Outcomes of adults who received liver transplant as young children.

BACKGROUND: Patient and graft survival 20-years after pediatric liver transplantation (pLT) are excellent. In children, attainment of normal growth, education and social adaptation to be an independent adult are equally important. This is particularly relevant for children who receive liver transplant at a young age, where infantile-onset liver disease, surgery and immunosuppression can adversely affect growth and neurodevelopment. The aim of this study was to evaluate the long-term physical and psychosocial outcomes of pLT recipients with normal graft function. We coin the term 'meaningful survival'. METHODS: We performed a cross-sectional study of pLT recipients who received transplants between 1985 and 2004. A 20-year evaluation of physical health (growth, renal function), mental wellbeing and social outcomes (substance abuse, adherence, education, employment) was performed. All patients included were considered to have normal graft function. FINDINGS: Eighty-four patients met study criteria. Median age at transplantation was 1.3 years (IQR 0·7-3·3 years), with median duration of follow-up of 20.2 years (18·0-23·5). At median of 20-years, 19 patients (23%) had chronic renal dysfunction and 3 patients (4%) had a BMI of >30 (mean 20·4). Evaluation of long-term psychosocial outcomes demonstrated 22 patients (26%) with mental health disorders. Substance abuse was lower than national average. 62 patients (74%) were in education, employment or training. Overall, only 26% of our cohort achieved a composite outcome of 'meaningful survival'. INTERPRETATION: This is the largest reported long-term study of biopsychosocial outcomes of pLT recipients with normal liver biochemistry, with follow-up upon completion of physical growth and senior school education. Importantly, despite normal liver function, many patients did not demonstrate 'meaningful survival'. We must refocus our efforts towards better understanding the long-term outcomes of children. A 'meaningful survival' rather than mere survival should be our goal. FUNDING: None.

Molecular profiling of subclinical inflammatory lesions in long-term surviving adult liver transplant recipients.

BACKGROUND & AIMS: Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. METHODS: All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. RESULTS: Median time since transplantation to liver biopsy was 13 years (10-22). The most frequently observed histological abnormality was portal inflammation with different degrees of fibrosis, present in 45 biopsies (67%). Two modules of 102 and 425 co-expressed genes were significantly correlated with portal inflammation, interface hepatitis and portal fibrosis. These modules were enriched in molecular pathways known to be associated with T cell mediated rejection. Liver allografts showing the highest expression levels for the two modules recapitulated the transcriptional profile of biopsies with clinically apparent rejection and developed progressive damage over time, as assessed by non-invasive markers of fibrosis. CONCLUSIONS: A large proportion of adult liver transplant recipients who survive long-term exhibit subclinical histological abnormalities. The transcriptomic profile of these patients' liver tissue closely resembles that of T cell mediated rejection and may result in progressive allograft damage. LAY SUMMARY: A large proportion of adult liver transplant recipients who survive for a long time exhibit subclinical histological abnormalities. The expression profile (a measurement of the activity of genes) of liver tissue from a large fraction of these patients closely resembles the profile of T cell mediated rejection. Liver allografts showing the highest expression levels of rejection-related genes developed progressive damage over time.

Pigmented well-differentiated hepatocellular neoplasm with beta-catenin mutation.

According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the beta-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcinomas. We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver. The patient was a 48-year-old woman, who was asymptomatic, and had a clinical history of intra-uterine exposure to diethylstilbestrol, previous cancers and past oral contraceptive use. The recently proposed term "well-differentiated hepatocellular neoplasm of uncertain malignant potential" should be applied in such cases to highlight the different pathogenesis and risk of malignancy compared to the typical adenomas, and to suggest a careful and customized clinical management.

Papel do preceptor da atenção primária em saúde na formação da graduação e pós-graduação da Universidade Federal de Pernambuco: um termo de referência / The primary health care preceptor in undergraduate and graduate training at Pernambuco Federal University: a reference term

O objetivo principal deste artigo é apresentar uma orientação teórica e prática aos preceptores da atenção primária à saúde vinculados à Universidade Federal de Pernambuco. Pressupõe a atenção primária à saúde como um cenário de prática para estudantes de diferentes graduações e pós-graduações com características próprias. Aborda aspectos importantes do processo ensino-aprendizagem no ambiente comunitário, articulando os diferentes atores deste, entre os quais o conceito de conhecimento na atenção primária; a relação preceptor-estudante; a correlação teoria e prática; a avaliação processual; o ensino e a pesquisa no trabalho; a inserção político-social da aprendizagem; a interdisciplinaridade; o trabalho em equipe e a interinstitucionalidade na integração ensino-serviço. Por fim, propõe a reintegração do espaço da educação, da pesquisa e do trabalho.

This article aims to present a theoretical and practical guideline to primary health care preceptors connected to the Pernambuco Federal University. Primary health care is presumed as a practical setting for students of different undergraduate and graduate courses, with their own characteristics. Important aspects of the teaching-learning process in the community are addressed, including the concept of knowledge in primary care; the preceptor-student relationship; theory-practice correlation; procedural assessment; education and research at work; socio-political context of learning; interdisciplinarity; teamwork and cross-institutional service-learning integration. Finally, it proposes the reintegration of the learning, research and work space.