Strategies of Cell Signaling and Critical Focus on Etiology of Hepatocellular Carcinoma

Hepatocellular carcinoma is an atypical biological cell process that is frequently identified at an advanced stage, with no promising therapeutic options available. Hepatocarcinogenesis is connected to a range of cellular signaling pathways, notably Wnt-β-catenin (canonical Wnt pathway), nuclear factor-B, and YAP-HIPPO (Yes-associated protein Salvador-Warts-Hippo pathway); each of these is considered a potential pharmacological candidate. Inflammation in the liver for a long time and damage play a big role in the incidence and development of HCC. HCC incidence rates go up by the many variables such as sex, age, ethnicity, and demographics are all factors to consider, and the leading causes of infection by the chronic or hepatitis B virus (HBV), hepatitis C virus (HCV), nutrient pollutants, ecological poisons, tobacco smoldering, and genetic disorders, which are all carcinogens. In this review, we expanded on our existing empathetic of the signaling pathways involved in the development and genesis of HCC. We also encapsulated the etiology of HCC, with a focus on HCC triggered by non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). In this review, we forecasted potential therapeutic drug targets.

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Role of silymarin in the management of non-alcoholic fatty liver disease: Time to clear the mist

Bioactive Compounds in Health and Disease ◽

10.31989/bchd.v2i5.622 ◽

2019 ◽

Vol 2 (5) ◽

pp. 126

Author(s):

Kuhu Roy ◽

Uma Lyer

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Wide Spectrum ◽

Therapeutic Drug ◽

Alcoholic Fatty Liver ◽

Metabolic Conditions ◽

Drug Regimens ◽

Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) has become a common chronic liver disease, global in nature. Occurring in individuals without a history of significant ethanol consumption, it encompasses a wide spectrum of hepatic disorders. It ranges from simple steatosis, to its advanced form, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis to even hepatocellular carcinoma. Infact, hepatocellular carcinoma (HCC) can also develop even in the absence of cirrhosis. The prevalence of NAFLD is on the rise primarily because of the already prevalent metabolic conditions like insulin resistance, type 2 diabetes, central obesity and dyslipidemia. Therefore, NAFLD is associated with adverse metabolic consequences. Other than the detrimental hepatic outcomes mentioned above, cases of NAFLD have a very high predisposition to cardiovascular disease. Therefore, management of NAFLD is of paramount importance. However, the challenge lies in the fact that there are no approved therapeutic drug regimens for the treatment of NAFLD. Currently, the standard care comprises of treating the underlying co-existing metabolic abnormalities along with a strong focus on lifestyle modification.Keywords: Non—alcoholic fatty liver disease, antioxidants, milk thistle, silymarin, flavonolignans, silibin

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

Cancers ◽

10.3390/cancers13040790 ◽

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.

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

Metabolites ◽

10.3390/metabo11010054 ◽

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.

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