Pathogenesis of Non-alcoholic Steatohepatitis (NASH)-Related Hepatocellular Carcinoma (HCC)

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

Deadline for manuscript submissions: closed (27 December 2024) | Viewed by 9922

Special Issue Editor


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Guest Editor
Department of Pathology, Keio University School of Medicine, Tokyo, Japan
Interests: hepatocellular carcinoma (HCC); early HCC; metabolic associated fatty liver disease (MAFLD); NASH; HCC tumor markers; liver pathology

Special Issue Information

Dear Colleagues,

The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and NASH is increasing worldwide. NASH is expected to become a leading cause of HCC, replacing viral hepatitis-associated HCC. Several factors including genetic and external lifestyle factors contribute to the progression of NASH into HCC, and the presence of metabolic syndrome has also been linked to this process as risk factors flare up the liver damage. More efforts to implement effective management in NAFLD/NASH-related HCC are needed to overcome its future impact.

The purpose of this Special Issue is to understand current mechanism of the complex pathogenesis and progression of NASH-related HCC in multidisciplinary approaches. Potential submissions may focus on (1) early prediction for those at risk of HCC; (2) pathological markers, or inflammatory process mediating the progression of NASH; (3) preventive strategies that can modulate carcinogenic pathways in NAFLD/NASH-related HCC.

For this Special Issue we welcome reviews, as well as original research articles, until 01 February 2024. We look forward to receiving your contributions.

Dr. Kathryn Effendi
Guest Editor

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Keywords

  • hepatocellular carcinoma
  • non-alcoholic fatty liver disease
  • metabolic syndrome
  • fibrosis
  • chronic inflammation
  • biomarkers
  • pathogenesis
  • immune microenvironment

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Published Papers (5 papers)

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Research

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15 pages, 1717 KiB  
Article
Machine Learning-Based Assessment of Survival and Risk Factors in Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma for Optimized Patient Management
by Miguel Suárez, Sergio Gil-Rojas, Pablo Martínez-Blanco, Ana M. Torres, Antonio Ramón, Pilar Blasco-Segura, Miguel Torralba and Jorge Mateo
Cancers 2024, 16(6), 1114; https://doi.org/10.3390/cancers16061114 - 10 Mar 2024
Cited by 7 | Viewed by 2294
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of developing NAFLD-related HCC and the prevalence of NAFLD. There is limited evidence regarding prognostic factors at the diagnosis of HCC. This study compares the prognosis of HCC in patients with NAFLD against other etiologies. It also evaluates the prognostic factors at the diagnosis of these patients. For this purpose, a multicenter retrospective study was conducted involving a total of 191 patients. Out of the total, 29 presented NAFLD-related HCC. The extreme gradient boosting (XGB) method was employed to develop the reference predictive model. Patients with NAFLD-related HCC showed a worse prognosis compared to other potential etiologies of HCC. Among the variables with the worst prognosis, alcohol consumption in NAFLD patients had the greatest weight within the developed predictive model. In comparison with other studied methods, XGB obtained the highest values for the analyzed metrics. In conclusion, patients with NAFLD-related HCC and alcohol consumption, obesity, cirrhosis, and clinically significant portal hypertension (CSPH) exhibited a worse prognosis than other patients. XGB developed a highly efficient predictive model for the assessment of these patients. Full article
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Review

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19 pages, 345 KiB  
Review
Exploring the Role of Metabolic Hyperferritinaemia (MHF) in Steatotic Liver Disease (SLD) and Hepatocellular Carcinoma (HCC)
by Nikolaos-Andreas Anastasopoulos, Alexandra Barbouti, Anna C. Goussia, Dimitrios K. Christodoulou and Georgios K. Glantzounis
Cancers 2025, 17(5), 842; https://doi.org/10.3390/cancers17050842 - 28 Feb 2025
Viewed by 574
Abstract
The increasing prevalence of the spectrum of Steatotic Liver Disease (SLD), including Metabolic-Associated Steatotic Liver Disease (MASLD), Metabolic-Associated Steatohepatitis (MASH), and progression to Cirrhosis and Hepatocellular Carcinoma (HCC) has led to intense research in disease pathophysiology, with many studies focusing on the role [...] Read more.
The increasing prevalence of the spectrum of Steatotic Liver Disease (SLD), including Metabolic-Associated Steatotic Liver Disease (MASLD), Metabolic-Associated Steatohepatitis (MASH), and progression to Cirrhosis and Hepatocellular Carcinoma (HCC) has led to intense research in disease pathophysiology, with many studies focusing on the role of iron. Iron overload, which is often observed in patients with SLD as a part of metabolic hyperferritinaemia (MHF), particularly in the reticuloendothelial system (RES), can exacerbate steatosis. This imbalance in iron distribution, coupled with a high-fat diet, can further promote the progression of SLD by means of oxidative stress triggering inflammation and activating hepatic stellate cells (HSCs), therefore leading to fibrosis and progression of simple steatosis to the more severe MASH. The influence of iron overload in disease progression has also been shown by the complex role of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. Ferroptosis depletes the liver’s antioxidant capacity, further contributing to the development of MASH, while its role in MASH-related HCC is potentially linked to alternations in the tumour microenvironment, as well as ferroptosis resistance. The iron-rich steatotic hepatic environment becomes prone to hepatocarcinogenesis by activation of several pro-carcinogenic mechanisms including epithelial-to-mesenchymal transition and deactivation of DNA damage repair. Biochemical markers of iron overload and deranged metabolism have been linked to all stages of SLD and its associated HCC in multiple patient cohorts of diverse genetic backgrounds, enhancing our daily clinical understanding of this interaction. Further understanding could lead to enhanced therapies for SLD management and prevention. Full article
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27 pages, 3414 KiB  
Review
Tristetraprolin Family Members and Processing Bodies: A Complex Regulatory Network Involved in Fatty Liver Disease, Viral Hepatitis and Hepatocellular Carcinoma
by Noémie Gellée, Noémie Legrand, Mickaël Jouve, Pierre-Jean Devaux, Laurent Dubuquoy and Cyril Sobolewski
Cancers 2025, 17(3), 348; https://doi.org/10.3390/cancers17030348 - 21 Jan 2025
Viewed by 996
Abstract
Chronic liver diseases, such as those encountered with obesity, chronic/abusive alcohol consumption or viral infections, represent not only major public health concerns with limited therapeutic options but also important risk factors for the onset of hepatocellular carcinoma (HCC). Deciphering the molecular traits underlying [...] Read more.
Chronic liver diseases, such as those encountered with obesity, chronic/abusive alcohol consumption or viral infections, represent not only major public health concerns with limited therapeutic options but also important risk factors for the onset of hepatocellular carcinoma (HCC). Deciphering the molecular traits underlying these disorders is of high interest for designing new and effective treatments. The tristetraprolin (TTP) family members are of particular importance given their ability to control the expression of a wide range of genes involved in metabolism, inflammation and carcinogenesis at the post-transcriptional level. This regulation can occur within small cytoplasmic granules, namely, processing bodies (P-bodies), where the mRNA degradation occurs. Increasing evidence indicates that TTP family members and P-bodies are involved in the development of chronic liver diseases and cancers. In this review, we discuss the role of this regulatory mechanism in metabolic-dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), hepatic viral infections and HCC. Full article
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23 pages, 863 KiB  
Review
Surgical Implications for Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma
by Centura R. Anbarasu, Sophia Williams-Perez, Ernest R. Camp and Derek J. Erstad
Cancers 2024, 16(16), 2773; https://doi.org/10.3390/cancers16162773 - 6 Aug 2024
Viewed by 1505
Abstract
Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are [...] Read more.
Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are frequently obese and medically complex, posing challenges for clinical management. In this review, we discuss NASH-specific challenges and the associated implications, including benefits of minimally invasive operative approaches in obese patients; the value of y90 as a locoregional therapy; and the roles of weight loss and immunotherapy in disease management. The relevant literature was identified through queries of PubMed, Google Scholar, and clinicaltrials.gov. Provider understanding of clinical nuances specific to NASH-HCC can improve treatment strategy and patient outcomes. Full article
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17 pages, 592 KiB  
Review
Metabolic Dysfunction-Associated Steatohepatitis and Progression to Hepatocellular Carcinoma: A Literature Review
by Haider Ghazanfar, Nismat Javed, Abeer Qasim, George Sarin Zacharia, Ali Ghazanfar, Abhilasha Jyala, Elona Shehi and Harish Patel
Cancers 2024, 16(6), 1214; https://doi.org/10.3390/cancers16061214 - 20 Mar 2024
Cited by 10 | Viewed by 3696
Abstract
The prevalence of metabolic-associated fatty liver disease (MAFLD) is increasing globally due to factors such as urbanization, obesity, poor nutrition, sedentary lifestyles, healthcare accessibility, diagnostic advancements, and genetic influences. Research on MAFLD and HCC risk factors, pathogenesis, and biomarkers has been conducted through [...] Read more.
The prevalence of metabolic-associated fatty liver disease (MAFLD) is increasing globally due to factors such as urbanization, obesity, poor nutrition, sedentary lifestyles, healthcare accessibility, diagnostic advancements, and genetic influences. Research on MAFLD and HCC risk factors, pathogenesis, and biomarkers has been conducted through a narrative review of relevant studies, with a focus on PubMed and Web of Science databases and exclusion criteria based on article availability and language. Steatosis marks the early stage of MASH advancement, commonly associated with factors of metabolic syndrome such as obesity and type 2 diabetes. Various mechanisms, including heightened lipolysis, hepatic lipogenesis, and consumption of high-calorie diets, contribute to the accumulation of lipids in the liver. Insulin resistance is pivotal in the development of steatosis, as it leads to the release of free fatty acids from adipose tissue. Natural compounds hold promise in regulating lipid metabolism and inflammation to combat these conditions. Liver fibrosis serves as a significant predictor of MASH progression and HCC development, underscoring the need to target fibrosis in treatment approaches. Risk factors for MASH-associated HCC encompass advanced liver fibrosis, older age, male gender, metabolic syndrome, genetic predispositions, and dietary habits, emphasizing the requirement for efficient surveillance and diagnostic measures. Considering these factors, it is important for further studies to determine the biochemical impact of these risk factors in order to establish targeted therapies that can prevent the development of HCC or reduce progression of MASH, indirectly decreasing the risk of HCC. Full article
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