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BACKGROUND & AIMS: The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant. METHODS: UK Transplant Registry data on patient registrations and transplants were analysed to build statistical models for survival on the list (M1) and survival post-transplantation (M2). A separate cohort of registrations - not seen by the models before - was analysed to simulate what liver allocation would have been under M1, M2 and a transplant benefit score (TBS) model (combining both M1 and M2), and to compare these allocations to what had been recorded in the UK Transplant Registry. The number of deaths on the waiting list and patient life years were used to compare the different simulation scenarios and to select the optimal allocation model. Registry data were monitored, pre- and post-NLOS, to understand the performance of the scheme. RESULTS: The TBS was identified as the optimal model to offer donation after brain death (DBD) livers to adult and large paediatric elective recipients. In the first 2 years of NLOS, 68% of DBD livers were offered using the TBS to this type of recipient. Monitoring data indicate that mortality on the waiting list post-NLOS significantly decreased compared with pre-NLOS (p <0.0001), and that patient survival post-listing was significantly greater post- compared to pre-NLOS (p = 0.005). CONCLUSIONS: In the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, delivering on the scheme's objectives. IMPACT AND IMPLICATIONS: The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to increase transparency of the deceased donor liver offering process, maximise the overall survival of the waiting list population, and improve equity of access to liver transplantation. To our knowledge, it is the first scheme that offers organs based on statistical prediction of transplant benefit: the transplant benefit score. The results are important to the transplant community - from healthcare practitioners to patients - and demonstrate that, in the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, thus delivering on the scheme's objectives. The scheme continues to be monitored to ensure that the transplant benefit score remains up-to-date and that signals that suggest the possible disadvantage of some patients are investigated.
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Trasplante de Hígado , Sistema de Registros , Donantes de Tejidos , Obtención de Tejidos y Órganos , Listas de Espera , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/estadística & datos numéricos , Reino Unido , Obtención de Tejidos y Órganos/métodos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Donantes de Tejidos/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Adulto , Masculino , Femenino , Persona de Mediana Edad , Niño , AdolescenteRESUMEN
BACKGROUND: Mutations in the ABCB4 gene are associated with failure of bile acid emulsification leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3) in childhood, to milder forms seen in adulthood. AIMS: We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined. METHODS: Four unrelated adults (three female, mean age 39 years) and three sisters presenting with cholestatic liver disease in adulthood, associated with variants in the ABCB4 gene, were identified. Clinical review and detailed blinded histopathological analysis were performed. RESULTS: Two novel pathogenic ABCB4 variants were identified: c.620 T > G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26). Sub-phenotypes observed included low-phospholipid-associated cholelithiasis syndrome (LPAC), intrahepatic cholestasis of pregnancy (ICP), drug-induced cholestasis, idiopathic adulthood ductopenia, and adult PFIC3. Of note, 5/7 had presented with gallstone complications (4 meeting LPAC definition) and 4/6 females had a history of ICP. Considerable overlap was observed phenotypically and liver transplantation was required in 3/7 of patients. Histologically, cases generally demonstrated ductopenia of the smaller tracts, mild non-ductocentric portal inflammation, bilirubinostasis, significant copper-associated protein deposition, and varying degrees of fibrosis. CONCLUSIONS: Adults with ABCB4 mutations may harbor a spectrum of cholestatic disease phenotypes and can progress to liver transplantation. We observed a distinct histological pattern which differs from classical biliary disease and describe two novel pathogenic ABCB4 variants. ABCB4 sequencing should be considered in patients with relevant cholestatic phenotypes and/or suggestive histology; accurate diagnosis can guide potential interventions to delay progression and inform family screening.
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Colestasis Intrahepática , Colestasis , Enfermedades de la Vesícula Biliar , Cálculos Biliares , Femenino , Humanos , Embarazo , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/genética , MutaciónRESUMEN
The COVID-19 global pandemic is a threat not only to the health of millions of individuals, but also to the stability of infrastructure and economies around the world. The disease will inevitably place an overwhelming burden on healthcare systems that cannot be effectively dealt with by existing facilities or responses based on conventional approaches. We believe that a rigorous clinical and societal response can only be mounted by using intelligence derived from a variety of data sources to better utilize scarce healthcare resources, provide personalized patient management plans, inform policy, and expedite clinical trials. In this paper, we introduce five of the most important challenges in responding to COVID-19 and show how each of them can be addressed by recent developments in machine learning (ML) and artificial intelligence (AI). We argue that the integration of these techniques into local, national, and international healthcare systems will save lives, and propose specific methods by which implementation can happen swiftly and efficiently. We offer to extend these resources and knowledge to assist policymakers seeking to implement these techniques.
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BACKGROUND & AIMS: Acute liver failure as the initial presentation of Wilson's disease is usually associated with onset in childhood, adolescence or early adulthood. Outcomes after transplantation for late-onset presentations, at or after 40 years, are seldom reported in the literature. METHODS: We report a case, review the literature and provide unpublished data from the UK Transplant Registry on late-onset acute liver failure in Wilson's disease. RESULTS: We describe the case of a 62-year-old man presenting with acute liver failure who was successfully treated with urgent liver transplantation. We identified 7 cases presenting at age 40 years or over in the literature, for which individual outcomes were reported; 3 were treated with transplantation and 2 survived. We identified a further 8 cases listed for transplantation in the UK between 1995 and 2014; 7 were treated with transplantation and 6 survived. One patient was de-listed for unknown reasons. CONCLUSIONS: Wilson's disease should be considered in older adults presenting with acute liver failure. We suggest that urgent liver transplantation has good outcomes for late-onset presentations and recommend that urgent transplantation should always be considered in Wilson's disease presenting as acute liver failure. LAY SUMMARY: Wilson's disease is a rare inherited disease that causes copper accumulation in the liver and brain and usually manifests during childhood, adolescence or early adulthood. We report the case of a 62-year-old who developed acute liver failure and was successfully treated with urgent liver transplantation. We discuss the outcomes of other late-onset cases of acute liver failure due to Wilson's disease in the literature and provide additional data from the UK Transplant Registry.
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PURPOSE OF REVIEW: Equitable allocation of organs for liver transplantation remains a major area of ongoing study. In United Kingdom, it was agreed that the success of any national donor offering scheme would be judged from the point of registration on a national list for a transplant, and would therefore include outcome while waiting for the procedure. RECENT FINDINGS: Standard minimal criteria for acceptance onto a transplant list have been developed for chronic liver disease, hepatocellular carcinoma and for a number of variant syndromes where current scores do not adequately reflect the risk of death without a transplant or symptom burden. Allocation by need, or on the basis of utility, or by transplant benefit (net life years gained) were compared in a simulation against current unit-based allocation. A transplant benefit model was shown to reduce deaths on the waiting list and maximise population life years. SUMMARY: Since March 2018, liver donors after brain death in United Kingdom have been offered to a national list prioritised by net life years gained - transplant benefit.
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Trasplante de Hígado/métodos , Obtención de Tejidos y Órganos/organización & administración , Humanos , Donantes de Tejidos , Reino Unido , Listas de EsperaRESUMEN
Following the introduction of direct-acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)-related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1-year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV-related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P < 0.001). Alcohol-related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P = 0.002). For patients with HCV-related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1 year were similar. For patients with HCV-related HCC, the proportion dying at 1 year reduced significantly from 2.9% to 0.0% (P = 0.04). These data demonstrate an association between DAA and reduced listing rates for HCV-related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.
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Antivirales/uso terapéutico , Carcinoma Hepatocelular/virología , Hepatitis C/tratamiento farmacológico , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Trasplante de Hígado/estadística & datos numéricos , Listas de Espera , Adulto , Hepatitis C/complicaciones , Humanos , Trasplante de Hígado/tendencias , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Reino UnidoRESUMEN
Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25-50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid-base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy.
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Conductos Biliares/metabolismo , Hepatocitos/metabolismo , Trasplante de Hígado , Preservación de Órganos/métodos , Perfusión/métodos , Disfunción Primaria del Injerto/prevención & control , Donantes de Tejidos/provisión & distribución , Adulto , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Daño por Reperfusión/prevención & control , Obtención de Tejidos y Órganos/normas , Adulto JovenRESUMEN
Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency characterized by antibody deficiency, recurrent bacterial infections, and autoimmunity. Advanced chronic liver disease occurs in a subset of patients with CVID and manifests with various histological features, such as nodular regenerative hyperplasia, inflammation, fibrosis, and cholangiopathy. We present a case series characterizing the outcomes in adult patients transplanted for primary CVID-related liver disease. We discuss the unique transplantation challenges faced in this primary immunodeficiency group including susceptibility to infections and early disease recurrence. There is a statistically significant decrease in 3-year and 5-year survival after liver transplantation in those with CVID-related liver disease (55% at 3 and 5 years) compared with all-comers (89% at 3 years, 81% at 5 years), prompting a need for discussion of suitability of transplantation in this group of patients as well as methods for reducing posttransplantation risk such as scrupulous search for infectious agents and reduction of immunosuppression. Liver Transplantation 24 171-181 2018 AASLD.
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Inmunodeficiencia Variable Común/inmunología , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Adulto , Enfermedad Crónica , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/diagnóstico , Resultado Fatal , Femenino , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Hepatopatías/diagnóstico , Hepatopatías/inmunología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Recurrencia , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: A program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia. METHODS: Declined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate. RESULTS: Twelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP. CONCLUSIONS: Normothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes.
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Selección de Donante , Hiperoxia/etiología , Trasplante de Hígado/métodos , Perfusión/métodos , Complicaciones Posoperatorias/etiología , Vasoplejía/etiología , Isquemia Tibia/métodos , Adulto , Anciano , Isquemia Fría , Estudios de Seguimiento , Humanos , Hiperoxia/prevención & control , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Perfusión/efectos adversos , Complicaciones Posoperatorias/prevención & control , Vasoplejía/prevención & control , Isquemia Tibia/efectos adversosRESUMEN
BACKGROUND & AIMS: Comparing liver transplant (LT) programmes internationally can improve outcomes by stimulating cross-national learning. Yet, comparison of crude outcomes, by using registry data, is limited by missing data, not allowing proper risk-adjustment for donor- and recipient-related factors. The objective of this study was to compare two European LT programmes based on high-quality national longitudinal databases prospectively collected in Italy and UK respectively. METHODS: We undertook a multicentre, international cohort study including all adults who underwent a first single organ LT in Italy (N = 1480) and the UK (N = 1003) between June 2007 and May 2009. RESULTS: Italian donors were much older compared to the UK ones. Hepatitis C virus infection and hepatocellular carcinoma had higher prevalence in the Italian cohort compared to the UK one (47.5% vs. 23.1%, and 47.2% vs. 17.1% respectively). Centres' volume differed significantly, with five centres out of seven in UK vs. only two out of 20 in Italy performing >60 transplants per year. No national strategies to drive the donor-recipient matching were identified in both countries. After appropriate adjustment, a higher risk of early transplant loss was identified in the Italian cohort, whereas no differences were found in the 3-year survival rates. CONCLUSIONS: International comparison of LT programmes provides the opportunity for benchmarking between heterogeneous healthcare systems and should ideally become a vital part of national quality assurance programmes. This requires the implementation of a standardized methodology for data collection to appropriately weigh each country's patient case-mix and donor and recipients risk factors.
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Carcinoma Hepatocelular/cirugía , Selección de Donante , Hepatitis C/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Adulto , Anciano , Benchmarking , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Rechazo de Injerto/epidemiología , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis de Regresión , Tasa de Supervivencia , Reino Unido/epidemiología , Adulto JovenRESUMEN
AIM: To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS: A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS: In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION: The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS.
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OBJECTIVES: Fully covered self-expanding metal stents (FCSEMS) constitute the first type of metal stent that can easily be removed endoscopically and/or intraoperatively, which may be advantageous in the management of distal malignant biliary strictures (DMBS). To assess the efficacy of FCSEMS as first-line treatment for DMBS, we compared patency, survival and complication rates between FCSEMS, uncovered self-expanding metal stents (USEMS) and plastic stents (PS). METHODS: This was a multicentre retrospective study of 315 consecutive patients with DMBS, who underwent endoscopic retrograde cholangiopancreatography and stenting (FCSEMS, USEMS or PS) at two hospitals between 1 January 2007 and 31 December 2013. Stent patency and patient survival were compared using the Kaplan-Meier method; complication rates were compared using Fisher's exact test; and Cox regression analysis was used to screen for confounding factors. RESULTS: FCSEMS were associated with prolonged stent patency (median=145 days) compared with USEMS (median=110 days, P<0.003) and PS (median=34 days, P<0.001). Biliary sepsis rates were lower for FCSEMS compared with PS (4.7 vs. 17.8%, P=0.02), whereas pancreatitis rates were higher for FCSEMS compared with USEMS (7.8 vs. 1.0%, P=0.04), but not PS (2.6%, P=NS). CONCLUSION: The use of FCSEMS as first-line management for DMBS is associated with longer patency and reduced complication rates compared with the use of PS. However, the higher rate of pancreatitis compared with USEMS requires further evaluation in a large randomized controlled trial.
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Neoplasias de los Conductos Biliares/complicaciones , Carcinoma/complicaciones , Colangiocarcinoma/complicaciones , Colestasis Intrahepática/terapia , Stents Liberadores de Fármacos , Neoplasias Pancreáticas/complicaciones , Stents Metálicos Autoexpandibles , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/etiología , Neoplasias de los Conductos Biliares/cirugía , Carcinoma/cirugía , Colangiocarcinoma/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Colestasis Intrahepática/etiología , Stents Liberadores de Fármacos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Pancreatitis/etiología , Plásticos , Estudios Retrospectivos , Stents Metálicos Autoexpandibles/efectos adversos , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: We assessed the impact of comorbidity on mortality in three periods after liver transplantation (first 90â days, 90â days-5â years and 5-10â years). DESIGN: Prospective cohort study using records from the UK Liver Transplant Audit (UKLTA) linked to Hospital Episode Statistics (HES), an administrative database of hospital admissions in the English National Health Service (NHS). Comorbidities relevant for liver transplantation were identified from the 10th revision of the International Classification of Diseases (ICD-10) codes in HES records of admissions in the year preceding their operation. Multivariable Cox regression was used to estimate HRs for three different time periods after liver transplantation. SETTING: All liver transplant centres in the NHS hospitals in England. PARTICIPANTS: Adults who received a first elective liver transplant between April 1997 and March 2010 in the linked UKLTA-HES database. OUTCOMES: Patient mortality in three different time periods after transplantation. RESULTS: Among 3837 recipients, 45.1% had comorbidities. Recipients with cardiovascular disease had statistically significantly higher mortality in all three periods after transplantation (first 90â days: HR=2.0; 95% CI 1.4 to 2.9, 90â days-5â years: 1.6; 1.2 to 2.2, beyond 5â years: 2.8; 1.7 to 4.4). Prior congestive cardiac failure (3.2; 2.1 to 4.9) significantly increased mortality only in the first 90â days. History of non-hepatic malignancy appeared to increase risk over all periods, but significantly only in the first 90â days (1.9; 1.0 to 3.6). A diagnosis of connective tissue disease, dementia, diabetes, chronic pulmonary and renal disease did not have a significant impact on mortality in any period. CONCLUSIONS: The impact of comorbidities present at the time of transplantation changes with time after transplantation. Renal disease, pulmonary disease and diabetes had no impact on mortality in contrast to previous reports.
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Mortalidad Hospitalaria , Hepatopatías/mortalidad , Trasplante de Hígado/mortalidad , Adulto , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medicina Estatal , Factores de Tiempo , Reino Unido/epidemiologíaRESUMEN
INTRODUCTION: The UK Liver Transplant Audit (UKLTA) database contains clinical information on all liver transplants carried out in the UK. To expand its potential for research and service evaluation, we linked it to the Hospital Episode Statistics (HES), an administrative database of all admissions to English National Health Service (NHS) hospitals. MATERIALS AND METHODS: In the UKLTA database, we identified the linkable records of first liver transplantation between April 1997 and March 2010. We linked UKLTA records to HES records on the basis of NHS number, gender, date of birth, and postcode, as well as procedure codes for liver transplantation and dates of transplant. In linked records, agreement of primary liver disease diagnoses according to both databases was expressed as a proportion of the linked records and using kappa statistic. RESULTS: There were 5,815 linkable records in the UKLTA database, of which 4,959 records were successfully linked with HES (85.3%). Among these, 4,922 records (99.3%) had at least one diagnosis coded in HES relevant to an indication for liver transplantation. The overall agreement of primary liver disease diagnoses between UKLTA data and HES was 77.8% (95% CI 76.6%-79.0%) with a kappa of 0.75 (0.74-0.76). Diagnostic agreement can be further improved by using broader groupings of clinically related diagnoses. CONCLUSION: Linkage of clinical data and administrative hospital data provides a rich resource for the study of liver transplantation.
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Bases de Datos Factuales , Trasplante de Hígado , Adulto , Femenino , Hospitales/estadística & datos numéricos , Humanos , Hepatopatías/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Reino UnidoRESUMEN
Liver is an integral part of the host-defense mechanism and facilitates clearance of pathogenic organisms in systemic infection by modulating the immunological response. It undergoes several cellular and molecular changes resulting in the release of pro-inflammatory cytokines, which regulate various metabolic and immunological signalling pathways. Some of these changes are pathogen-specific and essential in determining the host response to systemic infection. However, alterations in the immunological homeostasis can adversely affect the liver and lead to hepatic dysfunction. This article focuses on these molecular and immunological changes that occur within the liver in response to extra-hepatic systemic infection and its consequences.
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Hepatopatías/inmunología , Hígado/inmunología , Sepsis/inmunología , Citocinas/metabolismo , Humanos , Hígado/fisiopatología , Hepatopatías/fisiopatología , Sepsis/fisiopatologíaRESUMEN
OBJECTIVES: Outcomes of liver transplantations from donation after circulatory death (DCD) donors may be inferior to those achieved with donation after brain death (DBD) donors. The impact of using DCD donors is likely to depend on specific national practices. We compared risk-adjusted graft loss and recipient mortality after transplantation of DCD and DBD livers in the UK. DESIGN: Prospective cohort study. Multivariable Cox regression and propensity score matching were used to estimate risk-adjusted HR. SETTING: 7 liver transplant centres in the National Health Service (NHS) hospitals in England and Scotland. PARTICIPANTS: Adults who received a first elective liver transplant between January 2005 and December 2010 who were identified in the UK Liver Transplant Audit. INTERVENTIONS: Transplantation of DCD and DBD livers. OUTCOMES: Graft loss and recipient mortality. RESULTS: In total, 2572 liver transplants were identified with 352 (14%) from DCD donors. 3-year graft loss (95% CI) was higher with DCD livers (27.3%, 21.8% to 33.9%) than with DBD livers (18.2%, 16.4% to 20.2%). After adjustment with regression, HR for graft loss was 2.3 (1.7 to 3.0). Similarly, 3-year mortality was higher with DCD livers (19.4%, 14.5% to 25.6%) than with DBD livers (14.1%, 12.5% to 16.0%) with an adjusted HR of 2.0 (1.4 to 2.8). Propensity score matching gave similar results. Centre-specific adjusted HRs for graft loss and recipient mortality seemed to differ among transplant centres, although statistical evidence is weak (p value for interaction 0.08 and 0.24, respectively). CONCLUSIONS: Graft loss and recipient mortality were about twice as high with DCD livers as with DBD livers in the UK. Outcomes after DCD liver transplantation may vary between centres. These results should inform policies for the use of DCD livers.
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OBJECTIVES: Conventional imaging techniques are insensitive to liver fibrosis. This study assesses the diagnostic accuracy of MR elastography (MRE) stiffness values and the ratio of phosphomonoesters (PME)/phosphodiesters (PDE) measured using (31)P spectroscopy against histological fibrosis staging. METHODS: The local research ethics committee approved this prospective, blinded study. A total of 77 consecutive patients (55 male, aged 49 ± 11.5 years) with a clinical suspicion of liver fibrosis underwent an MR examination with a liver biopsy later the same day. Patients underwent MRE and (31)P spectroscopy on a 1.5 T whole body system. The liver biopsies were staged using an Ishak score for chronic hepatitis or a modified NAS fibrosis score for fatty liver disease. RESULTS: MRE increased with and was positively associated with fibrosis stage (Spearman's rank = 0.622, P < 0.001). PME/PDE was not associated with fibrosis stage (Spearman's rank = -0.041, p = 0.741). Area under receiver operating curves for MRE stiffness values were high (range 0.75-0.97). The diagnostic utility of PME/PDE was no better than chance (range 0.44-0.58). CONCLUSIONS: MRE-estimated liver stiffness increases with fibrosis stage and is able to dichotomise fibrosis stage groupings. We did not find a relationship between (31)P MR spectroscopy and fibrosis stage. KEY POINTS: Magnetic resonance elastography (MRE) and MR spectroscopy can both assess the liver. MRE is superior to ( 31 ) P MR spectroscopy in staging hepatic fibrosis. MRE is able to dichotomise liver fibrosis stage groupings. Gradient-echo MRE may be problematic in genetic haemochromatosis.
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Diagnóstico por Imagen de Elasticidad/métodos , Cirrosis Hepática/patología , Espectroscopía de Resonancia Magnética/métodos , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: Prediction of short-term survival probability is important in the selection and allocation of patients for liver transplantation, and the Mayo End-Stage Liver Disease (MELD) score has been used in these contexts. The aim of this study was to develop and validate a model for estimation of short-term prognosis of patients selected for elective liver transplantation in the United Kingdom. METHODS: A modeling dataset was based on 1103 adult patients registered for a first elective liver transplant in the United Kingdom between April 1, 2003, and March 31, 2006, and a validation dataset based on 452 patients registered between April 1, 2006, and March 31, 2007. The final model (United Kingdom End-Stage Liver Disease) included international normalized ratio, serum creatinine, bilirubin, and sodium. RESULTS: The model, based on the modeling dataset, accurately predicted mortality on the transplant list in the validation dataset and proved to be a better predictor than MELD or MELD-Na. The United Kingdom End-Stage Liver Disease score was not associated with overall posttransplant survival but was associated with both the duration of intensive care unit stay and overall initial hospital stay. CONCLUSION: This model, developed specifically for patients awaiting liver transplantation, provides a useful tool for the selection of patients for liver transplantation and the allocation of donor livers.
Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/mortalidad , Adolescente , Adulto , Anciano , Bilirrubina/sangre , Creatinina/sangre , Bases de Datos Factuales , Enfermedad Hepática en Estado Terminal/sangre , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Modelos Biológicos , Modelos Estadísticos , Selección de Paciente , Factores de Riesgo , Sodio/sangre , Análisis de Supervivencia , Reino Unido/epidemiología , Listas de Espera , Adulto JovenAsunto(s)
Conductos Biliares/cirugía , Divertículo/diagnóstico por imagen , Migración de Cuerpo Extraño/complicaciones , Perforación Intestinal/diagnóstico por imagen , Enfermedades del Yeyuno/diagnóstico por imagen , Laparotomía , Stents/efectos adversos , Tomografía Computarizada por Rayos X , Dolor Abdominal/etiología , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Remoción de Dispositivos , Diagnóstico Diferencial , Divertículo/complicaciones , Migración de Cuerpo Extraño/diagnóstico por imagen , Migración de Cuerpo Extraño/cirugía , Humanos , Perforación Intestinal/complicaciones , Perforación Intestinal/etiología , Enfermedades del Yeyuno/complicaciones , Enfermedades del Yeyuno/etiología , Enfermedades del Yeyuno/cirugía , Masculino , Neumoperitoneo/diagnóstico por imagen , Neumoperitoneo/etiología , Factores de TiempoRESUMEN
BACKGROUND: Potassium plays a key role in human metabolism in both health and disease. The impact of recipient serum potassium concentration [K] on mortality after liver transplantation has not been described previously. METHODS: We assessed the effect of recipient [K] on the survival of adult first single-organ liver transplant recipients in the United Kingdom and Ireland between March 1, 1994, and February 28, 2007 (n=5942), adjusting for recipient, donor, and graft characteristics. RESULTS: The overall risk-adjusted mortality significantly varied by [K], being higher among hyperkalemic ([K]>5.0 mmol/L) recipients (n=424, hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.01-1.88) and those with [K] of 4.5-5.0 mmol/L (n=1154, HR 1.47, 95% CI 1.13-1.91), compared with hypokalemic ([K]<3.5 mmol/L) recipients (n=360). However, the excess mortality was confined to the first posttransplant year among hyperkalemic recipients (HR 1.61, 95% CI 1.10-2.35) with no significant difference thereafter (HR 1.03, 95% CI 0.62-1.73). This was also true for recipients with [K] of 4.5 to 5.0 mmol/L (< or =1 year: HR 1.70, 95% CI 1.22-2.38; >1 year: HR 1.09, 95% CI 0.71-1.66). In contrast, those with [K] of 3.5 to 3.9 mmol/L (n=1518) and [K] of 4.0-4.4 mmol/L (n=2091) had similar risk-adjusted mortality at the above time points. When [K] was used as a continuous variable in the multivariable analysis, a mmol increase in [K] was associated with an increased adjusted risk of mortality of 27% (95% CI 12%-44%) at 1 year and 19% (95% CI 7%-31%) at 5 years. CONCLUSION: Recipient [K] is an independent predictor of death after liver transplantation. This finding could be of clinical utility in the management, risk stratification, selection, and prioritization of appropriate candidates for transplantation among patients with end-stage liver disease.