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N Heaton

Publications and source records attributed to N Heaton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Quality of life after liver transplantation for alcoholic liver disease.

There are few data on predictive factors for alcohol relapse or long-term functional outcome after liver transplantation for alcoholic liver disease (ALD). In all 56 surviving UK patients (47 men, 9 women; mean age: 51 years; range: 33 to 69 years) who underwent transplantation for ALD at King's College Hospital over a 10-year period, alcohol relapse and outcome were assessed by outpatient and case-note review and by postal questionnaire containing (1) the Nottingham Health Profile (NHP), (2) the Short-Form-36 (SF-36) Health Survey, and (3) a drug and alcohol questionnaire. At a median of 2.5 years (range: 0.5 to 10 years), 13 of the 47 respondents (28%) and 2 of the 9 nonrespondents (22%) had evidence of potentially harmful drinking (>3 units daily) at some time posttransplantation. An additional 13 patients admitted to drinking some alcohol at least once, corresponding to an overall relapse rate of 50%. The patients with harmful drinking (1) had started drinking regularly at a younger age (18 v 25 years; P =.01), (2) began drinking heavily at a younger age (30 v 40 years; P =.01), (3) had shorter pretransplantation abstinence periods (10 v 23 months; P =.02), and (4) had a longer time since transplantation (median, 5.7 v 1.5 years; P =.0004) than those with no or mild alcohol relapse. They were also more likely to report sleep disturbance (NHP sleep problem score, 45 v 16; P =.01) and use benzodiazepines regularly (7 of 13 v 3 of 34 patients; P =.002). Despite these differences, health dimension scores in the SF-36 and NHP posttransplantation were similar between the groups and to those of UK community controls. In the long term, at least 50% of the patients will drink again at some time posttransplantation, although at lower levels of alcohol intake than previously. Those patients with multiple predictive factors for alcohol relapse may be at greatest risk for harmful drinking and be the group that would benefit most from professional counseling. Overall, the quality of life after liver transplantation for ALD is high and broadly similar to the levels expected in the normal population.

Adult↗
PubMed2000

Renal glucose production compensates for the liver during the anhepatic phase of liver transplantation.

The extent of the renal contribution to postabsorptive endogenous glucose production (EGP) in humans is controversial. We measured EGP in the absence of the liver during the anhepatic phase (AH) of liver transplantation in five patients (aged 46.4+/-10.2 years, two women). Stable labeling of plasma glucose (PG) was achieved for a 2-h period before the AH by primed continuous infusion of di-deuterated 6,6[2H2]glucose (1.7 mg/min) and continued throughout the AH. PG was maintained above the fasting level (6.1+/-2.73 mmol/l) with 5% dextrose labeled with 6,6[2H2]glucose throughout the AH (mean level during the AH 0.98+/-0.45 mg x kg(-1) x min(-1)). Isotopic enrichment remained stable at 0.84+/-0.21% atom percent excess throughout. EGP, calculated by use of a modified Steele equation, decreased from 2.6+/-1.24 at baseline to 0.97+/-0.9 mg x kg(-1) x min(-1) (36% baseline, P = 0.045) but recovered at approximately 30 min to reach 1.38+/-0.83 mg x kg(-1) x min(-1) (54% baseline) by 60 min. Epinephrine, lactate, free fatty acid, and glycerol levels increased significantly (0.79+/-0.74 to 3.65+/-2.1 nmol/l, P = 0.005; 1.88+/-0.43 to 3.46+/-0.9 mmol/l, P = 0.024; 543.9+/-215.5 to 705.5+/-219.2 micromol/l, P = 0.012; 75.6+/-30.2 to 139+/-96.3 micromol/l, P = 0.003, respectively). These data show that postabsorptive nonhepatic glucose production in humans may contribute to greater than one-third of overall EGP, increasing when required, and that it is associated with a stress response and increased gluconeogenic substrate availability. We conclude that extrahepatic tissues, most notably those of the kidney, make a significant contribution to EGP in humans.

Adaptation, Physiological↗
PubMed2000

A complication associated with the use of neonatal liver in orthotopic liver transplantation.

BACKGROUND: Neonatal livers have been associated with a higher incidence of vascular complications but are nevertheless used because of donor shortage. AIMS: We report a complication of hepatic venous outflow obstruction because we retained the neonatal retrohepatic cava from the first transplant for retransplantation using a left lateral segment. METHODS: Technical and post-operative complications associated with a small "native" inferior cava and transplantation are described. RESULTS: Successful treatment with balloon angioplasty resulted in re-establishing the flow in the hepatic venous outflow tract. The child is well 3 years on with stable graft function. CONCLUSION: Percutaneous transluminal angioplasty is an effective non-surgical therapy for post liver transplant hepatic venous outflow obstruction. Replacement of the inferior venacava rather than retaining neonatal venacava may be a better option during retransplantation.

Angioplasty, Balloon↗
PubMed1999

Assessment of potential donors for living related liver transplantation.

BACKGROUND: Living related liver transplantation has been developed as an important potential source of organs for treatment of children with acute and chronic liver disease. A single UK centre performing living related liver transplantation was established in 1993. METHODS: Parents who were potential donors for their children for living related liver transplantation were assessed for suitability according to a protocol based on one developed and published by the University of Chicago Transplant Group. Records kept by the transplant coordinators were retrieved and data were extracted. RESULTS: Of 64 potential donors for 32 potential recipients ten were excluded at a preliminary stage. Fourteen ultimately became donors. Of 54 parents who began evaluation 23 were finally considered to be suitable. There were 19 non-disease-related reasons for unsuitability: blood group mismatch (eight cases), size discrepancy (six), pregnancy (two), oral contraceptive medication (one), vascular anatomy variant (one) and age (one). Sixteen were unsuitable because disease was found, namely fatty liver (four), thyroid disease (two), hepatitis B positivity (two), cardiac murmur (one), anaemia (one), glucose-6-phosphate dehydrogenase deficiency (one), diabetes mellitus (one) and psychological problems (one), and three parents were affected by the same disorder as the child (Alagille syndrome, one; mitochondrial disorder, one; recurrent cholestasis, one). Three parents were rejected for more than one reason. Both parents were unsuitable for donation in 21 per cent of cases. CONCLUSION: Parents approach living related liver transplantation with enthusiasm. They should be advised of the high chance of unsuitability, including the finding of significant pathology. The limitation of living related liver transplantation as the major source of organs for children is recognized.

Adolescent↗
PubMed1998

Role of HLA compatibility in pediatric liver transplantation.

BACKGROUND: The influence of HLA mismatching in liver transplantation remains controversial. To date, few studies have focused solely on the pediatric population, and none have investigated DR and DQ mismatches using molecular genotyping. We sought to investigate HLA-A, -B, -DR, and -DQ mismatches in a large series of primary pediatric liver transplant recipients. Living-related liver transplants were excluded. METHODS: A total of 138 consecutive first liver transplants performed between January 1991 and July 1996 were studied. Minimum follow-up was 1 year, and both patient and graft survival rates were assessed. The incidence of the most common complications was analyzed. HLA-A and -B phenotyping was performed by complement-dependent microcytotoxicity or polymerase chain reaction (PCR)-sequence-specific primer protocols in 133 of 138 patients. HLA-DR and -DQ genotyping was performed by standard PCR-sequence-specific oligonucleotide and/or PCR-sequence-specific primer protocols in 135 patients. RESULTS: Overall, there was no influence of HLA mismatching on either graft or patient survival rates. However, patients with two mismatches at the A locus showed a significantly lower incidence of acute rejection than those with one A mismatch (52% vs. 72%; P < 0.03) and patients with two B locus mismatches had a better graft survival rate at 5 years than those with one mismatch (76% vs. 62%), although this was of only borderline significance (P < 0.09). No differences were found in the severity of the episodes of rejection, incidence of chronic rejection, cytomegalovirus hepatitis, and other causes of graft loss. CONCLUSION: This study indicates that HLA-A, -B, -DR, and -DQ mismatches are not detrimental in primary pediatric liver transplantation.

Acute Disease↗
PubMed1998

Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.

Once defined clinical criteria are fulfilled in acetaminophen-induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty-four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors (7%) in this group fulfilled two of three combined criteria, and the finding of a high APACHE III score could be used as an indicator for the need for OLT. Of the 56 patients (45%) not listed, in only a small proportion was this caused by psychiatric reasons, and in the majority, it was a consequence of the rapid development of multiple organ failure and cerebral edema. This also applied to 24 (35%) of the 68 listed patients in whom the rapidity of clinical deterioration, reflected in increasing APACHE III scores, was such that even with the prompt availability of donor organs, OLT was not possible. In the final event, only 44 (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to leave the hospital. Survival was greatest in those receiving unreduced grafts, and markers of early graft function differed significantly between survivors and nonsurvivors. Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen-induced hepatotoxicity, and for a substantial proportion, transplantation was never an option because of the rapidity of clinical deterioration. APACHE III scoring may be of value in decision making and in better defining patients in clinical trials.

Acetaminophen↗
PubMed1998

Use of infrarenal conduits for arterial revascularization in orthotopic liver transplantation.

Arterial conduits that use donor iliac arteries represent a reliable technique for graft revascularization in orthotopic liver transplantation. We reviewed 757 consecutive liver transplantations performed between 1989 and 1995 for acute or chronic liver disease in adults and children. Of these, 218 patients received arterial conduits that used donor iliac arteries. The incidence of hepatic artery thrombosis (HAT) for conduits was 4.1% (9 of 218 patients) compared with 4% (22 of 539 patients) for direct arterial anastomosis. Patients in the arterial conduit group included 66% (99 of 159) of the children younger than 5 years of age, 75% (67 of 89) of all patients who underwent retransplantation, and, in particular, 25 patients regrafted for HAT. Arterial conduits provide an effective and reliable method of revascularization in patients at higher risk of arterial thrombosis. The actuarial 3-year patency rate for conduits is 95% and the incidence of HAT is similar to that in standard arterial anastomoses.

Adult↗
PubMed1998

Efficacy of Neoral in the immediate postoperative period in children post-liver transplantation.

Cyclosporine (Sandimmune) is an effective immunosuppressive drug but may be poorly absorbed in the early postoperative period after liver transplantation, exposing the recipient to an increased risk for rejection. Neoral is a new oral formulation of cyclosporine that uses a mixture of surfactant, lipophilic, and hydrophilic solvents to permit microemulsification that leads to potentially better absorption. This oral drug has not been evaluated in children immediately posttransplantation. The aim of this study was to evaluate the pharmacokinetics, bioavailability, and safety of Neoral during the first week post-liver transplantation in children. Twelve children, 8 boys and 4 girls, with a median age of 2.6 years (range, 1 to 8 years) were administered Neoral within 12 hours posttransplantation. Pharmacokinetic profiles were performed over a 12-hour period on each child on days 1, 3, and 5 and twice-daily trough levels were obtained on days 2, 4, 6, and 7. The maximum concentration (Cmax), time to reach Cmax (Tmax), 12-hour trough levels, and area under the curve were calculated, and rejection episodes and adverse events were documented over a 12-week period. Neoral was well absorbed, even on the first postoperative day. After the introduction of enteral feeding, the peak levels increased (Cmax, 655 ng/mL) and were achieved significantly sooner (Tmax, 2 hours). There was no significant difference in drug exposure between days 1, 3, and 5 (P > .05). The incidence of acute rejection was 25% and hypertension was reported in 4 of 12 patients during the first week. Neoral was well absorbed in the early post-liver transplantation period, provided effective immunosuppression, and was not associated with a high incidence of adverse events or toxicity. The introduction of enteral feeding improved absorption.

Area Under Curve↗
PubMed1998

Split liver transplantation: King's College Hospital experience.

BACKGROUND: The purpose of split liver transplantation is to increase the source of pediatric grafts without compromising the adult donor pool. Early results have been discouraging because of technical complications and selection of poor risk patients. METHODS: The results of a single center experience of 41 split liver transplantations were analyzed. Patient and graft survival and complications related to the technique were analyzed. RESULTS: Patient and graft survival for the whole group was 90% and 88% respectively at a median follow up of 12 months (range 6-70 months). Patient and graft survival for the right lobe graft was 95% and the left lateral segment 86% and 82% respectively. Four patients died, of which two of the patients were first two splits following technical complications. Two others died, one from cerebral lymphoma and the other of multiorgan failure secondary to sepsis. One patient has been retransplanted for chronic biliary sepsis. CONCLUSION: Split liver transplantation has now become an acceptable treatment option for both adult and pediatric recipients with end stage liver disease. Right lobe recipients are not disadvantaged by the procedure. Good results can be achieved with better patient selection and by the use of good quality organs.

Adolescent↗
PubMed1997

Clinical characteristics affecting the outcome of liver retransplantation.

BACKGROUND: The outcome of retransplantation remains unsatisfactory when compared with primary transplantation of the liver. The aim of the present study was to determine which preoperative clinical and laboratory risk variables are implicated in the poorer outcome. METHODS: The preoperative status of 70 retransplanted patients was compared with a group of 303 time-matched recipients receiving their first graft. RESULTS: Survival at 1 year was reduced in the retransplant versus the primary transplant group (50% vs. 80%, P<0.001). Preoperatively older age, high United Network of Organ Sharing score, inpatient status, elevated bilirubin, and creatinine levels were associated with increased mortality after a second transplant. Preoperatively, the retransplant group had higher encephalopathy grades, were more likely to be inpatients, and had higher serum creatinine, bilirubin, and white cell levels than the primary recipients (P<0.05 in all cases). The median length of inpatient stay was longer after the second transplant (25 vs. 19 days, P<0.001). CONCLUSIONS: These factors assist in the stratification of patients awaiting retransplantation; however, the outcome of this procedure is only likely to be improved with an earlier identification of the patients who require it, along with an increased priority in organ allocation.

Adolescent↗
PubMed1997

Hepatic artery resistance index can predict early death in children with biliary atresia.

Hepatic artery resistance index has been measured by ultrasonography Doppler and has been found to predict rapid deterioration and death in children with biliary atresia. Clinical, biochemical, ultrasonographic, and outcome data were collected prospectively and retrieved on 32 patients with resistance index of > or = 1.0 (group A). These were compared with the same data for 32 age- and sex-matched patients with biliary atresia and a resistance index of < 1.0 (group B). Group A was found to have significantly worse liver function tests than group B. In group A, all patients died (n = 11) or underwent transplantation (n = 21; of whom 4 died) compared with only 2 patients who died in group B and 4 patients who underwent transplantation without fatality. Survival at 2 years was 52% in group A v 94% in group B. It is suggested that regular ultrasonography Doppler examination in patients with biliary atresia can detect a group with a resistance index of > 1.0 who have a very high risk of early mortality. Such patients require early evaluation and listing for transplantation. Those listed for liver transplantation on other grounds require ultrasonography examinations every 2 to 3 months with immediate upgrading of the priority of those patients found to have a resistance index of > or = 1.0.

Actuarial Analysis↗
PubMed1997

Hepatic transplantation in children under 3 months of age: a single centre's experience.

Liver transplantation in neonates represents a major medical and technical challenge particularly in babies weighing less than 5 kg. The authors report the experience of 10 liver transplants in 9 babies (6 boys and 3 girls), mean age, 6 weeks (range, 2 to 11); median weight, 3.7 kg (range, 2.4 to 5). All had fulminant hepatic failure caused by neonatal haemochromatosis (n = 3), non-A non-B hepatitis (n = 3), total parenteral nutrition induced (n = 1), hepatitis B (n = 1), and hepatic haemangio-endothelioma (n = 1). One child underwent retransplantation for hepatic artery thrombosis. Immunosuppression was by Cyclosporine A-based triple therapy in all cases. All received a reduced size graft consisting of left lobe (n = 1), left lateral segment (n = 6) and monosegment III (n = 3). In nine cases the donor hepatic artery was anastomosed to an iliac artery conduit from the infrarenal aorta, and a Roux loop was used for bile duct reconstruction. Primary abdominal wound closure was possible in six patients, skin closure alone in one, and a silastic patch was used in three. Complications included infection (n = 5), bowel perforation (n = 2), diaphragmatic perforation (n = 2), bile leak (n = 1), hepatic artery thrombosis (n = 1), and portal vein thrombosis (n = 1). None of the babies experienced acute rejection. Currently five of the nine recipients are alive with good graft function at a mean follow-up of 22 months (range, 5 to 58). Of the four deaths, two were related to infection (one in combination with portal vein thrombosis), one to multiorgan failure and fluid overload, and one to early graft dysfunction and sepsis after undergoing retransplantation for hepatic artery thrombosis. From our experience liver transplantation offers a promising option for the treatment of severe liver disease in children less than 3 months old.

Age Factors↗
PubMed1997

Auxiliary partial orthotopic liver transplantation for acute liver failure.

BACKGROUND/AIMS: Auxiliary partial orthotopic liver transplantation holds potential advantages over conventional orthotopic liver transplantation, but experience with the technique in acute liver failure is limited. METHODS: We describe our initial experience in seven patients (4 men, 3 women; mean age 28, range 14-35 years) with acute liver failure (paracetamol 3, non A-E 2, autoimmune 1, Ecstasy 1) who fulfilled criteria for emergency transplantation. Preoperatively, the median international normalised ratio was seven (range 3.4-15), with a creatinine of 123 microM (51-389 microM) and bilirubin 320 microM (61-572 microM). The reasons for performing an auxiliary transplant were the patients' young age and stable preoperative condition (n = 5), or a significant psychiatric history precluding conventional transplantation (n = 2). RESULTS: All patients received blood group-matched left (n = 2) or right (n = 5) auxiliary grafts. Median duration of surgery was 8.5 h (7.3-10 h), with blood loss of 8.3 litres (4.6-14.6 litres). Post-transplant, the international normalised ratio and aspartate aminotransferase fell progressively in all patients, with median values at day 7 of 1.4 (1.0-2.4) and 108 IU/1 (78-910 IU/1). Three patients died from sepsis within the first postoperative month. At 2 weeks, four of six patients had partial regeneration of the native liver, which became complete in two of the survivors by 1 year. CONCLUSIONS: Although patient selection remains poorly defined, auxiliary partial orthotopic liver transplantation in acute liver failure is technically feasible and, in some patients, allows native liver regeneration and eventual immunosuppression withdrawal.

Acute Disease↗
PubMed1997

The clinical diversity and role of chemotherapy in lymphoproliferative disorder in liver transplant recipients.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disorder is a well-documented complication with an incidence ranging from 2 to 10%, depending on the organ transplanted. Yet despite our increased understanding of the pathophysiology of this disease and the various treatments available, the mortality remains high at 60-80%. We present the clinical and histological features of ten adult liver transplant recipients with post-transplant lymphoproliferative disorder presenting over a 15-year period and review the therapeutic options. METHODS: CD20/CD45RO immunostaining was used for T/B-cell markers; polymerase chain reaction and in-situ hybridisation for Epstein-Barr virus genome detection; kappa/lambda immunostaining and gene rearrangement analysis for clonality. RESULTS: There were six females and four males (age range 24-56) with onset of post-transplant lymphoproliferative disorder-symptoms ranging from 3 to 72 months post transplant. Sites of post-transplant lymphoproliferative disorder included liver (n=4), lymph nodes (n=5), bone marrow (n=2), lungs (n=2), kidneys (n=2), brain, ovaries,: and pancreas (n=1). All lesions were classified as high-grade lymphoma, of B-cell lineage (9 tested); Epstein-Barr virus genome was detected in 7/10 cases. Three tumours were monoclonal; four were polyclonal and three undetermined. Treatment included immunosuppression reduction, antiviral therapy with acyclovir and/or chemotherapy (CHOP or VAPEC-B). Survival times for those patients not treated with chemotherapy were from 9 days to 30 months, whereas those receiving chemotherapy had remission times of 4 to 48 months. CONCLUSIONS: Longer-term remissions can be achieved in patients treated with systemic chemotherapy, although not without morbidity. Clonality assessment is important but treatment decisions should be based primarily on clinical features of progression, as polyclonal tumours can behave as aggressively as monoclonal tumours.

Adult↗