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P Muiesan

Publications and source records attributed to P Muiesan.

At least 19 recordsLinked to original sources
PubMed2006

Segmental liver transplantation from non-heart beating donors--an early experience with implications for the future.

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.

Adolescent↗
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

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↗
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

Assessment of portal venous system patency in the liver transplant candidate: a prospective study comparing ultrasound, microbubble-enhanced colour Doppler ultrasound, with arteriography and surgery.

AIM: To determine the role of microbubble-enhanced colour Doppler ultrasound (CDUS) in assessing portal venous patency prior to liver transplantation. MATERIALS AND METHODS: Over a 2-year period, all patients with chronic liver disease undergoing routine pre-transplant CDUS examination in whom the portal venous system was inadequately demonstrated were recruited to the study. CDUS was performed in 368 patients and 33 patients (9%) were recruited. A repeat CDUS examination following an intravenous bolus injection of the microbubble contrast agent Levovist (Schering Healthcare AG, Berlin, Germany) was performed. Diagnostic confidence was recorded on a free linear analogue scale for both examinations. Findings were compared with indirect portography and surgery. RESULTS: Of the 33 patients with sub-optimal baseline examinations, improvement in portal vein visualization was achieved in 31 patients (94%). Median diagnostic confidence increased from 50% (interquartile range 30-60) to 90% (interquartile range 75-98) (P < 0.001) following administration of Levovist. Overall accuracy of portal vein assessment using microbubble-enhanced CDUS in 15 patients in whom a definitive diagnosis was made within 2 months was 87%. CONCLUSION: Microbubble-enhanced CDUS is a simple, inexpensive adjunct to standard pre liver transplant screening of the portal vein. It is particularly helpful in patients with end-stage cirrhosis who are at high risk of portal vein thrombosis and in whom the conventional examination is sub-optimal.

Adolescent↗
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

Use of cadaveric superior mesenteric artery as interpositional vascular graft in orthotopic liver transplantation.

BACKGROUND: Hepatic artery thrombosis remains the most common technical complication that causes graft failure following orthotopic liver transplantation. The development of split liver and living related liver transplantation has led to the use of shorter and smaller arteries for arterial reconstruction to the graft. The present aim was to assess the effectiveness of the superior mesenteric artery as an interpositional graft in arterial reconstruction during liver transplantation. METHODS: Cadaveric superior mesenteric artery was used to reconstruct small and short or multiple hepatic arteries in 35 liver transplants including 29 split, three living related, two whole liver transplants and one emergency revascularization post-transplantation. RESULTS AND CONCLUSION: A low incidence of hepatic artery thrombosis (one of 35 patients) was achieved utilizing cadaveric superior mesenteric artery as an interpositional vascular graft in liver transplantation.

Adolescent↗
PubMed2001

Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults.

In children, a type of graft dysfunction associated with autoimmune features has been described. We have identified 7 adult liver-transplant (LT) recipients from a series of over 1,000 consecutive transplant recipients who presented between 0.3 years and 7.2 years following transplantation with characteristic symptoms, autoantibody profiles, and histologic findings of autoimmune disease. The indications for transplantation were Ecstasy overdose, alcohol-related cirrhosis, primary sclerosing cholangitis (PSC) (2), primary biliary cirrhosis (PBC), hepatitis C cirrhosis, and cryptogenic cirrhosis. Two patterns of de novo autoantibody development were noted; anti-liver-kidney-microsome (LKM) antibody development at high titer in association with an aspartate transaminase (AST) > 500 and antinuclear (ANA) and antismooth muscle (AMA) antibody development at titers >1/80 with lower AST levels. All cases had elevated IgG. Liver biopsies showed changes of an autoimmune-type hepatitis with portal and periportal hepatitis in association with a marked infiltrate of plasma cells, lymphocytes, and bridging collapse. Two patients lost their grafts because of the disease. Patients were treated with reintroduction of steroids and azathioprine in cases in which it had been withdrawn. Major histocompatibility class I and II mismatching did not incur risk. Eight of 12 liver allografts were acquired from either DRB*0301- or DRB*0401-positive donors, and 4 recipients were DRB*0301-positive. This series illustrates that both symptoms and histologic findings of graft dysfunction compatible with autoimmune hepatitis (AIH) exist in adult LT recipients. Graft loss may be a consequence. This entity may represent a specific type of rejection that should currently be classified as "graft dysfunction mimicking autoimmune hepatitis."

Adult↗
PubMed2001

Successful outcome of orthotopic liver transplantation in patients with preexisting malignant states.

Preexisting malignancy is considered a relative contraindication to orthotopic liver transplantation (OLT) because of the risk of tumor recurrence. The purpose of this study is to assess the outcome of OLT in patients with a preexistent malignant state. Of 1,097 OLTs performed between 1989 and 1999 at King's College Hospital (London, UK), 18 patients had a pretransplantation malignant state, including 6 cases of myeloproliferative disorder (MPD) presenting as Budd-Chiari syndrome. Those patients with solid-organ malignancies had their tumor detected at an early stage and underwent curative treatment before or during OLT. Patients were followed up for a median of 71 months (range, 1 to 119 months) post-OLT, and the rates of rejection and malignancy were compared with those of transplant recipients without preexisting malignancy during the same period. One patient had a recurrence of his primary malignancy (non-Hodgkin's lymphoma) after 27 months, whereas another patient developed a de novo posttransplant lymphoproliferative disorder after 57 months. One patient with MPD developed acute leukemia 72 months after OLT. In comparison, of 1,079 OLTs performed in patients without preexisting malignancy during the same period, there were 34 cases of de novo malignancies. The rate of rejection in patients with and without preexisting malignancy was similar. Successful medium-term outcome after OLT can be achieved in carefully selected patients with preexisting malignancy providing the malignancy is amenable to curative treatment before or at OLT. Primary MPDs responsible for Budd-Chiari syndrome should not be considered a contraindication to OLT.

Adult↗
PubMed2001

Living related liver transplantation in biliary atresia with absent inferior vena cava.

The success of the triangulation technique for hepatic venous anastomosis in left lateral segment liver transplantation has led to standardization of this procedure. We report a case of syndromic biliary atresia with absent inferior vena cava in which we constructed a neo cava to implant a living related left lateral segment graft by using the triangulation technique.

Biliary Atresia↗
PubMed2001

Survival and outcome after hepatic artery thrombosis complicating pediatric liver transplantation.

BACKGROUND/PURPOSE: Hepatic artery thrombosis (HAT) represents a significant cause of graft loss and mortality after pediatric orthotopic liver transplantation (OLT). The incidence and etiology of this complication have been investigated in detail but relatively little is known about outcome. METHODS: A review was conducted of all children with confirmed HAT complicating OLT during a 10-year period (1990 through 1999) in a single center. HAT was established by angiography or at operation in all cases. RESULTS: From a consecutive series of 400 pediatric OLTs, there were 31 (7.8%) instances of HAT in 29 children of median age 3.8 years (range, 8 days to 16 years). Twenty-four (83%) are alive after a median follow-up of 3.6 years. Fourteen cases occurred after transplantation of whole grafts and 17 after reduced or split livers. Of the 18 episodes resulting in retransplantation, there were 5 deaths and 2 second episodes of HAT; surviving children are alive with good graft function. Of the 13 episodes managed without retransplantation, 4 patients underwent attempted early revascularisation of the graft, which was successful in 2, and the remainder initially were treated conservatively. All 13 children are alive after a median follow-up of 4.1 years (range, 0.6 to 5.8), but 5 required radiologic or surgical intervention for biliary or septic complications; biochemical liver function is normal in 8, mildly abnormal in 3, and poor in 2. Retransplantation was less likely in those who had received reduced or split grafts (7 of 17) compared with those who had received whole grafts (11 of 14), but this difference just failed to reach statistical significance (chi(2) = 3.01, 0.1 > P > .05). CONCLUSIONS: Using a selective policy of retransplantation, revascularisation, and conservative treatment, 83% of children survived HAT complicating OLT. Approximately 40% of children with HAT survived without retransplantation. J Pediatr Surg 36:888-891.

Child↗
PubMed2001

Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation.

OBJECTIVE: To determine the relative contribution of the gastrointestinal tract and the liver in lactate metabolism in patients with acute liver failure (ALF) and the effect of liver transplantation on this. We hypothesized that the liver and gut are net producers of lactate in ALF and that this is reversed after liver transplantation. SETTING: A university-affiliated specialist liver transplant operating theater. SUBJECTS: Eleven patients with ALF undergoing liver transplantation. MEASUREMENTS AND INTERVENTIONS: After ethical approval, 11 patients with ALF listed for orthotopic hepatic transplantation were studied. Whole blood was analyzed for lactate concentration from radial artery (RA) catheter, portal vein (PV), and hepatic vein (HV) during the dissection phase and was repeated postreperfusion of the liver graft. Gradients across the gut and the liver were calculated to see if there was net production or consumption. RESULTS: HV lactate was significantly higher than arterial (p =.028) in patients with ALF before liver transplantation, suggesting splanchnic production of lactate. Total splanchnic lactate gradient (HV-RA) is positive in ALF. Both the gut (PV-RA) and the liver (HV-PV) were net producers of lactate. After liver transplantation, hepatic venous lactate falls below arterial levels but not significantly. The gradient across the gut (PV-RA) remained positive, but the transhepatic gradient (HV-PV) became significantly negative, showing consumption by the graft (p =.021). The magnitude of lactate consumption after transplantation correlated positively with portal venous lactate concentration (p =.029) and inversely with graft cold ischemic time (p =.007). CONCLUSION: The liver is a net producer of lactate in patients with ALF and an elevated whole blood lactate. After liver transplantation, the graft becomes a consumer of lactate as shown by the negative lactate gradient. The degree of consumption is dependent on portal venous lactate concentration and cold ischemic time.

Female↗
PubMed2000

Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children.

Liver dysfunction is a well-recognized complication of intestinal failure in children. Advances in total parenteral nutrition (TPN) have allowed these children to survive while their intestinal tract gradually adapts. Unfortunately TPN may lead to cholestatic liver disease particularly in the young children. Progression of liver disease is associated with a poor prognosis and is an indication for small bowel transplantation. We report our experience of orthotopic liver transplantation in four children with short gut and sequential liver and small bowel transplantation in one child. All children had TPN-related liver failure. Causes of intestinal failure included necrotising enterocolitis (n=2), gastroschisis (n=1), intestinal atresia (n=1), and megacystic, microcolon syndrome (n=1). At the time of liver transplantation the children's mean age was 10.9 months (2.5-24) and weight 6.7 kg (4.8-10.1). The mean serum bilirubin was 522 micromol/liter (299-823), aspartate transaminase 423 IU/liter (49-1024) and international normalized ratio 2.8 (2-3.9). There were two deaths both from respiratory failure secondary to adenovirus pneumonia including the child who received a sequential small bowel transplant. Three children with isolated liver grafts are alive and off TPN at 20 months (mean) follow up (range 6-35). Isolated orthotopic liver transplantation has a role in selected children with intestinal failure, particularly those with short but normally functioning gut and progressing with satisfactory intestinal adaptation but developing liver disease. Those children with TPN-related liver disease and unadapted gut or irreversible intestinal disease need combined liver and small bowel transplantation. Sequential small bowel transplantation is feasible after orthotopic liver transplantation and may provide an option for the child with terminal liver and small bowel failure.

Adolescent↗
PubMed2000

Size reduction of small bowels from adult cadaveric donors to alleviate the scarcity of pediatric size-matched organs: an anatomical and feasibility study.

BACKGROUND: Small bowel transplantation in children weighing less than 10 kg is hindered by the lack of size-matched donors. The ability to create reduced size small bowel grafts from adult cadaveric donors suitable for use in young children has been studied. METHODS: Volumetric assessment of computed tomography scans were used to evaluate abdominal cavity and small bowel volumes in children. Small bowels were retrieved from adult cadaveric donors and reduced in size. RESULTS: Computed tomography studies of the abdominal cavity showed that the mean volume available for a small bowel graft was 260 ml in children less than 5 kg (n = 5) and 460 ml in children weighing 5-10 kg (n = 5). Fifteen small bowels were successfully reduced to provide an ileal graft of one meter while keeping the whole length of the superior mesenteric artery and vein after their dissection in the proximal part of the mesentery. The mean volume of the grafts created was 270 ml in seven thin patients (body mass index [BMI] <25), 390 ml in five preobese patients (25< BMI<30), and 490 ml in three obese patients (BMI>30). Mesenteric transillumination in thin donors allowed safe dissection and complete hemostasis. No diameter reduction was required. Technical modifications permitted the creation of two grafts, one ileal and the other jejunal from a single donor. Volumetric and surgical data show that implantation of up to two meters of ileum from a thin adult weighing up to 80 kg is feasible in children weighing less than 10 kg. CONCLUSION: Size reduction of adult cadaveric small bowels can provide suitable grafts for children of less than 10 kg and could expand the potential pool of donors for these patients.

Adult↗
PubMed2000

Liver transplantation for alpha-1-antitrypsin deficiency in children.

Alpha-1-antitrypsin (a1-AT) deficiency is an inborn error of metabolism, which can cause liver disease. The condition is one of the most common genetic disorders in the Caucasian population. Here we review our experience with 21 children suffering from end-stage liver disease due to a1-AT deficiency. All children are PIZZ homozygotes. Nineteen of them initially presented with neonatal jaundice and two with hepatosplenomegaly in childhood. Twenty-five liver transplantations were performed. All children are currently alive at a median followup of 40 months. Liver replacement provides the only definite treatment for children with end-stage liver disease associated with a1-AT deficiency. Excellent results can be achieved by reducing waiting time for transplantation and by early referral to a liver transplant centre.

Adolescent↗