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2.
Aliment Pharmacol Ther ; 60(6): 749-764, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38973133

RESUMEN

BACKGROUND/AIMS: Although it is well admitted that cirrhotic patients display various causes of neurocognitive impairment (NI) hampering the diagnosis of covert hepatic encephalopathy (CHE), those are almost never investigated per se. The aims of this study were, in cirrhotic patients displaying cognitive complaints explored by a complete multimodal work-up, to assess: (1) the prevalence of CHE and/or that of other causes of NI and (2) their outcomes, according to the cause of NI. METHODS: Prospective cohort of cirrhotic patients referred in a dedicated clinic because of cognitive complaints. Work-up included a complete neuropsychological assessment, electroencephalogram (EEG) and brain magnetic resonance imaging with spectroscopy. The diagnosis of CHE was made by an adjudication committee involving the physicians/neuropsychologist. RESULTS: One hundred and twenty-three patients were included (alcohol/MASLD/virus in 63/53/14%, MELD = 11). Sixty-six per cent of them were diagnosed with CHE; among them, 73% exhibited also other causes of NI, mainly cerebrovascular diseases/psychiatric. Among patients without CHE, 48% and 59% displayed pathological Psychometric Hepatic Encephalopathy Score and animal naming test, respectively. Clinical improvement was observed in 77% of the patients re-evaluated after specific management. CHE, but not the other causes of NI, was independently associated with OHE occurrence. CONCLUSION: Other causes of NI than CHE are frequent in patients with cirrhosis, and not ruled-out by the classical tests dedicated to CHE. Prognosis was influenced by the cause of NI. The management of patients even without CHE led to clinical improvement, underlining the need for a multifaceted approach of cirrhotic patients with cognitive complaints.


Asunto(s)
Disfunción Cognitiva , Encefalopatía Hepática , Cirrosis Hepática , Pruebas Neuropsicológicas , Humanos , Encefalopatía Hepática/psicología , Masculino , Femenino , Cirrosis Hepática/complicaciones , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Disfunción Cognitiva/etiología , Electroencefalografía , Imagen por Resonancia Magnética , Adulto , Prevalencia
3.
Aliment Pharmacol Ther ; 60(6): 796-810, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39034817

RESUMEN

BACKGROUND AND AIMS: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related cirrhosis has been increasing these last decades. There are no data regarding the prevalence of MASLD-related cirrhosis in intensive care unit (ICU). METHODS: Prospective single-centre study in a cohort of patients hospitalized in the ICU of Hepatology La Pitié-Salpêtrière Hospital between January 2019 and September 2021. We analysed three groups of patients: MASLD-cirrhosis (alcohol ≤210 g for men and 140 g weekly for women), ALD (alcohol-related liver disease, alcohol>140 g weekly for women or >210 g for men)-cirrhosis alone and MetALD (metabolic and alcohol-related liver disease)-cirrhosis. Endpoints were 1-year transplant-free survival (TFS), further acute decompensation (AD) and re-admission. RESULTS: A total of 410 patients were hospitalized, and 315 analysed: 39 in MASLD, 160 in ALD and 116 in MetALD groups. The global prevalence was 10% for MASLD, 41% ALD and 29.7% for MetALD. Patients in the MASLD group were significantly older (65 vs. 57 and 59 years, p < 0.001), and had lower Child-Pugh (8 vs. 11 vs. 10, p < 0.001) and MELD score (17 vs. 22 vs. 21, p < 0.001). The 1-year TFS was not different between groups (53% vs. 54% vs. 54%, p = 0.96). Cardiovascular mortality was <5% in all groups. The 1-year probability of developing hepatic encephalopathy was significantly higher in the MASLD group (73% vs. 27% and 21%, p < 0.001). There was no difference regarding the development of other complications between groups. CONCLUSION: MASLD or MetALD was responsible for 1/3 of the causes of cirrhosis in the ICU. MASLD-related cirrhosis is as severe as ALD-related cirrhosis. Liver transplantation should be rapidly discussed.


Asunto(s)
Hospitalización , Unidades de Cuidados Intensivos , Cirrosis Hepática , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Francia/epidemiología , Prevalencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/epidemiología , Anciano , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pronóstico , Hospitalización/estadística & datos numéricos , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Adulto
4.
JHEP Rep ; 6(8): 101104, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39035069

RESUMEN

Background & Aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation. Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication. Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.

5.
Hepatol Commun ; 8(5)2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38701395

RESUMEN

BACKGROUND: Minimal hepatic encephalopathy, defined by the portosystemic hepatic encephalopathy score (PHES), is associated with a higher risk of subsequent OHE. It remains unclear if there is a stepwise increase in OHE risk with worse PHES results. METHODS: In this multicenter study, patients with minimal hepatic encephalopathy, as defined by abnormal PHES, were followed for OHE development. RESULTS: In all, 207 patients were included. There was no stepwise increase in OHE risk with worse PHES results. CONCLUSIONS: Abnormal PHES is associated with a higher OHE risk, but we found no stepwise increase in OHE risk with worse PHES results below the established cutoff.


Asunto(s)
Encefalopatía Hepática , Humanos , Masculino , Encefalopatía Hepática/etiología , Femenino , Persona de Mediana Edad , Anciano , Índice de Severidad de la Enfermedad , Factores de Riesgo , Medición de Riesgo , Adulto
6.
J Intensive Med ; 4(2): 222-230, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38681783

RESUMEN

Background: Hepatic encephalopathy (HE) is highly prevalent in patients with liver diseases. The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation. However, some data suggest altered functioning of the blood-brain barrier (BBB). Assessing BBB function is challenging in clinical practice and at the bedside. Protein-S-100 Beta (PS100-Beta) could be a useful peripheral marker of BBB permeability in HE. This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit (ICU) with decompensated cirrhosis with and without overt HE. Methods: We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement. Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded. Overt HE was defined as West-Haven grades 2 to 4. The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes. After ICU discharge, the patients were followed for at least 3 months for the occurrence of overt HE. Adverse outcomes (liver transplantation or death) were collected. The ability of PS100-Beta - in combination with other factors - to predict overt HE was evaluated in a multivariate analysis using logistic regression. Likelihood ratios were used to determine the effects and calculate odds ratios (OR). Survival analysis was performed by using the Kaplan-Meier method and survival between groups was compared using a Log-rank test. Results: A total of 194 ICU patients and 207 outpatients were included in the study. Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients ([0.15±0.01] mg/L vs. [0.08±0] mg/L, P <0.001). ICU patients with overt HE had higher levels of PS100-Beta ([0.19±0.03] mg/L) compared with the ICU patients without overt HE ([0.13±0.01] mg/L) (P=0.003). PS100-Beta levels did not differ in outpatients with F 0-3 compared to F 4 fibrosis (P=0.670). PS100-Beta values were correlated with Child-Pugh score (P <0.001), Model for End-Stage Liver Disease (MELD) score (P=0.004), C-reactive protein (P <0.001), ammonemia (P <0.001), and chronic liver failure consortium (CLIF-C) organ failure (P <0.001) and CLIF-C acute-on-chronic (P=0.038) scores, but not with leukocytes (P=0.053), procalcitonin (PCT) (P=0.107), or the lymphocyte-to-neutrophil ratio in ICU patients (P=0.522). In a multivariate model including age, ammonemia, PS100-Beta, PCT, MELD, presence of transjugular portosystemic shunt, and sodium level, the diagnostic performance was 0.765 for the diagnosis of overt HE. Patients with a PS100-Beta level <0.12 mg/L had a better overall survival (P=0.019) and a better survival without liver transplantation (P=0.013). Conclusions: Serum levels of PS100-Beta are elevated in ICU patients with decompensated cirrhosis, and even more so in those displaying overt HE, and the levels are correlated with outcome. This suggests an increase in the permeability of the BBB in these patients.

7.
Dig Liver Dis ; 56(9): 1621-1630, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38548580

RESUMEN

BACKGROUND: Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence. METHODS: A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves). RESULTS: Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03-3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52-3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB. CONCLUSIONS: PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Ascitis , Bevacizumab , Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Hipertensión Portal , Neoplasias Hepáticas , Humanos , Masculino , Femenino , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Persona de Mediana Edad , Anciano , Bevacizumab/uso terapéutico , Bevacizumab/efectos adversos , Bevacizumab/administración & dosificación , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Várices Esofágicas y Gástricas/etiología , Estudios Prospectivos , Ascitis/etiología , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/etiología , Sorafenib/uso terapéutico , Sorafenib/efectos adversos , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Modelos de Riesgos Proporcionales
8.
Liver Int ; 44(4): 931-943, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38291735

RESUMEN

INTRODUCTION: It has been suggested that in patients with hepatocellular carcinoma (HCC) of metabolic aetiology, the efficacy of immunotherapy may be reduced. The aim was to investigate the impact of metabolic-associated steatotic liver disease (MASLD) and metabolic risk factors (MRF) on the outcomes of Atezolizumab-Bevacizumab (AtezoBev). METHODS: We collected data from 295 AtezoBev-treated patients, starting in 2020. MASLD was defined by the current/past presence of MRF, namely BMI ≥ 30 kg/m2, type 2 diabetes, arterial hypertension or dyslipidaemia and no other cause of liver disease (daily alcohol ≤30 g in males and ≤20 g in females). The influence of baseline characteristics on progression (PFS) and overall survival (OS) was assessed by uni/multivariate analysis using the Cox model. RESULTS: Risk factors for cirrhosis were viral infection in 47%, excessive alcohol consumption in 45% and MASLD in 13%. In the whole cohort, 27% had 1 MRF, 23% had 2 MRF, 15% had 3 MRF and 6% had 4 MRF. Median PFS and OS were 6.5 and 15.6 months, respectively, and similar in patients with or without MASLD in Log rank analysis. The number of MRF or MALSD was not associated with PFS or OS in the univariate analysis. Factors associated with PFS in multivariate analysis included ALBI grade 3 (HR = 1.60, p = .03), AFP (HR = 1.01, p = .01) and metastasis (HR = 1.77, p < .001). During follow-up, 10% of patients experienced immune-related adverse events, with age and female gender, but not MRF or MASLD, as independent predictors. CONCLUSION: Our study suggests that the presence of MASLD or the number of MRF did not lead to worse outcomes in advanced HCC patients treated with AtezoBev.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hígado Graso , Neoplasias Hepáticas , Enfermedades Metabólicas , Masculino , Humanos , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico
9.
Hepatology ; 79(1): 49-60, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37870270

RESUMEN

BACKGROUND AND AIMS: We aim to assess the role of radiological response to atezolizumab-bevacizumab in patients with HCC to predict overall survival. APPROACH AND RESULTS: We retrospectively included patients with HCC treated by atezolizumab-bevacizumab in 2 tertiary centers. A retrospective blinded analysis was performed by 2 radiologists to assess Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and modified RECIST (mRECIST) criteria at 12 weeks. Imaging response and treatment decisions in the multidisciplinary tumor board at 12 weeks were registered. Among 125 patients, 9.6% and 20.8% had a response, 39.2% and 35.2% had stable disease, and 51.2% and 44% had progression, according to RECIST 1.1 and mRECIST, respectively, with a substantial interobserver agreement (k coefficient=0.79). Metastasis was independently associated with a higher risk of progression. Patients classified as responders did not reach median survival, which was 16.2 and 15.9 months for patients classified as stable and 9.1 and 9.0 months for patients classified as progressors, in RECIST 1.1 and mRECIST criteria, respectively. We observed a wide variability in the identification of progression in the multidisciplinary tumor board in clinical practice compared with the blind evaluation by radiologists mainly due to discrepancy in the evaluation of the increase in size of intrahepatic lesions. The appearance of new extrahepatic lesions or vascular invasion lesions was associated with a worse overall survival ( p =0.032). CONCLUSIONS: RECIST 1.1 and mRECIST criteria predict overall survival with more responders identified by mRECIST and the appearance of new extrahepatic lesion or vascular invasion was associated with a poor prognosis. A noticeable discrepancy was observed between patients classified as progressors at reviewing and the decision reached during the multidisciplinary tumor board.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Bevacizumab/uso terapéutico , Tomografía Computarizada por Rayos X
10.
J Intern Med ; 295(3): 331-345, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37983845

RESUMEN

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. METHODS: Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). RESULTS: A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. CONCLUSIONS: This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival.


Asunto(s)
Encefalopatía Hepática , Humanos , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/diagnóstico , Cirrosis Hepática/complicaciones , Psicometría , Europa (Continente)
11.
Clin Res Hepatol Gastroenterol ; 48(3): 102274, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38154597

RESUMEN

Hepatic encephalopathy (HE) is a severe complication of cirrhosis, independently associated with a poor survival. The objectives of this study were to describe the prevalence of overt hepatic encephalopathy (OHE) requiring hospitalization, and the healthcare pathways and outcomes of patients hospitalized for OHE in France. Data from the French Hospital-Discharge Database (Programme de Medicalisation des Systemes d'information, PMSI) within the 5-year period from 2014 to 2018 were analysed. Since the disease lacks a PMSI code in the ICD-10, an identification algorithm was developed. The analysis identified 57,191 patients with OHE including 48,566 patients (85 %) who had been hospitalized twice or more during the study period. Each year, an average of over 20,000 patients were hospitalized in France for OHE as the primary or secondary reason for hospitalization. Among these patients, between 11,500 and 13,500 had been hospitalized at least twice in that year with an average of 3.4 hospitalisations per year. 25 % of admissions occurred following consultation at the emergency unit. Among hospitalisations, 15 % involved admission to the critical care resuscitation unit or intensive care. For all patients identified as suffering from OHE and hospitalized, the 5-year mortality was 46.5 % (26,621 patients). This pioneering study revealed that, in France, despite a probable underestimation of OHE episodes due to the lack of specific PMSI coding, the prevalence of OHE was very high, with frequent recurrences and readmissions, and high mortality.


Asunto(s)
Encefalopatía Hepática , Alta del Paciente , Humanos , Encefalopatía Hepática/epidemiología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/terapia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Francia/epidemiología , Hospitales
12.
Clin Res Hepatol Gastroenterol ; 47(8): 102199, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37666414

RESUMEN

BACKGROUND: Long-term albumin infusions have been associated with improved outcomes in decompensated cirrhotic patients. This study aimed to evaluate the impact of albumin infusion on the prognosis of Child-Pugh B patients undergoing treatment with AtezoBev for advanced hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective multicentric study that included all Child-Pugh B cirrhotic patients treated with AtezoBev since 2020. We examined the effects of albumin infusion (40 g every 3 weeks) on overall survival (OS) and the occurrence of cirrhosis-related complications. Time-to-event data were analyzed using Kaplan-Meier with the log-rank test and Cox models. RESULTS: Forty-seven HCC patients with a Child-Pugh B score who received AtezoBev were included, of whom 26% also received albumin infusions every 3 weeks. The two groups were similar in terms of liver function and HCC parameters. The median OS was 4.4 and 5.8 months (p = 0.42) for patients who did or did not receive albumin, respectively. The occurrence of hepatic encephalopathy and variceal bleeding was similar between the two groups. However, albumin infusions were associated with a significantly lower rate of ascites expansion/development (13% versus 57%, p = 0.005). Cox analysis revealed that a history of ascites (HR=3.82 [95% CI: 1.73-8.48]) was independently associated with a higher risk of ascites expansion/development, whereas albumin infusions were protective (HR=0.07 [95% CI: 0.01-0.54]). CONCLUSIONS: Albumin infusion did not improve overall survival in Child-Pugh B HCC patients treated with AtezoBev, but it significantly reduced the expansion/development of ascites.


Asunto(s)
Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Retrospectivos , Várices Esofágicas y Gástricas/complicaciones , Ascitis/complicaciones , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Albúminas
13.
Hepatology ; 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37183906

RESUMEN

Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.

14.
Am J Gastroenterol ; 118(12): 2191-2200, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36940426

RESUMEN

INTRODUCTION: The prevalence of minimal hepatic encephalopathy (MHE), in particular in different subgroups, remains unknown. This study aimed to analyze the prevalence of MHE in different subgroups to identify patients at high risk and to pave the way for personalized screening approaches. METHODS: In this study, data of patients recruited at 10 centers across Europe and the United States were analyzed. Only patients without clinical signs of hepatic encephalopathy were included. MHE was detected using the Psychometric Hepatic Encephalopathy Score (PHES, cut-off < or ≤-4 depending on local norms). Clinical and demographic characteristics of the patients were assessed and analyzed. RESULTS: In total, 1,868 patients with cirrhosis with a median model for end-stage liver disease (MELD) of 11 were analyzed (Child-Pugh [CP] stages: A 46%, B 42%, and C 12%). In the total cohort, MHE was detected by PHES in 650 patients (35%). After excluding patients with a history of overt hepatic encephalopathy, the prevalence of MHE was 29%. In subgroup analyses, the prevalence of MHE in patients with CP A was low (25%), whereas it was high in CP B or C (42% and 52%). In patients with a MELD score <10, the prevalence of MHE was only 25%, but it was 48% in patients with a MELD score ≥20. Standardized ammonia levels (ammonia level/upper limit of normal of each center) correlated significantly, albeit weakly with PHES (Spearman ρ = -0.16, P < 0.001). DISCUSSION: The prevalence of MHE in patients with cirrhosis was high but varied substantially between diseases stages. These data may pave the way for more individualized MHE screening approaches.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Encefalopatía Hepática , Humanos , Encefalopatía Hepática/epidemiología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Prevalencia , Amoníaco , Índice de Severidad de la Enfermedad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Psicometría
15.
Liver Int ; 42(12): 2843-2854, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36254617

RESUMEN

BACKGROUND: Atezolizumab-bevacizumab is the new standard for advanced hepatocellular carcinoma (HCC) but its impact on portal hypertension (PHT) is unknown. We aimed to identify predictive factors of acute variceal bleeding (AVB) and to monitor PHT parameters under treatment. METHODS: We conducted a prospective study including all cirrhotic patients treated with atezolizumab-bevacizumab since 2020. We performed monitoring of PHT using upper endoscopy at inclusion and at 6 months and hepatic venous pressure gradient (HVPG) at inclusion, 3 and 6 months after the beginning of treatment. We also included a retrospective series of patients treated with sorafenib. Time-to-events data were estimated by Kaplan-Meier with the log-rank test, along with Cox models. RESULTS: Forty-three patients treated with atezolizumab-bevacizumab were included (male 79.1%, Child-Pugh A 86%). At baseline, 48.8% were treated with curative anticoagulation, 16.3% already experienced AVB and 25.6% had large oesophageal varices (EV). Sorafenib group characteristics were similar. Vascular invasion was present in 60.5% and median was HVPG 8.5 mm Hg. No significant modification in HVPG and EV size was observed at 6 months in the whole cohort but also when considering vascular invasion and radiological response. 14% presented AVB within a median time of occurrence of 3 months, without bleeding-related death. In multivariate analysis, history of AVB (HR = 10.58, p = .03) was associated with AVB. AVB incidence was higher in atezolizumab-bevacizumab compared to sorafenib group (21% vs. 5% at 1 year, p = .02). CONCLUSIONS: Atezolizumab-bevacizumab treatment was associated with a higher risk of AVB compared to sorafenib. A history of AVB was associated with AVB during follow-up, which questions the use of bevacizumab in this setting.


Asunto(s)
Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Neoplasias Hepáticas , Humanos , Masculino , Várices Esofágicas y Gástricas/complicaciones , Carcinoma Hepatocelular/complicaciones , Bevacizumab/efectos adversos , Estudios Retrospectivos , Estudios Prospectivos , Hemorragia Gastrointestinal/etiología , Cirrosis Hepática/complicaciones , Sorafenib/uso terapéutico , Neoplasias Hepáticas/complicaciones
16.
Anal Biochem ; 657: 114873, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36108794

RESUMEN

Ammonia is one of the main players in the pathogenesis of hepatic encephalopathy (HE) in patients with chronic liver diseases. The usefulness of measuring ammonemia has been debated since many years. New data reveal that besides helping in the differential diagnosis of HE, ammonemia could be a prognostic marker not only in patients with HE, but also in patients without any neurological symptoms, suggesting a potential toxic role of ammonia beyond the brain. Finally, targeting ammonemia while monitoring therapeutic response could be a way to improve outcomes in patients with HE.


Asunto(s)
Amoníaco , Encefalopatía Hepática , Encéfalo , Diagnóstico Diferencial , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Humanos , Cirrosis Hepática
18.
Clin Res Hepatol Gastroenterol ; 45(6): 101593, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33667917

RESUMEN

BACKGROUND: Salvage transjugular intrahepatic portosystemic shunts (TIPS) are associated with poor prognosis, especially in patients with Child-Pugh C cirrhosis. Since preemptive TIPS improved prophylaxis of variceal bleeding in those patients, recourse to salvage TIPS may now affect patients with a better prognosis. AIM: To assess the impact of the preemptive TIPS policy on outcomes after salvage TIPS placement. METHODS: We conducted a retrospective monocentric study on cirrhotic patients undergoing salvage TIPS with polytetrafluoroethylene-covered stents from 2002 to 2017 (period 1 until February 2011; period 2 after the preemptive TIPS policy in March 2011). The primary endpoint was one-year transplant-free survival. RESULTS: We included 106 patients (period 1/2 = 53/53 patients, male gender 82%, age 54 ±â€¯9 years, alcoholic cirrhosis 70%, Child-Pugh score B/C 94%). One-year transplant-free survival was 46.0% during period 1 compared to 40.2% during period 2 (p = 0.65). Amongst 61 patients with history of variceal bleeding, 32 (52.5%) had an inadequate secondary prophylaxis, including 19 (59.4%) with a previous indication of preemptive TIPS. One-year transplant-free survival was 33.2% if inadequate secondary prophylaxis vs 65.2% if adequate (p = 0.008). Independent factors associated with survival were a lower Child-Pugh or MELD score, infection, failure to control bleeding, and hepatic encephalopathy after TIPS. CONCLUSION: Prognosis after salvage TIPS remained poor in our series. Optimizing secondary prophylaxis, including preemptive TIPS placement, should be the main concern to improve prognosis.


Asunto(s)
Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Terapia Recuperativa , Várices Esofágicas y Gástricas/cirugía , Femenino , Hemorragia Gastrointestinal/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
19.
Orbit ; 40(6): 455-460, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32912011

RESUMEN

Introduction: Acquired nasolacrimal duct obstruction (NLDO) is a major cause of epiphora. Balloon dacryoplasty (BD) is a minimally invasive procedure effectively used for congenital NLDO which has also been used in adults, instead of dacryocystorhinostomy (DCR), the current gold standard technique. The main objectives were to assess the results of BD with and without silicone tube insertion (STI) in NLDO in adults.Materiel and Method: A systematic review of literature was conducted on PubMed, SCOPUS and Cochrane databases. The articles were scanned to identify all studies that evaluated the outcomes of primary BD for NLDO in adults. The mean success rates were calculated and compared using the multiple comparisons Sidak's T-testResults: Sixty-seven articles were identified but only 13 publications matched the inclusion criteria. For partial NLDO, BD had a mean, success rate of 73.29% (64.86% with STI) with a mean follow-up of 16 months. For complete NLDO, BD had a success rate of 36.67% (52.50% with STI) with a mean follow-up of 15.5 months. Altogether the success rate of BD was significantly higher for partial NLDO compared to complete stenosis (p = 0,002).Conclusion: BD is significantly more successful for partial NLDO, without significant additional benefit from subsequent STI. The main complication would be the high recurrence rate. BD is not effective for complete NLDO with very low success rates. However, BD could be proposed for partial NLDO, as it is a safe procedure, with minimal invasiveness in comparison to DCR. Further prospective and controlled studies are required to confirm these encouraging results.


Asunto(s)
Dacriocistorrinostomía , Obstrucción del Conducto Lagrimal , Conducto Nasolagrimal , Adulto , Humanos , Obstrucción del Conducto Lagrimal/terapia , Conducto Nasolagrimal/cirugía , Resultado del Tratamiento
20.
Clin Chim Acta ; 510: 522-530, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32735981

RESUMEN

BACKGROUND: Hyperammonemia is neurotoxic and as such can be a medical emergency. Preanalytical factors greatly influence the blood ammonia concentration results. AIMS AND METHODS: Ammonia concentrations measured in the real life setting of a large hospital after pneumatic transport of blood samples and various time periods before centrifugation were compared to those based on the indications of the reagent manufacturer. In the same routine context, the effects of waiting times of centrifuged samples or after plasma storage at -20 °C and -80 °C were determined. RESULTS: Despite the pneumatic transport, the lead times for sample arrival to the lab were even longer than those recommended for their complete handling until ammonia assay. Ammonia concentration results were not affected by the pneumatic transport of blood samples and by waiting times up to a maximum of 1.75 h before their centrifugation and 1 h after centrifugation. Ammonia stability was superior when plasma was stored at -80 °C. CONCLUSION: Pneumatic transport and sample handling in the routine practice of our lab do not affect ammonia concentration results provided that waiting times are limited to 1.75 h before and 1 h after centrifugation and samples are kept cold. Otherwise, it is better to freeze plasma at -80 °C.


Asunto(s)
Amoníaco , Transportes , Centrifugación , Congelación , Hospitales , Humanos , Manejo de Especímenes , Temperatura
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