Carlos Fasola

Corticosteroid‐free immunosuppression with daclizumab in HCV+ liver transplant recipients: 1‐year interim results of the HCV‐3 study

This work is a 1‐yr interim analysis of a prospective, randomized, multicenter trial evaluating the effect of corticosteroid‐free immunosuppression on hepatitis C virus–positive (HCV+) liver transplant recipients following liver transplantation (LT). Patients received tacrolimus and corticosteroids (Arm 1; n = 80); tacrolimus, corticosteroids, and mycophenolate mofetil (MMF) (Arm 2; n = 79); or daclizumab induction, tacrolimus, and MMF (Arm 3; n = 153). At 1 yr, 64.1%, 63.4%, and 69.4% of patients achieved the composite primary endpoint of freedom from rejection, freedom from HCV recurrence, and freedom from treatment failure, respectively. Excellent patient and graft survival did not differ significantly among treatment arms. Freedom from HCV recurrence at 1 yr was 61.8 ± 6.2%, 60.1 ± 6.1%, and 67.0 ± 4.3% in Arms 1, 2, and 3, respectively (P = not significant). Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 (93.0 ± 2.2% vs. 81.9 ± 4.4%; P = 0.011). Multivariate analysis identified acute rejection (hazard ratio = 2.692; P = 0.001) and donor age (hazard ratio = 1.015; P = 0.001) as significant risk factors for HCV recurrence. HCV recurrence was not influenced by recipient demographics, HCV genotype, or immunosuppression. In conclusion, these results suggest that a corticosteroid‐free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV+ liver transplant recipients. Liver Transpl 13:1521–1531, 2007.

Successful ABO-incompatible pediatric liver transplantation utilizing standard immunosuppression with selective postoperative plasmapheresis

Transplanting blood group A, B, or O (ABO)‐incompatible (ABO‐I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO‐I liver grafts—regardless of recipient age—have comparable long‐term survival (mean follow‐up of 3.25 yr) with ABO‐compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One‐year actuarial patient survival for ABO‐matched grafts vs. ABO‐I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO‐I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO‐compatible group. There were no vascular complications and 2 biliary strictures in the ABO‐I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO‐I grafts in a more elective setting associated with split and living donor liver transplants. Liver Transpl 12:972–978, 2006.

Incidence, impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single-center 12 year experience

Heffron TG, Pillen T, Smallwood G, Henry S, Sekar S, Casper K, Solis D, Tang W, Fasola C, Romero R. Incidence, impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single‐center 12 year experience.u2028Pediatr Transplantation 2010: 14:722–729.

Low incidence of hepatic artery thrombosis after pediatric liver transplantation without the use of intraoperative microscope or parenteral anticoagulation

Abstract:u2002 The risk of hepatic artery thrombosis (HAT) after pediatric liver transplantation (PLT) has been reported to range from 0 to 25%. We report our experience focusing on the interrelationships between risk factors, surgical technique and the incidence of HAT after liver transplantation in the pediatric age group. From February 18, 1997 to December 31, 2003, 150 consecutive liver transplants were performed in 132 pediatric patients. There were similar numbers of whole grafts when compared with partial grafts, 80 (53.3%) vs. 70 (46.7%), pu2003=u20030.30. Four grafts (2.7%) developed HAT. Of the grafts with HAT, three were successfully revascularized within the first 24u2003h. Only one graft (0.66%) was lost to HAT. A single surgeon utilizing 3.5–6.0 magnification loupes performed all but one hepatic arterial anastomoses. All patients were followed postoperatively by a daily ultrasound protocol and with anticoagulation of aspirin and alprostadil only. Living and deceased donor left lateral segment grafts had an increased rate of HAT when compared with whole liver grafts. HAT with subsequent graft loss may be minimized in PLT with the use of surgical loupes only, anticoagulation utilizing aspirin, alprostadil, and daily ultrasounds.

Pediatric hepatopulmonary syndrome is seen with polysplenia/interrupted inferior vena cava and without cirrhosis

Hepatopulmonary syndrome (HPS) is a triad of liver dysfunction, hypoxemia, and intrapulmonary vascular dilatation. We describe the prevalence and clinical features of HPS at a pediatric liver transplant center. Patients referred to Childrens Healthcare of Atlanta/Emory University transplant program from February 1999 to May 2005 were reviewed. Oxygen saturation in room air was screened by percutaneous pulse oximetry. HPS cases were compared with similar age non‐HPS recipients (n = 38) to determine differences in clinical characteristics, Pediatric End‐Stage Liver Disease (PELD) scores, and posttransplantation survival. Of 211 patients referred and 114 patients transplanted, 7 met criteria for HPS (3.3% and 6.1%, respectively). Patients with HPS had lower PELD score (−0.4 ± 5.9 vs. 11 ± 11; P = 0.01) and total bilirubin (1.7 ± 1.1 vs. 11.2 ± 10.1; P = 0.02) at the time of transplantation. Four of 7 patients with HPS had polysplenia/interrupted inferior vena cava (PS/IVC) compared with 0 of 38 age‐matched controls (P = 0.0002). Three patients with HPS did not have cirrhosis; 2 of these 3 had PS/IVC. All HPS cases normalized room air oxygen saturation by 6 months, and survival after transplantation in HPS cases was 100%. Marked hepatic synthetic or biochemical dysfunction may not be present, and cirrhosis is not a requirement for the development of HPS in children. HPS in children is frequently associated with PS/IVC. Histologic evidence of abnormal intrahepatic portal vein flow and the demonstration of portosystemic communications at any level should be sought in children presenting with unexplained intrapulmonary vascular dilatation. Liver transplantation for HPS in childhood may be appropriate even in the absence of cirrhosis. Liver Transpl 13:680–686, 2007.

Medical and surgical treatment of neonatal hemochromatosis: single center experience.

Abstract:u2002 NH is a rare disorder of iron storage in newborns resulting in rapid liver failure. Outcomes are dismal with 20–30% survival. We report our experience in eight children with NH. Assessment of liver function included admission PT and serum levels of FV and FVII. Medical treatment (antioxidant cocktail) was started in all patients, with chelation therapy in six. Of these six, three survived with medical treatment alone. The other three underwent liver transplant. One died 158u2003days after transplant to sepsis: two are well more than five yr after transplant. The two neonates who did not receive chelation therapy, died to multi‐organ failure and sepsis. In summary, five children (62.5%) survived long‐term. In the three transplanted, one‐ and five‐yr‐survival was 66%. Older children with compromised synthetic liver function (FVII levelsu2003≤u200315%) required liver replacement for survival. Early referral to a tertiary care center is essential to increase survival of these children with a rare and otherwise fatal disease. Single center experience of children with NH is here presented. Potentials for survival improvement with of medical and surgical treatment are examined.

Resistance to Combined Ganciclovir and Foscarnet Therapy in a Liver Transplant Recipient with Possible Dual-Strain Cytomegalovirus Coinfection

We present a case report of a cytomegalovirus (CMV)‐seronegative, 58‐year‐old male who received a CMV‐seropositive donor liver transplant without CMV prophylaxis. On postoperative day 30, the patient developed primary CMV disease that responded to ganciclovir. On postoperative day 114, however, he was diagnosed with recurrent CMV infection. Despite aggressive, combined antiviral treatment with ganciclovir and foscarnet and reduction of immunosuppression, viral clearance was never achieved. Serum samples were collected throughout the infectious process for viral DNA analysis. Portions of the UL97 and UL54 genes were amplified and compared to the AD169 wild‐type strain. Sequencing studies revealed the presence of mutations in viral isolates obtained after clinical resistance was observed. These mutations were not present in samples obtained during the primary CMV infection. Our findings suggest the presence of coinfection with at least 2 different strains of CMV rather than induction of mutations after ganciclovir therapy. Liver Transpl 13:1396–1400. 2007.

Pediatric liver transplantation for acute liver failure at a single center: a 10-yr experience.

Heffron TG, Pillen T, Smallwood G, Rodriguez J, Sekar S, Henry S, Vos M, Casper K, Gupta NA, Fasola CG, Romero R. Pediatric liver transplantation for acute liver failure at a single center: A 10‐yr experience.u2028Pediatr Transplantation 2010:14:228–232.

Liver retransplantation in children: The Atlanta experience

Heffron TG, Pillen T, Smallwood G, Henry S, Sekar S, Solis D, Casper K, Fasola C, Romero R. Liver retransplantation in children: The Atlanta experience.u2028Pediatr Transplantation 2010: 14:417–425.

Successful outcome after early combined liver and en bloc-kidney transplant in an infant with primary hyperoxaluria type 1: a case report.

Abstract:u2002 PH1 is a metabolic disorder characterized by urolithiasis and the accumulation of oxalate crystals in the kidneys and other organs. Although patients often first present with renal failure, PH1 results from a deficiency of the hepatic peroxisomal enzyme AGT. Ultimately only liver transplantation will cure the underlying metabolic defect. Herein, we report the case of a three‐month‐old male infant diagnosed with PH and treated using a combined liver and en bloc‐kidney transplant from a single donor. At the time of transplant, the patient was 11u2003months old and weighed 7.9u2003kg. He received a full size liver graft and en bloc kidneys from a two‐yr‐old donor. At 36u2003months post‐transplant, the patient is steadily growing with normal renal and hepatic function. This is one of the first reports of successful liver and en bloc‐kidney transplantation with abdominal compartment expansion by PTFE for the infantile form of PH1 in a high risk child before one yr of age. Prompt diagnosis and early referral to a specialized center for liver and kidney replacement offer the best chance for survival for infants with this otherwise fatal disease.