Molecular Therapy for Non-Alcoholic Fatty Liver Disease: Angiotensin-(1-7) Delivery via Cyclic RGD-Modified Vesicles Activates Mas Receptor to Ameliorate Fibrosis Through Autophagy and Metabolic Reprogramming.

nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to steatohepatitis (NASH), increasing fibrosis and eventually, cirrhosis ([22][1]). Importantly, NASH accompanied by fibrosis and severe inflammation is the most relevant predictor for disease progression

Nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric disorder, is diagnosed and managed not only by both pediatric gastroenterologists/hepatologists but also frequently by the general pediatrician. This article updates recent advances in diagnostic and therapeutic approach, which may be applied to everyday practice. Diagnosis of NAFLD takes into account the risk factor profile and is a diagnosis of exclusion. Techniques such as transient elastography and specific biomarkers aimed at improving diagnosis and monitoring of NAFLD need further validation in the pediatric population. Defining the risk to develop cirrhosis seems to be of primary importance already in childhood and a combination of genetic, clinical, and environmental factors can help in monitoring and making decisions on therapy. Weight reduction therapy should be the aim of treatment approach, but the compliance is poor and pharmacological treatment would be helpful; docosahexaenoic acid, some probiotics, and vitamin E are to be considered, but evidence is not sufficient to recommend widespread use.

Biomarkers in Fatty Liver Disease—Here is the Skinny

From Fat to Inflammation

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

Extracellular vesicles and ceramide: new mediators for macrophage chemotaxis?

Non-alcoholic fatty liver disease (NAFLD) is a widespread threat to human health. However, the present screening methods for NAFLD are time-consuming or invasive. The present study aimed to assess the potential of microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) as a biomarker of NAFLD. C57BL/6J mice were fed either a 12-week high-fat diet (HFD) or standard chow to establish NAFLD and control groups, respectively. Serum samples were obtained from the mouse model of NAFLD, as well as 50 patients with NAFLD and 50 healthy individuals, and EVs were extracted and verified. Using reverse transcription-quantitative PCR, the mRNA expression level of selected miRNAs in the serum and EVs was analyzed. In order to determine the diagnostic value, receiver operating characteristic (ROC) curves were used. The mice treated with HFD showed notable hepatic steatosis and higher concentrations of serum alanine aminotransferase (ALT). There was also a significant decrease in the expression levels of miR-135a-3p, miR-129b-5p and miR-504-3p, and an increase in miR-122-5p expression levels in circulating EVs in mice treated with HFD and patients with NAFLD. There were also similar miR-135a-3p and miR-122-5p expression patterns in the serum. ROC analysis demonstrated that miR-135a-3p in circulating EVs was highly accurate in diagnosing NAFLD, with the area under the curve value being 0.849 (95% CI, 0.777–0.921; P<0.0001). Bioinformatics analysis indicated that dysregulated miR-135a-3p was associated with ‘platelet-derived growth factor receptor signaling pathway’ and ‘AMP-activated protein kinase signaling pathway’. In summary, circulating miR-135a-3p in EVs may serve as a potential non-invasive biomarker to diagnose NAFLD. This miRNA was a more sensitive and specific biological marker for NAFLD compared with ALT.

Sulfonated albumin from hepatocytes accelerates liver fibrosis in nonalcoholic fatty liver disease through endoplasmic reticulum stress.

Nonalcoholic Fatty Liver Disease and Fibrosis Progression: The Good, the Bad, and the Unknown

Acetyl-CoA Carboxylase Inhibition as a Therapeutic Tool in the Battle Against NASH: Hitting More Than Just One Mechanism?

A call to action for fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), the major reason for abnormal liver function in the Western world, is associated with obesity and diabetes and is characterized by insulin resistance (IR). IR is regulated by mediators released from cells of the immune system or adipocytes and proinflammatory cytokines such as tumor necrosis factor-α (TNFα). The importance of TNFα in human and animal fatty liver diseases, both caused by genetic manipulation and overnutrition, has been shown convincingly. Furthermore, neutralization of TNFα activity improves IR and fatty liver disease in animals. Adiponectin is a potent TNFα-neutralizing and anti-inflammatory adipokine and in vitro and experimental animal studies have proven the importance of this mediator in counteracting inflammation and IR. Anti-inflammatory effects of adiponectin are exerted both by suppressing TNFα synthesis and by induction of anti-inflammatory cytokines such as interleukin-10 or interleukin-1–receptor antagonist. Therefore, the balance between various mediators, either derived from the immune system or adipose tissue, appears to play an important role in hepatic and systemic insulin action and in the development of fatty liver disease.

Referral pathways for NAFLD fibrosis in primary care – No longer a ‘needle in a haystack’

Focus

The role of the gut microbiome in chronic liver disease: the clinical evidence revised.