scholarly journals Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Benjamin Buchard ◽  
Camille Teilhet ◽  
Natali Abeywickrama Samarakoon ◽  
Sylvie Massoulier ◽  
Juliette Joubert-Zakeyh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Monounsaturated Fatty Acids ◽  
Metabolic Reprogramming ◽  
Resonance Spectroscopy ◽  
Alcoholic Fatty Liver ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.

The impact of a dedicated metabolic hepatology clinic for the treatment of non-alcoholic fatty liver disease

2017 ◽  
Author(s):  
Kenzo Motohashi ◽  
Ahmad Moolla ◽  
Tom Marjot ◽  
Mark Ainsworth ◽  
Jeremy Tomlinson ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

scholarly journals Performance of Ultrasound Techniques and the Potential of Artificial Intelligence in the Evaluation of Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 790
Author(s):  
Monica Lupsor-Platon ◽  
Teodora Serban ◽  
Alexandra Iulia Silion ◽  
George Razvan Tirpe ◽  
Alexandru Tirpe ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Lesion ◽  
Focal Liver Lesion ◽  
Ultrasound Contrast Agents ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Global statistics show an increasing percentage of patients that develop non-alcoholic fatty liver disease (NAFLD) and NAFLD-related hepatocellular carcinoma (HCC), even in the absence of cirrhosis. In the present review, we analyzed the diagnostic performance of ultrasonography (US) in the non-invasive evaluation of NAFLD and NAFLD-related HCC, as well as possibilities of optimizing US diagnosis with the help of artificial intelligence (AI) assistance. To date, US is the first-line examination recommended in the screening of patients with clinical suspicion of NAFLD, as it is readily available and leads to a better disease-specific surveillance. However, the conventional US presents limitations that significantly hamper its applicability in quantifying NAFLD and accurately characterizing a given focal liver lesion (FLL). Ultrasound contrast agents (UCAs) are an essential add-on to the conventional B-mode US and to the Doppler US that further empower this method, allowing the evaluation of the enhancement properties and the vascular architecture of FLLs, in comparison to the background parenchyma. The current paper also explores the new universe of AI and the various implications of deep learning algorithms in the evaluation of NAFLD and NAFLD-related HCC through US methods, concluding that it could potentially be a game changer for patient care.

scholarly journals RIPK3 acts as a lipid metabolism regulator contributing to inflammation and carcinogenesis in non-alcoholic fatty liver disease

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321767
Author(s):  
Marta B Afonso ◽  
Pedro M Rodrigues ◽  
Miguel Mateus-Pinheiro ◽  
André L Simão ◽  
Maria M Gaspar ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Body Weight Gain ◽  
Control Diet ◽  
Peroxisome Proliferator ◽  
Functional Link ◽  
Alcoholic Fatty Liver ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

ObjectiveReceptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD.DesignRIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or Ripk3-deficient (Ripk3−/−) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks.ResultsRIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly, Ripk3 deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were reduced in Ripk3−/− mice. Furthermore, Ripk3 deficiency hampered tumourigenesis. Intriguingly, Ripk3−/− mice displayed increased body weight gain, while lipidomics showed that deletion of Ripk3 shifted hepatic lipid profiles. Peroxisome proliferator-activated receptor γ (PPARγ) was increased in Ripk3−/− mice and negatively correlated with hepatic RIPK3 in patients with NAFLD. Mechanistic studies established a functional link between RIPK3 and PPARγ in controlling fat deposition and fibrosis.ConclusionHepatic RIPK3 correlates with NAFLD severity in humans and mice, playing a key role in managing liver metabolism, damage, inflammation, fibrosis and carcinogenesis. Targeting RIPK3 and its intricate signalling arises as a novel promising approach to treat NASH and arrest disease progression.

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