E Geuken

Altered bile composition after liver transplantation is associated with the development of nonanastomotic biliary strictures

BACKGROUND/AIMS Nonanastomotic biliary strictures are troublesome complications after liver transplantation. The pathogenesis of NAS is not completely clear, but experimental studies suggest that bile salt toxicity is involved. METHODS In one hundred and eleven adult liver transplants, bile samples were collected daily posttransplantation for determination of bile composition. Expression of bile transporters was studied perioperatively. RESULTS Nonanastomotic biliary strictures were detected in 14 patients (13%) within one year after transplantation. Patient and donor characteristics and postoperative serum liver enzymes were similar between patients who developed nonanastomotic biliary strictures and those who did not. Secretions of bile salts, phospholipids and cholesterol were significantly lower in patients who developed strictures. In parallel, biliary phospholipids/bile salt ratio was lower in patients developing strictures, suggestive for increased bile cytotoxicity. There were no differences in bile salt pool composition or in hepatobiliary transporter expression. CONCLUSIONS Although patients who develop nonanastomotic biliary strictures are initially clinically indiscernible from patients who do not develop nonanastomotic biliary strictures, the biliary bile salts and phospholipids secretion, as well as biliary phospholipids/bile salt ratio in the first week after transplantation, was significantly lower in the former group. This supports the concept that bile cytotoxicity is involved in the pathogenesis of nonanastomotic biliary strictures.

Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults

Abstract:  The aim of this study is to analyse a single centres experience with two techniques of liver transplantation (OLT), conventional (CON‐OLT) and piggyback (PB‐ES), and to compare outcome in terms of survival, morbidity, mortality and post‐operative liver function as well as operative characteristics. A consecutive series (1994–2000) of 167 adult primary OLT were analysed. Ninety‐six patients had CON‐OLT and 71 patients had PB‐ES. In PB‐ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB‐seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB‐sim). One‐, 3‐ and 5‐yr patient survival in the CON‐OLT and PB‐ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p = ns). Apart from the higher number of patients with cholangitis and sepsis in CON‐OLT group, morbidity, retransplantation rate and post‐operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4 h in PB‐ES vs. 10.0 h in CON‐OLT), but in PB‐ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs. 114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC use in the PB‐ES group was lower compared to the CON‐OLT group (4.0 min vs. 10.0 units, p < 0.05). Except for WIT and REVT there were no differences in operative characteristics between PB‐Sim and PB‐Seq groups. The WIT was significantly longer in PB‐Sim group compared with PB‐Seq group (64 min vs. 50 min, p < 0.05); however REVT was significantly shorter in PB‐Sim group (64 min vs. 97 min, p < 0.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB‐ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB‐ES group there seems to be no adavantage for any of the revascularization protocols.

Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients

The adenosine triphosphate (ATP)‐binding cassette (ABC)‐transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2‐week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real‐time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8. (HEPATOLOGY 2005;42:1166–1174.)