Fat and hepatocellular carcinoma

Abstract

Obesity and diabetes are associated with the onset of hepatocellular carcinoma (HCC). These two illnesses correlate also with the development of non-alcoholic fatty liver disease (NAFLD). Currently, NAFL is considered the leading form of chronic liver disease in the Western industrialized countries. Insulin resistance is the common pathogenic factor among these three pathologies. NAFL is characterized by fat accumulation in the liver that involves greater than 5% of the liver parenchyma with no evidence of hepatocyte injury. However, NAFL may progress toward non-alcoholic steatohepatitis that in turn may lead to advanced fibrosis, cirrhosis and HCC. It is alarming that NAFLD related HCC has been, at present, considered as a growing burden worldwide, and its prevalence is tending to further increase together with the increasing incidence of obesity and diabetes. Worthy of note is that in the presence of chronic accumulation of fat in the liver it has been reported the emergence of HCC during chronic liver disease in absence of liver cirrhosis, usually the major risk factor for the development of HCC. Thus, in the future NAFLD related HCCs will place a growing strain on health-care systems from the need for their management. Unfortunately, most of the NAFLD related HCC patients are diagnosed at advanced stages and are characterized by a poor prognosis, because they are ineligible to radical treatments. Thus, it is urgent to boost up new screening policies to make early diagnoses, as well as to develop preventive-therapeutic strategies.

Repin1 deficiency in liver tissue alleviates NAFLD progression in mice

“…Low-grade chronic inflammation resulting from chronic intracellular oxidative stress and the presence of local inflammatory cells, particularly Kupffer cells and neutrophils, has been suggested to play a crucial role in the progression to NAFLD-related HCC [37] , [38] , [39] . Of particular interest, STZ/HFD-treated LRep1−/− mice had relatively lighter livers than Wt mice, which were increased in size proportionally to body weight.…”

Hepatocelular carcinoma on non alcoholic fatty liver

“…El desarrollo de CHC en la EHNA implica la asociación de múltiples factores entre ellos una respuesta inflamatoria sistémica crónica de bajo grado, incremento del depósito de lípidos y lipotoxicidad, alteraciones genéticas, estrés oxidativo, obesidad, hiper-insulinemia y resistencia a la insulina así como una alteración de la microbiota intestinal (21,22).…”

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications

“…In detail, NAFLD precedes and appears to contribute to the development of the MetS, and the stage of liver fibrosis has been a strong determinant of such a metabolic risk [ 13 ]. In addition, with the progression of NAFLD, there is a possibility of transition to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in the future [ 14 ]. As the worst outcome of NAFLD, HCC is strongly associated with diabetes, suggesting that NAFLD is also the precursor of T2D [ 15 ].…”