Amino Acids / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001706:Biopsy; D006801:Humans; D007902:Length of Stay; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D011183:Postoperative Complications / Q000401:mortality*; D011517:Prothrombin Time
D000596:Amino Acids; D001219:Aspartate Aminotransferases; D001663:Bilirubin