Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Infla...Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet(MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and antioxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.展开更多
Helicobacter pylori(H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopat...Helicobacter pylori(H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in thelast decades, abetted by modern clinical practices, may have other health consequences.展开更多
Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within ...Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic cirrhosis.NAFLD has become the most common cause of chronic liver disease in children and adolescents.The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide.NAFLD is strongly associated with abdominal obesity,type 2 diabetes,and dyslipidemia,and most patients have evidence of insulin resistance.Thus,NAFLD shares many features of the metabolic syndrome(MetS),a highly atherogenic condition,and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis.Accumulating evidence suggests thatNAFLD is associated with a significantly greater overall mortality than in the general population,as well as with increased prevalence of cardiovascular disease(CVD),independently of classical atherosclerotic risk factors.Yet,several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS.Therefore,the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes.In children,the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively.Therapeutic goals for NAFLD should address nutrition,physical activity,and avoidance of smoking to prevent not only end-stage liver disease but also CVD.展开更多
Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with...Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.展开更多
AIM To establish a threshold value for liver fat content between healthy children and those with nonalcoholic fatty liver disease(NAFLD) by using magnetic resonance imaging(MRI), with liver biopsy serving as a referen...AIM To establish a threshold value for liver fat content between healthy children and those with nonalcoholic fatty liver disease(NAFLD) by using magnetic resonance imaging(MRI), with liver biopsy serving as a reference standard. METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel pointresolved 1H MR-Spectroscopy(1H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cutoff value. Lin coefficient test was used to evaluate thecorrelation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF.CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children.展开更多
Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is ...Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the hu-man stomach for many decades without adverse con-sequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae.展开更多
AIM： To determine in obese children with nonalcoholic fatty liver disease （NAFLD） the accuracy of magnetic resonance imaging （MRI） in assessing liver fat concentration. METHODS： A case-control study was performe...AIM： To determine in obese children with nonalcoholic fatty liver disease （NAFLD） the accuracy of magnetic resonance imaging （MRI） in assessing liver fat concentration. METHODS： A case-control study was performed. Cases were 25 obese children with biopsy-proven NAFLD. Controls were 25 obese children matched for age and gender, without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin. Hepatic fat fraction （HFF） by MRI was obtained using a modification of the Dixon method.RESULTS： HFF ranged from 2% to 44% [mean, 19.0% （95% CI, 15.1-27.4）] in children with NAFLD, while in the controls this value ranged from 0.08% to 4.69% [2.0% （1.3-2.5）, P 〈 0.0001]. HFF was highly correlated with histological steatosis （r = 0.883, P 〈 0.0001） in the NAFLD children. According to the histological grade of steatosis, the mean HFF was 8.7% （95% CI, 6.0-11.6） for mild, 21.6% （15.3-27.0） for moderate, and 39.7% （34.4-45.0） for severe fatty liver infiltration. With a cutoff of 4.85%, HFF had a sensitivity of 95.8% for the diagnosis of histological steato- sis ≥ 5%. All control children had HFF lower than 4.85%; thus, the specificity was 100%. Alter 12 mo, children with weight loss displayed a significant decrease in HFF. CONCLUSION： MRI is an accurate methodology for liver fat quantification in pediatric NAFLD.展开更多
The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin r...The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.展开更多
AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80...AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.展开更多
The combination of a proton pump inhibitor and two antibiotics(clarithromycin plus amoxicillin or metronidazole)has been the recommended first-line therapy since the first guidelines for Helicobacter pylori(H.pylori)i...The combination of a proton pump inhibitor and two antibiotics(clarithromycin plus amoxicillin or metronidazole)has been the recommended first-line therapy since the first guidelines for Helicobacter pylori(H.pylori)infection in children were published.In recent years,the success of eradication therapies has declined,in part due to the development of H.pylori resistant strains.Alternative anti-H.pylori treatments are currently becoming more popular than the traditional eradication methods.Components that may be used either as a monotherapy or,in combination with antimicrobials,resulting in a more effective anti-H.pylori therapy have been investigated in depth by several researchers.One of the potential therapies is probiotic cultures;promising results have been observed in initial studies with numerous probiotic strains.Nevertheless,many questions remain unanswered.In this article,we comprehensively review the possible mechanisms of action of probiotics on H.pylori infection,and present the results of published studies using probiotics as possible agents to control H.pylori infection in children.The effect of the addition of probiotics to the standard H.pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.展开更多
The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determin ing the population prevalence of NAFLD include the type of test (and the reference intervals used to define ...The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determin ing the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nat ure of the study design. The natural history of pediat ric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk popul ation, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninv asive alternatives that will allow the prognosis of pediat ric NAFLD to be followed in large community or populat ionbased studies.展开更多
AIM: To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD).
AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein...AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP). METHODS: A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1-basis) with thecases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMDZ-scores were calcu- lated using race and gender specific LMS curves. RESULTS: Obese children with NAFLD had a significantly lower LS BMDZ-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0.01) and HSCRP (standardized β coefficient, -0.192; P < 0.05) were significantly and independently associated with LS BMD Z-score. Similar results were obtained when NAFLD (instead of NASH) was included in the model. WB BMD Z-scores were significantly and independently associated with NASH (standardized β coefficient, -0.248;P < 0.05) and fat mass (standardized β coefficient, -0.224;P < 0.05). CONCLUSION: This study reveals that NAFLD is associated with low BMD in obese children, and that systemic, low-grade inflammation may accelerate loss of bone mass in patients with NAFLD.展开更多
Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As descr...Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.展开更多
Celiac disease(CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs...Celiac disease(CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability. The HLA system has a fundamental role in identifying the antigens introduced into the host with the vaccines and in the development of specific antibodies, and some HLA phenotypes have been associated with a less effective immunological response. The available literature indicates that the immunological response to vaccines in CD children does not differ markedly from that of general population and antibody titres are high enough to provide long-term protection, except for hepatitis B virus vaccine. In this article, we review and discuss the scarce literature in this field in order to provide clinical practice guidelines to achieve the most efficient monitoring of the response to vaccines in pediatric CD patients.展开更多
Celiac disease(CD) is an immune-mediated systemic condition evoked by gluten and related prolamines in genetically predisposed subjects. It is characterised by a variable combination of gluten-dependent clinical sympt...Celiac disease(CD) is an immune-mediated systemic condition evoked by gluten and related prolamines in genetically predisposed subjects. It is characterised by a variable combination of gluten-dependent clinical symptoms, CDspecific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. The only therapy of CD consists of a life-long gluten free diet(GFD). Strict GFD adherence results in full clinical, serological and histological remission, avoiding long-term complications in CD patients. However, this diet is not without problems. Gluten free products have high levels of lipids, sugar and salt to improve food palatability and consistency, and subjects with CD show an excessive consumption of hypercaloric and hyperlipidic foods to compensate dietetic restriction. GFD may therefore have a negative impact on cardiometabolic risk factors such as obesity, serum lipid levels, insulin resistance, metabolic syndrome, and atherosclerosis. In adults, some studies have suggested that GFD have a beneficial effect on cardiovascular profile, whereas others have shown an atherogenic effect of GFD. In children, very few studies are available on the issue. Thus, the aim of the present narrative review was to analyze the current clinical evidence on the impact of GFD on cardiometabolic risk factors in children with CD.展开更多
Diet is an important modifiable risk factor for obesity and obesity-related complications,and there has been growing interest in plant-based diets,mainly defined as“vegetarian”diets,which have been associated with a...Diet is an important modifiable risk factor for obesity and obesity-related complications,and there has been growing interest in plant-based diets,mainly defined as“vegetarian”diets,which have been associated with a lower prevalence rate of overweight/obesity as well as a lower risk of coronary heart disease,type 2 diabetes,other cardiometabolic diseases,and all-cause mortality(1).Such dietary patterns are also a major determinant of environmental sustainability(1).Of note,however,vegetarian diets can include less healthy plant foods,such as refined grains and sugar-sweetened beverages which have detrimental effects on health(2).展开更多
Concurrent with the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)is rapidly becoming the leading cause of chronic liver disease worldwide(1).NAFLD,particularly its histological phenotype non-alcoholic stea...Concurrent with the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)is rapidly becoming the leading cause of chronic liver disease worldwide(1).NAFLD,particularly its histological phenotype non-alcoholic steatohepatitis(NASH),can progress to advanced liver disease,cirrhosis and hepatocellular carcinoma and indication for liver transplantation(2).Although remarkable advances have been made in the understanding of the pathophysiology of NAFLD,the exact mechanism of hepatic fat accumulation and the progression to NASH is not fully understood.Thus,in order to reduce the burden associated with these diseases,it is imperative that all major factors that contribute to the development of NAFLD are identified.展开更多
文摘Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet(MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and antioxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.
文摘Helicobacter pylori(H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in thelast decades, abetted by modern clinical practices, may have other health consequences.
文摘Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic cirrhosis.NAFLD has become the most common cause of chronic liver disease in children and adolescents.The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide.NAFLD is strongly associated with abdominal obesity,type 2 diabetes,and dyslipidemia,and most patients have evidence of insulin resistance.Thus,NAFLD shares many features of the metabolic syndrome(MetS),a highly atherogenic condition,and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis.Accumulating evidence suggests thatNAFLD is associated with a significantly greater overall mortality than in the general population,as well as with increased prevalence of cardiovascular disease(CVD),independently of classical atherosclerotic risk factors.Yet,several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS.Therefore,the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes.In children,the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively.Therapeutic goals for NAFLD should address nutrition,physical activity,and avoidance of smoking to prevent not only end-stage liver disease but also CVD.
文摘Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.
文摘AIM To establish a threshold value for liver fat content between healthy children and those with nonalcoholic fatty liver disease(NAFLD) by using magnetic resonance imaging(MRI), with liver biopsy serving as a reference standard. METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel pointresolved 1H MR-Spectroscopy(1H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cutoff value. Lin coefficient test was used to evaluate thecorrelation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF.CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children.
文摘Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the hu-man stomach for many decades without adverse con-sequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae.
基金Supported by A grant from Sapienza University of Rome (Progetti di Ricerca Universitaria 2008-2009)
文摘AIM： To determine in obese children with nonalcoholic fatty liver disease （NAFLD） the accuracy of magnetic resonance imaging （MRI） in assessing liver fat concentration. METHODS： A case-control study was performed. Cases were 25 obese children with biopsy-proven NAFLD. Controls were 25 obese children matched for age and gender, without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin. Hepatic fat fraction （HFF） by MRI was obtained using a modification of the Dixon method.RESULTS： HFF ranged from 2% to 44% [mean, 19.0% （95% CI, 15.1-27.4）] in children with NAFLD, while in the controls this value ranged from 0.08% to 4.69% [2.0% （1.3-2.5）, P 〈 0.0001]. HFF was highly correlated with histological steatosis （r = 0.883, P 〈 0.0001） in the NAFLD children. According to the histological grade of steatosis, the mean HFF was 8.7% （95% CI, 6.0-11.6） for mild, 21.6% （15.3-27.0） for moderate, and 39.7% （34.4-45.0） for severe fatty liver infiltration. With a cutoff of 4.85%, HFF had a sensitivity of 95.8% for the diagnosis of histological steato- sis ≥ 5%. All control children had HFF lower than 4.85%; thus, the specificity was 100%. Alter 12 mo, children with weight loss displayed a significant decrease in HFF. CONCLUSION： MRI is an accurate methodology for liver fat quantification in pediatric NAFLD.
文摘The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.
基金Supported by Sapienza University of Rome(Progetti di Ricerca Universitaria 2011-2012)
文摘AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.
文摘The combination of a proton pump inhibitor and two antibiotics(clarithromycin plus amoxicillin or metronidazole)has been the recommended first-line therapy since the first guidelines for Helicobacter pylori(H.pylori)infection in children were published.In recent years,the success of eradication therapies has declined,in part due to the development of H.pylori resistant strains.Alternative anti-H.pylori treatments are currently becoming more popular than the traditional eradication methods.Components that may be used either as a monotherapy or,in combination with antimicrobials,resulting in a more effective anti-H.pylori therapy have been investigated in depth by several researchers.One of the potential therapies is probiotic cultures;promising results have been observed in initial studies with numerous probiotic strains.Nevertheless,many questions remain unanswered.In this article,we comprehensively review the possible mechanisms of action of probiotics on H.pylori infection,and present the results of published studies using probiotics as possible agents to control H.pylori infection in children.The effect of the addition of probiotics to the standard H.pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.
文摘The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determin ing the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nat ure of the study design. The natural history of pediat ric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk popul ation, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninv asive alternatives that will allow the prognosis of pediat ric NAFLD to be followed in large community or populat ionbased studies.
文摘AIM: To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD).
基金Supported by A Grant from Sapienza University of Rome,Progetti di Ricerca Universitaria 2010-2011
文摘AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP). METHODS: A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1-basis) with thecases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMDZ-scores were calcu- lated using race and gender specific LMS curves. RESULTS: Obese children with NAFLD had a significantly lower LS BMDZ-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0.01) and HSCRP (standardized β coefficient, -0.192; P < 0.05) were significantly and independently associated with LS BMD Z-score. Similar results were obtained when NAFLD (instead of NASH) was included in the model. WB BMD Z-scores were significantly and independently associated with NASH (standardized β coefficient, -0.248;P < 0.05) and fat mass (standardized β coefficient, -0.224;P < 0.05). CONCLUSION: This study reveals that NAFLD is associated with low BMD in obese children, and that systemic, low-grade inflammation may accelerate loss of bone mass in patients with NAFLD.
文摘Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.
文摘Celiac disease(CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability. The HLA system has a fundamental role in identifying the antigens introduced into the host with the vaccines and in the development of specific antibodies, and some HLA phenotypes have been associated with a less effective immunological response. The available literature indicates that the immunological response to vaccines in CD children does not differ markedly from that of general population and antibody titres are high enough to provide long-term protection, except for hepatitis B virus vaccine. In this article, we review and discuss the scarce literature in this field in order to provide clinical practice guidelines to achieve the most efficient monitoring of the response to vaccines in pediatric CD patients.
文摘Celiac disease(CD) is an immune-mediated systemic condition evoked by gluten and related prolamines in genetically predisposed subjects. It is characterised by a variable combination of gluten-dependent clinical symptoms, CDspecific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. The only therapy of CD consists of a life-long gluten free diet(GFD). Strict GFD adherence results in full clinical, serological and histological remission, avoiding long-term complications in CD patients. However, this diet is not without problems. Gluten free products have high levels of lipids, sugar and salt to improve food palatability and consistency, and subjects with CD show an excessive consumption of hypercaloric and hyperlipidic foods to compensate dietetic restriction. GFD may therefore have a negative impact on cardiometabolic risk factors such as obesity, serum lipid levels, insulin resistance, metabolic syndrome, and atherosclerosis. In adults, some studies have suggested that GFD have a beneficial effect on cardiovascular profile, whereas others have shown an atherogenic effect of GFD. In children, very few studies are available on the issue. Thus, the aim of the present narrative review was to analyze the current clinical evidence on the impact of GFD on cardiometabolic risk factors in children with CD.
文摘Diet is an important modifiable risk factor for obesity and obesity-related complications,and there has been growing interest in plant-based diets,mainly defined as“vegetarian”diets,which have been associated with a lower prevalence rate of overweight/obesity as well as a lower risk of coronary heart disease,type 2 diabetes,other cardiometabolic diseases,and all-cause mortality(1).Such dietary patterns are also a major determinant of environmental sustainability(1).Of note,however,vegetarian diets can include less healthy plant foods,such as refined grains and sugar-sweetened beverages which have detrimental effects on health(2).
文摘Concurrent with the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)is rapidly becoming the leading cause of chronic liver disease worldwide(1).NAFLD,particularly its histological phenotype non-alcoholic steatohepatitis(NASH),can progress to advanced liver disease,cirrhosis and hepatocellular carcinoma and indication for liver transplantation(2).Although remarkable advances have been made in the understanding of the pathophysiology of NAFLD,the exact mechanism of hepatic fat accumulation and the progression to NASH is not fully understood.Thus,in order to reduce the burden associated with these diseases,it is imperative that all major factors that contribute to the development of NAFLD are identified.
