RESUMEN

Acute hyperammonaemia is a medical emergency as it can progress to cerebral oedema, seizures, coma and death. Hepatic encephalopathy secondary to cirrhotic disease or portosystemic shunting are relatively well-known causes, but non-cirrhotic aetiologies of acute hyperammonaemia are less well-known, especially in the emergency department. However, an elevated ammonia is not required to make the diagnosis of hepatic encephalopathy. Although measurement of plasma ammonia is recommended for patients with acute, unexplained, altered mental status, as early identification allows early effective management which may prevent irreversible brain damage, there is currently reduced awareness among physicians of the non-cirrhotic aetiologies of acute hyperammonaemia. Furthermore, measurement of ammonia in patients with cirrhosis has been shown to have low sensitivity and specificity, and not to have altered management in the majority of cases; thus, measurement of ammonia is currently not recommended in guidelines for management of hepatic encephalopathy. We sought to describe the pathophysiology of hyperammonaemia and review the non-cirrhotic causes. This was achieved by review of MEDLINE, PubMed and Web of Science databases to include published English literature within the last 20 years. We also present a framework for investigating the acute non-cirrhotic causes of hyperammonaemia to assist both chemical pathologists and clinicians managing these often challenging cases.

Asunto(s)

Amoníaco , Encefalopatía Hepática , Hiperamonemia , Humanos , Hiperamonemia/etiología , Hiperamonemia/diagnóstico , Hiperamonemia/fisiopatología , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Encefalopatía Hepática/fisiopatología , Amoníaco/sangre

RESUMEN

Patients with cirrhosis who have cognitive complaints are presumed to have hepatic encephalopathy (HE), which leads to unwarranted medications while ignoring the underlying disease process causing these complaints. Since neuropsychological testing, the current gold standard for HE diagnosis, is not readily available, an orderable test is needed. We aimed to develop and validate a rapid gut microbiota test to exclude HE and determine stakeholder input on this approach. Stool was collected from two cohorts: a two-center training cohort (n = 305, on/not on HE-related therapy) and a multicenter validation cohort (n = 30, on HE treatment). Stool microbiota was analyzed rapidly using nanopore analysis. Stakeholder (patients and clinicians) needs assessment was evaluated using semi-quantitative questionnaires. In the training cohort, machine learning using neural network identified a 20-species signature that differentiated HE vs no-HE with 84% specificity compared to the gold standard neuropsychological testing. This high specificity persisted regardless of whether patients were on HE-related therapy or not. In the validation cohort, application of this profile led to reevaluation of the HE diagnosis and treatment in > 40% of the patients. This approach was acceptable to patients (Veterans in the validation cohort) and clinician (n = 40 nationwide) stakeholders. We conclude that a machine learning stool signature based on 20 microbial species developed in a training set and validated in a separate multicenter prospective cohort differentiated those with vs. without HE, identified patients misdiagnosed with HE, and was acceptable to patients and clinician stakeholders.

Asunto(s)

Heces , Microbioma Gastrointestinal , Encefalopatía Hepática , Cirrosis Hepática , Humanos , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/microbiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/microbiología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Heces/microbiología , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/genética , Estudios de Cohortes , Aprendizaje Automático

RESUMEN

Minimal hepatic encephalopathy (MHE) is common in liver cirrhosis and is identified by psychometric tests. The portosystemic hepatic encephalopathy score (PHES) is the most widely used and serves as an inter-study comparator. PHES has not been standardised for use in the Danish population, where German normal values have been applied until now based on the notion that the populations are comparable. This study aimed to evaluate if German PHES normal values can be applied in the Danish population and establish Danish normal values if needed. 200 Danish and 217 German healthy persons underwent Number Connection Test A and B (NCT), Line Tracing Test (LTT), Digit Symbol Test (DST), and Serial Dotting Test (SDT), and based on performance, PHES was calculated. German and Danish PHES performance declined with age in all subtests but more rapidly in Danes. Both German and Danish norms were impacted by gender and education, but to a different extent in the single tests of the test battery. Accordingly, there was a need for specific Danish normal values, which are presented here. Applying the new Danish normal values instead of the German in patients with cirrhosis yielded a lower percentage of out-of-norm performances (58% vs. 66%) and, hence, a lower prevalence of MHE. Danes and Germans perform differently on PHES, and therefore, normal German values cannot be used in Danish patients. Danish normal values are presented here and yield a lower number of 'out of norm' performances.

Asunto(s)

Encefalopatía Hepática , Humanos , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/psicología , Encefalopatía Hepática/epidemiología , Masculino , Dinamarca/epidemiología , Femenino , Alemania/epidemiología , Persona de Mediana Edad , Adulto , Anciano , Pruebas Neuropsicológicas , Adulto Joven , Valores de Referencia , Cirrosis Hepática/diagnóstico , Psicometría , Comparación Transcultural

RESUMEN

INTRODUCTION: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. MATERIALS AND METHODS: We studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Twenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). CONCLUSIONS: A brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

Asunto(s)

Disfunción Cognitiva , Encefalopatía Hepática , Cirrosis Hepática , Medición de Resultados Informados por el Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Estudios Prospectivos , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/epidemiología , Trasplante de Hígado , Anciano , Hospitalización , Pruebas Neuropsicológicas , Cognición

RESUMEN

Liver diseases are a significant global cause of morbidity and mortality. Liver cirrhosis can result in severe complications such as bleeding, hepatic encephalopathy (HE), and infections. Implementing a clear strategy for intensive care unit (ICU) admission management improves patient outcomes. Hemodynamically significant esophageal/gastric variceal bleeding (E/GVB) and grade 4 HE, when accompanied by the need for renal replacement therapy (RRT), are definitive indications for ICU admission. E/GVB, spontaneous bacterial peritonitis (SBP), and infections with multidrug-resistant organisms (MDRO) require close and stringent critical assessment. Patients with severe hepatorenal syndrome (HRS) or respiratory failure have increased baseline mortality and most likely benefit from early ICU treatment. Rapid identification of sepsis in patients with liver cirrhosis is a crucial criterion for ICU admission. Prioritizing cases based on mortality risk and clinical urgency enables efficient resource utilization and optimizes patient management. In addition, "Liver Units" provide an intermediate care (IMC) level for patients with liver diseases who require close monitoring but do not need immediate intensive care.

Asunto(s)

Hemorragia Gastrointestinal , Encefalopatía Hepática , Síndrome Hepatorrenal , Unidades de Cuidados Intensivos , Cirrosis Hepática , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/terapia , Cirrosis Hepática/diagnóstico , Encefalopatía Hepática/terapia , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/mortalidad , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/mortalidad , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/diagnóstico , Peritonitis/mortalidad , Peritonitis/diagnóstico , Peritonitis/terapia , Cuidados Críticos , Várices Esofágicas y Gástricas/terapia , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/mortalidad , Admisión del Paciente , Hepatopatías/terapia , Hepatopatías/mortalidad , Hepatopatías/diagnóstico , Terapia de Reemplazo Renal , Farmacorresistencia Bacteriana Múltiple , Sepsis/terapia , Sepsis/diagnóstico , Sepsis/mortalidad , Pronóstico

RESUMEN

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005-1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130-0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117-0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE.

Asunto(s)

Biomarcadores , Encefalopatía Hepática , Cirrosis Hepática , Proteínas de Neurofilamentos , Humanos , Encefalopatía Hepática/sangre , Encefalopatía Hepática/diagnóstico , Masculino , Femenino , Proteínas de Neurofilamentos/sangre , Persona de Mediana Edad , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Biomarcadores/sangre , Anciano , Adulto

RESUMEN

Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.

Asunto(s)

Encefalopatía Hepática , Cirrosis Hepática , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/terapia , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/terapia , Ascitis/etiología , Ascitis/terapia , Ascitis/diagnóstico , Trombocitopenia/etiología , Trombocitopenia/diagnóstico , Trombocitopenia/terapia , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia

RESUMEN

BACKGROUND: In India, cirrhosis is becoming a growing concern, leading to an unmet need for new non-invasive markers to assess the severity of liver disease. Serum prolactin is one such marker. AIM: To determine the association between serum prolactin, the severity of liver cirrhosis, and its complications such as ascites, hepatic encephalopathy, and esophageal varices. METHODS: This cross-sectional study involved 117 patients with liver cirrhosis. They were evaluated for some complications such as ascites, esophageal varices, and hepatic encephalopathy, as well as for severity by using the Child-Turcotte-Pugh (CTP) score. Serum prolactin levels were measured, and their relationship with both the severity and complications of liver cirrhosis was determined. A P value of < 0.05 was considered significant. RESULTS: The mean age of the patients was 48.3 ± 12.08 years, and the majority (80.3%) were males. Seventy-one percent of the patients had elevated serum prolactin levels (>19.40 ng/mL). Elevated serum prolactin was found in approximately 95.0% and 86.8% of patients with hepatic encephalopathy and ascites, respectively. The median serum prolactin levels were significantly associated with esophageal varices grades (P = 0.043) and hepatic encephalopathy (P < 0.001). The sensitivity and specificity of serum prolactin for predicting severe CTP scores were 81.6% and 91.2%, respectively, with a diagnostic accuracy of 87.2%. On multivariate regression analysis, ascites (AOR = 3.8, 95%CI = 1.29-10.98, P = 0.015), hepatic encephalopathy (AOR = 6.1, 95%CI = 0.68-53.78, P = 0.012), CTP class B (AOR = 5.9, 95%CI = 1.39-24.68, P = 0.016), and CTP class C (AOR = 13.4, 95%CI = 2.25-82.21, P = 0.004) were significantly associated with elevated serum prolactin levels. CONCLUSION: There was a significant association between serum prolactin levels and CTP classes, esophageal varices, ascites, and hepatic encephalopathy in patients with liver cirrhosis.

Asunto(s)

Ascitis , Biomarcadores , Várices Esofágicas y Gástricas , Encefalopatía Hepática , Cirrosis Hepática , Prolactina , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ascitis/sangre , Biomarcadores/sangre , Estudios Transversales , Várices Esofágicas y Gástricas/sangre , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Encefalopatía Hepática/sangre , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/epidemiología , India/epidemiología , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Prolactina/sangre , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria

RESUMEN

INTRODUCTION: Little has been reported about the clinical relevance and trajectories of symptoms in end-stage liver disease (ESLD). The purpose of this prospective study was to identify trajectories of change in symptom burden over the course of 12 months in adults with ESLD. METHODS: Patients were recruited from hepatology clinics at 2 healthcare systems. Validated measures were used to assess physical and psychological symptoms. Latent growth mixture modeling and survival and growth modeling were used to analyze the survey data. RESULTS: Data were available for 192 patients (mean age 56.5 ± 11.1 years, 64.1% male, mean Model for ESLD (MELD) 3.0 19.2 ± 5.1, ethyl alcohol as primary etiology 33.9%, ascites 88.5%, encephalopathy 70.8%); there were 38 deaths and 39 liver transplantations over 12 months. Two symptom trajectories were identified: 62 patients (32.3%) had high and unmitigated symptoms, and 130 (67.7%) had lower and improving symptoms. Patients with high and unmitigated symptoms had twice the hazard of all-cause mortality (subhazard ratio 2.53, 95% confidence interval: 1.32-4.83) and had worse physical ( P < 0.001) and mental quality of life ( P = 0.012) compared with patients with lower and improving symptoms. Symptom trajectories were not associated with MELD 3.0 scores ( P = 0.395). Female sex, social support, and level of religiosity were significant predictors of symptom trajectories ( P < 0.05 for all). DISCUSSION: There seems to be 2 distinct phenotypes of symptom experience in patients with ESLD that is independent of disease severity and associated with sex, social support, religiosity, and mortality. Identifying patients with high symptom burden can help optimize their care.

Asunto(s)

Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Calidad de Vida , Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/etiología , Enfermedad Hepática en Estado Terminal/cirugía , Estudios Prospectivos , Anciano , Índice de Severidad de la Enfermedad , Adulto , Estudios Longitudinales , Pronóstico , Progresión de la Enfermedad , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Encefalopatía Hepática/psicología , Ascitis/etiología , Carga Sintomática

RESUMEN

In recent years, the pathophysiological concept of decompensated liver cirrhosis has undergone significant changes. Until a few years ago, the focus of pathophysiological considerations was on the hyperdynamic circulation resulting from portal hypertension. In recent years, emerging data suggests that increased bacterial translocation leading to systemic inflammation plays an important role in patients with decompensated liver cirrhosis. This inflammation affects a variety of extrahepatic organs. Nowadays, liver cirrhosis is considered not only a condition confined to the liver but rather an inflammatory-triggered multisystem disease. The existing inflammation serves as the common pathophysiological explanation for the diverse impact of liver cirrhosis on several extrahepatic organs. It plays a significant role in the development of conditions such as hepatorenal syndrome, cirrhotic cardiomyopathy, hepatopulmonary syndrome, hepatic encephalopathy, and even in the emergence of cirrhosis-associated relative adrenal insufficiency. These new pathophysiological insights hold clinical significance as they influence the prophylaxis and treatment of patients with decompensated liver cirrhosis.

Asunto(s)

Cirrosis Hepática , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Inflamación , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Hipertensión Portal/terapia , Encefalopatía Hepática/fisiopatología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico

RESUMEN

INTRODUCTION: Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics. AREAS COVERED: We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms. EXPERT OPINION: We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

Asunto(s)

Encefalopatía Hepática , Cirrosis Hepática , Cuidados Paliativos , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/terapia , Encefalopatía Hepática/terapia , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Hipertensión Portal/terapia , Hipertensión Portal/etiología , Hipertensión Portal/diagnóstico , Progresión de la Enfermedad , Pruebas de Función Hepática

RESUMEN

OBJECTIVES: Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS: The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS: As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of  ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION: INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER: Not applicable as this is a retrospective study.

Asunto(s)

Hepatitis A , Fallo Hepático Agudo , Humanos , Pronóstico , Hepatitis A/complicaciones , Hepatitis A/diagnóstico , Hepatitis A/mortalidad , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/diagnóstico , Femenino , Masculino , Niño , Preescolar , Lactante , Relación Normalizada Internacional , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Estudios de Cohortes , Adolescente , Biomarcadores/sangre , India/epidemiología , Ictericia/etiología , Valor Predictivo de las Pruebas

RESUMEN

A 63-year-old man with type 2 diabetes mellitus, alcohol consumption in moderation, and three episodes of hepatic encephalopathy presented with symmetrical lower limb distal weakness, sensory ataxia, thickened palpable nerves, mood disturbances for seven years, and a family history of schizophreniform disorders. Nerve conduction studies showed demyelinating sensorimotor polyradiculoneuropathy. CSF analysis showed mild albumino-cytological dissociation. MRI brain and lumbosacral plexus showed thickened fifth cranial nerves and lumbosacral roots. He was treated with steroids for a provisional diagnosis of chronic inflammatory polyneuropathy and became encephalopathic. EEG showed triphasic waves. Serum ammonia was 201 micrograms/dL. Further evaluation suggested ornithine transcarbamylase (OTC) deficiency. The patient underwent hemodialysis with a low protein diet, rifaximin, and sodium benzoate, with subsequent recovery.

Asunto(s)

Conducción Nerviosa , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa , Humanos , Masculino , Persona de Mediana Edad , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/complicaciones , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnóstico , Conducción Nerviosa/fisiología , Ataxia , Polineuropatías/diagnóstico , Imagen por Resonancia Magnética , Diabetes Mellitus Tipo 2/complicaciones , Electroencefalografía , Encefalopatía Hepática/diagnóstico , Diálisis Renal

RESUMEN

BACKGROUND: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD). METHODS/DESIGN: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival. DISCUSSION: The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care. ETHICS AND DISSEMINATION: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation. TRIAL REGISTRATION: EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.

Asunto(s)

Várices Esofágicas y Gástricas , Encefalopatía Hepática , Hipertensión Portal , Adulto , Humanos , Antagonistas Adrenérgicos beta/uso terapéutico , Ascitis/tratamiento farmacológico , Carvedilol/uso terapéutico , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/prevención & control , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/etiología , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Pragmáticos como Asunto

RESUMEN

BACKGROUND/AIMS: Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). METHODS: We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. RESULTS: Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484- 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). CONCLUSION: Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.

Asunto(s)

Insuficiencia Hepática Crónica Agudizada , Puntuaciones en la Disfunción de Órganos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/complicaciones , Adulto , Anciano , Pronóstico , Curva ROC , Escala de Coma de Glasgow , Modelos de Riesgos Proporcionales , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/complicaciones , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/complicaciones

RESUMEN

Pediatric acute liver failure (PALF) is a catastrophic clinical condition with very high morbidity and mortality without early detection and intervention. It is characterized by the acute onset of massive hepatocellular injury that releases circulating inflammatory mediators, resulting in metabolic disturbances, coagulopathy, hepatic encephalopathy and multi-organ failure. The etiological spectrum is dominated by hepatotropic viruses, drug-induced liver injury, metabolic and genetic disorders and immune-mediated diseases. Unlike adults, indeterminate causes for acute liver failure constitute a considerable proportion of cases of acute liver failure in children in the west. The heterogeneity of age and etiology in PALF has led to difficulties in developing prognostic scoring. The recent guidelines emphasize prompt identification of PALF, age-appropriate evaluation for hepatic encephalopathy and laboratory evaluation with careful monitoring. Current therapy focuses on supporting the failing liver and other organs, pending either spontaneous recovery or liver transplantation. Targeted therapy is available for a select group of etiologies. Liver transplantation can be lifesaving and a plan for the same should be organized, whenever indicated. The aim of this review is to define PALF, understand its etiopathogenesis, address the challenges encountered during the management and update the latest advances in liver transplantation and non-transplant treatment options in PALF.

Asunto(s)

Fallo Hepático Agudo , Trasplante de Hígado , Humanos , Fallo Hepático Agudo/terapia , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/diagnóstico , Niño , Preescolar , Lactante , Encefalopatía Hepática/terapia , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Pronóstico , Guías de Práctica Clínica como Asunto , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico

RESUMEN

INTRODUCTION AND OBJECTIVES: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). MATERIALS AND METHODS: We included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. RESULTS: ICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). CONCLUSIONS: Plasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.

Asunto(s)

Biomarcadores , Proteína Ácida Fibrilar de la Glía , Encefalopatía Hepática , Cirrosis Hepática , Proteínas de Neurofilamentos , Humanos , Encefalopatía Hepática/sangre , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Biomarcadores/sangre , Proteína Ácida Fibrilar de la Glía/sangre , Femenino , Masculino , Persona de Mediana Edad , Proteínas de Neurofilamentos/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Estudios Prospectivos , Anciano , Adulto , Índice de Severidad de la Enfermedad , Valor Predictivo de las Pruebas , Estudios de Casos y Controles

RESUMEN

Liver disease is increasingly common, estimated to affect over 25% of the world's population. Failure of the liver to maintain a normal metabolic milieu leads to impaired brain function (hepatic encephalopathy), and conditions that cause liver disease can themselves predispose to neurological disease. As neurologists' involvement with the acute take increases, it is important that we are familiar with the neurological complications of liver disease, their investigation and management, and to know which other neurological diseases occur in this patient population. In this article, we review the causes, presentation and treatment of hepatic encephalopathy, and discuss important differential diagnoses in patients with liver disease who present with neurological disturbance.

Asunto(s)

Encefalopatía Hepática , Neurólogos , Humanos , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/terapia , Diagnóstico Diferencial , Neurología/métodos

RESUMEN

BACKGROUND AND STUDY AIMS: The mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. PATIENTS AND METHODS: A total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). RESULTS: The mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r =  - 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). CONCLUSION: A significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

Asunto(s)

Encefalopatía Hepática , Cirrosis Hepática , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D , Vitamina D , Humanos , Encefalopatía Hepática/sangre , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Vitamina D/sangre , Vitamina D/análogos & derivados , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/sangre , Estudios de Casos y Controles , Adulto , Anciano

RESUMEN

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that is observed primarily in patients with liver disease. The pathophysiology is complex and involves many factors including ammonia toxicity, dysregulation of central nervous system activity, and excess inflammatory cytokines. Symptoms of HE range from subclinical to debilitating. HE can be difficult to treat and represents a large burden to patients, their caregivers, and the health-care system because of associated resource utilization. This review article provides an overview of the current understanding of the pathophysiology behind HE and where the current research and treatments are pointing toward.

Asunto(s)

Encefalopatía Hepática , Humanos , Encefalopatía Hepática/etiología , Encefalopatía Hepática/terapia , Encefalopatía Hepática/diagnóstico , Sistema Nervioso Central , Amoníaco