The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.

Association between Sleep Disturbances and Liver Status in Obese Subjects with Nonalcoholic Fatty Liver Disease: A Comparison with Healthy Controls.

The relevance of sleep patterns in the onset or evolution of nonalcoholic fatty liver disease (NAFLD) is still poorly understood. Our aim was to investigate the association between sleep characteristics and hepatic status indicators in obese people with NAFLD compared to normal weight non-NAFLD controls. Ninety-four overweight or obese patients with NAFLD and 40 non-NAFLD normal weight controls assessed by abdominal ultrasonography were enrolled. Hepatic status evaluation considered liver stiffness determined by Acoustic Radiation Force Impulse elastography (ARFI) and transaminases. Additionally, anthropometric measurements, clinical characteristics, and biochemical profiles were determined. Sleep features were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Hepatic status parameters, anthropometric measurements, and clinical and biochemical markers differed significantly in NAFLD subjects compared to controls, as well as sleep efficiency, sleep disturbance score, and sleep quality score. In the NAFLD group, a higher prevalence of short sleep duration (p = 0.005) and poor sleep quality (p = 0.041) were found. Multivariate-adjusted odds ratio (95% confidence interval) for NAFLD considering sleep disturbance was 1.59 (1.11⁻2.28). Regression models that included either sleep disturbance or sleep quality predicted up to 20.3% and 20.4% of the variability of liver stiffness, respectively, and after adjusting for potential confounders. Current findings suggest that sleep disruption may be contributing to the pathogenesis of NAFLD as well as the alteration of the liver may be affecting sleep patterns. Consequently, sleep characteristics may be added to the list of modifiable behaviors to consider in health promotion strategies and in the prevention and management of NAFLD.

Peritonitis meconial, una complicación no descrita de la hepatitis E durante la gestación / Meconium peritonitis, a non-described complication of hepatitis E during pregnancy

La infección por el virus de la hepatitis E es una causa clásica de hepatitis fulminante en la gestación que puede acarrear graves consecuencias materno-fetales. Las complicaciones fetales se derivan fundamentalmente de la transmisión vertical durante la gestación o el parto (hipotermia, hipoglucemia, hepatitis aguda, necrosis masiva hepática) y de un aumento de la prematuridad que conllevaría una mayor mortalidad neonatal. La peritonitis meconial se ha descrito como complicación de la infección materno-fetal por parvovirus B19, citomegalovirus, rubeola, virus de la hepatitis A y virus de la hepatitis B, sin que hayan sido comunicados en la bibliografía casos secundarios a la infección por virus de la hepatitis E. Presentamos el caso de una gestante de 19 semanas que ingresa por un cuadro de hepatitis aguda E, con diagnóstico fetal ecográfico prenatal compatible con peritonitis meconial (AU)

Hepatitis E virus infection is a classical cause of fulminant hepatitis during pregnancy, which can lead to severe maternal and fetal complications. Fetal complications are mainly derived from the vertical transmission during pregnancy or delivery (hypothermia, hypoglycaemia, acute hepatitis, massive liver necrosis) and from and increase in prematurity that would lead on to a greater neonatal mortality. Meconium peritonitis has been described as a complication of maternal and fetal infection by parvovirus B19, cytomegalovirus, rubella, hepatitis A virus and hepatitis B virus. There have been no published cases relating meconium peritonitis and hepatitis E virus infection. We present the case of a 19 week pregnant woman admitted with an acute hepatitis E, with a fetal prenatal ultrasound diagnosis of meconium peritonitis (AU)

Dificultades en el diagnóstico de los pacientes con enfermedad de Wilson en la práctica clínica: experiencia de 15 casos / Complexity of the diagnosis of Wilson disease in clinical practice: Our experience in 15 patients

INTRODUCCIÓN: La enfermedad de Wilson (EW) es un trastorno hereditario que cursa con depósito de cobre (Cu), provocando principalmente clínica hepática, neurológica y/o psiquiátrica. Ante la ausencia de algunos de sus rasgos típicos, el diagnóstico de la EW es difícil y se basa en la combinación de pruebas clínicas, analíticas y genéticas. El objetivo del estudio fue reflejar la complejidad del diagnóstico de la EW en la práctica clínica. MÉTODOS: Se realizó un análisis retrospectivo de la historia clínica de los pacientes diagnosticados de EW, describiendo la presentación clínica, hallazgos histológicos, analíticos y evolución tras tratamiento. Además se hizo estudio genético y se aplicó el «score» diagnóstico de Leipzig. RESULTADOS: Incluimos un total de 15 pacientes, 4 sintomáticos: clínica hepática (1), neurológica (1), psiquiátrica (1) y mixta (1) y 11 pacientes presintomáticos: hipertransaminasemia (8) y estudio familiar (3). Se objetivó anillo Kayser-Fleischer en 2 pacientes, ambos sin clínica neurológica. El 73% presentaba ceruloplasmina ≤5mg/dL y el 40% Cuo 24h>100μg. El Cu hepático superaba los 250μg/g t.s. en el 85% de los pacientes. El estudio genético (mutaciones gen ATP7B) permitió el diagnóstico final en 5 pacientes con mínimos rasgos de la enfermedad, uno de ellos sintomático (clínica psiquiátrica). Se identificaron 5 mutaciones previamente descritas (p.M645R, p.R827W, p.H1069Q, p.P768L y p.G869R) y 3 inéditas (p.L1313R, p.I1311T y p.A1179D), siendo p.M645R la mutación más frecuentemente encontrada. Tras el tratamiento se objetivó una mejoría de los parámetros analíticos (transaminasas, cupruria) y de la sintomatología, excepto en los pacientes con clínica neuropsiquiátrica. CONCLUSIONES: Nuestra serie refleja el papel relevante del estudio genético en el diagnóstico de EW. La identificación en nuestro medio de la mutación p.M645R en la mayoría de nuestros pacientes debe tenerse en cuenta en la estrategia para el análisis molecular del gen ATP7B en nuestra población

BACKGROUND: Wilson disease (WD) is an inherited disorder that causes copper (Cu) accumulation, leading to mainly liver, neurological and/or psychiatric manifestations. In the absence of some of the typical features, diagnosis of WD is difficult and is based on the combination of clinical, biochemical and genetic testing. The aim of this study was to illustrate the complexity of the approach to WD in daily clinical practice. METHODS: We retrospectively analyzed the medical records of patients with WD, including the clinical presentation, histological and biochemical findings, and follow up after treatment. We also carried out genetic testing, and the Leipzig diagnostic score was applied. RESULTS: We included 15 patients. Four were symptomatic, with liver (n=1), neurological (n=1), psychiatric (n=1) and mixed clinical manifestations (n=1), and 11 were presymptomatic, with elevated transaminases (n=8) and family study (n=3). We observed Kayser-Fleischer ring in 2 patients, both without neurologic symptoms. Ceruloplasmin ≤5mg/dL was present in 73%, and 24-hour urinary Cu>100μg in 40%. Liver Cu was >250μg/g.d.t. in 85% of the patients. The final diagnosis of WD was given by genetic testing (ATP7B gene mutations) in 5 patients with minimal disease features, including one symptomatic patient (psychiatric symptoms). We identified 5 previously reported mutations (p.M645R, p.R827W, p.H1069Q, p.P768L and p.G869R) and 3 unpublished mutations (p.L1313R, p.I1311T and p.A1179D); the most frequent mutation was p.M645R. After treatment, biochemical parameters (transaminases, urinary cooper) and symptoms improved, except in patients with neurological and psychiatric manifestations. CONCLUSIONS: Our series illustrates the important role of genetic testing in the diagnosis of WD. The identification of the p.M645R mutation in most of our patients should be kept in mind in the molecular analysis of the ATP7B gene in our region

[Complexity of the diagnosis of Wilson disease in clinical practice: our experience in 15 patients]. / Dificultades en el diagnóstico de los pacientes con enfermedad de Wilson en la práctica clínica: experiencia de 15 casos.

BACKGROUND: Wilson disease (WD) is an inherited disorder that causes copper (Cu) accumulation, leading to mainly liver, neurological and/or psychiatric manifestations. In the absence of some of the typical features, diagnosis of WD is difficult and is based on the combination of clinical, biochemical and genetic testing. The aim of this study was to illustrate the complexity of the approach to WD in daily clinical practice. METHODS: We retrospectively analyzed the medical records of patients with WD, including the clinical presentation, histological and biochemical findings, and follow up after treatment. We also carried out genetic testing, and the Leipzig diagnostic score was applied. RESULTS: We included 15 patients. Four were symptomatic, with liver (n=1), neurological (n=1), psychiatric (n=1) and mixed clinical manifestations (n=1), and 11 were presymptomatic, with elevated transaminases (n=8) and family study (n=3). We observed Kayser-Fleischer ring in 2 patients, both without neurologic symptoms. Ceruloplasmin ≤ 5 mg/dL was present in 73%, and 24-hour urinary Cu> 100 µg in 40%. Liver Cu was >250 µg/g.d.t. in 85% of the patients. The final diagnosis of WD was given by genetic testing (ATP7B gene mutations) in 5 patients with minimal disease features, including one symptomatic patient (psychiatric symptoms). We identified 5 previously reported mutations (p.M645R, p.R827W, p.H1069Q, p.P768L and p.G869R) and 3 unpublished mutations (p.L1313R, p.I1311T and p.A1179D); the most frequent mutation was p.M645R. After treatment, biochemical parameters (transaminases, urinary cooper) and symptoms improved, except in patients with neurological and psychiatric manifestations. CONCLUSIONS: Our series illustrates the important role of genetic testing in the diagnosis of WD. The identification of the p.M645R mutation in most of our patients should be kept in mind in the molecular analysis of the ATP7B gene in our region.