Matthew Bowles

Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts.

Background:To increase the number of livers available for transplantation a non-heartbeating donor (NHBD) liver transplant program was started after obtaining hospital ethical committee approval. Methods:Controlled donors with a warm ischemia of <30 minutes were considered. A 5-minute stand-off period was observed from asystole to skin incision. A super-rapid technique was used for the retrieval. Methods used to assess the suitability for transplantation included liver function tests, morphologic and histologic assessment, and hepatocyte viability testing. Results:Sixty livers were retrieved from NHBDs. Of these, 33 were judged suitable for transplantation. Of these one was exported and transplanted, and one could not be matched to a suitable recipient. A further 27 were not used because of liver appearance in 21, prolonged hypoxia and hypotension in 4, poor perfusion in 1, and donor malignancy in 1. Mean donor age was 39.4 years (range, 0.75–67 years). Causes of death were head trauma in 10 donors, intracranial bleed in 24, and anoxic/ischemic brain injury in 26. Mean warm ischemia time was 14.7 minutes (range, 7–40 minutes). Thirty-two patients were transplanted (one split liver), and the mean age of the recipients was 38.4 years (range, 0.7–72 years). All grafts had good early function except one right lobe split. There were 4 deaths resulting from ischemic brain injury, chronic rejection, biliary sepsis, and multiorgan failure following retransplantation for primary nonfunction. Overall patient and graft survival is 87% and 84%, respectively, at a median follow-up of 15 months. Conclusions:Early results suggest that controlled NHBDs are a significant new source of grafts, but careful donor selection and short cold ischemia are mandatory.

Outcome after wait-listing for emergency liver transplantation in acute liver failure: A single centre experience

BACKGROUND/AIMS Though emergency liver transplantation (ELT) is an established treatment for severe acute liver failure (ALF), outcomes are inferior to elective surgery. Despite prioritization, many patients deteriorate, becoming unsuitable for ELT. METHODS We examined a single-centre experience of 310 adult patients with ALF registered for ELT over a 10-year period to determine factors associated with failure to transplant, and in those patients undergoing ELT, those associated with 90-day mortality. RESULTS One hundred and thirty-two (43%) patients had ALF resulting from paracetamol and 178 (57%) from non-paracetamol causes. Seventy-four patients (24%) did not undergo surgery; 92% of these died. Failure to transplant was more likely in patients requiring vasopressors at listing (hazard ratio 1.9 (95% CI 1.1-3.6)) paracetamol aetiology (2.5 (1.4-4.6)) but less likely in blood group A (0.5 (0.3-0.9)). Post-ELT survival at 90-days and one-year increased from 66% and 63% in 1994-1999 to 81% and 79% in 2000-2004 (p<0.01). Four variables were associated with post-ELT mortality; age >45 years (3 (1.7-5.3)), vasopressor requirement (2.2 (1.3-3.8), transplantation before 2000 (1.9 (1.1-3.3)) and use of high-risk grafts (2.3 (1.3-4.2). CONCLUSIONS The data indicate improved outcomes in the later era, despite higher level patient dependency and greater use of high-risk grafts, through improved graft/recipient matching.

Results of split liver transplantation in children

ObjectiveTo analyze the outcome of 80 consecutive pediatric split liver transplants performed at the authors’ center between 1994 and 2000. Summary Background DataSplit liver transplantation has become an accepted method of increasing the number of available grafts for pediatric liver transplant recipients. MethodsThe age of the patients at the time of transplantation ranged from 5 days to 16 years (median 3 years). Sixteen transplants were performed for acute liver failure and 64 for chronic liver failure. The ex situ splitting technique was used for all but four grafts. Fourteen livers were split for two pediatric recipients. Posttransplant follow-up ranged from 6 to 84 months (median 42 months). ResultsOverall patient survival at 6 months follow-up was 96.2%. Graft survival at six months was 93.7%. The Kaplan-Meier patient survival rates at 1 and 3 years were 93.5% and 88.1%, and the graft survival rates were 89.7% and 86.1%, respectively. Four patients required retransplantation. In the acute group (n = 16), the patient survival rates were 93.7% at 1 year and 76.4% at 3 years; there were three deaths due to posttransplant lymphoproliferative disease (PTLD), sepsis, and chronic rejection. In the chronic group (n = 64), the 1- and 3-year patient survival rates were 93.6% and 90.9%, respectively. There were six deaths in this group. Four patients died in the first year after the transplant due to intracranial bleeding, cerebral tumor recurrence, PTLD, and chronic rejection. There were two deaths at 3 years, one due to progressive renal failure secondary to cyclosporin toxicity and the other due to sepsis, portal hypertension, and recurrent bleeding. Vascular complications occurred in six (7.5%) patients and biliary complications in seven (8.7%). ConclusionsThese results, which represent the experience of a single institution over the last 6 years, indicate that ex situ split liver transplantation can be performed in children with good overall outcome and acceptable morbidity.

Outcomes of liver transplantation in HIV‐infected individuals: The impact of HCV and HBV infection

Liver transplantation (LT) in human immunodeficiency virus (HIV)‐positive individuals is considered to be an experimental therapy with limited reported worldwide experience, and little long‐term survival data. Published data suggest that the short‐term outcome is encouraging in selected patients. Here, we report our experience in 14 HIV‐infected liver allograft recipients, and compare outcomes between those coinfected with hepatitis C virus (HCV) and the non‐HCV group. A total of 14 HIV‐infected patients (12 male, 2 female, age range 26‐59 years) underwent LT between January 1995 and April 2003. Indications for LT were HCV (n = 7), hepatitis B virus (HBV; n = 4), alcohol‐induced liver disease (n = 2), and seronegative hepatitis (n = 1); 3 patients presented with acute liver failure. At LT, CD4 cell counts (T‐helper cells that are targets for HIV) ranged from 124 to 500 cells/μL (mean 264), and HIV viral loads from <50 to 197,000 copies/mL. Nine of 12 patients were exposed to highly active antiretroviral therapy (HAART) before LT. In the non‐HCV group (n = 7), all patients are alive, all surviving more than 365 days (range 668‐2,661 days). No patient has experienced HBV recurrence, and graft function is normal in all 7 patients. However, 5 of 7 HCV‐infected patients died after LT at 95‐784 days (median 161 days). A total of 4 patients died of complications due to recurrent HCV infection and sepsis, despite antiviral therapy in 3 of them. A total of 3 patients experienced complications relating to HAART therapy. In conclusion, outcome of LT in HIV‐infected patients with HBV or other causes of chronic liver disease indicates that LT is an acceptable therapeutic option in selected patients. However, longer follow‐up in larger series is required before a conclusive directive can be provided for HCV / HIV coinfected patients requiring LT. (Liver Transpl 2004;10:1271–1278.)

Spontaneous rupture of hepatocellular carcinoma: a Western experience.

BACKGROUND Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening presentation, with an incidence of <3% of HCC patients in Western countries. The reported overall mortality is < or =50% in Asian countries, where the incidence is 12% to 14%. The aim of this study was to report a single centers experience of patients with ruptured HCC during a 11-year period. METHODS A retrospective review was performed of all patients who presented with ruptured HCC between 1995 and 2005. Data on clinical features, treatment strategies, and survival outcomes were collected. Statistical methods included univariate analysis and Kaplan-Meier survival estimates with log-rank test. RESULTS A cohort of 21 patients (15 male and 6 female) was identified. Fourteen (66.6%) patients had histologic evidence of underlying cirrhosis, ad the median age at presentation was 68 years (interquartile range [IQR] 61 to 69). Ten of these patients (71.4%) were hemodynamically unstable at presentation. The mean tumor size was 8.5 cm (range 3 to 13), and there was multifocal disease in 6 (42.8%) patients. The etiology of cirrhosis was hepatitis B infection in 3, hepatitis C in 3, alcohol in 4, and cryptogenic in 4 patients. Initial bleeding control was attempted by transarterial embolization (TAE) in 7 (50%) and by emergency surgery in 7 patients (50%). Four of the operations were performed at referring hospitals, and 3 were performed at our institution. Two patients (14.2%) underwent palliative treatment only. Definitive treatment included resection at emergency surgery in 1, staged hepatectomy in 1, and transarterial chemoembolization in 2 patients. There were 7 patients who were noncirrhotic and had a median age of 51 years (IQR 42 to 60). Of these, 6 (87.5%) were hemodynamically unstable at presentation. Mean tumor size was 9 cm (range 6 to 18) and confined to right lobe in all patients. Primary hemostasis was successfully achieved by TAE in 2 and perihepatic packing in 1 patient. Definitive treatment was provided by emergency hepatectomy in 4 and staged hepatectomy in 3 patients. Patients with cirrhosis (n = 14) had a median survival rate of <30 days. Child-Pugh score at presentation (median 7, IQR 5 to 8) correlated strongly with overall survival (P <.0001). Median survival for noncirrhotic patients was 20 months (IQR 2 to 31). One patient without cirrhosis survived for 122 months without disease recurrence. CONCLUSIONS Spontaneous rupture of HCC is an uncommon presentation in Western countries. Primary hemostasis, followed by emergency or staged hepatic resection, is the treatment of choice. Median survival in patients initially treated with surgery was better than that observed in patients who underwent initial TAE, although this was not statistically significant. Patients who had no underlying liver disease had better prognosis than those who had cirrhosis.

Long-term outcome of liver retransplantation in children.

Background. Retransplantation of the liver is the only means of prolonging survival in children whose initial graft has failed. Patient and graft survival rates after retransplantation in most series have been inferior to rates after first transplantation. Patients and methods. Of 450 pediatric liver transplantations performed between January1990 and March 2001, 50 were first retransplantations, 9 were second retransplantations, and 1 was a third retransplantation. The overall retransplantation rate was 13.3% (median age at retransplantation 4 years and median weight 15 kg). The median post-retransplantation follow-up was 73 (range, 6–139) months. Results. Kaplan-Meier patient survival rates for the group (n=50) were 71.7%, 64.7%, and 64.7% at 1, 3, and 5 years, respectively. Graft survival rates were 65.6%, 56.7%, and 56.7% at 1, 3, and 5 years, respectively. This is significantly worse than rates for children undergoing first liver transplantation. There were 17 deaths, of which 9 occurred in the first month. Biliary complications occurred in 5 (10%) patients and vascular complications in 6 (12%). Improved patient and graft survival rates were observed in the later phase of the program, although the difference was not significant. Higher preoperative serum creatinine (P =0.001) and serum bilirubin (P =0.02) levels were associated with a higher postoperative mortality. Conclusion. Results of retransplantation in children remain inferior to those after first transplantation. There is a trend toward improving results. Liver retransplantation makes an important contribution to overall survival in children.

Bile duct strictures after adult liver transplantation: A role for biliary reconstructive surgery?

There is no accurate method to determine the functional significance of bile duct strictures after liver transplantation, and although biliary reconstructive surgery (Roux‐en‐Y hepaticojejunostomy, HJ) is the second‐line treatment in patients with persistent allograft dysfunction following failed endoscopic therapy, there is no evidence to support this approach. Liver transplant recipients with allograft dysfunction and demonstrable bile duct strictures who had undergone hepaticojejunostomy were identified from a prospective database. Preoperative and follow‐up clinical, biochemical, and radiological data were collected. Perioperative liver biopsies were evaluated prospectively by two histopathologists blinded to clinical information. The biopsies were scored according to presence and severity of biliary features, fibrosis, and coexisting diseases. The effects of preoperative factors on postoperative allograft function were analyzed using SPSS statistical software. After hepatico‐jejunostomy, graft function returned to normal in 8/44 patients (18%), improved in 16/44 (36%), but remained abnormal in 20/44 (45%), including 4 patients who subsequently underwent retransplantation. Hepaticojejunostomy was more likely to yield a favorable outcome (improved or normal graft function) when performed within 2 years of transplantation. Prolonged duration of biliary obstruction was associated with development of advanced graft fibrosis at the time of surgery, but neither factor significantly influenced postoperative graft function. In conclusion, biliary reconstruction successfully restores graft function in the majority of patients who present with anastomotic strictures within the first 2 years after liver transplantation. In patients presenting with bile duct strictures late after transplantation, surgery should be reserved for selected patients without histological evidence of graft fibrosis (moderate–severe) or significant nonbiliary pathology. (Liver Transpl 2004;10:928–.934)

An uncommon cause of life-threatening gastrointestinal bleeding: 2 synchronous Dieulafoy lesions

Dieulafoy lesions are a rather uncommon cause of gastrointestinal bleeding that can be torrential and life-threatening. Extragastric location and pediatric cases are very rare. We report the first case of synchronous Dieulafoy lesions in the stomach and jejunum. This case is discussed in the light of the reported literature on this condition.

Pharmacokinetics, efficacy, and safety of mycophenolate mofetil in combination with standard-dose or reduced-dose tacrolimus in liver transplant recipients

The pharmacokinetics of mycophenolate mofetil (MMF) in liver transplant recipients may change because of pharmacokinetic interactions with coadministered immunosuppressants or because changes in the enterohepatic anatomy may affect biotransformation of MMF to mycophenolic acid (MPA) and enterohepatic recirculation of MPA through the hydrolysis of mycophenolate acid glucuronide to MPA in the gut. In the latter case, the choice of formulation (oral versus intravenous) could have important clinical implications. We randomized liver transplant patients (n = 60) to standard (10–15 ng/mL) or reduced (5–8 ng/mL) trough levels of tacrolimus plus intravenous MMF followed by oral MMF (1 g twice daily) with corticosteroids. Pharmacokinetic sampling was performed after the last intravenous MMF dose, after the first oral MMF dose, and at selected times over 52 weeks. The efficacy and safety of the 2 regimens were also assessed. Twenty‐eight and 27 patients in the tacrolimus standard‐dose and reduced‐dose groups, respectively, were evaluated. No significant differences between the tacrolimus standard‐dose and reduced‐dose groups were seen in dose‐normalized MPA values of the time to the maximum plasma concentration (1.25 versus 1.28 hours), the maximum plasma concentration (15.5 ± 7.93 versus 13.6 ± 7.03 μg/mL), or the area under the concentration‐time curve from 0 to 12 hours (AUC0–12; 53.0 ± 20.6 versus 43.8 ± 15.5 μg h/mL) at week 26 or at any other time point. No relationship was observed between the tacrolimus trough or AUC0–12 and MPA AUC0–12. Exposure to MPA after oral and intravenous administration was similar. Safety and efficacy were similar in the two treatment groups. In conclusion, exposure to MPA is not a function of exposure to tacrolimus. The similar safety and efficacy seen with MMF plus standard or reduced doses of tacrolimus suggest that MMF could be combined with reduced doses of tacrolimus. Liver Transpl 15:136–147, 2009.

Simultaneous combined liver and kidney transplantation: a single center experience

Chava SP, Singh B, Stangou A, Battula N, Bowles M, O’Grady J, Rela M, Heaton ND. Simultaneous combined liver and kidney transplantation: a single center experience.
Clin Transplant 2010: 24: E62–E68.