Genetics, Immunity and Nutrition Boost the Switching from NASH to HCC

Nonalcoholic fatty liver disease (NAFLD) is the leading contributor to the global burden of chronic liver diseases. The phenotypic umbrella of NAFLD spans from simple and reversible steatosis to nonalcoholic steatohepatitis (NASH), which may worsen into cirrhosis and hepatocellular carcinoma (HCC). Notwithstanding, HCC may develop also in the absence of advanced fibrosis, causing a delayed time in diagnosis as a consequence of the lack of HCC screening in these patients. The precise event cascade that may precipitate NASH into HCC is intricate and it entails diverse triggers, encompassing exaggerated immune response, endoplasmic reticulum (ER) and oxidative stress, organelle derangement and DNA aberrancies. All these events may be accelerated by both genetic and environmental factors. On one side, common and rare inherited variations that affect hepatic lipid remodeling, immune microenvironment and cell survival may boost the switching from steatohepatitis to liver cancer, on the other, diet-induced dysbiosis as well as nutritional and behavioral habits may furtherly precipitate tumor onset. Therefore, dietary and lifestyle interventions aimed to restore patients’ health contribute to counteract NASH progression towards HCC. Even more, the combination of therapeutic strategies with dietary advice may maximize benefits, with the pursuit to improve liver function and prolong survival.

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Enhanced liver fibrosis (ELF) score accurately detects advanced fibrosis in nonalcoholic fatty liver disease (NAFLD)

10.1055/s-0038-1654642 ◽

2018 ◽

Author(s):

K Staufer ◽

R Marculescu ◽

B Obermayer-Pietsch ◽

J Stift ◽

C Lackner ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Advanced Fibrosis ◽

Nonalcoholic Fatty Liver

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1254-P: Increased Health-Care Resource Utilization (HRU) and Costs among Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) Patients with Advanced Fibrosis (AF) having Diabetes Mellitus (DM)

Diabetes ◽

10.2337/db19-1254-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1254-P

Author(s):

STUART GORDON ◽

NANDITA KACHRU ◽

A. BURAK OZBAY ◽

ROBERT WONG

Keyword(s):

Diabetes Mellitus ◽

Health Care ◽

Liver Disease ◽

Resource Utilization ◽

Nonalcoholic Steatohepatitis ◽

Fatty Liver Disease ◽

Health Care Resource ◽

Advanced Fibrosis ◽

Nonalcoholic Fatty Liver ◽

Health Care Resource Utilization

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One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22115851 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5851

Author(s):

Takehito Sugasawa ◽

Seiko Ono ◽

Masato Yonamine ◽

Shin-ichiro Fujita ◽

Yuki Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Early Stage ◽

Droplet Deposition ◽

Nonalcoholic Fatty Liver ◽

Stress Markers ◽

Mitochondrial Dna Copy Number ◽

Short Period ◽

And Oxidative Stress

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.

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Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC

International Journal of Molecular Sciences ◽

10.3390/ijms22094495 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4495

Author(s):

Hyunmi Kim ◽

Da Som Lee ◽

Tae Hyeon An ◽

Hyun-Ju Park ◽

Won Kon Kim ◽

...

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Liver Failure ◽

Fatty Liver Disease ◽

Liver Diseases ◽

Biological Processes ◽

Chronic Liver Diseases ◽

Nonalcoholic Fatty Liver ◽

Diabetes And Obesity

Liver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type 2 diabetes contributes to biological processes driving the severity of NAFLD, the primary cause for development of chronic liver diseases. In the last 20 years, the rate of non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs for treatment of NAFLD and NASH, a class of thiazolidinediones (TZDs) drugs for the treatment of type 2 diabetes is sometimes used to improve liver failure despite the risk of side effects. Therefore, diagnosis, prevention, and treatment of the development and progression of NAFLD and NASH are important issues. In this review, we will discuss the pathogenesis of NAFLD/NASH and NAFLD/NASH-derived HCC and the current promising pharmacological therapies of NAFLD/NASH. Further, we will provide insights into “adipose-derived adipokines” and “liver-derived hepatokines” as diagnostic and therapeutic targets from NAFLD to HCC.

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