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Liver biopsy is an important diagnostic tool in the management of patients following orthotopic liver transplant. We evaluated complications following percutaneous liver biopsy in a group of liver transplant patients who had Roux-en-Y choledochojejunostomies fashioned as part of their biliary reconstruction during liver transplantation. Complications were divided into two major groups: septic complications (including fever, symptomatic bacteremia, cholangitis, infected hematoma and hypotension related to sepsis) and bleeding (defined as hypotension requiring volume expansion greater than 500 cm3 or blood transfusion, hemothorax, intrahepatic or peritoneal hemorrhage and hemobilia occurring within 1 wk of liver biopsy). One hundred ninety-two biopsies were performed in 46 patients with choledochojejunostomies, and 118 biopsies were carried out in an age- and sex-matched control group of patients with choledochocholedochostomy biliary anastomosis. There were no septic complications in the choledochojejunostomy patients and one (0.32%) septic complication in the choledochocholedochostomy patients (NS). Eight bleeding complications occurred (2.6%) in eight patients (8.3%). Five (2.6%) occurred in five (10.8%) of the choledochojejunostomy patients, vs. three (2.5%) in three (6.5%) choledochocholedochostomy patients (NS). None of the bleeding complications required surgical intervention or was fatal. We conclude that liver biopsy in posttransplant patients with Roux-en-Y choledochojejunostomies is a safe procedure and that the incidences of complications were similar in our two groups. The negligible incidence of septic complications in the choledochojejunostomy patients does not appear to warrant the administration of prophylactic antibiotics, as has been previously suggested.

Bile acid metabolism and biliary secretion were characterized in the first 2 wk after orthotopic liver transplantation in 15 patients receiving cyclosporine and in five patients receiving FK 506. Analyses were performed on hepatic bile obtained by T-tube drainage; values obtained were compared with literature values for bile samples obtained in patients who had undergone cholecystectomy. Biliary bile acid output, which is equivalent to bile acid biosynthesis from cholesterol, was low (mean +/- S.E.M.) and increased with time: day 1, 0.50 +/- 0.1 mmol/day; day 3, 0.8 +/- 0.1 mmol/day; and day 6, 1.6 +/- 0.5 mmol/day. Chenodeoxycholic acid biosynthesis, as percent of total bile acid biosynthesis, was abnormally low in patients receiving cyclosporine (16.2 +/- 1.1) but not in patients receiving FK 506 (38.2 +/- 4.8) (p < 0.005). Before the T-tube was clamped, the proportion of deoxycholic acid (a secondary bile acid formed by bacterial 7-dehydroxylation of cholic acid) was low in both groups: cyclosporine, 0.4 +/- 0.1; FK 506, 4.8 +/- 2.5 (p < 0.01). The mean concentration of bile acids in hepatic bile between days 4 and 11 did not differ significantly between groups: cyclosporine, 7.7 +/- 1.3 mmol/L; FK 506 4.3 +/- 0.7 mmol/L (mean +/- S.E.M.). (These values are similar to those reported for patients who have undergone cholecystectomy.) Bile acid-dependent bile flow, expressed as apparent choleretic activity (microliters of bile per micromole of bile acid output), was markedly elevated: in patients receiving cyclosporine the value was 129, and in patients receiving FK 506 the value was 220. (In patients who have undergone cholecystectomy, this value is less than 30).(ABSTRACT TRUNCATED AT 250 WORDS)

We have used extracorporeal liver perfusion (ECLP) to aid in the management of three patients with fulminant hepatic failure (FHF). Organs were used for ECLP only if they would have gone otherwise unused through United Network for Organ Sharing. In all three patients treated, serial serum bilirubin and arterial ammonia values trended toward the normal range. The neurologic examinations improved dramatically in two patients, and metabolic function of the extracorporeally perfused livers was unequivocally demonstrated by the clearance of theophylline in the last two patients. Two patients ultimately had successful liver transplants, whereas the third patient failed to improve neurologically despite evidence of metabolic function by the extracorporeally perfused liver, and died 7 days after ECLP was discontinued, from pulmonary and renal failure. These studies suggest that, 30 yr after initial clinical trials, ECLP can be applied safely without the need for arterial access 1) as a bridge to transplantation, 2) to assess whether patients in FHF will benefit from improved hepatic function and therefore transplantation, and 3) potentially, to evaluate the "usability" of questionable donor organs.

Cyclosporine is used in the postoperative management of rejection in liver allograft recipients. Despite its efficacy in the treatment of allograft rejection, the drug exhibits toxicity at elevated whole blood concentrations including nephrotoxicity with associated histologic changes, and evidence of hepatotoxicity as determined by liver function studies. To date, there have been few published reports describing histologic changes in liver biopsies from patients with elevated blood cyclosporine levels. In the present study, we retrospectively examined biopsies from 16 liver allograft recipients, seven patients with elevated whole blood cyclosporine levels (> 1000 ng/ml) and nine control patients who had whole blood cyclosporine levels in the therapeutic range (558 to 993 ng/ml). In each case, frozen liver biopsy tissue was available to measure tissue levels of cyclosporine and metabolites. The blood and tissue drug levels were then correlated with the histologic changes present in the biopsy specimens. Patients with increased cyclosporine levels displayed histologic changes consisting of hypertrophy of the bile ductal epithelium with cytoplasmic vacuoles and the presence of "foamy" material within the hepatic sinusoids that were either absent or occurred less frequently in the control group. The histologic changes correlated best with cyclosporine metabolite levels rather than tissue levels of native drug. When liver function studies were correlated with cyclosporine levels, only gamma glutamyl transpeptidase (GGT) demonstrated a significant positive correlation with the histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)