Nonalcoholic Fatty Liver Disease: Pathology and Pathogenesis

Abstract

Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies.

Elevated alanine aminotransferase activity is not associated with dyslipidemias, but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease

“…The pathogenesis of NAFLD is not clearly defined, but there is a strong evidence in the literature that insulin resistance and visceral adiposity play major roles [18][19][20] . In our study, the prevalence of metabolic syndrome in patients with NAFLD was 26.4%, which is higher than that in the US general population (23.7%) [21] but is surprisingly lower than that reported in Iranian general population which was reported to be as high as 30%-31% [22,23] .…”

“…ALT levels were considered pathologically high when it was over 30 IU/L for men and over 19 IU/L for women.…”

“…Thereby, at the first step, we need to know hypothesis on the pathogenesis of NAFLD and factors playing major roles in this process, to be able to adjust these factors in a way Alanine 30 IU/L for men and over 19 IU/L for women. Results: Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations (P=0.003).…”

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

“…NAFLD is defined as a liver pathologic spectrum, which is initiated by steatosis that may progress to nonalcoholic steatohepatitis (NASH). NASH manifestations beyond steatosis include necro-inflammation and fibrosis (2). The disease can progress to cirrhosis and eventual hepatocellular carcinoma (3).…”

Oleate-mediated activation of phospholipase D and mammalian target of rapamycin (mTOR) regulates proliferation and rapamycin sensitivity of hepatocarcinoma cells

“…Indeed, high-fat feeding and obesityassociated insulin resistance increase the delivery of NEFA to the liver, which, together with increased liver lipogenesis, contributes to NAFLD development and liver regeneration [4]. Furthermore, obesity-associated low-grade chronic inflammation favours NAFLD progression to NASH [5].…”