https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.25762

The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

Importance Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation. Objectives To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease. Evidence Review PubMed was queried for published articles through February 28, 2015, using the search termsNAFLD and cirrhosis, mortality, biomarkers,andtreatment. A total of 88 references were selected, including 14 randomized clinical trials, 19 cohort or case-control studies, 1 population-based study, 2 practice guidelines, 7 meta-analyses, 43 classified as other, and 2 webpages. Findings Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest ( Conclusions and Relevance Between 75 million and 100 million individuals in the United States are estimated to have nonalcoholic fatty liver disease and its potential morbidity extends beyond the liver. It is important that primary care physicians, endocrinologists, and other specialists be aware of the scope and long-term effects of the disease. Early identification of patients with nonalcoholic steatohepatitis may help improve patient outcomes through treatment intervention, including transplantation for those with decompensated cirrhosis.

https://jamanetwork.com/journals/JAMA/articlepdf/2319168/jrv150008.pdf

Nonalcoholic Fatty Liver Disease: A Systematic Review

Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes, many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower type 2 diabetes risk by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications.

https://care.diabetesjournals.org/content/diacare/33/12/2692.full.pdf

Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement.

https://www.gastrojournal.org/article/S0016-5085%2812%2900494-5/pdf

The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology

The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.23129

Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22220

Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders

Repetitive collapse of the upper airway during obstructive sleep apnea/hypopnea (OSA) exposes the brain of sufferers to frequent, transient, hypoxic episodes. The loss of cerebrovascular reactivity in sleep, and particularly in OSA, means that physiologic compensatory mechanisms may not ensure adequate brain oxygen levels. This (31)P magnetic resonance spectroscopy study, of 13 males with severe, untreated OSA undertaken after overnight sleep deprivation, represents the first, seconds time-scale analysis of human brain bioenergetics during transient hypoxia and demonstrates that a moderate degree of oxygen desaturation during sleep has significant effects on brain bioenergetic status. Oxygen desaturation >10% of sleeping baseline resulted in decreases in brain adenosine triphosphate levels (P<0.01), and increases in inorganic phosphate (P<0.0001) with no concomitant changes in phosphocreatine or brain pH. This indicates that the mechanism of adenosine triphosphate depletion in these patients is different to that observed in normoxic, awake working brain. These data show that the buffering capacity of phosphocreatine and the creatine kinase system is not active in mild transient hypoxia and that cerebrovascular compensatory mechanisms are not adequate to prevent decrements in brain high-energy phosphates in OSA. Transient hypoxia experienced during sleep may impair brain function more than previously thought.

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.2009.57

Dynamic changes in brain bioenergetics during obstructive sleep apnea

Eccentric exercise is known to cause changes to the ultrastructure of skeletal muscle and, in turn, may alter the ability of the muscle to store and utilise intracellular substrates such as intramyocellular lipid (IMCL). The purpose of this study was to test the hypothesis that exercise-induced muscle damage (EIMD) results in IMCL accumulation. Six males (31 ± 6 years; mean ± SD, and 72.3 ± 9.7 kg body mass) performed 300 unilateral, maximal, isokinetic, eccentric contractions (Ecc) (30° s−1) of the quadriceps on an isokinetic dynamometer, followed immediately by an equal amount of work by the contralateral leg but with concentric action (Con). Phosphate compounds and IMCL content of the vastus lateralis of both legs were measured using 31P and 1H magnetic resonance spectroscopy. IMCL content was higher in Ecc than Con 24 h post but the reverse was evident 48 h post-exercise (P = 0.046). A significant time × trial interaction for resting [Pi] (P = 0.045), showed increases in Ecc across time but no change in Con. A significant main effect of trial (P = 0.002) was apparent indicating the Ecc leg had marked metabolic dysfunction. The Pi/PCr ratio showed a significant effect of trial (P = 0.001) with an increase evident in Ecc leg, primarily due to increases in [Pi]. The present study highlights changes in IMCL content of skeletal muscle following EIMD.

David W. Walton

Papers

Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss

Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders

Dynamic changes in brain bioenergetics during obstructive sleep apnea

Effects of eccentric exercise-induced muscle damage on intramyocellular lipid concentration and high energy phosphates