Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis.

Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).

A portable single-sided magnetic-resonance sensor for the grading of liver steatosis and fibrosis.

Low-cost non-invasive diagnostic tools for staging the progression of non-alcoholic chronic liver failure from fatty liver disease to steatohepatitis are unavailable. Here, we describe the development and performance of a portable single-sided magnetic-resonance sensor for grading liver steatosis and fibrosis using diffusion-weighted multicomponent T2 relaxometry. In a diet-induced mouse model of non-alcoholic fatty liver disease, the sensor achieved overall accuracies of 92% (Cohen's kappa, κ = 0.89) and 86% (κ = 0.78) in the ex vivo grading of steatosis and fibrosis, respectively. Localization of the measurements in living mice through frequency-dependent spatial encoding led to an overall accuracy of 87% (κ = 0.81) for the grading of steatosis. In human liver samples, the sensor graded steatosis with an overall accuracy of 93% (κ = 0.88). The use of T2 relaxometry as a sensitive measure in fully automated low-cost magnetic-resonance devices at the point of care would alleviate the accessibility and cost limits of magnetic-resonance imaging for diagnosing liver disease and assessing liver health before liver transplantation.

Complications of Peripherally Inserted, Large-Bore, Rapid-Infusion Catheters in Orthotopic Liver Transplant Patients.

BACKGROUND: At our institution, peripherally inserted, 8.5-French rapid-infusion catheters (RICs) are placed for high-flow administration of intravenous fluids and blood products during liver transplant (LT). We sought to estimate the incidence of RIC placement-associated complications in LT patients. METHODS: Electronic health records of all patients who underwent LT from January 2008 through December 2017 were retrospectively reviewed. RIC-related complications were deemed clinically significant if they required surgical consultation or intervention due to infiltration. Univariable and multivariable logistic regression analyses were used to evaluate associations between patient characteristics and RIC complications. RESULTS: In total, 839 LT patients who received RICs were identified; of these, 14 (1.67%) had RIC-related complications, and 7 (0.83%) required surgical consultation. No patients needed fasciotomy or wound débridement due to a RIC complication, and no patients had permanent sequelae. In the multivariable logistic regression analysis, only an increase in international normalized ratio (INR) from 1.4 to 2.2 (equivalent to the interquartile range of observed INR values) increased the odds of complications due to RIC placement (odds ratio [95% CI], 1.98 [1.10-3.56]; P = .02). CONCLUSIONS: We observed a low incidence of perioperative RIC-related complications (1.7%). No patients had permanent RIC-related complications.

Biliary Internal Stents and Biliary Complications in Adult Liver Transplantation.

BACKGROUND: Biliary complications in liver transplantation (LT) can cause significant morbidity or even lead to a potential graft loss and patient mortality. Oftentimes biliary internal stents (ISs) are used at the time of LT to lower the risk for or prevent these biliary complications; however, their efficacy and outcomes remain controversial. METHODS: A retrospective cohort study was conducted on all of the adult patients who underwent a deceased-donor LT (DDLT) with an end-to-end choledococholedocostomy. An IS was placed across the biliary anastomosis, passing through the ampulla. We compared the demographic profiles and various outcomes between the 2 groups (no-IS group vs IS group) and examined risk factors associated with anastomotic biliary complications. RESULTS: The study comprised 350 patients in the no-IS group and 132 patients in the IS group. Anastomotic biliary fistula (ABF) occurred in 5 (1.4%) and 1 (0.8%) patients in the no-IS group and the IS group, respectively (P = .55). Anastomotic biliary stricture (ABS) occurred in 53 (15.1%) and 18 (13.6%) patients, respectively (P = .68). No significant difference was found in the overall biliary complications between the 2 groups (P = .33). In multivariate logistic regression analysis, acute rejection was the only risk factor for ABS (P = .02). One biliary complication-induced mortality occurred in the no-IS group in which the patient died of an ABF-induced hepatic artery pseudoaneurysm rupture. CONCLUSION: The use of biliary ISs in DDLT did not reduce the overall risk for biliary complications, but more research is needed to draw definite conclusions.

Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial.

With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT.

Biomarkers of Liver Injury during Transplantation in an Era of Machine Perfusion.

Liver ischaemia-reperfusion injury (IRI) is an intrinsic part of the transplantation process and damages the parenchymal cells of the liver including hepatocytes, endothelial cells and cholangiocytes. Many biomarkers of IRI have been described over the past two decades that have attempted to quantify the extent of IRI involving different hepatic cellular compartments, with the aim to allow clinicians to predict the suitability of donor livers for transplantation. The advent of machine perfusion has added an additional layer of complexity to this field and has forced researchers to re-evaluate the utility of IRI biomarkers in different machine preservation techniques. In this review, we summarise the current understanding of liver IRI biomarkers and discuss them in the context of machine perfusion.

Living donor liver transplantation in situs inversus totalis with a patient-specific three-dimensional printed liver model.

We utilized patient-specific 3D liver models based on preoperative computed tomography images as intraoperative navigation and describe our experience. A 1-year and 10-month-old girl with situs inversus totalis underwent living donor liver transplantation for biliary atresia. Information on the hepatic artery, portal vein, inferior vena cava, and liver parenchyma was extracted and segmented from computed tomography images using liver analysis software. Laser lithography produced each 3D part of the liver from these data. The 3D models of each part of the liver were molded from polyurethane resin using different colors for each part and combined together, resulting in a patient-specific liver model. The industrial computed tomography scan of the patient-specific 3D liver model revealed that the gaps between the liver model and the original data were <0.4 mm in the 90% area, <0.8 mm in the 98% area, and 1.53 mm at the maximum. The 3D liver model was brought into the operative field and used as intraoperative navigation for total liver resection. The procedure was finished successfully without any major intraoperative complications. In conclusion, the 3D model facilitates the identification of vessels during operations; it is possible to promptly share patients' anatomy with the operative team.

From in vitro evaluation to human postmortem pre-validation of a radiopaque and resorbable internal biliary stent for liver transplantation applications.

The implantation of an internal biliary stent (IBS) during liver transplantation has recently been shown to reduce biliary complications. To avoid a potentially morbid ablation procedure, we developed a resorbable and radiopaque internal biliary stent (RIBS). We studied the mechanical and radiological properties of RIBS upon in vivo implantation in rats and we evaluated RIBS implantability in human anatomical specimens. For this purpose, a blend of PLA50-PEG-PLA50 triblock copolymer, used as a polymer matrix, and of X-ray-visible triiodobenzoate-poly(ε-caprolactone) copolymer (PCL-TIB), as a radiopaque additive, was used to design X-ray-visible RIBS. Samples were implanted in the peritoneal cavity of rats. The radiological, chemical, and biomechanical properties were evaluated during degradation. Further histological studies were carried out to evaluate the degradation and compatibility of the RIBS. A human cadaver implantability study was also performed. The in vivo results revealed a decline in the RIBS mechanical properties within 3 months, whereas clear and stable X-ray visualization of the RIBS was possible for up to 6 months. Histological analyses confirmed compatibility and resorption of the RIBS, with a limited inflammatory response. The RIBS could be successfully implanted in human anatomic specimens. The results reported in this study will allow the development of trackable and degradable IBS to reduce biliary complications after liver transplantation. STATEMENT OF SIGNIFICANCE: Biliary reconstruction during liver transplantation is an important source of postoperative morbidity and mortality although it is generally considered as an easy step of a difficult surgery. In this frame, internal biliary stent (IBS) implantation is beneficial to reduce biliary anastomosis complications (leakage, stricture). However, current IBS are made of non-degradable silicone elastomeric materials, which leads to an additional ablation procedure involving potential complications and additional costs. The present study provides in vitro and human postmortem implantation data related to the development and evaluation of a resorbable and radiopaque internal biliary stent (RIBS) that could tackle these drawbacks.

Magnetic Spiderman, a New Surgical Training Device: Study of Safety and Educational Value in a Liver Transplantation Surgical Training Program.

INTRODUCTION: Difficulties with liver transplantation (LT)-related surgical techniques are great challenges for young surgeons. Thus, young surgeons need to undergo systematic preclinical training. However, an optimal training system for LT is still lacking. This study aims to evaluate the safety and educational value of the Magnetic Spiderman (MS) during LT-related surgical techniques training, particularly during training for the preparation of the donor's liver and vascular reconstruction. METHODS: For the donor liver preparation training, the pulling force of the MS was measured using 16 porcine livers. Another 40 porcine livers were divided into two groups: MS group (used MS in the preparation of the liver) (n = 25) and manual group (took manual assistance in the preparation of the liver) (MA group, n = 15). In vascular reconstruction training, 25 pairs of porcine iliac veins were used to practice reconstruction. Five LT experts evaluated the MS for its use in LT-related surgical techniques training. RESULTS: During the donor liver preparation training, the number of assistants required in the MS group was significantly less than the number required in the MA group (0 vs. 1.8 ± 0.1; P < 0.001). However, the number of vasculature leaking points was similar between the two groups (0.2 ± 0.1 vs. 0.4 ± 0.2; P = 0.51). In vascular reconstruction training, the trainee alone could complete the vascular reconstruction training, with a reconstruction success rate of 80% (20/25). All five experts considered the MS a viable alternative to assistants, with the ability to facilitate single surgeon training for LT. Four out of five (80%) experts considered MS quite safe for surgery and effective at keeping the surgical field clear. CONCLUSION: MS can reduce the number of assistants to zero in LT-related techniques training without increasing the risk of the operation, thus facilitating training for LT.

Factibilidad de la bipartición hepática derecha-izquierda in situ en el trasplante Hepático / Feasibility of in situ full-right full-left split liver transplantation

Debido a la falta de órganos para trasplantes se han desarrollado diferentes alternativas quirúrgicas, como la bipartición hepática (BH) y los trasplantes hepáticos con donantes vivos. En la BH clásica, de la división de un hígado de donante cadavérico se obtienen dos injertos, uno correspondiente a los segmentos 2-3 y otro a los segmentos 1, 4-8. Para poder utilizar los injertos de una BH, en pacientes adultos, se puede realizar una BH derecha/izquierda típica, donde se obtienen un injerto derecho (segmentos 5-8) y otro izquierdo (segmentos 1-4). La BH se puede realizar en el momento de la ablación (BH in situ) o en la cirugía de banco (BH ex situ). En este trabajo informamos el primer caso de BH in situ derecha/izquierda típica de la Argentina, resaltando los detalles de la cirugía del donante y del receptor.

Due to the shortage of organs for transplantation, different surgical alternatives have been developed, as split liver transplantation (SLT) and living-donor liver transplantation. In classical SLT, the liver of a cadaveric donor is divided and two allografts are obtained, one corresponding to segments 2-3 and the other to segments 1, 4-8. In order to produce two grafts from one liver for two adult recipients, splitting of the liver can create a right graft including segments 5-8 and a left graft with segments 1-4. Splitting of the liver can be performed during procurement (in situ) or on the bench (ex situ). The aim of our study is to describe the first case of in situ full-right full-left split liver transplantation, with focus on donor and recipient surgery.

Normothermic Machine Perfusion Enhances Intraoperative Hepatocellular Synthetic Capacity: A Propensity Score-matched Analysis.

BACKGROUND: Normothermic machine perfusion (NMP) of liver grafts is increasingly being incorporated in clinical practice. Current evidence has shown NMP plays a role in reconditioning the synthetic and energy capabilities of grafts. Intraoperative coagulation profile is a surrogate of graft quality and preservation status; however, to date this aspect has not been documented. METHODS: The liver transplantation recipients who received NMP liver grafts in the QEHB between 2013 and 2016 were compared in terms of intraoperative thromboelastography characteristics (R time, K time, α-angle, maximum amplitude, G value, and LY30) to a propensity score-matched control group, where the grafts were preserved by traditional static cold storage (SCS). RESULTS: After propensity matching, none of the thromboelastography characteristics were found to differ significantly between the 72 pairs of SCS and NMP organs when measured preimplantation. However, postimplantation, NMP organs had significantly shorter K time (median: 2.8 vs 3.6 min, P = 0.010) and R + K time (11.4 vs 13.7 min, P = 0.016), as well as significantly larger α-angle (55.9° vs 44.8°, P = 0.002), maximum amplitude (53.5 vs 49.6 mm, P = 0.044), and G values (5.8 vs 4.9k dynes/cm, P = 0.043) than SCS organs. Hyperfibrinolysis after implantation was also mitigated by NMP, with fewer patients requiring aggressive factor correction during surgery (LY30 = 0, NMP vs SCS: 83% vs 60%, P = 0.004). Consequently, NMP organs required significantly fewer platelet units to be transfused during the transplant procedure (median: 0 vs 5, P = 0.001). CONCLUSIONS: In this study, we have shown that NMP liver grafts return better coagulation profiles intraoperatively, which could be attributed to the preservation of liver grafts under physiological conditions.

Transplante de fígado para insuficiência hepática hiperaguda relacionada à febre amarela / Liver transplantation for yellow fever-related hyperacute liver failure

APRESENTAÇÃO: Algumas propostas de incorporação tecnológica no SUS são avaliadas pela CONITEC de forma simplificada, não sendo submetidas à consulta pública e/ou audiência pública. São propostas de relevante interesse público que tratam de ampliação de uso de tecnologias, nova apresentação de medicamentos ou incorporação de medicamentos com tradicionalidade de uso. Todas essas demandas envolvem tecnologias de baixo custo e baixo impacto orçamentário para o SUS e estão relacionadas à elaboração ou revisão de Protocolos Clínicos e Diretrizes Terapêuticas (PCDT). SOLICITAÇÃO DE INCORPORAÇÃO: Demandante: Secretaria de Atenção à Saúde ­ SAS Demanda: incorporação do Transplante de Fígado para Insuficiência Hepática Hiperaguda relacionada à Febre Amarela. TRANSPLANTE DE FÍGADO: O transplante de fígado é um tipo de tratamento proposto para doenças que afetam o sistema hepatobiliar. Consiste na substituição do fígado doente por um enxerto saudável de um doador falecido, ou parte do fígado de um doador vivo. É o tratamento de escolha para um grupo de pacientes com doenças hepáticas ou biliares, para as quais as demais alternativas terapêuticas foram esgotadas e cujo uso tem potencial curativo ou de importante repercussão na qualidade de vida dos doentes. Esses transplantes estão indicados em casos de doenças hepáticas (como cirrose descompensada, polineuropatia amiloidótica familiar e câncer primário do fígado) ou biliares (como cirrose biliar primária ou secundária e atresia de vias biliares) e ainda em casos de algumas doenças metabólicas capazes de alterar gravemente a função hepatobiliar (como doença de Wilson, hemocromatose e deficiência de alfa-1-antitripsina). TRANSPLANTE DE FÍGADO EM FEBRE AMARELA: A partir do final do ano de 2017, a Coordenação-Geral do Sistema Nacional de Transplantes - CGSNT passou a observar um aumento relevante do número de inscrições em lista de espera por Insuficiência Hepática Hiperaguda - IHH. Simultaneamente, o diagnóstico de Febre Amarela ­ FA passou a ser relacionado a esse súbito crescimento, seguido da confirmação clínica e laboratorial dos casos de IHH diretamente provocados pelo agravamento da infecção pelo vírus da FA, notadamente nos mesmos estados brasileiros considerados regiões de surto epidêmico de Febre Amarela, quais sejam: Minas Gerais, Rio de Janeiro e São Paulo. Todos esses estados registraram casos de FA por meio dos sistemas de vigilância em saúde. CONSIDERAÇÕES FINAIS: De acordo com a Nota Informativa constante no processo 25000.042688/2018-63, a presente proposta de incorporação tem o objetivo de admitir temporariamente a indicação de transplante de fígado para casos de IHHFA dados os benefícios potenciais deste tratamento no restabelecimento da função hepática, a justificar sua realização de forma compassiva neste momento, e as ações para prover o estudo destes casos, com a criação do Grupo Técnico e dos procedimentos de Transplante de Fígado em Febre Amarela e Tratamento de Intercorrência em Transplante de Fígado por FA - Pós-transplante Crítico. Ressalte-se que a repercussão da insuficiência hepática no acometimento sistêmico da Febre Amarela não está bem estabelecida, e será um dos objetos do estudo multicêntrico proposto à tentativa de resposta a esta questão. Estima-se que, excluídas as contraindicações e os casos de êxito letal em lista, sejam realizados cerca de 48 (quarenta e oito) transplantes de fígado em IHHFA por ano, considerando a sazonalidade dos surtos de Febre Amarela (dezembro a maio). Chega-se então a um gasto de R$ 9.030.394,56, que poderia traduzir-se no impacto, já que é uma nova indicação e um novo procedimento. RECOMENDAÇÃO DA CONITEC: Os membros da CONITEC, presentes na 64ª reunião ordinária, realizada nos dias 07 e 08 de março de 2018, deliberaram, por unanimidade, recomendar a incorporação do Transplante de fígado para Insuficiência Hepática Hiperaguda ­ IHH relacionada à Febre Amarela ­ FA. Desse modo, foi assinado o Registro de Deliberação nº 346/2018. DECISÃO: A PORTARIA Nº 23, DE 23 DE ABRIL DE 2019 - Torna pública a decisão de incorporar o transplante de fígado para insuficiência hepática hiperaguda-IHH relacionada à febre amarela - FA, no âmbito do Sistema Único de Saúde - SUS.

Transplante de fígado para insuficiência hepática hiperaguda relacionada à febre amarela / Liver transplant for yellow fever-related hyperacute liver failure

APRESENTAÇÃO: Algumas propostas de incorporação tecnológica no SUS são avaliadas pela CONITEC de forma simplificada, não sendo submetidas à consulta pública e/ou audiência pública. São propostas de relevante interesse público que tratam de ampliação de uso de tecnologias, nova apresentação de medicamentos ou incorporação de medicamentos com tradicionalidade de uso. Todas essas demandas envolvem tecnologias de baixo custo e baixo impacto orçamentário para o SUS e estão relacionadas à elaboração ou revisão de Protocolos Clínicos e Diretrizes Terapêuticas (PCDT). SOLICITAÇÃO DE INCORPORAÇÃO: Demandante: Secretaria de Atenção à Saúde ­ SAS. Demanda: incorporação do Transplante de Fígado para Insuficiência Hepática Hiperaguda relacionada à Febre Amarela. TRANSPLANTE DE FÍGADO: O transplante de fígado é um tipo de tratamento proposto para doenças que afetam o sistema hepatobiliar. Consiste na substituição do fígado doente por um enxerto saudável de um doador falecido, ou parte do fígado de um doador vivo. É o tratamento de escolha para um grupo de pacientes com doenças hepáticas ou biliares, para as quais as demais alternativas terapêuticas foram esgotadas e cujo uso tem potencial curativo ou de importante repercussão na qualidade de vida dos doentes. Esses transplantes estão indicados em casos de doenças hepáticas (como cirrose descompensada, polineuropatia amiloidótica familiar e câncer primário do fígado) ou biliares (como cirrose biliar primária ou secundária e atresia de vias biliares) e ainda em casos de algumas doenças metabólicas capazes de alterar gravemente a função hepatobiliar (como doença de Wilson, hemocromatose e deficiência de alfa-1-antitripsina). TRANSPLANTE DE FÍGADO EM FEBRE AMARELA: A partir do final do ano de 2017, a Coordenação-Geral do Sistema Nacional de Transplantes - CGSNT passou a observar um aumento relevante do número de inscrições em lista de espera por Insuficiência Hepática Hiperaguda - IHH. Simultaneamente, o diagnóstico de Febre Amarela ­ FA passou a ser relacionado a esse súbito crescimento, seguido da confirmação clínica e laboratorial dos casos de IHH diretamente provocados pelo agravamento da infecção pelo vírus da FA, notadamente nos mesmos estados brasileiros considerados regiões de surto epidêmico de Febre Amarela, quais sejam: Minas Gerais, Rio de Janeiro e São Paulo. Todos esses estados registraram casos de FA por meio dos sistemas de vigilância em saúde. CONSIDERAÇÕES FINAIS: De acordo com a Nota Informativa constante no processo 25000.042688/2018-63, a presente proposta de incorporação tem o objetivo de admitir temporariamente a indicação de transplante de fígado para casos de IHHFA dados os benefícios potenciais deste tratamento no restabelecimento da função hepática, a justificar sua realização de forma compassiva neste momento, e as ações para prover o estudo destes casos, com a criação do Grupo Técnico e dos procedimentos de Transplante de Fígado em Febre Amarela e Tratamento de Intercorrência em Transplante de Fígado por FA - Pós-transplante Crítico. Ressalte-se que a repercussão da insuficiência hepática no acometimento sistêmico da Febre Amarela não está bem estabelecida, e será um dos objetos do estudo multicêntrico proposto à tentativa de resposta a esta questão. Estima-se que, excluídas as contraindicações e os casos de êxito letal em lista, sejam realizados cerca de 48 (quarenta e oito) transplantes de fígado em IHHFA por ano, considerando a sazonalidade dos surtos de Febre Amarela (dezembro a maio). RECOMENDAÇÃO DA CONITEC: Os membros da CONITEC, presentes na 64ª reunião ordinária, realizada nos dias 07 e 08 de março de 2018, deliberaram, por unanimidade, recomendar a incorporação do Transplante de fígado para Insuficiência Hepática Hiperaguda ­ IHH relacionada à Febre Amarela ­ FA. Desse modo, foi assinado o Registro de Deliberação nº 346/2018. DECISÃO: PORTARIA Nº 23, DE 23 DE ABRIL DE 2019 Torna pública a decisão de incorporar o transplante de fígado para insuficiência hepática hiperaguda-IHH relacionada à febre amarela - FA, no âmbito do Sistema Único de Saúde - SUS.

First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion.

One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full-size liver graft was derived from a 13-year-old, female DCD donor and was end-ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16-year-old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation.

Selective Indication of T-Tube in Liver Transplantation: Prospective Validation of the Results of a Randomized Controlled Trial.

BACKGROUND AND AIMS: T-tube placement during choledochocholedochostomy (CCS) associated with liver transplantation (LT) remains controversial. This study was designed to validate the results of an earlier prospective randomized controlled trial (RCT) on use versus nonuse of the T-tube during CCS associated with LT. METHODS: Prospective cohort study. The primary outcome was the overall incidence of biliary complications (BCs). RESULTS: In total, 405 patients were included, and the median overall monitoring period was 29 months (interquartile range: 13-47 months). Selective use of the T-tube reduced BCs (23% vs 13%; P = .003), of which 75% were type IIIa or less in the Clavien-Dindo classification. The overall BC rate did not differ between patients with versus without T-tube placement. CONCLUSIONS: We confirmed that selective use of a rubber T-tube during CCS associated with LT, following the principles established in our prospective RCT, reduced the rate of BC by 10% without detriment, even after enrolling patients at an a priori greater risk of BCs than were the RCT patients.

Biliary Bicarbonate, pH, and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers.

BACKGROUND: Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers before implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI). METHODS: In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI. Livers were divided into groups with low or high BDI, based on a clinically relevant histological grading system. During NMP, bile was analyzed biochemically and potential biomarkers were correlated with the degree of BDI. Receiver operating characteristics curves were generated to determine optimal cutoff values. For clinical validation, identified biomarkers were subsequently included as viability criteria in a clinical trial (n = 6) to identify transplantable liver grafts with low BDI. RESULTS: Biliary bicarbonate and pH were significantly higher and biliary glucose was significantly lower in livers with low BDI, compared with high BDI. The following cutoff values were associated with low BDI: biliary bicarbonate greater than 18 mmol/L (P = 0.002), biliary pH greater than 7.48 (P = 0.019), biliary glucose less than 16 mmol/L (P = 0.013), and bile/perfusate glucose ratio less than 0.67 (P = 0.013). In the clinical trial, 4 of 6 livers met these criteria and were transplanted, and none developed clinical evidence of posttransplant cholangiopathy. CONCLUSIONS: Biliary bicarbonate, pH, and glucose during ex situ NMP of liver grafts are accurate biomarkers of BDI and can be easily determined point of care, making them suitable for the pretransplant assessment of bile duct viability. This may improve graft selection and decrease the risk of posttransplant cholangiopathy.