Translational Studies of Obesity-Associated Hepatocellular Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 13282

Special Issue Editors


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Guest Editor
Department of Medicine, Biochemistry, Oncology, Genetics & Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Interests: energy balance; obesity cancer
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Guest Editor
Department of Cardiovascular & Metabolic Sciences, Center for Microbiome & Human Health, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, USA
Interests: lipid and lipoprotein metabolism; microbiome; obesity; diabetes; atherosclerosis

Special Issue Information

Dear Colleagues, 

Hepatocellular Carcinoma (HCC) is the most prevalent form of primary liver cancer, and is among the leading causes of cancer-related deaths around the world. With a 5 year survival rate of less than 15%, HCC is etiologically associated with viral hepatitis, alcohol excess, other hepatotoxins, and metabolic disorders including obesity and type 2 diabetes mellitus (T2DM). While hepatitis and hepatotoxins remain significant causes of HCC, its increasing incidence in many countries is associated with expansion of the obesity pandemic. HCC has been designated an obesity-associated cancer, particularly in men. This Special Issue of Cancers will focus on translational aspects of obesity-associated HCC across the spectrum,  from mechanisms and prevention to diagnosis and therapeutics. Articles are invited that study obesity-associated metabolic, immunologic, inflammatory, pathologic, microbiologic, genetic, and molecular alterations that impact obesity-associated HCC as well as their therapeutic implications. 

Manuscripts will be accepted up to and including March 2021 for this Special Issue, which we plan to publish on 31 March 2021.

Prof. Dr. Nathan A. Berger
Dr. J. Mark Brown
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • hepatocellular cancer
  • non-alcoholic fatty liver disease
  • non-alcoholic steato hepatitis
  • obesity

Published Papers (4 papers)

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Research

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11 pages, 762 KiB  
Article
Increased Visceral Adipose Tissue and Hyperinsulinemia Raise the Risk for Recurrence of Non-B Non-C Hepatocellular Carcinoma after Curative Treatment
by Kenji Imai, Koji Takai, Takao Miwa, Toshihide Maeda, Tatsunori Hanai, Makoto Shiraki, Atsushi Suetsugu and Masahito Shimizu
Cancers 2021, 13(7), 1542; https://doi.org/10.3390/cancers13071542 - 26 Mar 2021
Cited by 10 | Viewed by 2137
Abstract
We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted [...] Read more.
We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment. Full article
(This article belongs to the Special Issue Translational Studies of Obesity-Associated Hepatocellular Cancer)
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Review

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25 pages, 1557 KiB  
Review
Abnormal Metabolism in the Progression of Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma: Mechanistic Insights to Chemoprevention
by Danny Orabi, Nathan A. Berger and J. Mark Brown
Cancers 2021, 13(14), 3473; https://doi.org/10.3390/cancers13143473 - 11 Jul 2021
Cited by 12 | Viewed by 5299
Abstract
Nonalcoholic fatty liver disease (NAFLD) is on the rise and becoming a major contributor to the development of hepatocellular carcinoma (HCC). Reasons for this include the rise in obesity and metabolic syndrome in contrast to the marked advances in prevention and treatment strategies [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is on the rise and becoming a major contributor to the development of hepatocellular carcinoma (HCC). Reasons for this include the rise in obesity and metabolic syndrome in contrast to the marked advances in prevention and treatment strategies of viral HCC. These shifts are expected to rapidly propel this trend even further in the coming decades, with NAFLD on course to become the leading etiology of end-stage liver disease and HCC. No Food and Drug Administration (FDA)-approved medications are currently available for the treatment of NAFLD, and advances are desperately needed. Numerous medications with varying mechanisms of action targeting liver steatosis and fibrosis are being investigated including peroxisome proliferator-activated receptor (PPAR) agonists and farnesoid X receptor (FXR) agonists. Additionally, drugs targeting components of metabolic syndrome, such as antihyperglycemics, have been found to affect NAFLD progression and are now being considered in the treatment of these patients. As NAFLD drug discovery continues, special attention should be given to their relationship to HCC. Several mechanisms in the pathogenesis of NAFLD have been implicated in hepatocarcinogenesis, and therapies aimed at NAFLD may additionally harbor independent antitumorigenic potential. This approach may provide novel prevention and treatment strategies. Full article
(This article belongs to the Special Issue Translational Studies of Obesity-Associated Hepatocellular Cancer)
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14 pages, 1965 KiB  
Review
Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy
by Stephan Walrand, Michel Hesse, Philippe d’Abadie and François Jamar
Cancers 2021, 13(7), 1537; https://doi.org/10.3390/cancers13071537 - 26 Mar 2021
Cited by 4 | Viewed by 2555
Abstract
Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal [...] Read more.
Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible. Full article
(This article belongs to the Special Issue Translational Studies of Obesity-Associated Hepatocellular Cancer)
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15 pages, 1030 KiB  
Review
The Current View of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma
by Tomomi Kogiso and Katsutoshi Tokushige
Cancers 2021, 13(3), 516; https://doi.org/10.3390/cancers13030516 - 29 Jan 2021
Cited by 15 | Viewed by 2532
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can develop into hepatocellular carcinoma (HCC). The incidence of NAFLD-related HCC, which is accompanied by life-threatening complications, is increasing. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can develop into hepatocellular carcinoma (HCC). The incidence of NAFLD-related HCC, which is accompanied by life-threatening complications, is increasing. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes mellitus, are associated with HCC development. However, HCC is also observed in the non-cirrhotic liver. Often, diagnosis is delayed until the tumor is relatively large and the disease is advanced; an effective screening or surveillance method is urgently required. Recently, the NAFLD/nonalcoholic steatohepatitis (NASH) guidelines of Japan were revised to incorporate new strategies and evidence for the management and surveillance of NAFLD/NASH. Fibrosis must be tested for noninvasively, and the risk of carcinogenesis must be stratified. The treatment of lifestyle-related diseases is expected to reduce the incidence of NAFLD and prevent liver carcinogenesis. Full article
(This article belongs to the Special Issue Translational Studies of Obesity-Associated Hepatocellular Cancer)
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