Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma

2019 ◽  
Vol 20 (3) ◽  
pp. 197-214 ◽  
Author(s):  
Isabel Sánchez-Crisóstomo ◽  
Eduardo Fernández-Martínez ◽  
Raquel Cariño-Cortés ◽  
Gabriel Betanzos-Cabrera ◽  
Rosa A. Bobadilla-Lugo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Anticancer Agents ◽  
Liver Diseases ◽  
Membrane Receptors ◽  
New Drugs ◽  
Sexual Hormones ◽  
Steroid Nucleus ◽  
Alcoholic Fatty Liver ◽  
Prevention And Treatment

Background: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Emerging Role of Interleukins for the Assessment and Treatment of Liver Diseases

2021 ◽  
Vol 21 ◽  
Author(s):  
Aaliya L. Ali ◽  
Namrata P. Nailwal ◽  
Gaurav M. Doshi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Liver Diseases ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Alcoholic Fatty Liver ◽  
Assessment And Treatment

Background: The most common liver diseases are fibrosis, alcoholic liver disease, non-alcoholic fatty disease, viral hepatitis, and hepatocellular carcinoma. These liver diseases account for approximately 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of the worldwide burden. The most widely used liver function tests for diagnosis are alanine transaminase, aspartate transaminase, serum proteins, serum albumin, and serum globulins, whereas antivirals and corticosteroids have been proven to be useful for the treatment of liver diseases. A major disadvantage of these diagnostic measures is the lack of specificity to a particular tissue or cell type, as these enzymes are common to one or more tissues. The major adverse effect of current treatment methods is drug resistance. To overcome these issues, interleukins have been investigated. The balance of these interleukins determines the outcome of an immune response. Interleukins are considered interesting therapeutic targets for the treatment of liver diseases. In this review, we summarize the current state of knowledge regarding interleukins in the diagnosis, treatment, and pathogenesis of different acute and chronic liver diseases. Objective: To understand the role of interleukins in the assessment and treatment of different types of liver diseases. Methods: A literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: Interleukins, Acute Liver Failure, Alcoholic Liver Disease, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, Hepatocellular Carcinoma, Inflammation, Liver injury, Hepatoprotective effect. Clinical trial data on these interleukins have been searched on Clinicaltrials.gov. Results: Existing literature and preclinical and clinical trial data demonstrate that interleukins play a crucial role in the pathogenesis of liver diseases. Conclusion: Our findings indicate that IL-1, IL-6, IL-10, IL-17, IL-22, IL-35, and IL-37 are involved in the progression and control of various liver conditions via the regulation of cell signaling pathways. However, further investigation on the involvement of these interleukins is necessary for their use as a targeted therapy in liver diseases.

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 Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Hiraoka ◽  
Takashi Kumada ◽  
Toshifumi Tada ◽  
Joji Tani ◽  
Kazuya Kariyama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Hazard Analysis ◽  
Progression Free Survival ◽  
Significant Prognostic Factor ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Free Survival ◽  
Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

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.

Beneficial effects of dietary polyphenols in the prevention and treatment of NAFLD: cell-signaling pathways underlying health effects

2021 ◽  
Vol 28 ◽  
Author(s):  
Francisca Echeverría ◽  
Andrés Bustamante ◽  
Verónica Sambra ◽  
Daniela Álvarez ◽  
Luis Videla ◽  
...  
Keyword(s):  
Liver Disease ◽  
Health Effects ◽  
De Novo Lipogenesis ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Dietary Polyphenols ◽  
Beneficial Effects ◽  
Inflammatory Status ◽  
Pubmed Database ◽  
Prevention And Treatment

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accretion of triacylglycerides in the absence of alcohol intake that may progress to steatohepatitis, fibrosis and cirrhosis, becoming the main cause of chronic liver disease. This article discusses recent data concerning the use of dietary polyphenols in the prevention and treatment of NAFLD in vitro, in vivo, and in clinical trials. Methods: Study searches were performed using the PubMed database from the National Library of Medicine-National Institutes of Health. Results: Polyphenols exert beneficial effects in NAFLD, with positive outcomes being related to body weight gain, insulin resistance, liver fat accumulation, oxidative stress, pro-inflammatory status, mitochondrial dysfunction and ER stress. Data reported for hydroxytyrosol suggest that the activation of the hepatic PPAR-α-FGF21-AMPK-PGC-1α signaling cascade is associated with fatty acid oxidation enhancement, de novo lipogenesis diminution and recovery of mitochondrial function, a contention that is supported by the actions of several polyphenols on specific components of this signaling pathway. Besides, polyphenols downregulate NF-κB, suppressing the pro-inflammatory state developed in NAFLD and upregulate liver Nrf2, increasing the cellular antioxidant potential. The latter feature of polyphenols is contributed by chelation of pro-oxidant trace elements, reduction of free radicals to stable forms and inhibition of free radical generating systems. Conclusion: Polyphenols are relevant bioactive compounds in terms of prevention and treatment of NAFLD, which exhibit low bioavailability and instability in biological systems that could limit their health effects. These drawbacks reinforce the necessity of further studies to improve the efficacy of polyphenol formulations for human interventions.

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