Anita Verma

Hepatocyte transplantation for inherited factor VII deficiency.

Hepatocyte transplantation has been investigated in patients with liver-based metabolic disorders and acute liver failure. We report the first use of hepatocyte transplantation in two brothers with severe inherited coagulation factor VII deficiency. Patient 1 received a total of 1.09x10(9) cryopreserved hepatocytes, and patient received 2.18x10(9) fresh and cryopreserved hepatocytes through a Hickman line inserted in the inferior mesenteric vein. Infusion of isolated human hepatocytes improved the coagulation defect and markedly decreased the requirement for exogenous recombinant factor VII (rFVIIa) to approximately 20% of that before cell transplantation. In both patients, episodes of line sepsis were associated with an increase in rFVIIa requirement. Six months posthepatocyte transplantation, higher rFVIIa doses were required, suggesting loss of transplanted hepatocyte function. Because of increasing problems with venous access and long-term uncertainty of the efficacy of hepatocyte transplantation, orthotopic liver transplantation was performed successfully in both cases.

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.

Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: a preliminary experience1

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.

Neonatal herpes simplex virus infection presenting as acute liver failure : Prevalent role of herpes simplex virus type I

Background: Acute liver failure (ALF) in neonates is rare but carries a high mortality without liver transplantation. Herpes simplex virus (HSV) is one of the microbes that more commonly causes ALF and is potentially treatable; hence, early diagnosis and treatment are important to avoid progression to liver failure. Patients and Results: We have analysed retrospectively the case notes of 11 patients with HSV-induced ALF. A history of possible herpes infection was elicited in 5 parents, but HSV had not been suspected clinically. All patients were asymptomatic when discharged from postnatal units and were presented with nonspecific symptoms of poor feeding and lethargy within 2 weeks from birth. Seven of the 11 patients had HSV-1 infection, 4 HSV-2. Only 2 patients who received early treatment with intravenous acyclovir survived. Conclusions: HSV-related ALF in the neonatal period carries high morbidity and mortality and needs a high index of suspicion so that life-saving treatment can be started promptly. Both HSV-1 and HSV-2 can cause severe neonatal infection. It is important to recognise HSV infection in women of childbearing age and their sexual partners.

Immunization issues before and after solid organ transplantation in children

Abstract:  Solid‐organ transplant recipients are at risk from various infectious diseases, many of which can be prevented by immunizations that could reduce morbidity and mortality. However, it is not uncommon for children requiring transplantation to have received inadequate or no immunizations pre‐transplant. Every effort should be made to immunize transplant candidates early in the course of their disease according to recommended schedules prior to transplantation. It is also important to immunize their household contacts and healthcare workers. In this review, we summarize the major immunization issues for children undergoing transplantation, the data currently available on immunization safety and efficacy, and suggest immunization practices to reduce vaccine‐preventable disease. There is a real need for a standardized approach to the administration and evaluation of immunizations in this group of patients.

Risk factors for fungal infection in paediatric liver transplant recipients.

Abstract:  Fungal infection (FI) is a major and potentially fatal complication in liver transplantation (LT). Published experience of FI in paediatric LT is limited. We therefore reviewed case records of 79 children, aged between 0.16 and 16 yr, who underwent LT between 1997 and 1998 to document the incidence of, and identify risk factors for, FI. Sixty‐eight pre‐, peri‐ and post‐LT variables were assessed in relation to FI by univariate and multivariate analyses. The major indications for LT were biliary atresia in 26 (33%) patients, fulminant hepatic failure in 16 (20%) and intrahepatic cholestasis in 11 (14%); eight patients required re‐LT. Thirty‐two (40.5%) children developed a FI within 1 yr of LT. The median time to FI was 42 days (range 1–342 days). Candida spp. caused 29 (90.7%) FIs; 21 (66%) of these were Candida albicans. Although FI was associated with increased mortality, most patients responded well to antifungal treatment. The variables independently associated with FI were pre‐LT fungal colonization and pyrexia and, post‐LT, bacterial infection, Epstein–Barr virus (EBV) infection and tacrolimus administration. Identifying risk factors for FI should contribute to the development of strategies for prophylaxis or preemptive therapy.

Immunization status in children

Objective : Recent studies and surveys are observing a declining trend of routine immunization coverage and fully immunized children in India are reported to be 38%. A rapid assessment technique was used on National Immunization Day (PPI) to assess the immunization status among children in the age group of 12–23 months covering urban, rural and slum areas in UT, Chandigarh.Methods : The study covered 796 children in proportion of their distribution in urban, rural and slum areas.Results : Evaluation recorded fully immunized children as 72.23%, partially immunized as 22.99% and unimmunized as 4.64%. Only 58.66% children in urban slums were fully immunized. The overall coverage for various vaccines was BCG: 93.09%, DPT1/ OPV1: 93.97%, DPT2/OPV2 90.57%, DPT3/OPV3: 85.92% and measles: 76%. No sex-wise difference was noticed in the study.Conclusion. Efforts must be made to strengthen routine immunization programme especially in the underprivileged groups and areas such as slum in cities so that target of universal coverage can be achieved as envisaged at national level.

Sirolimus as renal and immunological rescue agent in pediatric liver transplant recipients

Basso M‐S, Subramaniam P, Tredger M, Verma A, Heaton N, Rela M, Mieli‐Vergani G, Dhawan A. Sirolimus as renal and immunological rescue agent in pediatric liver transplant recipients.
Pediatr Transplantation 2011: 15: 722–727.

Mycobacterium tuberculosis infection in pediatric liver transplant recipients.

Objectives. To study the incidence, clinical presentation, management, complications and outcome of tuberculosis in pediatric liver transplant recipients. Methods. A retrospective review of the medical records of children who underwent liver transplantation between 1991 and 1998. Results. Mycobacterium tuberculosis infection occurred in 6 of 254 (2.4%) children undergoing liver transplantation between 1991 and 1998. Cough, pyrexia and poor appetite were common presentations; one‐half had normal chest radiographs. The median time to confirmation of diagnosis was 8 months (range, 1 to 17 months). Tests contributing to diagnosis included: Ziehl‐Neelsen (ZN) stain (2 patients), M. tuberculosis polymerase chain reaction (1 patient), Mantoux test (1 patient) and histopathology (4 patients). Family health screening was productive for 4 patients. Duration of treatment varied from 9 to 18 months. Isoniazid‐induced hepatitis was observed in 2 patients but resolved with dose reduction. Two patients died while receiving treatment, one of Klebsiella spp. septicemia and the other of pulmonary hemorrhage. Conclusions. Tuberculosis after liver transplantation has a significant morbidity and mortality. Pretransplantation a personal and family history of tuberculosis must be sought, and screening of patients and their families should be considered. Standard regimens incorporating isoniazid and rifampin are effective, but regular monitoring of liver function is essential to detect drug‐induced hepatotoxicity.

Long‐term outcome of mycophenolate mofetil rescue therapy for resistant acute allograft rejection in pediatric liver transplant recipients

Mycophenolate mofetil (MMF) has been used to rescue liver allografts with steroid‐resistant rejection (SRR). However, the long‐term outcome of these patients is not known. This study evaluates the long‐term outcome of MMF rescue therapy for SRR in pediatric liver allograft recipients. Twenty‐six children (who received 28 liver transplants), including 16 girls, were given MMF for SRR. The median age at transplant was 1.7 (range 0.4‐13.6) years. Primary immunosuppression was cyclosporine‐based in 22 and tacrolimus‐based in 6. All patients except one had been converted to tacrolimus prior to MMF, having already received a median of 2 (1‐5) courses of high‐dose intravenous methylprednisolone. The median time to MMF rescue therapy was 1.8 (0.4‐35.8) months. Twenty‐one of 28 episodes of SRR responded to MMF therapy. The median follow‐up was 8.8 (7.7‐11.5) years. In responders, there was 1 death from posttransplant lymphoproliferative disease, and no grafts were lost to chronic rejection. In the 7 nonresponders, 3 grafts were lost to chronic rejection with 2 patient deaths. Surviving children are clinically well with good liver function, and 17 remain on MMF. Three children have glomerular filtration < 80 mL/minute/1.73 m2. Side effects of MMF were seen in 12 patients; diarrhea (n = 5) and leukopenia (n = 5) being the most common. MMF was found to be effective in treating SRR in pediatric allograft recipients, with good long‐term graft function and an acceptable side‐effect profile. Liver Transpl 14:1303–1308, 2008.