Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a western perspective

Farrell, Ann; Howell, Jessica

doi:10.20517/2394-5079.2019.019

Cited by 7 publications

(11 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepatocellular carcinoma (HCC) is the main subtype of liver tumor and the third-leading cause of cancer death worldwide, whose incidence reflects the etiologies of liver diseases and their geographical distribution [ 1 , 2 ]. The Asian population has the highest HCC prevalence, and it is amenable to viral hepatitis in more than 50% of cases.…”

Section: Introductionmentioning

confidence: 99%

“…The Asian population has the highest HCC prevalence, and it is amenable to viral hepatitis in more than 50% of cases. Viral hepatitis C (HCV) and alcohol abuse prevail in western countries, where HCC is much less frequent [ 2 ]. However, the global spreading of obesity and metabolic syndrome (MetS) have rapidly increased the incidence of nonalcoholic fatty liver disease (NAFLD) over the past two decades and, in parallel, that of NAFLD-related HCC in industrialized society due also to the development of anti-viral therapies and effective HBV immunization programs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC

Longo

Paolini

Meroni

et al. 2021

IJMS

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis, thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles that may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlights that mitochondrial dysfunction due to loss of mitochondrial flexibility may arise before overt NAFLD, and from the early stages of liver injury. Mitochondrial failure promotes not only hepatocellular damage, but also release signals (mito-DAMPs), which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by the remodeling of glucidic–lipidic metabolism combined with the reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research and for the development of potential preventive or curative strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC

Longo

Paolini

Meroni

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Hepatocellular carcinoma (HCC) is the main subtype of liver tumor and the third-leading cause of cancer death worldwide, whose incidence reflects the etiologies of liver diseases and their geographical distribution [1,2]. The Asian population has the highest HCC prevalence, and it is amenable to viral hepatitis for more than 50% of cases.…”

Section: Introductionmentioning

confidence: 99%

“…The Asian population has the highest HCC prevalence, and it is amenable to viral hepatitis for more than 50% of cases. Viral hepatitis C (HCV) and alcohol abuse prevail in Western countries, where HCC is much less frequent [2]. However, the global spreading of obesity and metabolic syndrome (MetS) have rapidly increased the incidence of nonalcoholic fatty liver disease (NAFLD) over the past two decades and, in parallel, those of NAFLD-related HCC in the industrialized society due also to the development of anti-viral therapies and effective HBV immunization programs.…”

Section: Introductionmentioning

confidence: 99%

“…Among them, the 14.1% of HCC was due to fatty liver, the 5% received NAFLD-related liver transplantation (LT) and the presence of NAFLD increased the risk of 1-year mortality, especially in older subjects with previous heart disease [6,7]. Therefore, NAFLD is currently representing not only a clinical and socio-economic burden for health, but it is predicted to overcome HCV, HBV and alcoholic hepatitis thus becoming the leading cause of HCC and LT [1][2][3][4]6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC

Longo¹,

Paolini²,

Meroni³

et al. 2021

Preprint

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles which may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlighted that mitochondrial dysfunction due to loss of mitochondrial flexibility, may arise before overt NAFLD and since the early stages of liver injury. Mitochondrial failure not only promotes hepatocellular damage, but also release signals (mito-DAMPs) which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by remodeling of glucidic-lipidic metabolism combined to reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research purposes and for development of potential preventive or curative strategies.

show abstract

Lipid droplets are intracellular mechanical stressors that promote hepatocyte dedifferentiation

Loneker

Alisafaei

Kant

et al. 2022

Preprint

View full text Add to dashboard Cite

Matrix stiffening and associated mechanical stress have been linked to disease and cancer development in multiple tissues. In the liver, cirrhosis, characterized by architectural rearrangements and an up to ten times increase in liver stiffness, is the most significant risk factor for hepatocellular carcinoma development. Patients with non-alcoholic fatty liver disease, typified by lipid-droplet-filled hepatocytes, can, however, develop cancer in non-cirrhotic, and relatively soft tissue. Here, we used primary human hepatocytes to show that lipid droplets are intracellular mechanical stressors with similar effects to tissue stiffening, including hepatocyte dedifferentiation. Specifically, we demonstrate that lipid droplets deform the nucleus, that expression of the hepatocyte transcription factor hepatocyte nuclear factor 4α decreases in proportion to the magnitude of lipid-droplet mediated nuclear deformation, that lipid droplets disrupt the cytoskeleton and resist contractility, preventing cells from properly adapting to stiffer environments, and that modulating contractility rescues hepatocyte differentiation. Mathematical modelling of lipid droplets as spherical inclusions that can have mechanical interactions with other cellular components generated results consistent with our experiments, further supporting the idea that these changes are due to mechanical stress. Taken as a whole, our data show that lipid droplets, and potentially other cytoplasmic inclusions, are intracellular sources of mechanical stress and that nuclear membrane tension may serve to integrate cell responses to combined internal and external stresses.

show abstract

Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a western perspective

Cited by 7 publications

References 63 publications

Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC

Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC

Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC

Lipid droplets are intracellular mechanical stressors that promote hepatocyte dedifferentiation

Contact Info

Product

Resources

About