AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions
National Operating Committee on Standards for Athletic Equipment1, University of Modena and Reggio Emilia2, University of Verona3, University of Bologna4, University of Pittsburgh5, University of Turin6, University of Florence7, Sapienza University of Rome8, University of Naples Federico II9, University of Palermo10, University of Milan11
TL;DR: The results of ongoing studies are eagerly expected to lead to introduce into the clinical arena new diagnostic and prognostic biomarkers, prevention and surveillance strategies as well as to new drugs for a tailored approach to the management of NAFLD in the individual patient.
About: This article is published in Digestive and Liver Disease.The article was published on 2017-05-01 and is currently open access. It has received 243 citations till now. The article focuses on the topics: Nonalcoholic fatty liver disease & Steatohepatitis.
Citations
More filters
TL;DR: A first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.
Abstract: Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples. Ldlr−/−.Leiden mice received one of three different energy-dense (ED)-diets (n = 15/group) for 15 weeks. All of the ED diets induced obesity and metabolic risk factors, altered short-chain fatty acids (SCFA), and increased gut permeability and NAFLD to various extents. ED diets reduced the diversity of high-abundant bacteria and increased the diversity of low-abundant bacteria in all of the gut compartments. The ED groups showed highly variable, partially overlapping microbiota compositions that differed significantly from chow. Correlation analyses demonstrated that (1) specific groups of bacteria correlate with metabolic risk factors, organ dysfunction, and NAFLD endpoints, (2) colon mucosa had greater predictive value than other compartments, (3) correlating bacteria differed per compartment, and (4) some bacteria correlated with plasma SCFA levels. In conclusion, this comprehensive microbiota analysis demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.
1,097 citations
Tulane University1, Cedars-Sinai Medical Center2, National Institutes of Health3, University of Arizona4, Karolinska Institutet5, Brigham and Women's Hospital6, Georgia State University7, University of Colorado Denver8, Washington University in St. Louis9, Johns Hopkins University10, University of Modena and Reggio Emilia11, University of Illinois at Chicago12, University of Texas Health Science Center at Houston13, University of Zurich14, Charité15, Georgetown University16, Duke University17, Veterans Health Administration18
TL;DR: Clinicians and researchers are guided to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
781 citations
TL;DR: The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD), and targeting obesity is a rational option for its management.
Abstract: The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis (SS), but also with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. As a consequence, apart from increasing all-cause mortality, obesity seems to increase liver-specific mortality in NAFLD patients. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management. As the first step, lifestyle modification (diet and exercise) is recommended, although it is difficult to achieve and sustain. When the first step fails, adding pharmacotherapy is recommended. Several anti-obesity medications have been investigated in NAFLD (e.g., orlistat, glucagon-like peptide-1 analogs), other anti-obesity medications have not been investigated (e.g., lorcaserin, phentermine hydrochloric, phentermine/topiramate and naltrexone/bupropion), whereas some medications with weight-lowering efficacy have not been approved for obesity (e.g., sodium-glucose cotransporter-2 inhibitors, farnesoid X receptor ligands). If the combination of lifestyle modification and pharmacotherapy also fails, then bariatric surgery should be considered in selected morbidly obese individuals. This review summarizes best evidence linking obesity with NAFLD and presents related therapeutic options.
550 citations
Cites background or methods from "AISF position paper on nonalcoholic..."
...According to the: a) American Association for the Study of Liver Diseases (AASLD) [143], b) APWP [134], c) Italian Association for the study of the Liver (AISF) [144] and d) combined European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) [126] guidelines, structured programs are recommended combining a healthy diet and regular physical activity, targeting to a gradual Please cite this article as: S.A. Polyzos, J. Kountouras and C.S. Mantzoros, O therapeutics, Metabolism Clinical and Experimental, https://doi.org/10.10 weight loss of 7%–10% [126]....
[...]
...EASL/EASD/EASO [126] and AISF [144] favor the Mediterranean diet supporting that, apart from weight loss, it is beneficial for other MetS risk factors closely related with NAFLD (IR, T2DM, hypertension, CVD) [144]....
[...]
...Regarding physical activity, all guidelines propose a combination of aerobic and resistance training [126,134,143,144], with minor differences, e....
[...]
...According to the: a) American Association for the Study of Liver Diseases (AASLD) [143], b) APWP [134], c) Italian Association for the study of the Liver (AISF) [144] and d) combined European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) [126] guidelines, structured programs are recommended combining a healthy diet and regular physical activity, targeting to a gradual...
[...]
...AASLD, AISF and EASL/EASD/EASO recommend a deficit of 500–1000 kcal/day, and the APWP a daily consumption of 1200–1600 kcal....
[...]
TL;DR: A rapidly expanding body of clinical evidence is critically discussed that supports the existence of a bi-directional relationship between NAFLD and various components of MetS, particularly T2DM and HTN, as well as the current knowledge regarding a strong association between NA FLD and CVD morbidity and mortality.
470 citations
Journal Article•
405 citations
References
More filters
TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Abstract: The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
10,126 citations
"AISF position paper on nonalcoholic..." refers background in this paper
...[45] Turnbaugh PJ, Ley RE, Mahowald MA, et al....
[...]
...Furthermore, several intestinal microorganisms can increase the efficiency of caloric extraction from the food, thus contributing to the development of obesity [45]....
[...]
TL;DR: Current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women, and increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
Abstract: background The influence of excess body weight on the risk of death from cancer has not been fully characterized. methods In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. results The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin’s lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. conclusions Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
7,095 citations
Additional excerpts
...[133] Calle EE, Rodriguez C, Walker-Thurmond K, et al....
[...]
TL;DR: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous, and random‐effects models were used to provide point estimates of prevalence, incidence, mortality and incidence rate ratios.
6,746 citations
"AISF position paper on nonalcoholic..." refers background in this paper
...Although NAFLD was highly prevalent in all continents, the ighest prevalence rates were reported from South America and he Middle East, whereas the lowest prevalence was reported from frica [58]....
[...]
...Compared to non-NAFLD control subjects, patients with NAFLD are exposed to an almost two-fold increased risk of liver-related mortality [58] and to a substantially increased risk of developing fatal and non-fatal CVD events [66]....
[...]
...09, and approximately 40% of these patients progressed to the more advanced stages over time [58]....
[...]
...7% for sia, respectively, among patients who are not candidates for liver iopsy [58]....
[...]
...[58] Younossi ZM, Koenig AB, Abdelatif D, et al....
[...]
TL;DR: It is found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice, demonstrating that changes in gut microbiota controls metabolic endotoxinemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability.
Abstract: OBJECTIVE— Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. RESEARCH DESIGN AND METHODS— We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. RESULTS— We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14 − / − mutant mice mimicked the metabolic and inflammatory effects of antibiotics. CONCLUSIONS— This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.
3,914 citations
"AISF position paper on nonalcoholic..." refers background in this paper
...[46] Cani PD, Bibiloni R, Knauf C, et al....
[...]
...Lastly, diet-induced dysbiosis has been associated with increased gut permeability in both mice [46] and humans [47]....
[...]
TL;DR: Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, the world will be in a better position to develop treatments for metabolic disease.
Abstract: The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.
3,436 citations
"AISF position paper on nonalcoholic..." refers background in this paper
...In particular, gut microbiota can trigger (directly or via the synthesis of end-products of bacterial metabolism, such as short-chain fatty acids), different signaling pathways, which eventually lead to an increased deposition of peripheral fat [42,44]....
[...]