Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.542
Filtrar
1.
JAMA ; 323(12): 1175-1183, 2020 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-32207804

RESUMEN

Importance: Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) and is associated with disease progression, development of cirrhosis, and need for liver transplant. Despite its importance, NASH is underrecognized in clinical practice. Observations: NASH affects an estimated 3% to 6% of the US population and the prevalence is increasing. NASH is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome. Although a number of noninvasive tests and scoring systems exist to characterize NAFLD and NASH, liver biopsy is the only accepted method for diagnosis of NASH. Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. Lifestyle modification is the mainstay of treatment, including dietary changes and exercise, with the primary goal being weight loss. Substantial improvement in histologic outcomes, including fibrosis, is directly correlated with increasing weight loss. In some cases, bariatric surgery may be indicated to achieve and maintain the necessary degree of weight loss required for therapeutic effect. An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the US. The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD, with annual all-cause mortality rate of 25.56 per 1000 person-years and a liver-specific mortality rate of 11.77 per 1000 person-years. Conclusions and Relevance: Nonalcoholic steatohepatitis affects 3% to 6% of the US population, is more prevalent in patients with metabolic disease and obesity, progresses to cirrhosis in approximately 20% of cases, and is associated with increased rates of liver-specific and overall mortality. Early identification and targeted treatment of patients with nonalcoholic steatohepatitis are needed to improve patient outcomes, including directing patients toward intensive lifestyle modification to promote weight loss and referral for bariatric surgery as indicated for management of obesity and metabolic disease.


Asunto(s)
Hígado/patología , Enfermedad del Hígado Graso no Alcohólico , Cirugía Bariátrica , Diagnóstico Diferencial , Progresión de la Enfermedad , Humanos , Estilo de Vida , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/complicaciones , Prevalencia , Estados Unidos/epidemiología
2.
Chem Biol Interact ; 323: 109054, 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32217109

RESUMEN

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) has been associated with fibrosis that may progress to cirrhosis. The purpose of this study was to examine hepatocytes and perisinusoidal cells in liver biopsies of 3 families (3 males and 4 females) with non-cirrhotic and cirrhotic NASH to determine unique histological changes during a period of 2-7 years from diagnosis. METHODS: In this study, hepatocytes, stellate cells and Kupffer cells were analyzed using light and electron microscopy, and immunohistochemistry with specific anti-macrophage antibody staining of liver biopsies. RESULTS: Body mass index of all patients was over 28, and all viral, metabolic markers were negative. Alcohol consumption was insignificant. In all liver biopsies, diffuse, non-zonal macrovesicular steatosis involved 40-70% of liver samples. The lobular hepatocytes showed prominent ballooning hepatocyte degeneration. No Mallory Denk hyaline bodies (MDBs) were observed in three of the patients. MDBs developed in ballooned hepatocytes of four individuals that also presented foci of lobular inflammation. The apoptotic bodies were stained by cytokeratin 18. The trichrome stain revealed portal to portal bridging fibrosis. In one family, there was a three-fold increase in relative numbers of perisinusoidal macrophages in the older sister with NASH compared to livers of the younger siblings. The special finding in livers of patients with NASH was accumulation of groups of perisinusoidal macrophages, which was not associated with focal necrosis. CONCLUSION: Perisinusoidal macrophages appear to accumulate in NASH. It is possible that collections of macrophages are a response to chronic portal endotoxemia or lipotoxic activation of immuno-mediators. The persistent activation of these macrophages could lead to the chronic release of pro-inflammatory cytokines and contribute to chronic inflammation, fibrosis and cirrhosis leading to HCC.


Asunto(s)
Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Biopsia , Carcinoma Hepatocelular/patología , Femenino , Células Estrelladas Hepáticas/patología , Humanos , Macrófagos del Hígado/patología , Gotas Lipídicas/metabolismo , Hígado/patología , Hígado/ultraestructura , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/patología
3.
Rev Med Suisse ; 16(687): 586-591, 2020 Mar 25.
Artículo en Francés | MEDLINE | ID: mdl-32216182

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases with an epidemiology correlated to obesity and metabolic syndrome. The last decade was rich of significant advances in understanding the pathophysiology of the disease, linking environmental elements, genetic factors and microbiota modifications, as well as in staging, screening and therapeutic development. The purpose of this article is to summarize recent advances in the field of NAFLD, on her way to become the first cause of cirrhosis and liver transplantation worldwide.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Cirrosis Hepática/etiología , Trasplante de Hígado , Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/complicaciones
4.
PLoS One ; 15(2): e0219412, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32106257

RESUMEN

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker. METHODS: Eighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control. One patient was excluded due to low RT-PCR signal. RESULTS: Compared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, low-density-lipoprotein cholesterol and non-high-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism-related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379. CONCLUSIONS: Serum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.


Asunto(s)
Hipercolesterolemia/sangre , MicroARNs/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Hipercolesterolemia/etiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Regulación hacia Arriba
5.
Z Gastroenterol ; 58(1): 57-62, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31931541

RESUMEN

The rising prevalence of the metabolic syndrome has led to an increase of non-alcoholic fatty liver disease (NAFLD), and its progressive-inflammatory form called non-alcoholic steatohepatitis (NASH). In recent years, NAFLD and NASH have become major risk factors for developing liver cirrhosis and hepatocellular carcinoma (HCC). In this case, we report a 46-year-old patient with type 2 diabetes mellitus and metabolic comorbidities including obesity and arterial hypertension, who was referred because of rising liver enzymes. After clinical and diagnostic evaluation, the patient was diagnosed with NASH-associated liver cirrhosis, Child-Pugh stage B. A normal blood sugar level was difficult to achieve, and the patient presented with consistently elevated HbA1c-levels irresponsive to insulin therapy. Due to the underlying liver cirrhosis, the patient was enrolled in the HCC-surveillance program. Sonography during follow up showed a focal lesion. On magnetic resonance imaging (MRI), the diagnosis of HCC (BCLC stage A) was confirmed based on typical contrast enhancement and portal-venous wash-out. The patient was evaluated for liver transplantation with a labMELD of 17, and an intermittent therapy with TACE was initiated. Only 2 months after liver transplantation, the patient developed severe and lethal complications. Overall, this case highlights the different medical issues of patients with metabolic syndrome developing a chronic liver disease. In this patient, a rapid progression from NASH-associated liver cirrhosis to HCC was seen, and therefore highlights the importance of close surveillance to identify and treat potential risk factors early in the course of the disease.


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neoplasias Hepáticas/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Comorbilidad , Resultado Fatal , Humanos , Hipertensión/complicaciones , Resistencia a la Insulina , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/complicaciones
6.
Metabolism ; 104: 154140, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31926204

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases that may progress to liver fibrosis or cancer. The present study aimed to investigate the role of microRNA-125b-5p (miR-125b-5p) in NAFLD and to further explore underlying molecular mechanisms. METHODS: A mouse model of NAFLD was constructed by high cholesterol diet feeding and a cell-model was developed by treating the mouse liver cell line NCTC1469 with palmitic acid. Gain- and loss-of-function experiments were performed to determine the effects of miR-125b-5p, integrin α8 (ITGA8), and the RhoA signaling pathway on liver fibrosis in NAFLD. After the expression levels of miR-125b-5p, ITGA8, and RhoA were determined, liver fibrosis was evaluated in vivo and in vitro. The binding relationship of miR-125b-5p and ITGA8 was then validated. Finally, miR-125b-5p promoter methylation in NAFLD liver tissues and cells was determined. RESULTS: In NAFLD clinical samples, mouse model, and cell-model, miR-125b-5p expression was reduced, while ITGA8 expression was increased. Moreover, miR-125b-5p targeted and downregulated ITGA8, leading to inhibition of the RhoA signaling pathway. In NAFLD liver tissues and cells, the CpG island in the miR-125b-5p promoter was methylated, causing epigenetic silencing of miR-125b-5p. Both miR-125b-5p silencing and ITGA8 overexpression promoted in vitro and in vivo liver fibrosis in NAFLD via activation of the RhoA signaling pathway. CONCLUSIONS: Collectively, epigenetic silencing of miR-125b-5p upregulates ITGA8 expression to activate the RhoA signaling pathway, leading to liver fibrosis in NAFLD.


Asunto(s)
Epigénesis Genética , Cadenas alfa de Integrinas/genética , Cirrosis Hepática/genética , MicroARNs/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Proteína de Unión al GTP rhoA/metabolismo , Animales , Línea Celular , Colesterol en la Dieta , Hígado/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Transducción de Señal/genética
7.
Transplant Proc ; 52(1): 276-283, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31889539

RESUMEN

BACKGROUND: Obesity is a major public health burden that affects the transplant community because of its key role in fatty liver disease and transplantation outcomes. OBJECTIVES: To evaluate the role of sleeve gastrectomy in treating recurrent and de novo nonalcoholic fatty liver disease (NAFLD) in liver transplant recipients. SETTING: A university hospital. METHODS: We describe 2 obese liver transplant recipients with recurrent and de novo NAFLD who underwent minimally invasive metabolic and bariatric surgery. RESULTS: The surgery was performed successfully, with much of the operative time consumed by enterolysis. There were no intraoperative or postoperative complications. At last follow-up appointment (16 months postoperatively), there was a mean reduction in weight (31.98 kg), body mass index (10.2 kg/m2), glycosylated hemoglobin (1.05%), alanine aminotransferase (38 IU/L), steatosis score (0.34), and fibrosis score (0.05). The mean decrease in 6-month postoperative hepatic fat quantification was 6%. CONCLUSIONS: These cases show that metabolic and bariatric surgery in obese, posttransplant recipients with recurrent and de novo nonalcoholic steatohepatitis lead to improved steatosis and reduced obesity and obesity-associated comorbidities.


Asunto(s)
Cirugía Bariátrica/métodos , Gastrectomía/métodos , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico/cirugía , Obesidad Mórbida/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad Mórbida/complicaciones , Complicaciones Posoperatorias/cirugía , Receptores de Trasplantes
8.
Dig Dis ; 38(2): 143-149, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31865317

RESUMEN

Metabolic syndrome and its components such as obesity, hypertriglyceridemia, type-2 diabetes mellitus (DM-T2), and arterial hypertension are unequivocally serious problems for every society. This is especially true in economically developed countries where the imbalance in lifestyle between caloric intake and caloric output still gets greater and greater. This fact is not only a concern for the adult population but for children as well. However, metabolic syndrome does not only affect society and health in regards to cardiovascular diseases, it significantly concerns gastroenterology where it is classified as nonalcoholic fatty pancreas disease (NAFPD). The data gained from several trials show that the prevalence of NAFDP is 33% (95% CI 24-41%). When it comes to the diagnostic procedures concerning the presence of pancreatic fat, a whole spectrum of suitable methods are recommended. Probably, the most exact method is the use of magnetic resonance imaging. However, for common clinical practice, the abdominal sonographic examination based on the comparison of the pancreatic parenchymatous echogenity versus renal or hepatic echogenity is used. The clinical consequences of pancreatic steatosis and steatopancreatitis are significant. These diseases are connected with DM-T2 and insulin resistance. In recent years, changes of exocrine pancreatic function, particularly its decrease, have also been described. It is known that there is a close correlation between NAFPD and nonalcoholic hepatic steatosis and also with the increased thickness of aortic intima-media. There is also an important relationship between NAFPD and pancreatic carcinoma. Pancreatic steatosis, and especially its NAFPD form, is a serious state which can be treatable by the possible effective management of metabolic syndrome parameters, including obesity.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedades Pancreáticas/patología , Humanos , Resistencia a la Insulina , Microbiota , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/microbiología , Obesidad/complicaciones , Enfermedades Pancreáticas/diagnóstico , Enfermedades Pancreáticas/epidemiología , Enfermedades Pancreáticas/microbiología , Factores de Riesgo
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1293-1297, 2019 Nov 30.
Artículo en Chino | MEDLINE | ID: mdl-31852647

RESUMEN

OBJECTIVE: To investigate the predictive value of body mass index (BMI) combined with waist circumference (WC) for new-onset nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This community-based prospective cohort study was conducted among 3501 T2DM patients without NAFLD recruited from the staff of Kailuan Company, who underwent routine physical examination in the year 2006 and 2007, and a total of 2920 subjects were included in the final analysis. According to the baseline BMI and WC, the subjects were divided into group A (with normal BMI and WC), group B (with normal BMI but elevated WC), group C (with elevated BMI but a normal WC) and group D (with elevated BMI and WC). The subjects in the 4 groups were followed for the occurrence of NAFLD by reviewing their reports of physical examinations during the periods of 2008-2009, 2010-2011, 2012-2013, 2014-2015 and 2016-2017. The cumulative incidence of NAFLD was compared across the 4 groups and Cox regression analysis was used to test the correlation of BMI and WC with new onset of NAFLD. RESULTS: The cumulative incidence of NAFLD increased progressively in the 4 groups (50%, 66%, 68% and 77%, respectively). Cox regression analysis showed that compared with group A, groups B, C and D had increased risks of NAFLD after adjusting for age, gender and other risk factors, with HR values of 1.62, 1.98 and 2.47, respectively. CONCLUSIONS: Elevated BMI and WC are both independent risk factors for NAFLD in type 2 diabetic patients, and the combination of BMI and WC has a greater predictive value for NAFLD than either of them alone.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad , Estudios Prospectivos , Factores de Riesgo , Circunferencia de la Cintura
10.
Dis Markers ; 2019: 2585409, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31885733

RESUMEN

Background and Aim: Little information is available about the assessment and optimal use of the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and transient elastography (TE) in predicting liver cirrhosis in patients with chronic hepatitis B (CHB) and concurrent nonalcoholic fatty liver disease (NAFLD). This study is aimed at comparing their diagnostic performances and developing an optimal approach for predicting liver cirrhosis in CHB patients with NAFLD. Methods: Consecutive CHB patients with NAFLD were enrolled. The GPR was calculated, and TE was performed using liver biopsy as a reference standard. The accuracy of predicting liver cirrhosis using GPR and TE was assessed and compared, and an optimal approach was developed. Results: Both TE and GPR correlated significantly with the histological fibrosis stage. TE and GPR had excellent performance in predicting liver cirrhosis, and the comparison of areas under the receiver operating characteristic curves revealed that TE was superior to GPR (0.95 vs. 0.85, P = 0.039). Moreover, the dual cutoffs established by the likelihood ratio showed that GPR had a similar misclassification but higher indeterminate rate than TE (54.5% vs. 11.7%, P < 0.001). Additionally, a 2-step approach using GPR followed by TE had comparable performance to that of both GPR and TE tests for all patients (misclassification: 8.9% vs. 8.3%, P = 0.866; indeterminate rate: 15.2% vs. 17.2%, P = 0.750) but could reduce TE scans by approximately one-third. Conclusions: Both TE and GPR show excellent performance in predicting liver cirrhosis in CHB patients with NAFLD. The 2-step approach using GPR followed by TE may be optimal for the assessment of cirrhosis in CHB patients with NAFLD.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Hepatitis B Crónica/complicaciones , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , gamma-Glutamiltransferasa/metabolismo , Adulto , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/metabolismo , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/metabolismo , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Recuento de Plaquetas , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
11.
Clin Appl Thromb Hemost ; 25: 1076029619888694, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31840531

RESUMEN

Thrombocytopenia (less than 100 × 109/L platelets) presents in around one quarter of patients with nonalcoholic fatty liver disease (NAFLD), the hepatic component of insulin resistance (IR). It is unknown whether IR, by itself, associates with thrombocytopenia. Persons with NAFLD and/or IR were prospectively accrued in the study after February 2018. Insulin resistance was defined by assessing α hydroxybutyrate, lynoleoyl glycerolphosphocoline, oleic acid, and insulin (Quantose IR), whereas the presence of NAFLD was defined by serologic determinations (Fibromax) and liver transient elastography (Fibroscan). In 78 patients with NAFLD, thrombocytopenia was identified in 22 (28%), whereas in 19 persons with IR, 14 (73%) were found to have NAFLD. In persons with IR + NAFLD, thrombocytopenia presented in 9 (64%). In the subset of patients with IR, the prevalence of thrombocytopenia was 52%. There was only 1 patient with IR/without NAFLD who displayed thrombocytopenia. Significant statistical association between NAFLD and thrombocytopenia was found (odds ratio [OR]: = 13, confidence interval [CI]: 1.5-162, P = .05), whereas there was no association between IR and thrombocytopenia (OR = 0.38, CI: 0.06-2.3, P = .61). Insulin resistance, by itself, was not found to be associated with diminished platelet counts. The presence of NAFLD, one of the consequences of IR, seems to be required to lead into thrombocytopenia.


Asunto(s)
Resistencia a la Insulina/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/genética , Trombocitopenia/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trombocitopenia/genética , Adulto Joven
12.
PLoS One ; 14(12): e0226375, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31856189

RESUMEN

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adolescente , Adulto , Fármacos Anti-VIH/efectos adversos , Asia/epidemiología , Niño , Estudios de Cohortes , Femenino , Humanos , Cirrosis Hepática/epidemiología , Masculino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Adulto Joven
13.
Am Fam Physician ; 100(12): 759-770, 2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31845776

RESUMEN

Cirrhosis is the 12th leading cause of death in the United States. Newer research has established that liver fibrosis is a dynamic process and that early cirrhosis may be reversible. Only one in three people with cirrhosis knows they have it. Most patients with cirrhosis remain asymptomatic until the onset of decompensation. When clinical signs, symptoms, or abnormal liver function tests are discovered, further evaluation should be pursued promptly. The most common causes of cirrhosis are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. Initial workup includes viral hepatitis serologies, ferritin, transferrin saturation, and abdominal ultrasonography as well as complete blood count, liver function tests, and prothrombin time/international normalized ratio, if not already ordered. Additional testing is based on demographics and risk factors. Common serum and ultrasound-based screening tests to assess fibrosis include the aspartate transaminase to platelet ratio index score, Fibrosis 4 score, FibroTest/FibroSure, nonalcoholic fatty liver fibrosis score, standard ultrasonography, and transient elastography. Generally, noninvasive tests are most useful in identifying patients with no to minimal fibrosis or advanced fibrosis. Chronic liver disease management includes directed counseling, laboratory testing, and ultrasound monitoring. Treatment goals are preventing cirrhosis, decompensation, and death. Varices are monitored with endoscopy and often require prophylaxis with nonselective beta blockers. Ascites treatment includes diuresis, salt restriction, and antibiotic prophylaxis for spontaneous bacterial peritonitis, when indicated. Hepatic encephalopathy is managed with lifestyle and nutritional modifications and, as needed, with lactulose and rifaximin. Hepatocellular carcinoma screening includes ultrasound screening every six months for patients with cirrhosis.


Asunto(s)
Cirrosis Hepática/diagnóstico , Cirrosis Hepática/terapia , Enfermedad Crónica , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/complicaciones
14.
Int J Mol Sci ; 21(1)2019 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-31861664

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the main causes of chronic liver disease worldwide. NAFLD comprises a group of conditions characterized by the accumulation of hepatic lipids that can eventually lead to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), the fifth most common cancer type with a poor survival rate. In this context, several works have pointed out perturbations in lipid metabolism and, particularly, changes in bioactive sphingolipids, as a hallmark of NAFLD and derived HCC. In the present work, we have reviewed existing literature about sphingolipids and the development of NAFLD and NAFLD-derived HCC. During metabolic syndrome, considered a risk factor for steatosis development, an increase in ceramide and sphigosine-1-phosphate (S1P) have been reported. Likewise, other reports have highlighted that increased sphingomyelin and ceramide content is observed during steatosis and NASH. Ceramide also plays a role in liver fibrosis and cirrhosis, acting synergistically with S1P. Finally, during HCC, metabolic fluxes are redirected to reduce cellular ceramide levels whilst increasing S1P to support tumor growth.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Ceramidas/metabolismo , Neoplasias Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Esfingolípidos/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Progresión de la Enfermedad , Detección Precoz del Cáncer , Humanos , Metabolismo de los Lípidos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Factores de Riesgo
15.
Korean J Gastroenterol ; 74(6): 341-348, 2019 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-31870140

RESUMEN

Background/Aims: The utility of asialo-α1-acid glycoprotein (AsAGP) for assessing the fibrotic burden is unknown. This study examined the diagnostic performance of the AsAGP level for advanced liver fibrosis or cirrhosis in patients with chronic hepatitis B (CHB) or nonalcoholic fatty liver disease (NAFLD). Methods: From July to December 2018, 48 patients with CHB and 75 with NAFLD were recruited prospectively. Transient elastography was used as the reference standard for liver fibrosis, and the cutoff liver stiffness values were defined as 10.0 kilopascal (kPa) for ≥F3 and 12.0 kPa for F4 in CHB patients, and 9.0 kPa for ≥F3 and 11.8 kPa for F4 in NAFLD patients. Results: To predict stage ≥F3 and F4 fibrosis, the areas under the receiver operating characteristic curves of the AsAGP level in patients with CHB were 0.788 (95% CI 0.647-0.930; p=0.005) and 0.825 (95% CI 0.674-0.976; p=0.004), respectively. The cutoff AsAGP levels in patients with CHB that maximized the sum of the sensitivity and specificity values were 1.31 (sensitivity 100.0%, specificity 52.6%) and 1.55 (sensitivity 75.0%, specificity 80.0%), respectively. In contrast, the AsAGP level was similar regardless of the fibrosis stage in patients with NAFLD (all p>0.05 between the stages). Conclusions: The AsAGP level showed acceptable diagnostic accuracy in predicting advanced liver fibrosis and cirrhosis in patients with CHB but not in those with NAFLD. Further studies will be needed to validate the diagnostic performance of the AsAGP level in patients with NALFD.


Asunto(s)
Asialoglicoproteínas/sangre , Hepatitis B Crónica/complicaciones , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Orosomucoide/análogos & derivados , Adulto , Área Bajo la Curva , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Hígado/fisiopatología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Curva ROC , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
16.
Metabolism ; 101: 154001, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31672448

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western societies and a major cause of hepatic disease worldwide. Its more severe type, namely nonalcoholic steatohepatitis (NASH), may result in the development of cirrhosis and hepatocellular carcinoma. NAFLD, and especially NASH, are also associated with increased cardiovascular morbidity and mortality. Type 2 diabetes mellitus (T2DM) predisposes to NAFLD development and progression via insulin resistance and hyperglycemia. It has also been reported that the majority of T2DM patients have NAFLD/NASH, thus potentially further increasing their cardiometabolic risk. Current guidelines recommend to screen for NAFLD in all T2DM patients and vice-versa. Lifestyle remains the first-line therapeutic option for NAFLD/NASH. Among antidiabetic drugs, pioglitazone was shown to improve histological features of NASH. More recently, there is an increasing interest regarding the effects of newer anti-diabetic drugs, such as dipeptidyl peptidase 4 inhibitors (DPP-4i), sodium glucose cotransporter 2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on NAFLD/NASH. The present narrative review considers the up-to-date data on the impact of DPP-4i, SGLT2i, and GLP-1 RAs on biochemical and/or histological markers of NAFLD/NASH. The potential clinical implications of these findings in daily practice are also discussed. Taking into consideration the global increasing prevalence of NAFLD/NASH, therapeutic options that can prevent or treat this disease will exert considerable benefits on human health.


Asunto(s)
Hígado Graso/tratamiento farmacológico , Hipoglucemiantes/farmacología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Pioglitazona/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
17.
Z Gastroenterol ; 57(10): 1209-1217, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31610584

RESUMEN

INTRODUCTION AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is increasing globally with an estimated prevalence of approximately 25 %. Nonalcoholic steatohepatitis as the progressive disease entity often leads to fibrosis and end-stage disease. The magnitude of NAFLD patients are not diagnosed and have no access to further clinical assessment. Diagnostic pathways for individual risk evaluation fitting with available resources are of utmost importance in real-world clinical practice. METHODS: Retrospective analysis of 1346 anonymized outpatient datasets at Würzburg University Hospital, Germany. Transient elastography (TE) with controlled attenuation parameter and laboratory-based risk scores (NFS, FIB-4) were the main diagnostic workup tools for risk stratification. RESULTS: After preselection based on questionnaire information NAFLD still accounts for one-fifth of patients in the liver outpatient service. More than 80 % of NAFLD patients receive their first-time diagnosis in our unit. Laboratory-based risk scores and TE are valuable tools for second-step risk assessment as shown in our clinical data analysis. Moreover, 65 % of NAFLD patients use inpatient services for at least 1 day. The policy to perform liver biopsy in high-risk patients above the recommended threshold of 9.6 kPa if any clinical doubt exists regarding the diagnosis of cirrhosis leads to a histological down staging in almost 80 %. CONCLUSION: Questionnaire-based referral from primary care followed by broadly available fast-track TE and eventually liver biopsy for selected patients is the standard practice in our unit. This approach represents a feasible model to handle the large gap between availability and clinical need for TE facilities.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Instituciones de Atención Ambulatoria , Alemania , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Estudios Retrospectivos , Encuestas y Cuestionarios
18.
BMJ ; 367: l5367, 2019 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-31594780

RESUMEN

OBJECTIVE: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). DESIGN: Matched cohort study. SETTING: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046). PARTICIPANTS: 120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database. MAIN OUTCOME MEASURES: Primary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses. RESULTS: 120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension. CONCLUSIONS: The diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.


Asunto(s)
Hipertensión/epidemiología , Hígado/patología , Infarto del Miocardio/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Fumar/epidemiología , Accidente Cerebrovascular/epidemiología , Adulto , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/fisiopatología , Países Bajos/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , España/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatología
19.
Medicine (Baltimore) ; 98(39): e17277, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31574842

RESUMEN

Breast cancer is the most common cancer among women worldwide, and it is a main cause of death in women. As with breast cancer, metabolic components are important risk factors for the development of nonalcoholic fatty liver disease (NAFLD). In this retrospective cohort study, we aimed to determine the prevalence of NAFLD in patients with breast cancer and the impact of NAFLD on the prognosis of breast cancer.Patients with breast cancer were enrolled in the study from January 2007 to June 2017. Hepatic steatosis was evaluated through non-enhanced computed tomography scan by measuring Hounsfield Units in the liver and spleen, respectively; 123 healthy controls who underwent non-enhanced computed tomography scan were also analyzed.The prevalence of NAFLD in patients with breast cancer was 15.8% (251/1587), which was significantly higher than in healthy controls (8.9%, 11/123) (P = .036). Overall survival did not significantly differ between the groups with and without NAFLD (P = .304). However, recurrence-free survival was significantly higher in patients without NAFLD than in those with NAFLD (P = .009). Among breast cancer patients receiving endocrine treatment, the NAFLD group showed a higher cumulative incidence of significant liver injury than the group without NAFLD (P < .001).The prevalence of NAFLD in patients with breast cancer is significantly higher than in healthy controls. Moreover, breast cancer patients with NAFLD showed poorer prognosis in terms of recurrence. Therefore, diagnostic evaluation for NALFD is important in managing patients with breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Mastectomía/efectos adversos , Recurrencia Local de Neoplasia/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Complicaciones Posoperatorias/epidemiología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
20.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 725-727, 2019 Sep 20.
Artículo en Chino | MEDLINE | ID: mdl-31594102

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes for chronic liver diseases, which progress gradually from nonalcoholic type simple fatty liver disease to hepatitis, cirrhosis and even liver failure and hepatocellular carcinoma. Sarcopenia is a progressive disease characterized by reduced skeletal muscle mass and function in association to metabolic dysfunctions. Recent studies have shown that the occurrence and development of NAFLD and sarcopenia are related, and there is a common base for the pathogenesis between the two, which may promote each other for mutual risk factors. This article reviews the current research progress of this field in order to clinically further understand the pathogenesis and intrinsic links between the two to look for appropriate interventions.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/complicaciones , Sarcopenia/complicaciones , Carcinoma Hepatocelular , Humanos , Cirrosis Hepática , Neoplasias Hepáticas , Factores de Riesgo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA