https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20973

Nonalcoholic fatty liver disease: From steatosis to cirrhosis

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2003.50193

Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.

/pdf/the-multiple-hit-pathogenesis-of-non-alcoholic-fatty-liver-4b2gfxdwuu.pdf

The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.23594

Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection.

http://www.giorgiobedogni.it/reprints/poj49.pdf

Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study†‡

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2002.30690

Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.

Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients

Objective
The purpose of this study is to investigate the respiratory mechanics, breathing pattern, and pressure-generating capacity of respiratory muscles during the early phases of an acute exacerbation of COPD.

/pdf/mechanical-determinants-of-early-acute-ventilatory-failure-10o8ajsn3q.pdf

Fabio Mecca

Papers

Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association

Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients

Mechanical determinants of early acute ventilatory failure in COPD patients: a physiologic study.