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E Sokal

Publications and source records attributed to E Sokal.

At least 19 recordsLinked to original sources
PubMed2006

Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological complications in 235 recipients.

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.

Adolescent↗
PubMed2005

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children.

This study was conducted to compare the reactogenicity, immunogenicity and safety of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720ELU HAV, 20 mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B vaccine (360ELU HAV, 10 mcg HBsAg). A total of 511 children aged 1-11 years who had not previously received a hepatitis A or B vaccine were enrolled in the study. Both vaccines were well tolerated, and were shown to be safe and immunogenic. The analysis, stratified according to two age groups (1-5 year and 6-11-year-old children) demonstrated that the reactogenicity profile of the two-dose schedule was at least as good as that of the established schedule. Both vaccines and schedules provided at least 98% seroprotection against hepatitis B and 100% seroconversion against hepatitis A, 1 month after the end of the vaccination course (Month 7).

Child↗
PubMed2005

Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type.

Peroxisomal biogenesis defects include a number of severe neurodevelopmental disorders, among which infantile Refsum disease (IRD) occupies the mildest end of the spectrum. Although high docosahexaenoic acid (DHA) and low phytanic acid diets can correct some of the biochemical defects, they have not consistently altered the progressive course of the disease. We carried out orthotopic liver transplantation (OLT) in a mildly symptomatic 6-month-old infant who was a sibling of a severely neurologically impaired older sister. After transplantation the clinical course of this young child appeared much improved by comparison to her older sister. She walked alone at 4 years, had acceptable social interaction and had a noticeable recovery of audition. After transplantation her biochemical parameters were significantly improved: phytanic acid and very long-chain fatty acid (VLCFA) serum concentrations decreased. Abnormal bile acids disappeared from plasma. Although the OLT did not result in a cure of the disorder, the clinical and biochemical results suggest that OLT should be considered in mildly symptomatic patients.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2005

Post-transplant lymphoproliferative disorder with supraglottic involvement.

OBJECTIVE: Transplant patients with primary Epstein-Barr virus (EBV) infection may develop post-transplant lymphoproliferative disorder (PTLD). Since many infants are seronegative at the time of transplantation, PTLD is a major concern for paediatric transplant centres. First manifestations of PTLD are frequently observed in the ENT area with adenoidal and/or tonsillar involvement. DESIGN: Retrospective study of two cases of PTLD with confirmed supraglottic involvement, their management and outcome. Only patients with pathologically and immunologically demonstrated B-cell proliferation were diagnosed as PTLD. RESULT: Two infants developed an acute stridor during PTLD respectively 8 and 10 months after orthotopic liver transplantation (OLT). These infants were seronegative for EBV at the time of transplantation. IgM anti-EBV and/or detection of EBV genome by polymerase chain reaction were positive. Laryngeal examination revealed hypopharyngeal and/or supraglottic mucosal hyperplasia. Immunostaining of laryngeal biopsy was positive for latent membrane protein-1 (LMP1). Patients were treated by a reduction in immunosuppression as far as tolerated with the intent to recover natural immune response by the patient over the proliferation of EBV-infected cells. Complete remission of PTLD was observed in these two cases. CONCLUSION: Tonsillar hypertrophy and adenoid enlargement are the most encountered features of PTLD in OLT occurring in the ENT area. Acute stridor with supraglottic involvement may also be observed in PTLD and must be promptly diagnosed as the prognosis of this disorder is related to rapid reduction in immunosuppression and consequently to the recovering of a natural immune response against the EBV infection.

Female↗
PubMed2005

Liver cell transplantation.

Liver cell transplantation is an emerging procedure, consisting of infusing mature adult hepatocytes in the portal system of the recipient. It aims to correct inborn errors of liver metabolism, bridge unstable patients to transplantation, or even allow bridge to recovery in fulminant liver failure. The technique addresses ideally patients with inborn errors of metabolism, unstable but not sick enough for orthotopic transplantation. Best results have so far been obtained in metabolic diseases, such as urea cycle disorders, glycogenosis type I, Crigler Najjar, Refsum disease and factor VII deficiency. Cryopreserved hepatocytes can be used, allowing delay between cell isolation and patient's transplantation. The percentage of engraftment obtained can reach up 10%, with de novo expression of deficient enzyme activity. Better results of engraftment have been obtained in animal studies by different chemical or physical techniques, but not yet applied in humans. Because supply of human cells can be limited, research also aims to obtain transplantable cells from other sources, such as embryonic or adult stem cells, or liver progenitor cells that could be expanded in vitro. Careful progression in this field, and collaboration between centers are mandatory to validate further the technique for wider clinical use.

Adult↗
PubMed2001

Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine.

BACKGROUND: Cases of so-called autoimmune hepatitis (AH) have been reported after liver transplantation. Our aim was to evaluate the incidence in a series of 471 pediatric liver transplant recipients. METHODS: Between 1984 and 1998, 471 children had orthotopic liver transplantation (OLT). Children are followed up on a regular basis, with full clinical, biochemical, and histologic evaluation at 6 months, 1, 2, 5, 7, and 10 years after OLT. Children with unexplained abnormal liver tests were screened for autoimmune markers (total gamma-globulins, smooth muscle antibodies [SMA], liver kidney microsome antibodies [LKM], antinuclear factor [ANA]). From January of 1998 until December of 1998, autoimmune markers were prospectively searched in all children admitted for regular posttransplant follow-up (n = 118). RESULTS: Eleven of 471 children (2.35%) were found with autoimmune hepatitis, 9 retrospectively and 2 prospectively. None had previous autoimmune liver disease. Patients had a history of steroid-dependent hepatitis. Histology showed variable degree of portal and lobular inflammation, piecemeal necrosis, and bridging collapse. Mean (+/-SDS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities at diagnosis were 173+/-145 and 196+/-157 IU/L, respectively (nl<32). Median gamma-globulin levels reached 1365 mg/dl versus 931 mg/dl in controls (P<0.05). Nine had ANA (titer 1/80 up to 1/10,000), 1 SMA (1/320), and 2 LKM1 antibodies (1/1280). Patients did not respond to increasing charge of cyclosporine (n=10) or tacrolimus (n=1). Eleven received steroids (prednisolone: 2 mg/kg per day, then tapered) and azathioprine (1.5 to 2.5 mg/kg per day). All patients normalized within 3 months (mean AST/ALT levels of 26+/-8 and 30+/-9 IU/L). Three had mild to moderate relapse with increase of ALT thereafter. Gamma-globulins decreased to 1190 mg/dl (ns). Amongst the 116 remaining prospectively evaluated patients, 85 had normal evaluation, despite low titers of autoantibodies in 15 (SMA< or =1/40, ANA 1/80). Thirty-one patients had graft dysfunction, related to well-explained posttransplant causes, among which 7 had similar low levels of autoantibodies. CONCLUSIONS: A total of 2.35% of our transplant children present evidence of immune hepatitis after transplantation. Patients do not respond to increasing cyclosporine or tacrolimus levels and require steroid and azathioprine. In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.

Adolescent↗
PubMed2001

Elevated right ventricular pressures are not a contraindication to liver transplantation in Alagille syndrome.

BACKGROUND: Elevated right ventricle pressure resulting from pulmonary artery stenoses may affect outcome and survival after liver transplantation in patients with Alagille syndrome. METHODS AND RESULTS: Between 1984 and 1997, among 444 pediatric liver transplant recipients, 17 had liver transplantation for Alagille syndrome (mean age 3.5 years, range 1.2-13 years), mainly because of poor quality of life with intractable pruritus, and failure to thrive. All patients had pulmonary artery stenosis. In 10 patients considered to have elevated RV pressure on ECG and/or Doppler-echocardiography, a cardiac catheterization was performed before liver transplantation. Mean RV systolic pressure was 55 mmHg (median 49.5 mmHg, range 35-98 mm Hg), mean RV to left ventricular systolic pressure ratio 0.53 (median 0.53, range 0.29-0.78) with a ratio above 0.5 in 6 patients (median 0.66, range 0.5-0.8). All patients underwent successful liver transplantation. Five patients died 1 to 9 months after transplantation from noncardiac causes. In two of them, cardiac catheterization before transplantation showed a RV to left ventricular pressure ratio of 0.51 in one and 0.37 in the second. In the three others, echocardiography before transplantation estimated RV pressures below 0.5 systemic pressures. At follow-up (median 6 years, range 1.5-15 years), liver tests were normal in all, none complained of pruritus and body weight was normalized in 70%. None of the patients presented cardiac symptoms, arrhythmias, or worsening of their cardiac status. CONCLUSIONS: Liver transplantation can be performed safely in children with Alagille syndrome, even in the presence of elevated right ventricular pressure.

Adolescent↗
PubMed2001

Use of mycophenolate mofetil as rescue therapy after pediatric liver transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has been increasingly used after liver transplantation (LT) in adults. We report our preliminary experience with MMF as rescue therapy after pediatric LT. METHODS: A total of 19 children received MMF for 21 indications. Median age at LT was 30 months (range 7-149). The median initial oral dose of MMF was 23 mg/kg/day (range 12-43) orally. Median follow-up after initiation of MMF therapy was 642 days (range 229-1606). RESULTS: 1) EFFICACY: MMF was indicated for rejection or insufficient immunosuppression in 16 cases, with normalization of both liver function tests and liver histology in 10 (62%). MMF was successfully used in one patient with post-LT immmune hepatitis and one patient with corticodependence. In three patients with renal function impairment, MMF allowed reduction of cyclosporine A or tacrolimus blood levels, without subsequent rejection. 2) Tolerance: Six patients (32%) experienced eight side effects, mainly gastrointestinal and hematological, which resolved after cessation of MMF in five cases and dose reduction in three. One case of posttransplant lymphoproliferative disease (PTLD) occurred under MMF therapy (5.2%). Four patients had EBV primary infection, while under MMF therapy, without subsequent PTLD. Three patients had CMV primary infection, and five CMV reactivation, under MMF therapy. Seven remained asymptomatic, and one presented with CMV enteritis. CONCLUSIONS: These preliminary results suggest that MMF is an effective and safe immunosuppressant in pediatric LT recipients. Its use is hampered by frequent gastrointestinal and hematological side-effects. MMF does not seem to increase the risk of PTLD nor CMV disease.

Burkitt Lymphoma↗
PubMed2001

Unusual evolution of an Epstein-Barr virus-associated leiomyosarcoma occurring after liver transplantation.

We report the case of a child who developed, 2 yr after orthotopic liver transplantation (OLTx) for biliary atresia, a multi-focal hepatic tumor with lymphonodular metastases, identified as an Epstein-Barr virus (EBV)-associated leiomyosarcoma. Chemotherapy was given without tumor response. Subsequently, slow growth of the tumor was observed. Immunosuppression was tapered and stopped 9 yr after transplantation. At the present time, 12 yr after the discovery of the first hepatic lesions, the patient is alive and completely symptom-free, the abdominal masses are stable, and liver function tests are completely normal. Smooth muscle tumors are increasingly recognized in children with various immunodeficiencies occurring after organ transplantation. This unusual evolution of a clinically aggressive tumor into a stable disease after restoration of immunity confirms that the immune status of the patient is a crucial factor.

Biliary Atresia↗
PubMed2001

Wide variety of genotypes and geographic origins of hepatitis B virus in Belgian children.

BACKGROUND: Belgium is a country with low endemicity for hepatitis B virus (HBV) infection. Few data are available on genotypes or serotypes of HBV among infected children. METHODS: The S region of the hepatitis B virus genome was amplified and sequenced in 23 children treated with interferon-alpha in Belgium. Nucleotide sequences were aligned and compared with other known sequences in a phylogenetic analysis. RESULTS: A high stability of the S gene was observed during treatment. Four genotypes were represented in this sample of Belgian patients (A, B, D, and E), reflecting the geographic diversity of origins. CONCLUSIONS: In this series, the wide variety of geographic origins is confirmed by the molecular characteristics of HBV. In Belgium, HBV infection of children is currently essentially an imported infection.

Antiviral Agents↗
PubMed2001

[Diagnosis and follow-up of a large intrahepatic portocaval fistula in a newborn].

Portocaval fistulas are rare and only exceptionally discovered in newborns. We report the case of a large portocaval fistula associated with portal hypoperfusion detected at Doppler US imaging in an otherwise asymptomatic 5 week old infant. The patient remained asymptomatic over the following two years. At that time, preoperative angiogram showed a normal portal venous system and the fistula was surgically closed. Postoperative US showed a normal and patent portal system, without evidence of portal hypertension.

Follow-Up Studies↗
PubMed2001

[Hepatitis B in children: natural history and therapy].

Children with chronic hepatitis B, face life long disease and complications of cirrhosis and hepatocarcinoma. Naturally, it is estimated that half to two third of the children will clear the hepatitis Be antigen during childhood. Treatments aim to increase the HBe Ag to Ab seroconversion rate, which may also favour the loss of HBs antigen, ultimate goal. Interferon alpha was the first approved treatment for pediatric chronic hepatitis B, and was shown to increase the HBe ag loss from 11% in control group to 26% in treated patients (5 MU/square meter body surface area for six months) at one year, and 33% at 18 months. Side effects include mainly fever, flu like symptoms, and growth impairment during the treatment phase. Nucleotide analogues have now emerged as a promising alternative to treat chronic hepatitis B. The optimal dose for children is established to 3 mg/kg once daily up to 12 years old. Efficacy trials show complete virologic response in 23% of all treated patients after one year, as compared to 13% in the placebo group, and in 34% of patients with basal transaminases above two times upper limit of normal; versus 16% in controls. Lamivudine inhibits viral DNA which favours cellular immune response. Lamivudine resistance due to variant viruses is observed in 19% of children after one year. Other nucleotide analogues, such as entecavir and adefovir will soon be tested in children, and combination with Lamivudine may improve results. Finally, vaccine technology is being tested in adults, to induce a cellular immune response towards hepatitis B antigens, but no clinical benefit has so far been established.

Antiviral Agents↗
PubMed2000

Predictive value of Epstein-Barr virus genome copy number and BZLF1 expression in blood lymphocytes of transplant recipients at risk for lymphoproliferative disease.

Epstein-Barr virus (EBV) genome numbers and RNA transcripts from the immediate-early EBV gene BZLF1 were monitored by means of polymerase chain reaction in peripheral blood lymphocytes (PBLs) of 44 children who received liver transplants. The 2 tests were compared, using several parameters to assess their value as predictors of posttransplantation lymphoproliferative disease (PTLD). All patients were infected with EBV. BZLF1 mRNA was positive in 70% of patients, with highest expression in those with largest virus load. Four patients developed PTLD that could not be unequivocally diagnosed by any of the parameters considered alone. Sensitivity of EBV genome number (>/=40,000 EBV copies/10(5) PBLs) and BZLF1 mRNA (BZLF1:glyceraldehyde-3-phosphate-dehydrogenase ratio >/=0.5) was 100%. Specificity of each of the 2 tests alone (98% and 58%, respectively) improved (to 100% and 83%, respectively) when measurement of serum IgG level was included. Because decreased virus load, but not BZLF1 mRNA expression, accurately predicted favorable responses of PTLD to therapy, monitoring of EBV genome numbers alone appears sufficient in children with liver transplants.

Adolescent↗
PubMed2000

Indications and results of chemotherapy in children with posttransplant lymphoproliferative disease after liver transplantation.

Among 39 posttransplant lymphoproliferative diseases (PTLD) in a cohort of 450 pediatric liver transplant recipients, 3 had a malignant lymphoma, unresponsive to arrest of immunosuppression and to gancyclovir, interferon, and anti-interleukin 6 antibodies. Lymphoma appeared 20, 46, and 96 months posttransplantation and 16, 43, and 90 months after primary Epstein-Barr virus infection. In one case, the patient had histological progression from plasmacytic hyperplasia PTLD, concomitant with symptomatic primary infection, to Burkitt-like lymphoma 43 months later. These three patients received five courses of chemotherapy, after a cyclophosphamide, doxorubicin, vincristine, and prednisone regimen for Burkitt-like or LH 89 scheme for Hodgkin-like PTLDs. Chemotherapy was well tolerated, and all three were free of disease and without immunosuppression 19, 14, and 4 months after chemotherapy. In Burkitt-like or Hodgkin-like PTLDs, immunomodulatory or antiviral drugs were inefficient. Chemotherapy is indicated and can be safely and successfully used. Long-term arrest of immunosuppression seems feasible without graft rejection.

Antineoplastic Agents↗
PubMed2000

Unusual early presentation of Gilbert syndrome in pediatric recipients of liver transplantation.

BACKGROUND: Gilbert syndrome as a rule becomes manifest in adolescence or in early adulthood; it may be transferred by the donor to orthotopic liver transplant (OLT) recipients. METHODS: We examined the frequency of Gilbert syndrome in 46 OLT pediatric recipients who had a follow-up of 1 year or more. Diagnostic criteria included unexplained chronic or recurrent unconjugated hyperbilirubinemia; its increase after reduced caloric intake plus prolonged fasting, without changes of the proportion of conjugated bilirubin; and high relative amounts of serum unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide. RESULTS: Of the 46 patients, 42 had normal bilirubin values. Only four otherwise healthy OLT recipients showed hyperbilirubinemia and normal conjugated fractions. Liver donors had been four men. Hyperbilirubinemia persisted with a fluctuating pattern for the whole follow-up after OLT in all. Total bilirubin level in blood samples obtained after reduced caloric intake and prolonged fasting became notably higher than basal values, whereas the proportion of conjugated bilirubin remained stable. High relative amounts of unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide were found. Finally, DNA from liver donors' lymphocytes was available for one jaundiced and two nonjaundiced patients: tests for abnormalities in the promoter region of the gene for the enzyme bilirubin uridine diphospho-glucuronosyltransferase were in agreement with a diagnosis of GS in the former one, CONCLUSIONS: Gilbert syndrome may have an unusual early presentation in pediatric OLT recipients.

Age Factors↗
PubMed1999

Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts.

STUDY DESIGN: Between July 1993 and March 1997, 110 children were listed for primary elective liver transplantation with cadaveric (Cad: n = 68) or living-related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and surgical and immunologic complications were retrospectively compared in both groups. RESULTS: The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of 42 in the Cad and LR groups, respectively (P =.049). Postliver transplantation 1-year patient and graft survival rates were 87% and 75% in the Cad group (n = 49) versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of post-transplant complications was as follows: hepatic artery thrombosis (Cad: 16%; LR: 0%, P =.020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary complications (Cad: 14%; LR: 34%, P =.044). The overall incidence of acute rejection was similar in both groups; however, a lower incidence of acute rejection occurred in LR graft recipients treated with tacrolimus. CONCLUSIONS: The introduction of an LR donor liver transplantation program allowed a significant decrease in the pretransplant mortality rate, with a consequent overall improvement in patient survival compared with the Cad series. The incidence of biliary complications was higher in the LR series, whereas better human leukocyte antigen matching in this subgroup did not result in a lower rejection incidence.

Adolescent↗