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BACKGROUND AND AIMS: Biopsy-proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation. METHODS: We analyzed data from all consecutive first adult full-graft donation after brain death (DBD) liver transplantations performed in the Eurotransplant region between 2010 and 2020. The presence of graft steatosis and metabolic risk factors was assessed through a review of donor (imaging) reports, and associations with recipient retransplantation-free survival were studied through survival analyses. RESULTS: Of 12 174 transplantations, graft steatosis was detected in 2689 (22.1%), and donor diabetes mellitus (DM), hypertension, and dyslipidemia were present in 1245 (10.2%), 5056 (41.5%), and 524 (4.3%). In multivariable Cox regression analysis, graft steatosis (adjusted HR [aHR] 1.197, p < 0.001) and donor DM (aHR 1.157, p = 0.004) were independently associated with impaired retransplantation-free survival. Graft steatosis and donor DM conferred an additive risk of retransplantation or death (DM alone, aHR: 1.156 [p = 0.0185]; steatosis alone, aHR: 1.200 [p < 0.001]; both steatosis and DM, aHR: 1.381 [p < 0.001]). Findings were consistent in sensitivity analyses focusing on retransplantation-free survival within 7 days. CONCLUSIONS: Graft steatosis and donor diabetes mellitus additively increase the risk of retransplantation or death in adult DBD liver transplantation. Future studies should focus on methods to assess and improve the quality of these high-risk grafts. Until such time, caution should be exercised when considering these grafts for transplantation.
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Hígado Graso , Supervivencia de Injerto , Trasplante de Hígado , Complicaciones Posoperatorias , Sistema de Registros , Donantes de Tejidos , Humanos , Femenino , Masculino , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Persona de Mediana Edad , Hígado Graso/patología , Hígado Graso/etiología , Hígado Graso/complicaciones , Hígado Graso/cirugía , Donantes de Tejidos/provisión & distribución , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Adulto , Europa (Continente)/epidemiología , Tasa de Supervivencia , Diabetes Mellitus , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Estudios Retrospectivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9-17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p <0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p <0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p <0.001, and aHR 1.34, 95% CI 1.15-1.56, p <0.001, respectively). Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that the threshold for combination treatment with Tac and MMF should be low. Impact and implications: This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.
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Portal vein thrombosis (PVT) refers to the development of a non-malignant obstruction of the portal vein, its branches, its radicles, or a combination. This Review first provides a comprehensive overview of all aspects of PVT, namely the specifics of the portal venous system, the risk factors for PVT, the pathophysiology of portal hypertension in PVT, the interest in non-invasive tests, as well as therapeutic approaches including the effect of treating risk factors for PVT or cause of cirrhosis, anticoagulation, portal vein recanalisation by interventional radiology, and prevention and management of variceal bleeding in patients with PVT. Specific issues are also addressed including portal cholangiopathy, mesenteric ischaemia and intestinal necrosis, quality of life, fertility, contraception and pregnancy, and PVT in children. This Review will then present endpoints for future clinical studies in PVT, both in patients with and without cirrhosis, agreed by a large panel of experts through a Delphi consensus process. These endpoints include classification of portal vein thrombus extension, classification of PVT evolution, timing of assessment of PVT, and global endpoints for studies on PVT including clinical outcomes. These endpoints will help homogenise studies on PVT and thus facilitate reporting, comparison between studies, and validation of future studies and trials on PVT.
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Vena Porta , Trombosis de la Vena , Humanos , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/terapia , Hipertensión Portal/diagnóstico , Hipertensión Portal/terapia , Hipertensión Portal/etiología , Hipertensión Portal/complicaciones , Factores de Riesgo , Anticoagulantes/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/diagnóstico , Embarazo , Femenino , Calidad de VidaRESUMEN
BACKGROUND: Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. METHODS: Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. RESULTS: Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69-2.68) or 90-day mortality (OR 1.22; 95% CI 0.62-2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41-1.41) or 90-day mortality (OR 0.60; 95% CI 0.33-1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36-4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31-4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36-4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30-3.87). CONCLUSION: In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.
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Neoplasias de los Conductos Biliares , Colangitis , Hígado Graso , Tumor de Klatskin , Cirrosis Hepática Biliar , Fallo Hepático , Neoplasias Hepáticas , Humanos , Anciano , Tumor de Klatskin/cirugía , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/cirugía , Complicaciones Posoperatorias , Hepatectomía/efectos adversos , Fallo Hepático/etiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/cirugía , Colangitis/complicaciones , Colangitis/cirugía , Neoplasias de los Conductos Biliares/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND: The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of neoadjuvant chemoradiotherapy in this scenario remains unclear. The aim of this study was to compare outcomes after transplantation for perihilar cholangiocarcinoma using strict selection criteria, either with or without neoadjuvant chemoradiotherapy. METHODS: This was an international, multicentre, retrospective cohort study of patients who underwent transplantation between 2011 and 2020 for unresectable perihilar cholangiocarcinoma using the Mayo selection criteria and receiving neoadjuvant chemoradiotherapy or not receiving neoadjuvant chemoradiotherapy. Endpoints were post-transplant survival, post-transplant morbidity rate, and time to recurrence. RESULTS: Of 49 patients who underwent liver transplantation for perihilar cholangiocarcinoma, 27 received neoadjuvant chemoradiotherapy and 22 did not. Overall 1-, 3-, and 5-year post-transplantation survival rates were 65 per cent, 51 per cent and 41 per cent respectively in the group receiving neoadjuvant chemoradiotherapy and 91 per cent, 68 per cent and 53 per cent respectively in the group not receiving neoadjuvant chemoradiotherapy (1-year hazards ratio (HR) 4.55 (95 per cent c.i. 0.98 to 21.13), P = 0.053; 3-year HR 2.07 (95 per cent c.i. 0.78 to 5.54), P = 0.146; 5-year HR 1.71 (95 per cent c.i. 0.71 to 4.09), P = 0.229). Hepatic vascular complications were more frequent in the group receiving neoadjuvant chemoradiotherapy compared with the group not receiving neoadjuvant chemoradiotherapy (nine of 27 versus two of 22, P = 0.045). In multivariable analysis, tumour recurrence occurred less frequently in the group receiving neoadjuvant chemoradiotherapy (HR 0.30 (95 per cent c.i. 0.09 to 0.97), P = 0.044). CONCLUSION: In selected patients undergoing liver transplantation for perihilar cholangiocarcinoma, neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications, such as omitting radiotherapy, may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Trasplante de Hígado , Humanos , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Conductos Biliares Intrahepáticos/patologíaRESUMEN
BACKGROUND: Small adult patients with lower bodyweight wait-listed for liver transplantation may face a shortage of size-matched whole-liver grafts. The objective of this study is to compare time to transplantation in adult patients with a bodyweight of <60 kg to patients with bodyweight ≥60 kg. METHODS: A matched case-control study was conducted. Patients aged 18 years and older listed for liver transplantation at our transplant center, from 2007 to 2016 with a bodyweight <60 kg were manually matched 1:2 to control patients ≥ 60 kg. Matching was performed based on ABO blood type, model for end-stage liver disease score, (non)-standard exception status, and eligibility for donation after cardiac death. Time to transplantation was assessed with univariable Cox-regression. RESULTS: In total, 23 cases with a bodyweight < 60 kg were matched to 46 average-sized control patients. Small adults were significantly disadvantaged for receiving a liver transplantation as compared to their average-sized counterpart (hazard ratio 0.47; 95% confidence interval 0.29-0.75, P = .002). At the end of follow-up, 14/23 (60.9%) of cases versus 35/46 of controls (76.1%) had received a liver transplantation. CONCLUSION: Small adults with a bodyweight below 60 kg are disadvantaged on the waitlist for a size-matched whole liver graft.
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Peso Corporal , Trasplante de Hígado/estadística & datos numéricos , Trasplante de Hígado/normas , Selección de Paciente , Obtención de Tejidos y Órganos/estadística & datos numéricos , Obtención de Tejidos y Órganos/normas , Receptores de Trasplantes/estadística & datos numéricos , Listas de Espera , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Orthotopic liver transplantation is an established treatment for end stage liver diseases as well as for some severe metabolic disorders. With increasing number of patients on the waiting list and the ongoing shortage of livers available, domino liver transplantation (DLT) became an option to further expand the organ donor pool. DLT utilizes the explanted liver of one liver transplant recipient as a donor graft in another patient. Despite being a surgically, and logistically demanding procedure, excellent results could be achieved in experienced high-volume transplant centers. In this review we present the current world status of DLT.
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Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Hígado/cirugía , Donadores Vivos , Receptores de Trasplantes , Trasplantes/cirugía , Neuropatías Amiloides Familiares/etiología , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/tendencias , Selección de Paciente , Sistema de Registros , Listas de EsperaRESUMEN
Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).
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Estudios Epidemiológicos , Microbioma Gastrointestinal/genética , Metaboloma/genética , Preparaciones Farmacéuticas , Índice de Masa Corporal , Factores de Confusión Epidemiológicos , Endofenotipos , Humanos , Hígado/metabolismo , Modelos Biológicos , Mapas de Interacción de ProteínasRESUMEN
BACKGROUND: Treatment with immunosuppressive drugs (IS) after transplantation is accompanied by severe side effects. A limited number of studies have investigated the effect of IS withdrawal on IS-related comorbidities after liver transplantation (LTx) and the results are contradictory. PATIENTS AND METHODS: We determined in a retrospective case-control study the clinical effects of complete IS withdrawal in operationally tolerant (TOL) LTx recipients who discontinued IS 10.8 ± 5.1 years after LTx (n = 13) compared with a completely matched control (CTRL) group with a regular IS regimen (n = 22). TOL recipients have been IS and rejection free for 4.0 ± 2.8 years. RESULTS: IS withdrawal in TOL recipients resulted in lower low-density lipoprotein levels (P = 0.027), whereas this was not observed in the CTRL group. Furthermore, persistent infections in individual recipients were resolved successfully by IS withdrawal. TOL recipients also had significantly fewer de novo infections after IS withdrawal (TOL pre vs. post withdrawal P = 0.0247) compared with recipients continued on IS during the same follow-up period (post withdrawal TOL vs. CTRL P = 0.044). Unfortunately, no improvement in kidney function, and lower rates of de novo occurrences of diabetes, hypertension, cardiovascular diseases, and malignancies were observed in the TOL group after IS withdrawal compared with the CTRL group during the same follow-up time period. CONCLUSION: IS withdrawal late after LTx reduces infection rates and low-density lipoprotein levels, but other IS-related side effects persist late after LTx. An accurate tolerance immune profile enabling identification of tolerant LTx recipients eligible for safe IS withdrawal earlier after transplantation is needed to prevent the development of irreversible IS-related side effects.
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Deprescripciones , Dislipidemias/inducido químicamente , Rechazo de Injerto/prevención & control , Tolerancia Inmunológica/inmunología , Inmunosupresores/efectos adversos , Infecciones/etiología , Trasplante de Hígado , Insuficiencia Renal/inducido químicamente , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares , Estudios de Casos y Controles , LDL-Colesterol/metabolismo , Diabetes Mellitus , Dislipidemias/metabolismo , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto/inmunología , Humanos , Hipertensión , Masculino , Persona de Mediana Edad , Neoplasias , Insuficiencia Renal/metabolismo , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.
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Capilares , Hipertensión Portal/clasificación , Enfermedades Vasculares/clasificación , Vénulas , Humanos , Hipertensión Portal/diagnóstico , Sistema Porta , Vena Porta , Enfermedades Vasculares/diagnósticoRESUMEN
In November 2018, yellow fever was diagnosed in a Dutch traveller returning from a bicycle tour in the Gambia-Senegal region. A complete genome sequence of yellow fever virus (YFV) from the case was generated and clustered phylogenetically with YFV from the Gambia and Senegal, ruling out importation into the Netherlands from recent outbreaks in Brazil or Angola. We emphasise the need for increased public awareness of YFV vaccination before travelling to endemic countries.
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Insectos Vectores/virología , Viaje , Fiebre Amarilla/diagnóstico , Virus de la Fiebre Amarilla/genética , Virus de la Fiebre Amarilla/aislamiento & purificación , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Animales , Brotes de Enfermedades , Gambia , Humanos , Mordeduras y Picaduras de Insectos , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/etiología , Países Bajos , Filogenia , Reacción en Cadena de la Polimerasa , Senegal , Secuenciación Completa del Genoma , Fiebre Amarilla/virología , Adulto JovenRESUMEN
The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1500 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
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Enfermedad Crónica/epidemiología , Diseño de Investigaciones Epidemiológicas , Esperanza de Vida/tendencias , Vigilancia de la Población/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. METHODS: We conducted an epigenome-wide association study in whole blood for liver enzyme levels, including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals. Significant DNA methylation changes were further analyzed to evaluate their relation with hepatic steatosis. Expression levels of the top identified gene were measured in 9 human liver cell lines and compared with expression profiles of its potential targets associated with lipid traits. The candidate gene was subsequently knocked down in human hepatoma cells using lentiviral vectors expressing small hairpin RNAs. RESULTS: Eight probes annotated to SLC7A11, SLC1A5, SLC43A1, PHGDH, PSORS1C1, SREBF1, ANKS3 were associated with GGT and 1 probe annotated to SLC7A11 was associated with ALT after Bonferroni correction (1.0 × 10-7). No probe was identified for AST levels. Four probes for GGT levels including cg06690548 (SLC7A11), cg11376147 (SLC43A1), cg22304262 (SLC1A5), and cg14476101 (PHGDH), and 1 for ALT cg06690548 (SLC7A11) were replicated. DNA methylation at SLC7A11 was associated with reduced risk of hepatic steatosis in participants (odds ratio, 0.69; 95% CI= 0.55-0.93; P value: 2.7 × 10-3). In functional experiments, SLC7A11 was highly expressed in human liver cells; its expression is positively correlated with expression of a panel of lipid-associated genes, indicating a role of SLC7A11 in lipid metabolism. CONCLUSIONS: Our results provide new insights into epigenetic mechanisms associated with markers of liver function and hepatic steatosis, laying the groundwork for future diagnostic and therapeutic applications.
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Alanina Transaminasa/sangre , Sistema de Transporte de Aminoácidos y+/genética , Aspartato Aminotransferasas/sangre , Metilación de ADN , Epigénesis Genética , Hígado Graso/genética , Metabolismo de los Lípidos/genética , gamma-Glutamiltransferasa/sangre , Anciano , Anciano de 80 o más Años , Sistema de Transporte de Aminoácidos ASC/genética , Sistema de Transporte de Aminoácidos ASC/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+L/genética , Sistema de Transporte de Aminoácidos y+L/metabolismo , Biomarcadores/sangre , Línea Celular Tumoral , Islas de CpG , Hígado Graso/sangre , Hígado Graso/enzimología , Hígado Graso/prevención & control , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Análisis de la Aleatorización Mendeliana , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor/genética , Antígenos de Histocompatibilidad Menor/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Países Bajos , Oportunidad Relativa , Fenotipo , Fosfoglicerato-Deshidrogenasa/genética , Fosfoglicerato-Deshidrogenasa/metabolismo , Factores Protectores , Interferencia de ARN , Medición de Riesgo , Factores de Riesgo , TransfecciónRESUMEN
AIMS: Increasing evidence suggests involvement of the amount of liver fat in the development of cardiovascular disease. We investigated the relation of liver fat with cardiovascular risk factors and subclinical vascular disease in the general population. METHODS AND RESULTS: Between 2003 and 2006, 2351 persons from the population-based Rotterdam Study (mean age 69.6 ± 6.7 years, 47.2% males) underwent non-enhanced computed tomography. We measured the mean liver attenuation value in Hounsfield units and quantified the following markers of subclinical vascular disease: epicardial fat volume and volumes of coronary (CAC), aortic (AAC), extracranial (ECAC), and intracranial carotid calcification (ICAC). Using linear regression, we investigated associations between traditional cardiovascular risk factors and mean liver attenuation. We also investigated relations of mean liver attenuation with markers of subclinical vascular disease, adjusting for cardiovascular risk factors. We found strong associations of waist circumference, diastolic blood pressure, and diabetes with lower mean liver attenuation [multivariable-adjusted beta per unit increase in waist circumference: -2.54 (95% CI: -3.10; -1.99); diastolic blood pressure: -0.52 (95% CI: -0.88; -0.17); and the presence of diabetes: -21.91 (95% CI: -31.76; -12.06)]. Moreover, we found that larger mean liver attenuation values were associated with smaller volumes of epicardial fat and CAC, independent of cardiovascular risk factors [beta per 1-SD increase in mean liver attenuation value: -0.05 (95% CI: -0.08; -0.02) and -0.05 (95% CI: -0.10; -0.01), respectively]. CONCLUSION: Larger amounts of liver fat are related to larger volumes of epicardial fat and CAC, independent of traditional cardiovascular risk factors, providing important novel insights into the role of liver fat as a marker of vascular disease.