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Arterial complications after orthotopic liver transplantation (OLT), including hepatic artery thrombosis (HAT), are important causes of early graft failure. The use of an arterial conduit is an accepted alternative to the utilisation of native recipient hepatic artery for specific indications. This study aims to determine the efficacy of arterial conduits and the outcome in OLT. We retrospectively reviewed 1,575 cadaveric adult OLTs and identified those in which an arterial conduit was used for hepatic revascularisation. Data on the primary disease, indication for using arterial conduit, type of vascular graft, operative technique and outcome were obtained. Thirty-six (2.3%) patients underwent OLT in which arterial conduits were used for hepatic artery (HA) revascularisation. Six of these were performed on the primary transplant, while the rest (n=30) were performed in patients undergoing re-transplantation, including six who had developed hepatic artery aneurysms. The incidence of arterial conduits was 0.4% (6/1,426 cases) in all primary OLTs and 20.1% (30/149 cases) in all re-transplants. Twenty-nine procedures utilised iliac artery grafts from the same donor as the liver, six used iliac artery grafts from a different donor, and a single patient underwent a polytetrafluoroethylene (PTFE) graft. Two techniques were used: infra-renal aorto-hepatic artery conduit and interposition between the donor and recipient native HAs, or branches of the HAs. The 30-day mortality rate for operations using an arterial conduit was 30.6%. Three conduits thrombosed at 9, 25 and 155 months, respectively, but one liver graft survived without re-transplantation. The arterial conduits had 1- and 5-year patency rates of 88.5% and 80.8%. The 1- and 5-year patient survival rates were 66.7% and 44%. We can thus conclude that an arterial conduit is a viable alternative option for hepatic revascularisation in both primary and re-transplantation. Despite a lower patency rate than that of native HA in the primary OLT group, the outcomes of arterial conduit patency and patient survival rates are both acceptable at 1 and 5 years, especially in the much larger re-OLT group.

Hepatic artery aneurysm (HAA) is a rare vascular complication, but has a high mortality rate in liver transplant recipients. This study reports the precipitating factors, clinical manifestation, pre-operative diagnosis, related micro-organism, management, and outcome, in a series of HAAs that developed after adult orthotopic liver transplantation (OLT). Data on the primary disease as well as on the above were obtained from a prospective database, and all case records were reviewed. There were eight (0.5%) HAAs in 1,575 adult cadaveric OLTs between 1982 and March 2001. All were pseudo-aneurysms around the native hepatic-artery (HA) anastomosis, and all occurred in whole-organ OLTs. There were three types of clinical presentations: sudden hypotension (n=4), gastrointestinal (GI) bleeding (n=2), and abnormal liver-function tests (LFTs) (n=2). The majority (n=7) presented within the first 2 months (median: 27.5 days, range: 12-760 days) following OLT. A pre-operative diagnosis of HAA was not determined in five cases. The sensitivity of abdominal ultrasound scan (USS), computed tomography (CT) scan and angiography for detection of HAAs was 3 of 5, 1 of 2 and 3 of 4, respectively. Micro-organisms could be identified in six patients (bacteria n=4 and fungi n=3). All patients underwent urgent operations (excision of HAA in six and ligation in two cases). Immediate reconstruction of the HA was carried out, two different methods being used: repair of native arteries (n=2) and arterial conduit (interposition n=3 and aortic conduit n=2). Two patients died peri-operatively, two died within 2 months, and the remaining four patients are alive at between 8.6 and 12.8 years after repair. HAA following OLT is unpredictable in its presentation, and the sensitivity of clinical and radiological detection is low. A high index of suspicion is required, and urgent surgery with immediate re-vascularisation and use of appropriate antibiotic/anti-fungal agents is recommended.

Fibrolamellar hepatocellular carcinoma (FL HCC) is an uncommon variant of hepatocellular carcinoma occurring usually in non-cirrhotic livers. Hepatic resection or transplantation offers the only chance of cure. We reviewed our experience of surgery for FL HCC from 1985-1998. Twenty patients with FL HCC (13 females and 7 males) median age 27 years (range 12-69) were treated either by hepatic resection [n = 11; extended right hepatectomy (5), extended left hepatectomy (1), right hemihepatectomy (2), left hemihepatectomy (2), left lateral segmentectomy (1)] or, if the disease was non-resectable, by transplantation (n = 9). The median follow up was 25 months (1-63). The prognostic factors analysed included size [less than 5 cm (3 patients), more than 5 cm (17 patients)], number [solitary (16 patients), multiple (4 patients)], capsular invasion (6 patients), vascular invasion (11 patients) and lymph node invasion (6 patients). The overall survival at 1, 3 and 5 years was 89.5, 75 and 50%, respectively. The liver resection survival was better than liver transplantation survival at 3 years 100 vs 76%, respectively (P < 0.025). Although all prognostic factors analysed did not show a significant difference, there is tendency that tumour stage was the most significant for prognosis. Most of the patients in this study are young and presented without specific symptoms, with normal liver function range and had no tumour marker to help in diagnosis. As a result most of our patients were diagnosed late. However the outcome of surgical intervention was favourable.

Repeat orthotopic liver transplantation (ReOLT) is controversial because of limited donor organ availability and increasing health care costs. The purpose of this study is to analyse and compare the outcome of reOLT in the 1990s and the 1980s. Prospective data of 1077 adult OLT from the Liver Unit database were used for the study. The log-rank test was used for statistical analysis. Between January 1982 and December 1996, a total of 1077 adult OLTs were performed including 107 reOLTs. The proportion of retransplants decreased from 13% in the 1980s to 9% in the 1990s. There was a significant improvement in outcome; the overall 1-year graft and patient survival for reOLT was 60% and 74% in the 1990s compared to 29% (P < 0.0001) and 51% (P < 0.0001) in the 1980s. In the second half of the study between January 1990 and December 1996, 732 adult OLTs were undertaken including 70 (9%) reOLTs which consisted of 62 second, 7 third and 1 fourth grafts. The main indications for retransplantation were chronic rejection (31%), hepatic artery thrombosis (30%), primary non-function (16%), ischaemic injury (11%), recurrent disease (6%) and biliary complications (6%). During this period, the 1-year graft survival for all reOLTs was significantly lower than for primary OLTs (67% vs 78%, P < 0.001). The timing of reOLT was found to be associated with graft survival; 1-year graft survival for early reOLT (< 30 days) was 50% compared to 73% for late reOLT (P < 0.001). The worse outcome associated with early reOLT is explained by the poor preoperative medical condition of patients who were retransplanted from intensive care. Subgroup analysis of indications for reOLT revealed 1-year graft survival of 81% for late vascular complications, 75% for early vascular complications, 69% for chronic rejection and 30% for primary non-function. One-year graft survival rates for third and fourth grafts were 42% and 0%, respectively. Graft survival and resource utilisation in patients who received a late regraft for the first time is now comparable to that for primary OLT. The favourable overall results should not preclude this group of patients from consideration for reOLT.

The impetus for the development of living related liver programmes lies with donor shortage, which relates inversely to the success of generating cadaveric donors. A shrinking or non-existent cadaveric donor pool leads to an increased death rate among potential recipients awaiting transplantation. The living related liver programmes have by and large been successful, though it is accepted that there is potentially a significant risk to the donors. The technique of live donor liver transplantation is clearly here to stay, but the selection of suitable donors is between the family and the unit. Consequently, because of the lack of international guidelines, the programmes are open to abuse. Steps should be taken to establish either mechanisms of control or a worldwide register to combat this potential.

The choledochochole-dochal (duct-duct, D-D) anastomosis in orthotopic liver transplantation (OLT) is usually splinted by a T-tube to facilitate easy cholangiography, monitor bile quality and allow biliary decompression. T-tubes, however, are a focus for sepsis and sludge deposition, and their removal may result in bile leakage. From January 1993 to December 1994, 199 consecutive adult OLTs in 183 patients (median age 50 years, range 16-69 years, 118 females) with a D-D anastomosis were studied prospectively with a median follow-up of 16 (3-27) months. Of the 199 OLTs, 110 had an 8 Fr T-tube (group 1) and 89 had no T-tube (group 2). The two groups were similar for indication, preservation solution, median cold and warm ischaemia times and early graft function parameters. Biliary complications developed in 26/110 patients, including 10 with bile leaks on T-tube removal in group 1 compared to 10/89 biliary complications in group 2 (P = 0.024). The use of T-tubes is associated with increased morbidity and their routine use should be discontinued.

Portal venous blood for rinsing out the University of Wisconsin solution (UWs) has the advantages of being a physiological fluid, removing acidotic mesenteric venous blood and perhaps resulting in more stable haemodynamic parameters during reperfusion. A group of 209 consecutive adult OLTs carried out between July 1993 and February 1995 were studied prospectively. The UWs was flushed out with 500 ml portal blood in 95 OLTs (group 1) and with 1.0 L 0.5% dextrose at 37 degrees C in 114 OLTs (group 2). The median day 1 and peak day 1-5 AST levels were significantly elevated in the 5% dextrose group: median 755 (118-11090) vs. 546 (121-6150) IU/I (P = 0.007, Wilcoxon); and median 1095 (159-11090) vs. 744 (157-7870) IU/l (p = 0.008, Wilcoxon), respectively. A median of 5 (0-27) units of blood were transfused in group 1 compared to 4 (0-54) units in group 2 (n.s.). There was no difference in peak bilirubin, lowest day 1-5 PT levels, primary nonfunction, median ITU stay, total inpatient stay and 1-month graft survival between the two groups (89% vs. 88%). Pre-reperfusion blood flush may be associated with less hepatocellular damage, without significant additional blood usage.

Eighty-one liver recipients were randomised to FK 506 or cyclosporin (CyA) and azathioprine (AzA), both in combination with steroids. Twenty-seven FK 506 and 29 CyA/AzA patients continued in the trial 3 months after transplantation. Steroids were ceased in 23 (85%) FK 506 patients and in 27 (93%) CyA patients. After steroid withdrawal, 2 FK 506 and 4 CyA patients were excluded from the study, all for reasons other than rejection. The median follow-up was 16 months for the FK 506, and 19 months for CyA group. There were no acute rejection episodes or graft losses in the FK 506 group. None of the CyA patients lost their graft but three (13%) had episodes of acute rejection requiring steroids to be recommenced in two cases. There was no evidence of chronic rejection in any of the annual review biopsies in either group. Our results suggested no advantage of FK 506 over CyA in its steroid-sparing effect.

We assessed the immunomodulatory effect of leflunomide (LEF) in a heterotopic abdominal model of rat heart transplantation using a major histocompatibility mismatch (DA X LEW). The endpoint of this study was cardiac rejection assessed by abdominal palpation of the ventricular impulse and confirmed by laparotomy and histology. In this study, LF was investigated using four dosages (5, 10, 20 and 30 mg/kg per day orally) against cyclosporine (CsA) (15 mg/kg per day orally) and FK 506 (1 mg/kg per day orally). The ability of LEF to prevent rejection and reverse ongoing acute rejection was assessed. The results showed that untreated hearts were fully rejected by day 5 and that LEF at 5 mg/kg was significantly better than any other dose tested, was superior to FK 1 mg/kg, and was as effective as CsA 15 mg/kg in preventing rejection after a short course of treatment. After a longer course, 10 and 20 mg/kg LEF proved more effective than 5 mg/kg in controlling rejection and as efficacious as 1 mg/kg FK and 15 mg/kg CsA. In the control of ongoing established early rejection. LEF proved to be equally effective, even at lower doses (5 mg/kg), to CsA 15 mg/kg and FK 1 mg/kg. In the control of ongoing established late rejection, 20 mg/kg LEF proved to be superior to 10 mg/kg LEF and 15 mg/kg CsA, and was as effective as FK 1 mg/kg. However, when higher doses of CsA (25 mg/kg) and FK (2 mg/kg) were tested against 20 mg/kg LEF in this mode of rescue, LEF proved as effective as CsA and superior to FK. In the assessment of drug toxicity using body weight as a parameter, 20 mg/kg LEF proved safer than any other LEF dose tested, and safer than 15 mg/kg CsA and 1 mg/kg FK in both short- and long term administration. We conclude that LEF is a relatively safe and potent immunosuppressant with promising clinical potential.

Steroid therapy was withdrawn in 85% of 152 orthotopic liver transplant recipients with grafts surviving for more than 3 months, and 87% of these remained steroid-free. Steroid therapy was restarted in 8% for reasons other than rejection. The most common was conversion of immunosuppression because of cyclosporine nephrotoxicity. The incidence of rejection after steroid withdrawal was low: 3.8% for chronic rejection (CR) and 4.5% for acute rejection. Only 3 grafts (1.9%) were lost because of CR. No risk factors have been identified for the development of CR after steroid withdrawal, but a protective role for azathioprine has been suggested.