Infections in pediatric patients submitted to hepatic transplant

OBJETIVO: Identificar infecções bacterianas, virais e fúngicas nos primeiros 20 pacientes pediátricos submetidos a transplante de fígado no HCPA. PACIENTES E MÉTODOS: 21 transplantes foram realizados em 20 crianças e adolescentes, no período de março de 1995 a setembro de 1997, no HCPA. Todos os transplantes foram de doador cadavérico, do mesmo grupo sangüíneo ABO. Nove transplantes foram de fígado inteiro e 11, de fígado reduzido. O diagnóstico de infecção bacteriana foi feito quando havia evidências clínico-laboratoriais e/ou hemocultura e/ou outros culturais positivos. Os vírus pesquisados foram citomegalo e Epstein Barr. Fungos eram pesquisados através de hemoculturas e culturas de secreções, drenos e coleções, cateteres e urina. RESULTADOS: Dos 20 pacientes transplantados, dois morreram nas primeiras 24-48 horas e apenas quatro não apresentaram infecção e/ou culturais positivos, clinicamente significativos. Quatorze pacientes apresentaram infecção bacteriana, sendo que nove pacientes apresentaram mais do que um episódio infeccioso. Os organismos mais freqüentes foram Staphylococus aureus e epidermidis e Xantomonas maltophilia. Cinco receptores positivaram antigenemia para CMV, sendo que apenas um apresentava sorologia negativa no pré-transplante. Infecção fúngica foi diagnosticada em dois pacientes e um terceiro paciente apresentou cultura do dreno biliar positiva. CONCLUSÕES: Dos 20 pacientes transplantados, quatro foram ao óbito por complicações infecciosas. Um controle cuidadoso e medidas profiláticas e terapêuticas adequadas podem diminuir infecções e suas conseqüências após transplante hepático.OBJECTIVE: To identify bacterial, viral, and fungal infections in the first 20 pediatric patients submitted to liver transplant at Hospital de Clínicas de Porto Alegre. PATIENTS AND METHODS: Twenty-one liver transplants were performed in 20 infant and adolescent patients from March 1995 to September 1997, at Hospital de Clínicas de Porto Alegre. All transplanted organs were taken from deceased donors with the same ABO blood type as the organ transplant recipient. Nine patients received a whole liver transplant, and 11 patients received a reduced liver transplant. Bacterial infection was diagnosed by the existence of clinical and laboratory evidence; and/or by hemoculture; and/or by positive cultures. For the diagnosis of viral infections, patients were examined for Epstein Barr virus and for cytomegalovirus. For the diagnosis of fungal infection, hemocultures and secretion cultures were taken, and patients were also submitted to draining and sample collections, such as urine samples using a catheter. RESULTS: Of the 20 organ transplant recipient patients, two died within the first 24- 48 hours, and only four of the patients did not present any infections and/or positive cultures that were clinically significant. Fourteen patients had bacterial infection, and nine patients had more than one case of infection. The most frequently found organisms were Staphylococus aureus and epidermidis, and Xanthomonas maltophilia. Five transplant recipients were positive for cytomegalovirus antigenemia, and only one of these recipients was seronegative before the transplant. Fungal infection was diagnosed in two patients, and a third patient presented a positive culture of the biliary drain. CONCLUSIONS: Of the 20 liver transplant recipients, four died due to infection complications. By exerting a careful control, and establishing appropriate prophylactic and therapeutic measures, infection and its consequences may be reduced

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. Homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC), in contrast to patients with two predicted protein truncating mutations (PPTM). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n=31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n=30), and with two PPTMs (BSEP3/3; n=77). We compared presentation, native liver survival (NLS), and effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (P<0.001). Without siEHC in their follow-up, NLS of BSEP1/3 was similar to BSEP3/3 patients, but considerably lower than BSEP1/1 patients (at age 10 years: 38%, 30%, and 71%, resp; P=0.003). After siEHC, BSEP1/3 and BSEP3/3 patients had similarly low NLS, while this was much higher in BSEP1/1 patients (10 years after siEHC, 27%, 14%, and 92%, resp.; P<0.001). Conclusions: BSEP deficiency patients with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as patients with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment

Resposta de crianças portadoras de síndrome de Down e de hepatopatia crônica a uma vacina inativada (HAVRIX) contra hepatite A

Objetivo: A vacina inativada contra HVA (Havrix) é altamente eficaz e segura em crianças saudáveis. Não há muitos dados disponíveis na literatura sobre a resposta de crianças imunocomprometidas à essa vacina. O objetivo deste estudo foi avaliar a resposta de pacientes pediátricos portadores de Síndrome de Down e de Hepatopatia Crônica à uma vacina inativada contra Hepatite A, comparando suas respostas com as de crianças saudáveis. Casuística e Métodos: Foi realizado um estudo prospectivo, aberto e controlado com 138 crianças e adolescentes, de 1 a 16 anos, suscetíveis à infecção pelo virus A (anti-HVA negativo). Os indivíduos foram divididos em 3 grupos: Grupo I: portadores de Síndrome de Down (n = 49), Grupo II: Hepatopatas Crônicos (n = 34) e Grupo III: controle, composto por crianças saudáveis (n = 55). Todos os indivíduos recebiam 2 doses, nos meses 0 e 6, da vacina Havrix 720 UE , aplicada intramuscular, no deltóide. Um mês após cada dose da vacina, as crianças e os adolescentes eram submetidas à coleta de sangue para realização de titulação de anticorpos anti-HVA. Resultados: As taxas de soroconversão, após a primeira dose da vacina, no mês 1, foram de 92%, 76% e 94% nos grupos I, II e III, respectivamente. Um mês após a segunda dose, as porcentagens de soroconversão foram de 100% x 97% x 100%, para os grupos, na mesma ordem. As médias geométricas dos títulos de anticorpos anti-HVA foram, na primeira e segunda coletas, de 164,02 e 1719,86 mUI/ml nas crianças com Síndrome de Down, de 107,77 e 812,40 mUI/ml nos cirróticos e de 160,77 e 2344,90 mUI/ml, no grupo controle. O grupo dos pacientes cirróticos apresentou diferença estatisticamente significativa em relação às taxas de soroconversão no primeiro mês, após 1 dose da vacina, e aos títulos de anticorpos anti-HVA no final do estudo, quando comparado aos controles saudáveis. Apenas 14% dos indivíduos vacinados apresentaram sintomas locais, como dor e vermelhidão. Cinco porcento apresentaram sintomas gerais. Não ocorreu nenhum efeito adverso sério ou reação imediata à vacina. Os efeitos adversos diminuíram por ocasião da segunda dose.Conclusões: A vacina inativada Havrix, contra Hepatite A, provoca altas taxas de soroconversão e é altamente segura em pacientes pediátricos portadores de Síndrome de Down e de Cirrose. As crianças e adolescentes com Cirrose respondem à vacina inativada anti-HVA com títulos de anticorpos mais baixos do que as crianças saudáveis e do que as portadoras de Síndrome de Down.Objective: The inactivated hepatitis A vaccine (Havrix) is highly immunogenic and safe in healthy children. However, data about the response of immunocompromised children to this vaccine are not very frequent in the literature. The objective of this study was to assess the response of pediatric patients with Down syndrome and chronic liver disease to an inactivated hepatitis A vaccine, and to compare their responses to those of healthy children. Patients and Methods: A prospective, open-label, controlled study was performed with 138 children and adolescents susceptible to hepatitis A virus (anti-HAV negative) with ages between 1 and 16 years. Patients were divided into three groups: Group I, Down syndrome patients (n = 49); Group II, patients with chronic liver disease (n = 34); and Group III, healthy children/controls (n = 55). All patients and controls received two intramuscular doses of Havrix 720 UE in the deltoid muscle at months 0 and 6. One month after each dose, patients underwent blood collection for the assessment of anti-HAV titers. Results: Seroconversion rates after the first dose (month 1) were 92%, 76%, and 94% in Groups I, II, and III, respectively; one month after the second dose, these percentages were 100%, 97%, and 100%. Geometric mean titers were 164.02 and 1719.86 mUI/ml in the first and second collections for Down syndrome children; 107.77 and 812.40 mUI/ml for cirrhotic patients; and 160.77 and 2344.90 mUI/ml for controls. The group of cirrhotic patients presented a statistically significant difference in seroconversion rates at month 1, and in anti-HAV titers in the end of the study when compared to healthy controls. Only 14% of the vaccinated individuals presented local symptoms, such as pain and redness; 5% presented general symptoms. No severe adverse effects or immediate reaction to the vaccine were observed. The occurrence of adverse reactions was lower in the application of the second dose. Conclusions: The inactivated hepatitis A vaccine (Havrix) presents high rates of seroconversion and is highly safe in pediatric patients with Down syndrome and cirrhosis. Cirrhotic children and adolescents have responded to the inactivated hepatitis A vaccine with lower antibody titers when compared to healthy children and Down syndrome