VII.9. Nonalcoholic fatty liver disease (NAFLD)
In NAFLD, the fat content of the liver exceeds 5% at an alcohol consumption of <10 g per day. A fatty liver (steatosis) is closely linked to insulin resistance, obesity and T2DM. It induces various circulatory diseases. A fatty liver may be caused (in addition to alcohol) by toxins, medical drugs, obesity, physical debilitation (cachexia), T2DM, hyperlipidemia, or a jejunum bypass operation. The probability of the development of liver cirrhosis is increased by regular alcohol consumption in obese individuals.
Insulin resistance is a risk factor for NAFLD development. One study has revealed that half of the NAFLD patients suffered from the symptoms of the MetS too.
During the development of NAFLD, the liver tissue is damaged (cirrhosis), which may lead to high portal BP and death. Fibrosis may develop. The progress of fibrosis means a scarring process in the liver: the liver tissue is replaced by connective tissue. Cirrhosis connected with inflammatory processes is NASH. Inflammatory processes damage the endoplasmic reticulum and mitochondrial function of the liver cells. From this disease, cancer may develop. NAFLD is frequently associated with OSA, which exacerbates the disease through hypoxia.
There are no markers for the disease. An increased alanine aminotransferase (ALT) level is used in clinical practice. An enhanced ALT level correlates well with the serious or fatal cardiovascular events.
In the event of an increased liver fat content, the levels of ALT and serum γ-glutamyltransferase (GGT) are enhanced too. These parameters reveal a malfunction of the liver parenchymal cells and bile duct. An increased GGT level is a risk factor for stroke or arteriosclerosis. The AST/ALT ratio is <1; it is does not correlate with the extent of NAFLD (though it does in the case of alcoholic fatty liver disease). The acetyl CoA carboxylases (ACC1 and ACC2) participate in the lipid metabolism in the liver. Blockade of these enzymes decreases lipid production in vitro and increases the insulin sensitivity of the liver cells. The blockade of stearoyl CoA desaturase-1 (SCD-1), which participates in the production of monounsaturated fatty acids, decreases the TG level.
The degree of NAFDL can be determined by imaging methods (ultrasonography, CT or magnetic resonance methods) or liver biopsy.
A regularly consumed high fat diet disturbs the regulation of the insulin and lipid metabolism. It increases liver FFA and TG release.
High TG, Chy and VLDL levels suggest the probability of fatty liver development. Interestingly, fructose-induced insulin resistance-caused symptoms (high VLDL, LDL, ApoA and ApoB proteins and TG) in the hamster are similar to the symptoms of human NAFLD. These studies demonstrated that a regularly consumed fructose-containing diet mainly increases the visceral adipose tissue, while a Glu-containing diet increases mainly the subcutaneous adipose tissue.
NAFLD can be ameliorated by losing body weight and an appropriate diet. A biochemical and histological amelioration may be achieved by a combination of physical activity and diet for at least 6 months.