The correlation between cytological patterns in bile and histological findings in liver transplantation.

The cytological patterns in bile were compared with the histological findings in concomitant specimens from liver transplants. In cases where cytology showed a moderate (n = 10) or high cell density (n = 8), histology demonstrated rejection in 14 of 18 specimens and cholangitis in 4. When the cell density was low (n = 22), histology was nearly normal in 3 specimens and showed cholangitis in 9, while rejection was observed in 10 specimens. Cell density in bile did not correlate quantitatively with the severity of cellular infiltration in the portal triads or with the percentage of bile ducts attacked by inflammatory cells. The results of the present study support our hypothesis that an increased concentration of cells in bile is indicative of liver transplant rejection (sensitivity 58%), while normal cytology does not rule out the possibility of rejection (specificity 75%).     

肝移植围手术期胆汁酸变化及意义

术前肝功能损害程度及术后肾功能衰竭是影响肝移植病人术后死亡率的蕈要因素.Caestecher等[1]报道,胆汁酸(TBA)可以同时反映肝脏分泌状态,肝脏合成与代谢及肝细胞损伤三方面的血清学指标,其代谢在一定程度上受肾功能的影响.笔者通过检测肝移植术后病人血清中胆汁酸变化,并与常规肝功能指标谷草转氨酶(AST)和总胆红素(TBIL)比较,探讨胆汁酸在肝移植围手术期变化的临床意义.     

Ursodeoxycholic acid increased bile flow and affects bile composition in the early postoperative phase following liver transplantation

Abstract Orally given ursodeoxycholic acid (UDCA) has beneficial effects on laboratory parameters in different cholestatic conditions. In order to investigate the effect on early graft function after liver transplantation, 33 patients were randomized to receive either UDCA 15 mg/kg per day or placebo from the 1st postoperative day until 3 months after transplantation. All liver grafts produced bile within 24 h after revascularization. In both groups there was an increasing bile flow each day until day 5 after transplantation. This increase was more pronounced in the UDCA group where the flow on day 2 reached a mean value of 183 ± 28 ml/day compared to 106 ± 17 ml/day in the placebo group ( P < 0.05). The average daily volume of bile produced during the first 10 days was also found to be higher in the UDCA group compared to the placebo group (242 ± 20 ml vs 176 ± 18 ml, P < 0.02). In the UDCA group a significant decrease in total bile acid output between the 5th and 10th postoperative days was found, while in the placebo group the amount of bile acids excreted remained stable over time. The composition of bile differed between the two groups with an increase in the portion of UDCA in the UDCA group from the 2nd postoperative day (25 % vs 4.6 %, P < 0.0003). The fraction of UDCA then remained high during the whole study period with a peak at day 3 when 38.1 ± 6.6% of the bile acids consisted of UDCA. In the placebo group, the fraction of UDCA was low from the beginning and diminished further over time. Prophylactic UDCA treatment was found to have a significant positive impact on the ALT level during the 4th and 5th postoperative days, but had no effect on bilirubin or GGT in the early postoperative phase (days 1–10). No differences in cyclosporin requirement were found between the two groups.     

Bile composition and bile cast formation after transplantation of the liver in man.

Transplantation of the liver in man is frequently complicated by biliary fistula and obstruction of the biliary tree by casts, which suggests that the composition of the bile may be abnormal. In part of the present study, bile composition was investigated in three recipients during the first few weeks after transplantation, when a T tube was in place. Supersaturation of bile with cholesterol was found in two patients immediately after surgery and during episodes of acute rejection, but bile was never lithogenic in the third. There was no evidence of bile stasis in the absence of acute rejection and bile viscosity was normal in all three patients throughout the study. Free bile acids and free bilirubin, which are relatively insoluble products of bacterial metabolism, were not present in the bile of any patient. However, chemical analysis of casts found at autopsy in a fourth recipient showed that the major component was free bilirubin. Escherichia coli was grown in cultures of the casts and the organisms were shown to possess glucuronidase activity, thus providing an explanation for the high bilirubin content. There was also some evidence in one case that damage to the bile duct mucosa has led to the precipitation of material upon it, and it is concluded that a number of factors, including infection, supersaturation with cholesterol, and mucosal damage, may be involved in bile case formation after transplantation of the liver.     

肝移植术后胆管狭窄发病机制的研究进展

肝移植术后胆管并发症是目前导致肝移植失败的主要原因,其中胆管狭窄的发病机制复杂,其机制研究是移植界热点问题,本文结合近年来该方面研究进展,认为其发病机制与肝动脉血栓形成、胆管血运的破坏、供肝胆管早期的充分冲洗、供肝的冷热缺血时间、排斥反应、巨细胞病毒感染ABO血型不符、受体原发性硬化性胆管炎等因素有关.     

Changes in bile salt composition after cholecystectomy and ileal resection

The effect of ileal resection and cholecystectomy on bile salt metabolism was studied in female prairie dogs 4 weeks after either a sham laparotomy, cholecystectomy, ileal resection, or cholecystectomy and ileal resection. Bile was collected from a common bile duct cannula at hourly intervals for 12 hours. Pool sizes and synthetic rates of primary and secondary bile salts were determined from washout curves. Cholate, chenodeoxycholate, deoxycholate, and lithocholate levels were determined by gas chromatography from pooled collections of bile. After cholecystectomy and ileal resection, the pool sizes of primary and secondary bile salts were significantly reduced to amounts that were much less than the pool sizes after either procedure alone. Primary bile salt synthesis was significantly increased after combined cholecystectomy and ileal resection, to the same degree as cholecystectomy alone. After the combined procedures, there was a decrease in the proportion of cholate in hepatic bile associated with an increase in chenodeoxycholate, deoxycholate, and lithocholate levels. The data suggest that after the loss of both ileum and gallbladder the bile salt pool sizes are drastically reduced, the synthesis of primary bile salts is increased, and the proportion of secondary bile salts is increased. Cholecystectomy should be avoided, if possible, in patients with ileal resection in order to conserve the bile salt pool and prevent severe fat malabsorption.     

Changes in intragastric bile acid composition in patients receiving cimetidine postoperatively

Enterogastric reflux has been implicated as a possible etiologic mechanism in gastritis both after partial gastrectomy and in those with an intact pylorus. We studied the effects of cimetidine on bile acid concentration and composition by high-performance liquid chromatography. The gastric aspirates collected for this study came from 27 prospectively randomized patients receiving intravenous cimetidine (200 mg every 6 hours) and 25 patients given a placebo. Total bile acid concentration of aspirates was determined spectrophotometrically. Marked differences were noted in conjugated bile acids. Glycochenodeoxycholic acid, a toxic dihydroxy bile acid, was decreased after cimetidine compared with results from the placebo. The ratio of less toxic trihydroxylated to more toxic dihydroxylated bile acids was significantly increased. Enterogastric reflux itself seemed unaltered by cimetidine; likewise, the concentration of total bile acids in the cimetidine group was similar to that among patients receiving placebo. These changes in bile salt composition with cimetidine may help explain its salutary effects in gastritis, over and above its ability to reduce gastric hydrogen ion secretion.     

Changes in the composition of serum bile acid as a predictor of small bowel allograft rejection in rats

Composition of bile acid was studied as a noninvasive rejection marker after small bowel transplantation (SBT). Orthotopic SBT were performed in rats, and they were divided into four groups: group 1, sham-operated rats; group 2, recipients with isografts; group 3, recipients with allografts treated with FK506; and group 4, recipients with untreated allografts. On postoperative days (POD) 5 and 7, the graft histology, intraluminal bacterial overgrowth, individual bile acids concentration of the recipient serum and bile were examined. On POD 5, early histological findings of acute rejection were observed in group 4, and the ratio of secondary bile acids of this group were significantly higher than the other groups. The bile acid changes were enhanced by bacterial overgrowth on POD 7. The ratio of secondary bile acids changed in relation to acute rejection after SBT, suggesting that they can be useful for early diagnosis of acute SBT allograft rejection.     

Examination of lymph and bile composition following experimental liver transplantation in rat

The lymph flow of the thoracic duct, the protein content of the lymph, bile flow and bile composition are studied during the first three hours of the recirculation phase in experimental liver transplantation. It is established that the lymph flow and the protein content of the thoracic duct decrease as a result of the interruption of hepatic lymph flow of a high protein concentration. The change in bile composition and flow is due to the reduced bile acid excretion of the transplanted hepatic tissue.     

Raised pressure in the bile ducts after orthotopic liver transplantation

Biliary complications are common after orthotopic liver transplantation. Bile leakage in the immediate postoperative period and on removal of the T-tube could possibly be caused by a raised bile duct pressure. In order to test this hypothesis, bile duct pressure was studied in seven consecutive liver transplant patients. During the operation, the common bile duct was anastomosed end-to-end over a T-tube. The initial bile duct pressure measurement was performed a median of 12 days (range 10–17 days) after the transplantation and on one or two more occasions during the following 3 months. Seven cholecystectomized gallstone patients with indwelling T-tubes were used as controls. The bile duct pressure at the level of the xiphoid process in the transplanted group was 7.7±1.4 cm H₂O and in the control group 0.5±0.8 cm H₂O (P<0.001). The initially increased bile duct pressure after liver transplantation decreased with time (P<0.05) towards normal during the following 3 months. The raised pressure may increase the risk of bile leakage in the postoperative period.     

Intrahepatic bile duct strictures after human orthotopic liver transplantation

One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin-steroid era (March 1980–June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility.