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BACKGROUND: Central collection of distributed medical patient data is problematic due to strict privacy regulations. Especially in clinical environments, such as clinical time-to-event studies, large sample sizes are critical but usually not available at a single institution. It has been shown recently that federated learning, combined with privacy-enhancing technologies, is an excellent and privacy-preserving alternative to data sharing. OBJECTIVE: This study aims to develop and validate a privacy-preserving, federated survival support vector machine (SVM) and make it accessible for researchers to perform cross-institutional time-to-event analyses. METHODS: We extended the survival SVM algorithm to be applicable in federated environments. We further implemented it as a FeatureCloud app, enabling it to run in the federated infrastructure provided by the FeatureCloud platform. Finally, we evaluated our algorithm on 3 benchmark data sets, a large sample size synthetic data set, and a real-world microbiome data set and compared the results to the corresponding central method. RESULTS: Our federated survival SVM produces highly similar results to the centralized model on all data sets. The maximal difference between the model weights of the central model and the federated model was only 0.001, and the mean difference over all data sets was 0.0002. We further show that by including more data in the analysis through federated learning, predictions are more accurate even in the presence of site-dependent batch effects. CONCLUSIONS: The federated survival SVM extends the palette of federated time-to-event analysis methods by a robust machine learning approach. To our knowledge, the implemented FeatureCloud app is the first publicly available implementation of a federated survival SVM, is freely accessible for all kinds of researchers, and can be directly used within the FeatureCloud platform.
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Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Hipertensão Portal , Cirrose Hepática , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Hipertensão Portal/complicações , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/fisiopatologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologiaRESUMO
BACKGROUND & AIMS: The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. METHODS: We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. RESULTS: A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. CONCLUSIONS: The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. IMPACT AND IMPLICATIONS: The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.
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Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Antineoplásicos Imunológicos/efeitos adversos , Masculino , Melanoma/tratamento farmacológico , Melanoma/imunologia , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Fígado/patologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Pessoa de Meia-Idade , IdosoRESUMO
INTRODUCTION: Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites. METHODS AND ANALYSIS: ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis. ETHICS AND DISSEMINATION: The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion. TRIAL REGISTRATION NUMBER: NCT05056220 EU CT: 2022-501006-34-01.
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Transplante de Fígado , Albumina Sérica Humana , Humanos , Albumina Sérica Humana/uso terapêutico , Ascite/terapia , Cirrose Hepática/complicações , Resultado do Tratamento , Biomarcadores , Método Duplo-CegoRESUMO
Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Humanos , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/terapia , Qualidade de Vida , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , BiomarcadoresRESUMO
BACKGROUND & AIMS: Alcoholic foamy degeneration (AFD) is a condition with similar clinical presentation to alcohol-associated hepatitis (AH), but with a specific histologic pattern. Information regarding the prevalence and prognosis of AFD is scarce and there are no tools for a noninvasive diagnosis. METHODS: A cohort of patients admitted to the Hospital Clinic of Barcelona for clinical suspicion of AH who underwent liver biopsy was included. Patients were classified as AFD, AH, or other findings, according to histology. Clinical features, histology, and genetic expression of liver biopsy specimens were analyzed. The accuracy of National Institute on Alcohol Abuse and Alcoholism criteria and laboratory parameters for differential diagnosis were investigated. RESULTS: Of 230 patients with a suspicion of AH, 18 (8%) met histologic criteria for AFD, 184 (80%) had definite AH, and 28 (12%) had other findings. In patients with AFD, massive steatosis was more frequent and the fibrosis stage was lower. AFD was characterized by down-regulation of liver fibrosis and inflammation genes and up-regulation of lipid metabolism and mitochondrial function genes. Patients with AFD had markedly better long-term survival (100% vs 57% in AFD vs AH; P = .002) despite not receiving corticosteroid treatment, even in a model for end-stage liver disease-matched sensitivity analysis. Serum triglyceride levels had an area under the receiver operating characteristic of 0.886 (95% CI, 0.807-0.964) for the diagnosis of AFD, whereas the National Institute on Alcohol Abuse and Alcoholism criteria performed poorly. A 1-step algorithm using triglyceride levels of 225 mg/dL (sensitivity, 0.77; specificity, 0.90; and Youden index, 0.67) is proposed for differential diagnosis. CONCLUSIONS: AFD in the setting of suspicion of AH is not uncommon. A differential diagnosis is important because prognosis and treatment differ largely. Triglyceride levels successfully identify most patients with AFD and may be helpful in decision making.
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Doença Hepática Terminal , Hepatite Alcoólica , Humanos , Índice de Gravidade de Doença , Hepatite Alcoólica/patologia , Prognóstico , TriglicerídeosRESUMO
BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
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Doença Hepática Terminal , Cirrose Hepática , Humanos , Prognóstico , Estudos Prospectivos , Cirrose Hepática/complicações , Interleucina-6 , Índice de Gravidade de Doença , BiomarcadoresRESUMO
Background & Aims: : The accumulation of adipose tissue macrophages (ATMs) in obesity has been associated with hepatic injury. However, the contribution of ATMs to hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Herein, we investigate the relationship between ATMs and liver fibrosis in patients with patients with NAFLD and evaluate the impact of modulation of ATMs over hepatic fibrosis in an experimental non-alcoholic steatohepatitis (NASH) model. Methods: Adipose tissue and liver biopsies from 42 patients with NAFLD with different fibrosis stages were collected. ATMs were characterised by immunohistochemistry and flow cytometry and the correlation between ATMs and liver fibrosis stages was assessed. Selective modulation of the ATM phenotype was achieved by i.p. administration of dextran coupled with dexamethasone in diet-induced obesity and NASH murine models. Chronic administration effects were evaluated by histology and gene expression analysis in adipose tissue and liver samples. In vitro crosstalk between human ATMs and hepatic stellate cells (HSCs) and liver spheroids was performed. Results: Patients with NAFLD presented an increased accumulation of pro-inflammatory ATMs that correlated with hepatic fibrosis. Long-term modulation of ATMs significantly reduced pro-inflammatory phenotype and ameliorated adipose tissue inflammation. Moreover, ATMs modulation was associated with an improvement in steatosis and hepatic inflammation and significantly reduced fibrosis progression in an experimental NASH model. In vitro, the reduction of the pro-inflammatory phenotype of human ATMs with dextran-dexamethasone treatment reduced the secretion of inflammatory chemokines and directly attenuated the pro-fibrogenic response in HSCs and liver spheroids. Conclusions: Pro-inflammatory ATMs increase in parallel with fibrosis degree in patients with NAFLD and their modulation in an experimental NASH model improves liver fibrosis, uncovering the potential of ATMs as a therapeutic target to mitigate liver fibrosis in NAFLD. Impact and implications: We report that human adipose tissue pro-inflammatory macrophages correlate with hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Furthermore, the modulation of adipose tissue macrophages (ATMs) by dextran-nanocarrier conjugated with dexamethasone shifts the pro-inflammatory phenotype of ATMs to an anti-inflammatory phenotype in an experimental murine model of non-alcoholic steatohepatitis. This shift ameliorates adipose tissue inflammation, hepatic inflammation, and fibrosis. Our results highlight the relevance of adipose tissue in NAFLD pathophysiology and unveil ATMs as a potential target for NAFLD.
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BACKGROUND: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS: We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).
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Cirrose Hepática , Humanos , Prognóstico , Estudos Prospectivos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Fatores de Risco , FibroseRESUMO
Acute-on-chronic liver failure (ACLF) is a complex syndrome defined by the existence of different organ failures (OFs) in patients with chronic liver disease, mainly cirrhosis. Several definitions have been proposed to define the syndrome, varying in the grade of the subjacent liver disease, the type of precipitants and the organs considered in the definition. Liver, coagulation, brain, kidney, circulatory and pulmonary are the six types of OFs proposed in the different classifications, with different prevalence worldwide. Irrespective of the definition used, patients who develop ACLF present a hyperactive immune system, profound haemodynamic disturbances and several metabolic alterations that finally lead to organ dysfunction. These disturbances are triggered by different factors such as bacterial infections, alcoholic hepatitis, gastrointestinal bleeding or hepatitis B virus flare, among others. Because patients with ACLF present high short-term mortality, a prompt recognition is needed to start treatment of the trigger event and specific organ support. Liver transplantation is also feasible in carefully selected patients and should be evaluated.
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Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Humanos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Biomarcadores , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/complicações , RimRESUMO
BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).
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Técnicas de Imagem por Elasticidade , Cirrose Hepática , Programas de Rastreamento , Biópsia , Técnicas de Imagem por Elasticidade/métodos , Europa (Continente) , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Programas de Rastreamento/métodosRESUMO
Impairment of kidney function is common in acute-on-chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill-defined. Aims of the current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. This prospective study includes 639 admissions for AD (232 with ACLF; 407 without) in 518 patients. Data were collected at admission and during hospitalization, and patients were followed up for 3 months. Urine samples were analyzed for kidney biomarkers. Most patients with ACLF (92%) had associated acute kidney injury (AKI), in most cases without previous chronic kidney disease (CKD), whereas some had AKI-on-CKD (70% and 22%, respectively). Prevalence of AKI in patients without ACLF was 35% (p < 0.001 vs. ACLF). Frequency of CKD alone was low and similar in both groups (4% and 3%, respectively); only a few patients with ACLF (4%) had no kidney dysfunction. AKI in ACLF was associated with poor kidney and patient outcomes compared with no ACLF (AKI resolution: 54% vs. 89%; 3-month survival: 51% vs. 86%, respectively; p < 0.001 for both). Independent predictive factors of 3-month survival were Model for End-Stage Liver Disease-Sodium score, ACLF status, and urine neutrophil gelatinase-associated lipocalin (NGAL). AKI is almost universal in patients with ACLF, sometimes associated with CKD, whereas CKD alone is uncommon. Prognosis of AKI depends on ACLF status. AKI without ACLF has good prognosis. Best predictors of 3-month survival are MELD-Na, ACLF status, and urine NGAL.
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Injúria Renal Aguda , Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Insuficiência Renal Crônica , Injúria Renal Aguda/diagnóstico , Insuficiência Hepática Crônica Agudizada/diagnóstico , Doença Hepática Terminal/complicações , Humanos , Lipocalina-2 , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND AIMS: Stigmatization is a well-documented problem of some diseases. Perceived stigma is common in alcohol-related liver disease and hepatitis C, but little information exists on stigma in patients with non-alcoholic fatty liver disease (NAFLD). Aim of the study was to investigate frequency and characteristics of perceived stigma among patients with NAFLD. METHODS: One-hundred and ninety-seven patients seen at the liver clinic were included: a study group of 144 patients with NAFLD, 50 with cirrhosis (34 compensated, 16 decompensated), and a control group of 53 patients with alcohol-related cirrhosis. Demographic, clinical, and laboratory data were collected. Quality-of-life was assessed by chronic liver disease questionnaire (CLDQ). Perceived stigma was assessed using a specific questionnaire for patients with liver diseases categorized in 4 domains: stereotypes, discrimination, shame, and social isolation. RESULTS: Perceived stigma was common in patients with NAFLD (99 patients, 69%) and affected all 4 domains assessed. The frequency was slightly higher, yet not significant, in patients with NAFLD cirrhosis vs those without (72% vs 67%, respectively; p = 0.576). In patients without cirrhosis perceived stigma was unrelated to stage of disease, since frequency was similar in patients with no or mild fibrosis compared to those with moderate/severe fibrosis (66% vs 68%, respectively). There were no differences in perceived stigma between patients with compensated cirrhosis and these with decompensated cirrhosis. Among patients with cirrhosis, stigmatization was more common in alcohol-related vs NAFLD-cirrhosis, yet differences were only significant in two domains. In patients with NAFLD, perceived stigma correlated with poor quality-of-life, but not with demographic or clinical variables. CONCLUSIONS: Perceived stigmatization is common among patients with NAFLD independently of disease stage, is associated with impaired quality-of-life, and may be responsible for stereotypes, discrimination, shame, and social isolation, which may affect human and social rights of affected patients.