RESUMEN
Background: recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis. Aim and methods: six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divided into three groups according to the tertile levels of serum uric acid and gender. Results: the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pressure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08-3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87). Conclusion: higher levels of serum uric acid were independently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage
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Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Hiperuricemia/complicaciones , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Hígado Graso/fisiopatología , Hipercolesterolemia/epidemiología , Hipertrigliceridemia/epidemiología , Factores de Edad , Hiperuricemia/fisiopatología , Biomarcadores/análisis , Hipercolesterolemia/complicaciones , Creatinina/sangre , Cirrosis Hepática/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis. AIM AND METHODS: six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divided into three groups according to the tertile levels of serum uric acid and gender. RESULTS: the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pressure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08-3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87). CONCLUSION: higher levels of serum uric acid were independently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage.
Asunto(s)
Hiperuricemia/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Ácido Úrico/sangre , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores/sangre , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , Creatinina/sangre , Hígado Graso/sangre , Hígado Graso/patología , Femenino , Humanos , Hiperuricemia/sangre , Hígado/patología , Cirrosis Hepática/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/patología , Sistema de Registros , Estudios Retrospectivos , Factores Sexuales , Triglicéridos/sangre , Adulto JovenRESUMEN
The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.
Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Hipertensión Portal/etiología , Intestinos/microbiología , Cirrosis Hepática/complicaciones , Hepatopatías/fisiopatología , Hígado/metabolismo , Antagonistas Adrenérgicos beta/uso terapéutico , Infecciones Bacterianas/complicaciones , Traslocación Bacteriana/genética , Ácidos y Sales Biliares/metabolismo , Endotoxemia/etiología , Endotoxemia/metabolismo , Trasplante de Microbiota Fecal/efectos adversos , Trasplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/genética , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/microbiología , Humanos , Hipertensión Portal/metabolismo , Hipertensión Portal/microbiología , Mucosa Intestinal/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/terapia , Hepatopatías/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/terapia , Peritonitis/microbiología , Probióticos/uso terapéutico , Receptores Citoplasmáticos y Nucleares/metabolismoRESUMEN
INTRODUCCIÓN: El tratamiento de la hepatitis crónica B antígeno e negativa (HCB HBeAg negativa) con antivíricos orales (AO) suele prolongarse de forma indefinida debido a que la pérdida del antígeno de superficie como objetivo para su suspensión es un hecho infrecuente. Recientemente han aparecido las primeras evidencias que sugieren finalizar la terapia con AO en casos seleccionados. OBJETIVOS: Analizar la tasa de rebote virológico en pacientes con HCB Age negativa que suspendieron el tratamiento con AO. MATERIAL Y MÉTODOS: Estudio retrospectivo observacional que incluyó 140 casos de HCB HBeAg negativa. Veintidós pacientes, que recibieron exclusivamente AO, los suspendieron por diversos motivos realizándose un seguimiento posterior. Todos presentaban transaminasas normales, ADN indetectable y ausencia de cirrosis o comorbilidades importantes al finalizar el tratamiento. RESULTADOS: Doce pacientes presentaron rebote virológico (54,54%), transcurriendo una media de 6,38 meses (± 1,9) desde la suspensión hasta el rebote (el 75% dentro de los 12 primeros meses tras la suspensión). Cinco recibieron adefovir, uno lamivudina más adefovir, uno tenofovir y 5 lamivudina. La duración media del tratamiento, desde el inicio hasta la suspensión, fue de 38,5 meses (± 4,5). El grupo con respuesta sostenida presentaba una edad media y duración del tratamiento superior a los sujetos con rebote, si bien estas diferencias no resultaron estadísticamente significativas. CONCLUSIONES: Los resultados sugieren que es posible suspender la terapia con AO en casos seleccionados de HCB Age negativa, siempre que no exista cirrosis, se cumpla un tiempo mínimo de tratamiento, las transaminasas sean normales y el ADN indetectable de forma mantenida. En estos casos, se debe realizar un seguimiento estrecho durante el primer año y posteriormente de forma indefinida
BACKGROUND: Treatment of HBeAg-negative chronic hepatitis B (CHB) with nucleos(t)ide analogues (NA) is usually indefinite, since the loss of HBsAg, as a criterion for its discontinuation, is a rare event. Recent evidence suggests that discontinuing NA therapy may be feasible in selected patients. OBJECTIVES: To analyze the rate of virological relapse in patients with HBeAg-negative CHB who discontinued treatment with NAs. METHODS: We performed a single-center observational study that included 140 patients with HBsAg-negative CHB. Twenty-two patients, who received only NAs, discontinued treatment for different reasons and were subsequently monitored. All had normal ALT and AST, undetectable DNA and absence of cirrhosis or significant comorbidities before stopping treatment. RESULTS: Twelve patients showed virologic relapse (54.54%). The mean interval between discontinuation and relapse was 6.38 months (± 1.9) (75% relapsed during the first 12 months after discontinuation). Five received adefovir, 1 lamivudine and adefovir, 1 tenofovir and 5 lamivudine alone. The mean treatment duration in this group was 38.5 months (± 4.5). The sustained response group had a higher mean age and longer treatment duration than patients with virologic relapse but these differences were not statistically significant. CONCLUSIONS: The results suggest that NA treatment can be stopped in selected patients with CHB as long as they are not cirrhotic, have completed a minimum period of treatment, have normal ALT and sustained undetectable DNA. These patients should be closely monitored during the first year and then indefinitely
Asunto(s)
Humanos , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Privación de Tratamiento , Virus de la Hepatitis B/patogenicidad , Efecto Rebote , Antígenos de la Hepatitis B , Carga Viral , Estudios RetrospectivosRESUMEN
BACKGROUND: Treatment of HBeAg-negative chronic hepatitis B (CHB) with nucleos(t)ide analogues (NA) is usually indefinite, since the loss of HBsAg, as a criterion for its discontinuation, is a rare event. Recent evidence suggests that discontinuing NA therapy may be feasible in selected patients. OBJECTIVES: To analyze the rate of virological relapse in patients with HBeAg-negative CHB who discontinued treatment with NAs. METHODS: We performed a single-center observational study that included 140 patients with HBsAg-negative CHB. Twenty-two patients, who received only NAs, discontinued treatment for different reasons and were subsequently monitored. All had normal ALT and AST, undetectable DNA and absence of cirrhosis or significant comorbidities before stopping treatment. RESULTS: Twelve patients showed virologic relapse (54.54%). The mean interval between discontinuation and relapse was 6.38 months (± 1.9) (75% relapsed during the first 12 months after discontinuation). Five received adefovir, 1 lamivudine and adefovir, 1 tenofovir and 5 lamivudine alone. The mean treatment duration in this group was 38.5 months (± 4.5). The sustained response group had a higher mean age and longer treatment duration than patients with virologic relapse but these differences were not statistically significant. CONCLUSIONS: The results suggest that NA treatment can be stopped in selected patients with CHB as long as they are not cirrhotic, have completed a minimum period of treatment, have normal ALT and sustained undetectable DNA. These patients should be closely monitored during the first year and then indefinitely.
Asunto(s)
Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Nucleótidos/uso terapéutico , Adulto , Anciano , Aspartato Aminotransferasas/sangre , ADN Viral/aislamiento & purificación , Quimioterapia Combinada , Femenino , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/inmunología , Humanos , Cirrosis Hepática/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
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