Long-term survival after choriocarcinoma transmitted by liver graft: A successful report in pediatric transplantation.

BACKGROUND: LT is the standard of care for many pediatric liver disorders. Although long-term outcomes have improved, some rare complications such as transmission of occult donor tumors have been reported. CASE REPORT: An adolescent diagnosed with tyrosinemia was submitted to LT from a previous healthy donor due to HCC. Almost 8 months after LT, the patient presented a nodular hepatic lesion. Clinically, he had mild weight loss, lower limb edema, and gynecomastia. Thorax CT found lesions in the left lung parenchyma, which showed no increased uptake in PET SCAN. Liver biopsy revealed a carcinoma with desmoplastic stroma. ISS was withdrawn, and palliative chemotherapy was started for presumptive HCC relapse. AFP remained normal, but HCG had reached unexpected values of 1984 IU/L. As we requested detailed information about the other organ recipients from the same donor, we found that one of them passed away due to disseminated tumor. Five months after the beginning of chemotherapy, the patient underwent resection of liver segments V and VI. Histological examination confirmed liver metastatic choriocarcinoma. At the time of writing, with 11 years of follow-up, the patient had sustained remission with no signs of relapse. DISCUSSION: This case reports a diagnostic challenge in an adolescent with a particular unique background and a very rare pattern of tumor transmission. The authors aim to highlight the risk of cancer-bearing organs reveled post-LT and to testimony the experience of the successful outcome after a choriocarcinoma transmitted by liver graft.

Is Cholecystectomy Really Harmful? A Long-Term Quality of Life Study in Living Donor Liver Transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) is an accepted option for patients with end-stage liver disease. However, it potentially carries the risk of donor morbi-mortality, as well as long-term functional impairment. Cholecystectomy is performed routinely in the donor intervention, but the long-term effect on gastrointestinal (GI)-related quality of life (QoL) has never been explored previously. This study evaluated living donors' overall, abdominal wall-related, activity-level, and GI-related QoL. MATERIALS AND METHODS: In total, 21 living liver donors (LLD) (57% women, mean age 45 ± 9 years) were compared to a control group (29 patients) undergoing cholecystectomy for gallbladder polyps (45% women, mean age of 46 ± 7 years). LLD and controls (Ctl) were divided into 2 age groups: LLD-Y and Ctl-Y (25-45 years); and LLD-O and Ctl-O (46-65 years). Generic SF-36, Gastrointestinal Quality of Life Index, EuraHS for abdominal wall status assessment, and International Physical Activity Questionnaire were performed. Standard age-adjusted Portuguese population SF-36 scores were used. RESULTS: Global QoL results were better than Portuguese population scores and not inferior when compared to controls, scoring higher in the LLD-Y group in domains as vitality and mental health (P < .05). The abdominal wall impact was minimal among LLD. The activity level was significantly higher in LLD-Y than in Ctl-Y. Overall GI-related QoL was very close to the maximum score, and GI symptoms were significantly less in LLD-O compared with Ctl-O. CONCLUSION: LDLT had no impact on donors' general, abdominal wall-related QoL or activity level. The performance of cholecystectomy apparently had no impact on the development of GI-related symptoms.

Tumor Resection Induces Alterations on Serum Phospholipidome of Liver Cancer Patients.

Hepatocellular carcinoma and cholangiocarcinoma are the most common primary malignant liver tumors. Since the liver plays a key role in lipid metabolism, the study of serum phospholipid (PL) profiles may provide a better understanding of alterations in hepatic lipid metabolism. In this study, we used a high-resolution HILIC-LC-MS lipidomic approach to establish the serum phospholipidome profile of patients with liver cancer before (T0) and after tumor resection (T1) and a control group (CT) of healthy individuals. After the analysis of PL profiles, we observed that the phospholipidome of patients with liver cancer was significantly modified after the tumor resection procedure. We observed an upregulation of some phosphatidylcholine (PtdCho) species, namely, PtdCho(36:6), PtdCho(42:6), PtdCho(38:5), PtdCho(36:5), PtdCho(38:6) and choline plasmalogens (PlsCho), and/or 1-O-alkyl-2-acyl-glycerophosphocholine (PakCho) in patients with liver cancer at T0 compared to the CT group, and a downregulation after tumor resection (T1) when compared to T0. These results show that LC-MS can detect different serum PL profiles in patients with liver cancer, before and after tumor resection, by defining a specific PL fingerprint that was used to determine the effect of tumor and tumor resection on lipid metabolism.

Mild hypothermia during the reperfusion phase protects mitochondrial bioenergetics against ischemia-reperfusion injury in an animal model of ex-vivo liver transplantation-an experimental study.

The organ preservation paradigm has changed following the development of new ways to preserve organs. The use of machine perfusion to preserve organs appears to have several advantages compared with conventional static cold storage. For liver transplants, the temperature control provided by machine perfusion improves organ preservation. In this experimental study, we measured the effects of different temperatures on mitochondrial bioenergetics during the reperfusion phase. An experimental model of ex-vivo liver transplantation was developed in Wistar rats (Rattus norvegicus). After total hepatectomy, cold static preservation occurred at 4ºC and reperfusion was performed at 37ºC and 32ºC using a Langendorff system. We measured parameters associated with mitochondrial bioenergetics in the livers. Compared with the livers that underwent normothermic reperfusion, mild hypothermia during reperfusion caused significant increases in the mitochondrial membrane potential, the adenosine triphosphate content, and mitochondrial respiration, and a significant reduction in the lag phase (all P < 0.001). Mild hypothermia during reperfusion reduced the effect of ischemia-reperfusion injury on mitochondrial activity in liver tissue and promoted an increase in bioenergetic availability compared with normothermic reperfusion.

Leiomyomatosis peritonealis disseminata: a rare disease with a difficult diagnosis.

Leiomyomatosis peritonealis disseminata (LPD) is a rare condition, characterised by the proliferation of peritoneal smooth muscle nodules. LPD is a benign disease with a low rate of malignant degeneration. We describe the case of a 46-year-old, asymptomatic, woman presenting with a mass on the left renal hilum, identified by ultrasound. A CT scan showed three nodules near the left kidney, a mass anterior to the vena cava and bilateral iliac nodules. Biopsy revealed a mesenchymal low-grade tumour. The patient underwent a left nephrectomy and excision of the other masses. The histological diagnosis revealed smooth muscle nodular proliferation with no malignant features, compatible with LPD. The differential diagnosis between LPD and metastatic leiomyosarcoma is sometimes very difficult because they are clinically very similar and even on histology the diagnosis can be tricky. Treatment is conservative in most cases, with surgical excision reserved for high-risk patients.

Functional Impairment of Circulating FcεRI+ Monocytes and Myeloid Dendritic Cells in Hepatocellular Carcinoma and Cholangiocarcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. METHODS: In this study, we have functionally characterized, by flow cytometry, circulating myeloid dendritic cells (mDCs) and FcεRI+ monocytes in a group of healthy individuals (n = 10) and in a group of patients with HCC (n = 19) and CCA (n = 8), at the time point of the surgical resection (T0) and once the patient had recovered from surgery (T1). Moreover, we proceeded to a more in depth phenotypic characterization of the FcεRI+ monocyte subpopulation. RESULTS: A significant decrease in the frequency of TNFα producing FcεRI+ monocytes and mDCs in HCC and CCA patients when compared to the group of healthy individuals was observed, and a close association between FcεRI+ monocytes and mDCs dysfunction was identified. In addition, the phenotypic characteristics of FcεRI+ monocytes from healthy individuals strongly suggest that this population drives to mDCs, which matches with the fact that both populations are functionally affected. CONCLUSIONS: The frequency and the function of circulating mDCs and FcεRI+ monocytes are affected in both HCC and CCA patients, and FcεRI+ monocytes could represent those fated to become mDCs. © 2019 International Clinical Cytometry Society.

Evaluation of bioenergetic and mitochondrial function in liver transplantation.

BACKGROUND/AIMS: We measured changes in mitochondrial function and bioenergetics that occur during ischemia/ reperfusion in fresh liver samples of patients undergoing liver transplantation. These variations correlated with markers of liver function and clinical outcome. Ischemia/reperfusion injury related to liver transplantation affects mitochondrial function and bioenergetics. Experimental studies were conducted to identify the role of bioenergetics and mitochondrial dysfunction. To the best of our knowledge, no investigation of these two factors' impacts on liver transplantation has been performed. METHODS: This was a prospective study of 28 patients who underwent liver transplantation. We measured parameters of mitochondrial function and bioenergetics in biopsies performed during the procedure. RESULTS: We observed a statistically significant reduction in mitochondrial membrane potential, an increase in lag phase, and decreases in mitochondrial respiration and adenosine triphosphate content (P<0.010). Higher postoperative aminotransferase peaks correlated with worse mitochondrial function; mitochondrial respiration correlated with arterial lactate (P<0.010). CONCLUSION: There is a relationship between mitochondrial function and ischemia/reperfusion injury. The future use of these clinical markers as prognostic factors may allow early identification of post-transplant liver failure and may indicate the need to perform a new transplant.

Pacemaker implantation in familial amyloid polyneuropathy: when and for whom?

BACKGROUND: Despite the important role of cardiac pacing in preventing syncope and sudden cardiac death in familial amyloid polyneuropathy (FAP), we lack clear guidelines as to the ideal timing and indications for permanent pacemaker implantation. PURPOSE: The purpose of this study was to evaluate the ideal timing for pacemaker implantation in FAP patients submitted to liver transplantation. METHODS: Retrospective study of 258 FAP patients submitted to liver transplantation between 1992 and 2012. Comparison of three groups: (A) patients without pacemaker (N = 122); (B) patients submitted to pacemaker implantation after liver transplantation, with documented conduction disorders (N = 73); and (C) patients submitted to "prophylactic" pacemaker implantation before transplantation, (N = 73). Patients were followed up for 12.2 ± 6.7 years. RESULTS: The majority of patients (57%) were referred for pacemaker implantation, which occurred before liver transplantation in 50% of cases. Patients who required pacemaker after transplantation presented significantly higher Machado-Joseph Score during pre-transplant evaluation than those who did not require pacemaker (24 ± 10 vs 20 ± 10, p = .025), and also exhibited higher levels of hepatic cytolysis enzymes and hyperbilirubinemia. The most common indication for permanent pacemaker was first degree atrioventricular block, with a mean time between transplantation and pacemaker implantation of 8.7 ± 4.2 years. During long-term follow-up, all-cause mortality was 27% and was lowest in the group submitted to pacemaker implantation only after liver transplantation (p = 0.002). CONCLUSION: The majority of FAP patients submitted to liver transplantation will need a pacemaker at some time of follow-up. However, it seems that there is no benefit in "prophylactic" cardiac pacing before liver transplantation.

Successful liver transplantation using a whole liver graft with gallbladder agenesis: First report in pediatric liver transplantation.

INTRODUCTION: Gallbladder agenesis (GA) is a rare congenital condition, occurring in approximately 40/100.000. It is likely due to an embryologic mishap in the development of the gallbladder bud and can be associated with other congenital variations in biliary anatomy. However, the liver likely suffers no functional impairment and can be safely used for transplantation. To the best of our knowledge, this is the first case report describing a pediatric liver transplantation (PLT) using a graft with GA. CASE REPORT: A 10-year-old boy with methylmalonic aciduria underwent isolated liver transplant with a deceased graft from a donor with no relevant medical or surgical history and normal laboratory tests. During the back-table liver preparation procedure, no evidence of gallbladder was found, raising the possibility of a GA, confirmed by intraoperative cholangiography. The liver transplantation procedure was uneventful despite the particularly rare combination of biliary tree anatomic distribution found in the cholangiography. At 1 year of follow-up, there were no clinical, laboratory, or imagological signs of bile leaks or anastomotic site stricture. DISCUSSION: The present report highlights the importance of the accurate knowledge of the vasculobiliary anatomic variation, particularly in extremely rare cases, such as GA, and in complex hepatobiliary procedures, such as PLT. In our opinion, grafts with GA should not be discarded for transplantation.

Efficacy of Endoscopic Retrograde Cholangiopancreatography in the Treatment of Biliary Complications following Liver Transplant: 10 Years of a Single-Centre Experience.

BACKGROUND AND AIMS: Biliary tract complications following liver transplant remain an important source of morbidity and mortality. Endoscopic retrograde cholangiopancreatography (ERCP) has become a common therapeutic option before other invasive procedures. The aim of this study was to evaluate ERCP efficacy in managing this type of complications. METHODS: Retrospective study of all patients who underwent therapeutic ERCP due to post-liver transplant biliary complications between September 2005 and September 2015, at a deceased donor liver transplantation centre. RESULTS: Therapeutic ERCP was performed in 120 patients (64% men; mean age 46 ± 14 years). Biliary complications were anastomotic strictures (AS) in 70%, non-anastomotic strictures (NAS) in 14%, bile leaks (BL) in 5.8%, and bile duct stones (BDS) in 32%. The mean time between liver transplant and first ERCP was: 19 ± 30 months in AS, 17 ± 30 months in NAS, 61 ± 28 months in BDS, and 0.7 ± 0.6 months in BL (p < 0.001). The number of ERCP performed per patient was: 3.8 ± 2.4 in AS, 3.8 ± 2.1 in NAS, 1.9 ± 1 in BDS, and 1.9 ± 0.5 in BL (p = 0.003). The duration of the treatment was: 18 ± 19 months in AS, 21 ± 17 months in NAS, 10 ± 10 months in BDS, and 4 ± 3 months in BL (p = 0.064). Overall, biliary complications were successfully managed by ERCP in 46% of cases, either as an isolated procedure (43%) or rendez-vous ERCP (3%). Per complication, ERCP was effective in 39% of AS, in 12% of NAS, in 91% of BDS, and in 86% of BL. Globally, the mean follow-up of the successful cases was 43 ± 31 months. Percutaneous transhepatic cholangiography and/or surgery were performed in 48% of patients in whom ERCP was unsuccessful. The odds ratio for effective endoscopic treatment was 0.2 for NAS (0.057-0.815), 12.4 for BDS (1.535-100.9), and 6.9 for BL (0.798-58.95). No statistical significance was found for AS (p = 0.247). CONCLUSIONS: ERCP allowed the treatment of biliary complication in about half of patients, avoiding a more invasive procedure. Endoscopic treatment was more effective for BDS and BL.

INTRODUÇÃO: As complicações biliares após transplante hepático são uma fonte importante de morbilidade e mortalidade. A colangiopancreatografia retrógrada endoscópica (CPRE) é a primeira opção de tratamento em muitos casos, previamente a procedimentos mais invasivos. O objetivo deste trabalho foi avaliar a eficácia da CPRE no tratamento destas complicações. DOENTES E MÉTODOS: Estudo retrospetivo de todos os doentes submetidos a CPRE terapêutica devido a complicações biliares após transplante hepático, entre setembro de 2005 e setembro de 2015. RESULTADOS: Incluídos 120 doentes submetidos a CPRE terapêutica, sendo 64% do sexo masculino, com idade média de 46 ± 14 anos. Complicações biliares: estenose da anastomose (EA) em 70%, estenose não anastomótica (ENA) em 14%, coledocolitíase em 32% e fuga biliar (FB) em 5,8%. Tempo entre transplante e primeira CPRE (meses): 19 ± 30 nas EA, 17 ± 30 nas ENA, 61 ± 28 na coledocolitíase e 0,7 ± 0,6 na FB (p < 0,001). Número de CPRE por doente: 3,8 ± 2,4 nas EA, 3,8 ± 2,1 nas ENA, 1,9 ± 1 na coledocolitíase e 1,9 ± 0,5 na FB (p = 0,003). Duração do tratamento (meses): 18 ± 19 nas EA, 21 ± 17 nas ENA, 10 ± 10 na coledocolitíase e 4 ± 3 nas FB (p = 0,064). Globalmente, a CPRE terapêutica foi eficaz em 46% dos casos (como procedimento isolado em 43% e por rendez-vous em 3%). Eficácia por complicação: 39% nas EA, 12% nas ENA, 91% na coledocolitíase e 86% nas FB. O tempo médio de follow-up foi de 43 ± 31 meses. Em 48% dos doentes, foi realizada terapêutica por colangiografia percutânea e/ou cirurgia por ineficácia da CPRE. Odds ratio para um tratamento endoscópico eficaz: 0,2 para ENA (0,057­0,815), 12,4 para coledocolitíase (1,535­100,9) e 6.9 para FB (0,798­58,95). Não houve diferenças estatisticamente significativas para a presença de uma EA. CONCLUSÕES: A CPRE foi eficaz no tratamento de complicações biliares após transplante hepático em cerca de metade dos casos, evitando outros procedimentos invasivos. O tratamento endoscópico foi particularmente eficaz em casos de coledocolitíase e FB.

Recent insights into mitochondrial targeting strategies in liver transplantation.

Ischemia/reperfusion (I/R) injury in liver transplantation can disrupt the normal activity of mitochondria in the hepatic parenchyma. This potential dysfunction of mitochondria after I/R injury could be responsible for the initial poor graft function or primary nonfunction observed after liver transplantation. Thus, determining the mechanisms that lead to human hepatic mitochondrial dysfunction might contribute to improving the outcome of liver transplantation. Furthermore, early identification of novel prognostic factors involved in I/R injury could serve as a key endpoint to predict the outcome of liver grafts and also to promote the early adoption of novel strategies that protect against I/R injury. Here, we briefly review recent advances in the study of mitochondrial dysfunction and I/R injury, particularly in relation to liver transplantation. Next, we highlight various pharmacological therapeutic strategies that could be applied, and discuss their relationship to relevant mitochondrion-related processes and targets. Lastly, we note that although considerable progress has been made in our understanding of I/R injury and mitochondrial dysfunction, further investigation is required to elucidate the cellular and molecular mechanisms underlying these processes, thereby identifying biomarkers that can help in evaluating donor organs.

Addition of Berberine to Preservation Solution in an Animal Model of Ex Vivo Liver Transplant Preserves Mitochondrial Function and Bioenergetics from the Damage Induced by Ischemia/Reperfusion.

Liver transplantation is a therapeutic regimen to treat patients with non-malignant end-stage liver diseases and malignant tumors of hepatic origin. The ischemia/reperfusion (I/R) injury in liver transplantation is associated with disruption of mitochondrial function in the hepatic parenchyma. Several studies have been conducted in animal models to identify pharmacological therapeutic strategies to minimize the injury induced by the cold/warm I/R in liver transplantation. Most of these studies were conducted in unrealistic conditions without the potential to be translated to clinical usage. Berberine (BBR) is a pharmacological compound with a potential protective effect of the mitochondrial function in the context of I/R. For the future clinical application of these pharmacological strategies, it is essential that a close resemblance exists between the methodology used in the animals models and real life. In this study, we have demonstrated that the addition of BBR to the preservation solution in an I/R setting preserves mitochondrial function and bioenergetics, protecting the liver from the deleterious effects caused by I/R. As such, BBR has the potential to be used as a pharmacological therapeutic strategy.

Survival of children after liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.

Auxiliary Liver Transplantation as a Transient Treatment for Acute Liver Failure: Two Cases.

INTRODUCTION: Acute liver failure is an uncommon condition associated with a high mortality. Most patients do not survive without liver transplantation. In the last decades, auxiliary liver transplantation has emerged as a therapeutic option. CLINICAL CASE: The authors present two cases of acute liver failure that required liver transplantation. Given the patients' young age and the preserved macroscopic liver pattern evaluated in surgery, auxiliary liver transplantation was executed using different surgical approaches. Afterwards, following confirmed full native liver regeneration, the patients were submitted to auxiliary liver hepatectomy, which was accomplished without complications. CONCLUSION: Auxiliary liver transplantation can be regarded as an effective temporary treatment for acute liver failure in selected cases, allowing an immunosuppression-free life.

INTRODUÇÃO: A falência hepática aguda é uma entidade clínica pouco comum, mas associada a elevada mortalidade. A maioria dos doentes não sobreviverá sem transplante hepático. Nas últimas décadas, o transplante hepático auxiliar tem sido utilizado como uma opção terapêutica valorizável. CASO CLÍNICO: Apresentam-se dois casos de falência hepática aguda tratados com transplante hepático. Tendo em conta a idade jovem dos doentes e a noção de preservação macroscópica do fígado, recorreu-se à opção de transplante hepático auxiliar utilizando técnicas diferentes. Posteriormente, após confirmação de regeneração hepática completa, procedeu-se à hepatectomia do fígado auxiliar. CONCLUSÃO: O transplante hepático auxiliar constitui uma terapêutica transitória eficaz em alguns casos de falência hepática aguda, permitindo um futuro isento de imunossupressão.

Combined liver and kidney transplantation in two women with primary hyperoxaluria: Different roads led to different outcomes / Trasplante combinado de hígado y riñón en dos pacientes con hiperoxaluria primaria - quando diferentes caminos conducen a diferentes resultados

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[The Importance of Early Referral in Pediatric Acute Liver Failure]. / A Importância da Referenciação Precoce na Falência Hepática Aguda Pediátrica.

INTRODUCTION: Acute liver failure is a rare disorder associated to high morbidity and mortality despite survival improvement through liver transplantation. The importance of a multidisciplinary approach and early referral to a pediatric liver transplantation center were important conclusions of a national meeting in 2008, from which resulted an actuation consensus. OBJECTIVES: To characterize acute liver failure admissions in a Pediatric Intensive Care Unit of the portuguese pediatric livertransplantation center. To compare results before (A) and after (B) 2008. MATERIAL AND METHODS: Observational, retrospective study during a 20 year period (1994-2014). INCLUSION CRITERIA: age < 18 years old and acute liver failure (INR ≥ 2 without vitamin K response and hepatocellular necrosis). Children with previous liver disease were excluded. RESULTS: Fifty children were included, with median age of 24.5 months. The most common etiology under 2 years old was metabolic (34.6%) and above that age was infectious (29.2%). Forty six percent were submitted to liver transplantation and 78% of them survived. Overall mortality was 34%. Median referral time was 7 days in period A (n = 35) and 2 days in period B (n = 15; p = 0.006). Pediatric risk of mortality's median was 14.7 in period A and 6.5 in B (p = 0.019). Mortality was 37% vs 26% in periods A and B, respectively (p = 0.474). DISCUSSION AND CONCLUSIONS: Overall mortality was similar to the observed in other European centers. Liver transplantation is in fact the most effective therapeutic option. After 2008, there was a reduction in referral time and cases severity on admission; however, mortality has not reduced so far.

Introdução: A falência hepática aguda é uma doença rara associada a elevada morbilidade e mortalidade apesar do aumento da sobrevida devido ao transplante hepático. Em 2008, decorreu em Portugal uma reunião sobre esta patologia em pediatria, resultando num consenso de atuação que salientou a importância da abordagem multidisciplinar e referenciação precoce para um centro de transplantação hepática. Objetivos: Caracterizar as admissões por falência hepática aguda no Serviço de Cuidados Intensivos Pediátricos do centro português com transplante hepático pediátrico. Comparar resultados antes (A) e depois de 2008 (B). Material e Métodos: Estudo observacional retrospetivo de 20 anos (1994-2014). Critérios de inclusão: idade < 18 anos e falência hepática aguda (INR ≥ 2 sem resposta à vitamina K e necrose hepatocelular). Excluíram-se as crianças com doença hepática crónica. Resultados: Incluíram-se 50 crianças com idade mediana de 24,5 meses. A causa mais comum de falência hepática aguda abaixo dos 2 anos foi metabólica (34,6%) e acima infeciosa (29,2%). Foram submetidos a transplante hepático 46%, tendo sobrevivido 78%. A mortalidade global foi 34%. A mediana do tempo de referenciação foi 7 dias no período A (n = 35) e 2 no B (n = 15; p = 0,006). A mediana do risco de mortalidade prevista pelo PRISM foi 14,7% no período A e 6,5% no B (p = 0,019). A mortalidade foi 37% vs 26% no período A e B respetivamente (p = 0,474).Discussão e Conclusões: A mortalidade global foi sobreponível à de outros centros europeus, sendo o transplante hepático a opção terapêutica mais eficaz. Após 2008 o tempo de referenciação e a gravidade dos casos na admissão reduziram, ainda sem tradução significativa na mortalidade.

Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years Still the Best Therapeutic Alternative?

BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison. METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry. RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease. CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.