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N D Heaton

Publications and source records attributed to N D Heaton.

At least 19 recordsLinked to original sources
PubMed2006

Organ transplantation in hereditary apolipoprotein AI amyloidosis.

Patients with hereditary apolipoprotein AI (apoAI) amyloidosis often have extensive visceral amyloid deposits, and many develop end-stage renal failure as young adults. Solid organ transplantation to replace failing organ function in systemic amyloidosis is controversial due to the multisystem and progressive nature of the disease and the risk of recurrence of amyloid in the graft. We report the outcome of solid organ transplantation, including dual transplants in 4 cases, among 10 patients with apoAI amyloidosis who were followed for a median (range) of 16 (4-28) and 9 (0.2-27) years from diagnosis of amyloidosis and transplantation, respectively. Eight of 10 patients were alive, seven with a functioning graft at censor. Two patients died, one of disseminated cytomegalovirus infection 2 months after renal transplantation and the other of multisystem failure following severe trauma more than 13 years after renal transplantation. The renal transplant of one patient failed due to recurrence of amyloid after 25 years. Amyloid disease progression was very slow and the natural history of the condition was favorably altered in both cases in which the liver was transplanted. Failing organs in hereditary apoAI amyloidosis should be replaced since graft survival is excellent and confers substantial survival benefit.

Adolescent↗
PubMed2006

Artificial neural network is superior to MELD in predicting mortality of patients with end-stage liver disease.

BACKGROUND: Despite its accuracy, the model for end-stage liver disease (MELD), currently adopted to determine the prognosis of patients with liver cirrhosis, guide referral to transplant programmes and prioritise the allocation of donor organs, fails to predict mortality in a considerable proportion of patients. AIMS: To evaluate the possibility to better predict 3-month liver disease-related mortality of patients awaiting liver transplantation using an artificial neural network (ANN). PATIENTS AND METHODS: The ANN was constructed using data from 251 consecutive people with cirrhosis listed for liver transplantation at the Liver Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival on 188 patients, tested on the remaining 63 (internal validation group) unknown by the system and finally on 137 patients listed for liver transplantation at the King's College Hospital, London, UK (external cohort). Predictions of survival obtained with ANN and MELD on the same datasets were compared using areas under receiver-operating characteristic (ROC) curves (AUC). RESULTS: The ANN performed significantly better than MELD both in the internal validation group (AUC = 0.95 v 0.85; p = 0.032) and in the external cohort (AUC = 0.96 v 0.86; p = 0.044). CONCLUSIONS: The ANN measured the mortality risk of patients with cirrhosis more accurately than MELD and could better prioritise liver transplant candidates, thus reducing mortality in the waiting list.

Area Under Curve↗
PubMed2006

The impact of diabetes mellitus on fibrosis progression in patients transplanted for hepatitis C.

Despite the recognition of numerous factors for aggressive hepatitis C virus (HCV) recurrence after liver transplantation (LT) our understanding of this phenomenon is incomplete. We tested the hypothesis that diabetes mellitus (DM) was implicated. One hundred sixty-three patients undergoing primary LT for HCV from 1990 to 2004 were evaluated and biopsies were scored according to the modified Ishak score. Severe recurrence of HCV was defined as a fibrosis score > or = 4 within 6 years of LT. Risk factors assessed included recipient, donor and transplant variables. Fifty-four patients (33.1%) had a fibrosis score > or = 4 at the end of the study period. Factors associated with progression to severe fibrosis was donor age (p = 0.008) especially donor age >55 (p = 0.038, HR 2.43), pre-LT DM (p = 0.039, HR 2.68) and DM post-LT (p = 0.004, HR 3.28). The combination of receiving a liver from a donor older than 55 years and having DM post-LT was associated with an 8.38-fold risk of progression to severe fibrosis (p = 0.000124) when compared to patients not diabetic post-LT who received livers from donors aged <55 years. These data indicate that diabetic status is one of the more important variables determining the severity of HCV recurrence and is synergistic with donor age. This observation may provide an additional management opportunity to modify the impact of HCV recurrence.

Adult↗
PubMed2005

Ex vivo liver surgery for extraadrenal pheochromocytoma.

A case of a 15-year-old girl with a malignant extraadrenal pheochromocytoma situated between the inferior vena cava and the portal triad is described. Using ex vivo technique, the tumour was successfully resected on the bench, as a previous attempt to remove the tumour in situ had been abandoned. The surgical aspects and implications of ex vivo surgery are discussed, highlighting the increased operative risk, perioperative mortality, and poor long-term results in patients with malignant tumours.

Adolescent↗
PubMed2005

Long-term outcome of immunosuppression withdrawal after liver transplantation.

Eighteen liver transplant recipients were followed up for 10 years after a trial of immunosuppression withdrawal. Three groups were identified according to the early outcome of complete (group A, n = 5), partial (group B, n = 9), and unsuccessful (group C, n = 4) withdrawal of immunosuppression. The indications for liver transplantation (LT) (August 1983-December 1988) were as follows: primary biliary cirrhosis (n = 3), primary sclerosing cholangitis (n = 3), Budd-Chiari syndrome (n = 3), acute liver failure (n = 3), hepatitis C virus (HCV) cirrhosis (n = 1), HCV and autoimmune hepatitis (n = 1), HCV and alcohol-related cirrhosis (n = 1), HCV and hepatocellular carcinoma (HCC) (n = 1), cystic fibrosis (n = 1), and liver metastases from testicular teratoma (n = 1). Immunosuppression was based on cyclosporine. All patients experienced 1 or more complications of prolonged immunosuppression (median, 7 years; range, 5-11). Thirteen patients (72%) are alive at a median interval of 17 years (range, 16-21) after LT. Of the 5 patients in group A, 2 currently have normal graft function with no rejection episodes, and 3 have restarted immunosuppression following late low-grade acute rejection (n = 1), retransplantation for chronic rejection (n = 1), and kidney transplantation (n = 1). Of the 9 patients in group B, 5 died. The deaths were due to ruptured arterial pseudoaneurysm following retransplantation, HCC recurrence, cardiac failure, renal failure, and posttransplant lymphoma at 5, 7, 7, 14, and 17 years after LT, respectively. All 4 patients in group C are alive on a full immunosuppressive regimen. Long-term follow-up of 18 LT recipients withdrawn from immunosuppression has shown that at a median of 17 years 10% of patients remain off all immunosuppression.

Adolescent↗
PubMed2005

Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure.

BACKGROUND: The potential for immunosuppression withdrawal is the rationale for auxiliary liver transplantation (AUX) in patients with acute liver failure (ALF). PATIENTS AND METHODS: Forty-four AUX were performed in 28 adults and 16 children with ALF secondary to seronegative hepatitis (n = 20; 45%), paracetamol hepatotoxicity (n = 14; 32%), acute viral hepatitis (hepatitis B virus [HBV] n = 3, Epstein-Barr virus n = 1; 9%), drug-induced hepatitis (n = 3; 7%), autoimmune hepatitis (n = 2; 5%), and mushroom poisoning (n = 1; 2%). All patients fulfilled the King's College Hospital transplant criteria for ALF. After partial hepatectomy, 38 patients received a segmental auxiliary graft and six, a whole auxiliary graft. Immunosuppression was based on calcineurin inhibitors and steroids. RESULTS: Thirty-four patients (77%) are alive after a median follow-up of 30 months (range 4 to 124). Eight adults and two children died of sepsis (n = 6; 14%) at a median interval of 30 days (range 2 to 66), intraoperative cardiac failure (n = 1), brain edema on postoperative day 8 (n = 1), sudden death on day 35 (n = 1), and multiple organ failure associated with HBV recurrence 4 years after transplantation (n = 1). Three patients underwent retransplantation for small-for-size graft syndrome with sepsis on postoperative day 15 (n = 1) and for ductopenic rejection 4 and 15 months after AUX (n = 2). In 10/31 (32%) survivors (6/18 adults and 4/13 children) immunosuppression was completely withdrawn after a median of 19 months. CONCLUSION: Complete immunosuppression withdrawal can be achieved in a significant proportion of patients after AUX for ALF.

Adolescent↗
PubMed2005

Anti-interleukin 2 receptor antibodies and mycophenolate mofetil for treatment of steroid-resistant rejection in adult liver transplantation.

BACKGROUND: Steroid-resistant rejection (SRR) results in significant morbidity and mortality from the adverse effects of rescue therapy and in graft loss from chronic rejection. In our knowledge, the efficacy and safety of anti-interleukin (IL) 2r antibodies (daclizumab and basiliximab) for the treatment of SRR in adult liver transplantation has not previously been evaluated. METHODS: Twenty-five patients received either daclizumab or basiliximab as rescue therapy for SRR. Outcome and biochemical parameters were recorded before and after treatment with an anti-IL-2r antibody. RESULTS: The median time from transplantation to SRR was 25 days. Secondary immunosuppression included mycophenolate mofetil in 18 patients. Twelve patients (48%) had complete resolution of SRR. Aspartate transaminase levels normalized at a median of 37 days (range, 1-168 days). In 13 patients (52%) progressive hepatic dysfunction developed. Four of these patients received another transplant, and 6 patients had chronic rejection. Three patients died with graft failure. Of 16 patients with acute cellular rejection, 12 (75%) had resolution, 2 had chronic rejection, 1 required a repeat transplantation, and 1 died with graft failure. In contrast, all 9 patients with established chronic rejection in their pretreatment biopsy continued to have significant graft dysfunction, with 4 having persistent chronic graft dysfunction, 3 requiring repeat transplantation, and 2 dying with graft failure. CONCLUSION: Twelve (48%) of 25 patients who received an anti-IL-2r antibody because of SRR were successfully treated. All successfully treated patients had ongoing acute cellular rejection at liver biopsy (75%), whereas patients with histologic evidence of chronic rejection responded poorly.

Adolescent↗
PubMed2004

Paediatric liver transplantation: the surgical view.

Liver transplantation is the accepted treatment for a wide variety of liver diseases in children. Over the past 10 years a number of innovative surgical techniques have been developed to overcome the shortage of size matched donors particularly in children less than 5 years of age. Graft and patient survival at one year after liver transplantation has continued to improve, and is now over 85% and higher for good risk cases. Complications are relatively common, but provided graft function is satisfactory, long term survival for these children is to be expected. The need for retransplantation has fallen significantly. Causes of early mortality include graft dysfunction and sepsis. Late mortality is due to sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long term survival with good graft function and excellent quality of life is possible for the majority of children undergoing liver transplantation.

Child↗
PubMed2003

Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: a preliminary experience.

BACKGROUND: The role of interleukin-2 receptor antibodies as rescue therapy in steroid-resistant rejection (SRR) has not been studied. We evaluated the safety and efficacy of an interleukin-2 receptor antibody, basiliximab (Simulect, Novartis, East Hanover, NJ), in treating SRR in pediatric liver transplant recipients. METHODS: This was a prospective study of seven pediatric liver transplant recipients with biopsy-proven SRR who would have otherwise received OKT3 or antithymocyte globulin. The primary immunosuppression consisted of cyclosporine (Neoral, Novartis), azathioprine, and prednisolone in four patients and tacrolimus and prednisolone in three patients who had undergone retransplantation for chronic rejection (n=2) and hyperacute rejection (n=1). Four patients had received two cycles of high-dose steroids, and three patients had received a single cycle; all had been converted to tacrolimus, followed by the addition of mycophenolate mofetil. RESULTS: The median time from transplant to SRR was 30 days (range, 8 days-23 months). Five children received two doses of basiliximab (10 mg, 3-7 days apart), and two children received a single dose. Aspartate aminotransferase levels normalized in three children 12, 21, and 30 days after basiliximab treatment. Aspartate aminotransferase levels decreased without normalizing in two children, but there was no further evidence of cellular rejection on repeat biopsies. All five children are rejection-free with a median follow-up of 22 months (range, 5-32 months). Biochemical abnormalities persisted in the remaining two children, and both developed chronic rejection. There were no immediate side effects associated with basiliximab. Two patients were treated empirically for possible cytomegalovirus infection 21 and 57 days after basiliximab treatment, with no evidence of cytomegalovirus disease. CONCLUSION: Five of seven pediatric liver transplant recipients with SRR experienced successful outcomes with basiliximab treatment without major side effects, indicating that it is a safe alternative to OKT3 and other antilymphocyte antibodies.

Antibodies, Monoclonal↗
PubMed2002

Surgical anatomy of segmental liver transplantation.

BACKGROUND: The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. METHODS AND RESULTS: The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. CONCLUSION: A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.

Adult↗
PubMed2001

Liver transplantation in adults coinfected with HIV.

OBJECTIVE: To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN: Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS: The medical records of five HIV-positive patients who received liver transplants in King's College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS: All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION: The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Adolescent↗
PubMed2001

Calcineurin-inhibitor related nephrotoxicity- reversibility in paediatric liver transplant recipients.

AIM: To study the efficacy of mycophenolate mofetil (MMF) as renal rescue in paediatric liver transplant recipients with calcineurin-inhibitor- (CI) related nephrotoxicity. METHODS: Pediatric liver transplant recipients with stable graft function and a glomerular filtration rate (GFR) <80 ml/min/1.73 m2 were enrolled. MMF was introduced at 20 mg/kg/day and increased to 40 mg/kg/day after 1 week. CI dose was then reduced 6 weeks to achieve blood levels 25% of baseline. GFR was reassessed after 6 and 12 months. RESULTS: Fourteen children with a median (range) interval from transplant of 57 (4-111) months were studied. Their median (range) GFR in ml/min/1.73 m2 increased from a baseline of 52 (31-71), to 69 (38-111) and 73 (35-98) at 6 and 12 months, respectively (P=0.00014). Side effects of MMF include leucopaenia in two and backache in one, two of whom discontinued MMF. Acute allograft rejection occurred in three children. All 14 are well with a median (range) follow-up of 24 (14-38) months from MMF introduction. CONCLUSION: MMF allows the recovery of renal function from CI related nephrotoxicity in more than 70% of paediatric liver transplant recipients with renal impairment.

Adolescent↗
PubMed2001

Clinical and biochemical outcome of hepatorenal transplantation for hereditary systemic amyloidosis associated with apolipoprotein AI Gly26Arg.

BACKGROUND: Treatment of systemic amyloidosis comprises measures to support failing organ function coupled with attempts to reduce the supply of the respective amyloid fibril precursor protein. Orthotopic hepatic transplantation is effective in familial amyloid polyneuropathy associated with variant transthyretin, because this protein is produced almost exclusively in the liver. Hepatic transplantation has not been performed in hereditary apolipoprotein AI (apoAI) amyloidosis, and the liver's contribution to plasma apoAI levels has not been determined in vivo. METHODS: A 57-year-old Irish man with hereditary systemic amyloidosis associated with apoAI Gly26Arg, which had led to end-stage renal failure and progressive liver dysfunction, underwent hepatorenal transplantation. His outcome was followed clinically and his amyloid deposits were monitored with serum amyloid P component scintigraphy. The proportion of variant apoAI in the plasma was estimated by quantitative isoelectric focusing before and after liver transplantation. RESULTS: Plasma levels of variant apoAI decreased by 50% after liver transplantation, and the patient was asymptomatic 2 years after surgery. Subclinical amyloid deposits that were present in his spleen and heart preoperatively have regressed and stabilized respectively. CONCLUSIONS: Orthotopic liver transplantation substantially reduces the supply of the amyloid fibril precursor protein in hereditary apoAI amyloidosis, and the excellent outcome in this patient probably reflects the balance between deposition and turnover of amyloid having been altered in favor of the latter. These findings support the use of liver transplantation in patients with hereditary apoAI amyloidosis who develop hepatic dysfunction.

Amino Acid Substitution↗
PubMed2001

Sclerosing encapsulating peritonitis after orthotopic liver transplantation.

BACKGROUND: The etiology of abdominal cocoon (a rare cause of intestinal obstruction) is unknown. It has occurred in adolescent girls, cirrhotic patients after peritoneal-venous shunting, and patients undergoing peritoneal dialysis. We report our experience with patients after orthotopic liver transplantation (OLT). METHODS: Five patients (4 male, 1 female, aged 16 to 57 years) underwent OLT (3 whole liver, 2 right lobe grafts) and subsequently developed abdominal cocoon. RESULTS: All developed pyrexia by 66 +/- 21 hours posttransplant. Additional symptoms (epigastric discomfort and intermittent vomiting) occurred 12 +/- 10 days later. Bacterial peritonitis was confirmed by microbiology in 2 cases and diagnosed by exclusion in the others. C-reactive protein levels were persistently elevated in all patients (35 to 82 mg/L). While abdominal CT consistently demonstrated marked ascites with the small intestine confined to a particular area of the abdomen, intestinal contrast studies and ultrasound were not diagnostic. All patients underwent surgical removal of the cocoon membrane by 58 +/- 22 days after transplant. CONCLUSIONS: Sclerosing peritonitis may complicate liver transplantation and occurs because of low-grade intra-abdominal sepsis.

Adolescent↗