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Biomedical subjects

N Heaton

Publications and source records attributed to N Heaton.

At least 19 recordsLinked to original sources
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

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↗
PubMed1997

N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction.

OBJECTIVES: To investigate whether the beneficial systemic hemodynamic effects of N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP) concentration in fulminant hepatic failure, are present in a range of liver disorders and what concurrent effect this agent has on the hepatic-splanchnic circulation. SETTING: Liver Failure Unit, King's College Hospital, London, UK. PATIENTS: Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder. INTERVENTIONS: Prostacyclin was administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a washout period, the hemodynamic effects of this infusion were compared with the effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL of 5% dextrose for 45 mins at an infusion rate of 62.5 mL/hr. MEASUREMENTS AND MAIN RESULTS: Following N-acetylcysteine infusion, the baseline oxygen delivery (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (p< .01). Indocyanine green clearance, as determined by a fiberoptic physiologic monitoring system, also improved in 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change 100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as responders in relation to systemic hemodynamics (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N-acetylcysteine increases systemic VO2 in a proportion of patients with a wide variety of hepatic disorders. In addition, N-acetylcysteine elicits an improvement in indocyanine green clearance. These properties may be clinically useful in a range of critical illnesses where systemic or hepatic-splanchnic circulations are compromised.

Acetylcysteine↗
PubMed1997

Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting.

Adolescent↗
PubMed1997

Liver transplantation for extra hepatic biliary atresia.

Kasai portoenterostomy has transformed the prognosis for children with Extra Hepatic Biliary Atresia (EHBA). However, for children developing end stage liver disease following portoenterostomy, liver transplantation (OLT) is the treatment of choice. Between February 1989 and March 1996, 64 children with EHBA underwent 79 transplants (26 males, 38 females; median age 2.2 years, range 5 months-17 years; median weight 11.4 kg, range 5-65 kg). Of these, 58 (85%) had undergone previous portoenterostomy. Nineteen patients (30%) had gastrointestinal bleeding prior to OLT assessment. Mean serum bilirubin was 229 mumol/liter (range 11-801 muml/liter). Four children had associated polysplenia syndrome. Of the 79 transplants, 30 received whole and 41 reduced-size cadaveric grafts and 9 living related grafts. Eleven patients (17%) died, nine within one month of surgery. Thirteen patients were retransplanted once and one twice. There were 16 vascular complications (10 hepatic artery thrombosis, 3 portal vein thrombosis, 3 venous outflow obstruction) and 10 biliary complications (4 anastomotic leaks, 6 strictures). Ten patients (16%) had bowel perforation following the transplant. The 5 year actuarial patient and graft survival for this group is 84% and 69% respectively with normal physical and mental development in the majority. OLT provides satisfactory treatment for children with EHBA with end stage liver disease with long term survival in the majority.

Adolescent↗
PubMed1996

Liver transplantation for haemophiliacs with hepatitis C cirrhosis.

BACKGROUND: Experience of liver transplantation in haemophiliacs with end stage hepatitis C liver disease is limited and particularly difficult questions are raised when there is also HIV infection. AIMS: This is the first report in Great Britain to describe the operative replacement therapy and initial outcome in four haemophiliacs with end stage HCV cirrhosis. PATIENTS: Two patients had factor VIII, one had factor IX, and one had factor X deficiency. One patient had also contracted HIV infection from factor replacement but had no AIDS defining illnesses. METHODS: Intraoperatively patients were given either factor VIII infusions, factor IX bolus, or fresh frozen plasma, according to formulae devised to calculate exact clotting factor requirements. Baseline preoperative coagulation studies included prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and factor VIII, IX, and X concentrations. Factor concentrations were then assayed at 12, 24, 48, and 72 hours postoperatively. RESULTS: Postoperatively all patients had coagulation factor concentrations sustained within the normal ranges by 72 hours unsupported (137, 125, 95, 104 IU/dl), representing de novo synthesis by the graft. Transfusion requirements during the operative and immediate post-transplant period were no greater than those of patients without clotting disorders. Two patients had episodes of bleeding postoperatively, one of which was fatal, occurring at the site of a previous untreated subdural bleed. In both instances the bleeding occurred in the presence of normal concentrations of clotting factor. The remaining three patients are at 6, 6, and 12 months post-transplant and remarkably improved clinically with sustained factor concentrations. One patient has evidence of graft dysfunction from HCV recurrence and all have evidence of recurrent viraemia with HCV on polymerase chain reaction studies. CONCLUSIONS: Orthotopic liver transplantation should be considered in haemophiliac patients with end stage liver disease from hepatitis C infection with or without concomitant HIV infection. Their clinical condition is likely to be greatly improved by orthotopic liver transplantation and the haemophilia cured with only a small risk of severe graft dysfunction from recurrent HCV infection.

Adult↗
PubMed1995

Importance of concomitant viral infection during late acute liver allograft rejection.

We have determined accompanying events and reviewed the management and outcome of late acute cellular rejection episodes in 384 consecutive liver recipients. A significant proportion of patients experienced concomitant viral infection (group 1, n = 15 [41%]), with CMV infection comprising the largest group and smaller contributions from other viruses (CMV, 30%; HSV, 5%; EBV, 3%; varicella zoster virus, 3%). Thirteen (35%) patients (group 2) developed late rejection associated with low maintenance immunosuppression, and in a further 10 patients (group 3), no accompanying factor could be identified. Refractory rejection was higher in late compared with early rejection episodes in our series (29% vs. 9.2%, P < 0.05). Antiviral chemotherapy administered in rejection episodes with concomitant viral infection, either as sole treatment in cases with accompanying hepatitis or as adjunctive therapy to further supplemental immunosuppression in episodes of steroid-resistant rejection, controlled the rejection process in all treated patients.

Adolescent↗