Pathogenesis, diagnosis and treatment of non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of alterations that go from simple steatosis to steatohepatitis and cirrhosis. Type 2 diabetes mellitus (DM-2) and obesity are the principle factors associated to NAFLD. A 20-30 % prevalence in general population has been described. The survival of this type of patient is lower than the general population's, showing a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear, but we know the intervention of different factors that produce fatty-acid accumulation in hepatic parenchyma, causing oxidative stress, oxygen-free radicals and the synthesis of an inflammatory cascade, that determine the progression of this disease from steatosis up to advanced fibrosis.The diagnostic gold-standard is still the liver biopsy, even though the development of newer non-invasive techniques, like serological and imaging (radiology), have opened a new field for research that allows bloodless testing of these patients and better study of the natural history of this disease. Nowadays, there is still no specific treatment for NAFLD. The development of healthy life habits and moderate exercise continue to be the pillars of treatment. Different pharmacological approaches have been studied and applied, such as the control of insulin resistance, lowering cholesterol levels, antioxidants, and other alternatives in experimental trials.

Effect of incretin therapies compared to pioglitazone and gliclazide in non-alcoholic fatty liver disease in diabetic patients not controlled on metformin alone: An observational, pilot study

“…As regards diagnosis, it should be noted that 69% of diabetic patients had an indeterminate risk of fibrosis. While liver biopsy is considered the reference test in the diagnostic evaluation of NAFLD, it is not free from potentially severe complications such as bleeding 3 or inter-and intra-observer variability, 30 hence the interest of noninvasive tests to determine the probability of advanced hepatic fibrosis such as FibroScan ® . An area under the ROC curve of 0.94, with 0.94 sensitivity and 0.95 specificity, was found for FibroScan in a metaanalysis of 32 articles on patients with NAFLD, 18 although its diagnostic yield was significantly lower in patients with obesity.…”

Sarcopenia in hiding: The risk and consequence of underestimating muscle dysfunction in nonalcoholic steatohepatitis

“…IR leads to a compensatory hyperinsulinemia, which, in the steatotic hepatocyte, leads to impaired suppression of gluconeogenesis, decreased glycogen synthesis, increased uptake of FFAs and lipogenesis, altered transport of triglycerides (TGs), and inhibition of beta‐oxidation. These changes lead to accumulation of TGs in both muscle tissue (myosteatosis) and the liver (steatosis) …”

“…Cytokine levels, such as tumor necrosis factor‐α (TNFα) and transforming growth factor‐β (TGFβ), are frequently elevated in NAFLD . Chronic inflammation leads to direct liver injury and progression of fibrosis . In addition, these cytokines stimulate protein catabolism, which results in loss of muscle mass and sarcopenia …”

“…These changes lead to accumulation of TGs in both muscle tissue (myosteatosis) and the liver (steatosis). (14) The promotion of gluconeogenesis, in a state of IR, exacerbates proteolysis and leads to muscle depletion. (4) IR itself can be involved in age-related muscle protein loss and sarcopenia.…”

Clinical and pathological features of sarcopenia‐related indices in patients with non‐alcoholic fatty liver disease

“…Because skeletal muscle is the tissue responsible for glucose disposal, the existence of sarcopenia promotes IR . Chronic inflammation injures the liver and leads to fibrosis progression . In addition, cytokines such as tumor necrosis factor‐α and transforming growth factor‐β exacerbate protein catabolism and lead to sarcopenia …”