Nathan Bar-Nathan

Primary hyperoxaluria type 1 : Improved outcome with timely liver transplantation : A single-center report of 36 children

Background. The appropriate use of liver transplantation in children with type-1 primary hyperoxaluria (PH-1) is not well established. We reviewed our experience with 36 children with PH-1, including 12 who underwent liver transplantation. Patients and Methods. From 1989–1998, 36 children from 10 families in northern Israel were diagnosed with PH-1. Eight children presented with renal failure; seven of these eight had the severe infantile form of the disease. One child was treated with kidney transplantation alone. Combined liver-kidney transplantation has been performed in nine children and preemptive liver transplantation in three children. A review of the patients’ charts for the following parameters was performed: age, clinical signs, and renal sonographic findings at diagnosis, age at onset of dialysis, and current status. Type of transplant, pre- and posttransplant urine oxalate excretion, current renal function, survival, and complications were recorded in liver recipients. Results. Of the 23 nontransplanted children, 9 died of complications related to severe systemic oxalosis and 14 are alive (mean follow-up, 7.4 years), including 2 who are candidates for transplantation. The child who underwent only kidney transplantation died of unrelated causes. Of the 12 liver recipients, 2 died within the first 3 months posttransplant and another child underwent retransplantation due to hepatic arterial thrombosis. At intervals after transplant ranging from 6–54 months, 10 recipients are alive (7 of the 9 recipients of combined liver-kidney transplants and all 3 recipients of preemptive liver transplants). Mean GFR in the 10 survivors is 77 ml/min/m2. In 9 of these 10, daily urinary oxalate excretion normalized. Renal function has improved (mean GFR 86 vs. 58 ml/min/m2) but renal oxalate deposits remain in the three recipients of isolated liver grafts. Conclusions. Our decade-long experience with children with PH-1 supports strategies for early diagnosis and timely liver transplantation. Preemptive isolated liver transplantation should be considered in children who develop the disease during infancy or in those with slowly progressive disease when significant symptoms develop. Combined liver-kidney transplantation is suggested for children with end-stage renal disease.

Kidney transplantation from living-unrelated donors: comparison of outcome with living-related and cadaveric transplants under current immunosuppressive protocols

OBJECTIVES Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation. METHODS Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters. RESULTS LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01). CONCLUSIONS Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants.

Hepatic artery thrombosis in pediatric liver transplantation: Graft salvage after thrombectomy

Abstract: Hepatic artery thrombosis (HAT) is a devastating complication that may occur after orthotopic liver transplantation (OLT). A higher incidence has been reported in children. Salvage of the graft by thrombectomy has been suggested as an alternative to re‐transplantation. In this study we report the outcome of three children who underwent thrombectomy for HAT. Between January 1992 and June 1998, 14 children (< 17 yrs of age) underwent liver transplantation. Three developed HAT (one a whole‐liver graft recipient, age 17; two living‐related graft recipients, ages 4 and 4.5 yr). In the first patient, thrombosis of the hepatic artery was associated with scattered areas of parenchymal necrosis on computed tomography. In the two living‐related patients, HAT was found incidentally during re‐exploration for bleeding (day 2 and day 10). Thrombectomy was performed in all three patients. At 18–24 months after thrombectomy, all three children had normal graft function. In the first patient, complete regeneration of the liver has been documented by computed tomography and a late asymptomatic recurrent thrombosis is suggested by absence of arterial flow on Doppler examination. The hepatic artery is patent in the two living‐related recipients. One of these living‐related recipients developed ischemic bile duct stricture and underwent successful percutaneous balloon dilatation. We conclude that long‐term normal graft function can be achieved by thrombectomy in pediatric liver recipients with HAT, even in the presence of limited parenchymal damage.

Serum cholestasis markers as predictors of early outcome after liver transplantation

Abstract:  Background:  Early cholestasis is not uncommon after liver transplantation and usually signifies graft dysfunction. The aim of this study was to determine if serum synthetic and cholestatic parameters measured at various time points after transplantation can predict early patient outcome, and graft function.

BK polyoma virus nephropathy in kidney transplant recipient: the role of new immunosuppressive agents.

BK POLYOMA virus (BKV) is a newly described agent causing renal dysfunction and failure among kidney transplant recipients. The virus remains latent following primary exposure at childhood and becomes activated in immunocompromised states. Clinically, the virus rarely causes symptoms such as hemorrhagic cystitis in bone marrow transplant recipients. Although viral shedding is detected in urine specimens of many renal transplant recipients, only a few will develop BKV transplant nephropathy. This disease process is characterized by a rapidly progressive loss of graft function. Introduction of new and more aggressive immunosuppressive protocols may explain the emergence of this new infectious complication. We describe our experience with 7 patients with BKV nephropathy with specific attention to possible risk factors.

Nonfunctioning renal allograft embolization as an alternative to Graft nephrectomy: Report on seven years' experience

Purpose: Graft nephrectomy is the treatment of choice in patients with graft intolerance syndrome, but it is associated with high morbidity and mortality rates. Renal vascular embolization has been suggested as a possible alternative. The aim of this study was to evaluate the efficacy and safety of arterial embolization of these nonfunctioning transplanted kidneys. Methods: Twenty-six transplanted kidneys in 25 patients with irreversible renal graft rejection and graft intolerance who underwent arterial embolization at our center from August 1994 to April 2001 were analyzed for procedural success and long-term outcome. Embolization was performed with absolute alcohol or with polyvinyl alcohol (Ivalon) and coils. Results: Twenty-four of the 26 (92%) procedures were technically successful, but in one patient only partial occlusion of one of two renal arteries was achieved, and in another the renal artery was already completely occluded. There were two major complications: emphysematous pyelonephritis necessitating nephrectomy and groin abscess that was drained. Follow-up ranged from 8 to 84 months. Clinical success was achieved in 24 of the 26 procedures (92%), and only in one patient did embolization fail to relieve the symptoms, and nephrectomy was performed 3 months later. Conclusion: Renal vascular embolization is a simple, safe and effective technique for the treatment of nonfunctioning renal allografts associated with graft intolerance syndrome. We suggest that it be considered the treatment of choice.

Defibrotide for the treatment of veno-occlusive disease after liver transplantation.

Background. Veno-occlusive disease (VOD) after liver transplantation is associated with acute rejection and poor outcome. The use of antithrombotic and thrombolytic agents is limited by their toxicity. Defibrotide is a polydeoxyribonucleotide with thrombolytic and antithrombotic properties and no systemic anticoagulant effect. Methods. Defibrotide, 35–40 mg/kg/day, was administered intravenously for 21 days on a compassionate-use basis to two patients aged 66 and 49 years. VOD had developed 6 weeks and 4 months after orthotopic liver transplantation for hepatitis C and hepatitis B infection, respectively. VOD was diagnosed clinically by findings of weight gain (8.5% and 16%), ascites, jaundice (serum bilirubin 5.4 mg/dl and 21.7 mg/dl), and severe coagulopathy (in one patient), and histologically by the presence of hemorrhagic centrilobular necrosis and fibrous stenosis of the hepatic venules. One of the patients had received azathioprine as part of the immunosuppressive regimen. There was no evidence of acute cellular rejection histologically. Results. After 3 weeks of defibrotide administration, the first patient showed complete clinical resolution of the VOD, and serum bilirubin level normalized. He is alive 6 months after transplantation. The second patient, treated at a later stage of disease, showed marked improvement in the coagulopathic state, but there was no resolution of the VOD. He died 2 months later of multiorgan failure due to Escherichia coli sepsis. Neither patient had side effects from the drug. Conclusions. Defibrotide is a promising drug for the treatment of VOD after liver transplantation and needs to be evaluated in large, prospective studies.

Renal Transplantation in the Amyloidosis of Familial Mediterranean Fever: Experience in Ten Cases

Ten patients with familial Mediterranean fever (FMF) and histologically confirmed amyloidosis received cadaver kidney transplants for treatment of terminal renal disease. Colchicine, 1 mg daily, was included in the routine postoperative regimen from 1974 for amyloidotic patients. Graft and patient survival were compared with ten nonamyloidotic recipients of renal grafts matched for age, sex, type of allograft, and HLA compatibility. In the FMF group, five of ten grafts have survived from 20 to 64 months; in the control group, six of ten. While only recipients with functioning grafts survived in the FMF group, patient survival in the control group is eight of ten after one year. In all five FMF survivors, graft function is satisfactory, proteinuria is absent, and blood creatinine levels are normal. Amyloid involvement of an allograft was documented 16 months after transplantation in the only patient whose maintenance colchicine dosage had been reduced to 0.5 mg daily.

Postshunt hepatic encephalopathy in liver transplant recipients.

Background. Preexisting spontaneous portosystemic shunts increase the risk of posttransplantation portal vein thrombosis. Portosystemic shunts may also be placed surgically to manage posttransplant portal vein stenosis/thrombosis. Both types may be complicated by hepatic encephalopathy. Methods. The database of a major tertiary medical center from 1999 to 2006 was searched for liver transplant recipients with hepatic encephalopathy and stable liver function. The medical and imaging files were reviewed for risk factors, management, and outcome. Results. Of the 244 patients who underwent liver transplantation during the study period, four (1.6%) met the inclusion criteria. Median age at transplantation was 49 years (range 39–54); median time to the first episode of hepatic encephalopathy after transplantation was 23 months (range 2–40). In two patients, a distal splenorenal shunt placed at 1 and 7 months after transplantation to treat portal vein thrombosis led to hepatic encephalopathy at 1 and 33 months later. Both responded to medical therapy. The other two patients had spontaneous splenorenal shunts, and hepatic encephalopathy appeared 33 months and 12 months after transplantation. Treatment consisted of transhepatic percutaneous portal vein dilatation with stent insertion in the first patient and interposition of a venous graft between the superior mesenteric and left intrahepatic portal veins to reroute splanchnic flow in the second patient. Conclusions. Portosystemic shunts in liver transplant recipients with stable graft function may be associated with hepatic encephalopathy. Pretransplant assessment to detect unknown spontaneous shunts is important. Restoration of portal flow is the preferred procedure in this setting.

Transhepatic Balloon Dilatation of Early Biliary Strictures in Pediatric Liver Transplantation: Successful Initial and Mid-Term Outcome

AbstractPurpose: To evaluate the initial and mid-term outcomes of transhepatic balloon dilatation for the treatment of early biliary strictures in lateral left-segment liver transplants in young children. Methods: Between April 1997 and May 2001, seven children aged 9 months to 6 years with nine benign strictures in left-segment liver grafts were treated percutaneously. Sessions of two or three dilations were performed three or four times at average intervals of 10–20 days. In each session, the biliary stenoses were gradually dilated using balloons of 3–7 mm. Follow-up ranged from 12 to 54 months (mean 27 months, median 12 months). Clinical success was defined as resolution of the stenosis, normalization of liver enzymes and lack of clinical symptoms Results: Technical success was achieved in all nine strictures. Hemobilia occurred in one patient and was successfully treated. On follow-up, all patients had complete clinical recovery with normalization of liver function and imaging of patent bile ducts. Conclusion: Balloon dilatation is an effective and relatively safe method for the treatment of early biliary strictures in left-segment liver transplantation in young children. We recommend this approach as the initial treatment for early strictures. Metal stents or surgery should be reserved for patients with late appearance of strictures or failure of balloon dilatation.