Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma

Abstract

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a “multi-hit” or “multi-parallel hit” model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.

Impaired Response to Immunotherapy in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma?

“…The weakening of immune response and immune surveillance functions discussed in the Nature article is another important factor involved in the development of NAFLD-related HCC, in addition to various causative factors of NASH-HCC that have been proposed to date, including genetic and epigenetic mechanisms, the microbiome, metabolic pathways, molecular signaling pathways, endocrine pathways, and immunological pathways [8,[10][11][12][13]. In patients with NAFLD, HCC develops not only from cirrhosis [14], but also from even mild fibrosis at a rate of 25-50% [15][16][17][18][19], which does not occur in viral HCC.…”

Fitossanitários e doenças hepáticas: Um desafio à saúde pública no Brasil

“…A incidência da esteatose aumentou consideravelmente nos últimos anos devido, principalmente, ao estilo de vida populacional e a contaminação ambiental (Qin et al, 2020). Infelizmente, os quadros iniciais de acometimento do fígado nem sempre são identificados, o que favorece a progressão da patologia a quadros mais graves como a esteatohepatite, a fibrose, a cirrose hepática e, em alguns casos o carcinoma hepatocelular (Ramai et al, 2021). Research, Society and Development, v. 10, n. 9, e15910917835, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i9.17835…”

“…Caracterizada pela Organização Mundial da Saúde (OMS) como uma das 10 causas primárias de morte em diferentes países (WHO, 2020), as doenças hepáticas possuem diversas etiologias entre as quais a exposição a drogas e a toxinas ambientais (Armstrong & Guo, 2019). Uma vez que se estabeleça, as anomalias hepáticas podem progredir a quadros clínicos mais severos e até mesmo conduzir os indivíduos ao óbito, sendo esses fatos cada vez mais recorrente no Brasil (Ramai et al, 2021), considerando-se a escassez de tratamentos eficazes no controle e/ou cura dessas anomalias. Nesse contexto, a atenção às políticas públicas em seus mais variados aspectos e aos hábitos populacionais pode ser considerada uma importante aliada no controle e/ou prevenção do surgimento de doenças hepáticas na população.…”

Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

“…In contrast, current evidence proposes a "multi-hit" or "multi-parallel hit" model that includes multiple pathways promoting progressive fibrosis and oncogenesis. This model includes multiple cellular, genetic, immunological, metabolic, and endocrine pathways leading to HCC development, underscoring the complexity of this disease [ 13 ].…”