Benign liver tumours: understanding molecular physiology to adapt clinical management

Nault, Jean‐Charles; Paradis, Valérie; Ronot, Maxime; Zucman‐Rossi, Jessica

doi:10.1038/s41575-022-00643-5

Cited by 27 publications

(28 citation statements)

References 120 publications

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“…that a single chromosomal translocation that constitutively activates Gli1 transcription in nonmalignant hepatocytes is sufficient to trigger hepatic adenoma development 62 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…This is exemplified by the fact that a single chromosomal translocation that constitutively activates Gli1 transcription in nonmalignant hepatocytes is sufficient to trigger hepatic adenoma development. 62 Although mutations in genes that encode Hedgehog pathway components are relatively rare in liver cancers, dysregulated over-activation of Hedgehog signaling is common in both HCC and CCA. Moreover, the level of Hedgehog pathway activity is typically inversely correlated with prognosis such that cancers with high Hedgehog activity are more aggressive, leading to worse tumor-free and overall survival.…”

Section: Liver Cancermentioning

confidence: 99%

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Hedgehog Signaling: Implications in Liver Pathophysiology

Dutta,

Jun,

et al. 2023

Semin Liver Dis

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The purpose of this review is to summarize current knowledge about the role of the Hedgehog signaling pathway in liver homeostasis and disease. Hedgehog is a morphogenic signaling pathway that is active in development. In most healthy tissues, pathway activity is restricted to stem cell and/or stromal cell compartments, where it enables stem cell self-renewal and tissue homeostasis. Aberrant over-activation of Hedgehog signaling occurs in many cancers, including hepatocellular and cholangio- carcinoma. The pathway is also activated transiently in stromal cells of injured tissues and orchestrates normal wound healing responses, including inflammation, vascular remodeling and fibrogenesis. In liver, sustained Hedgehog signaling in stromal cells plays a major role in the pathogenesis of cirrhosis. Hedgehog signaling was thought to be silenced in healthy hepatocytes. However, recent studies show that targeted disruption of the pathway in hepatocytes dysregulates lipid, cholesterol, and bile acid metabolism and promotes hepatic lipotoxicity, insulin resistance and senescence. Hepatocytes that lack Hedgehog activity also produce a secretome that activates Hedgehog signaling in cholangiocytes and neighboring stromal cells to induce inflammatory and fibrogenic wound healing responses that drive progressive fibrosis. In conclusion, Hedgehog signaling must be precisely controlled in adult liver cells in order to maintain liver health.

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“…that a single chromosomal translocation that constitutively activates Gli1 transcription in nonmalignant hepatocytes is sufficient to trigger hepatic adenoma development 62 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Liver Cancermentioning

confidence: 99%

Hedgehog Signaling: Implications in Liver Pathophysiology

Dutta,

Jun,

et al. 2023

Semin Liver Dis

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“…[42] Thus, the clinical course of HCA is more often benign in women than in men. [43][44][45] The surgical resection of HCA, regardless of the tumor size, is recommended in men due to the high probability of malignant transformation. [43] For women, lifestyle changes including oral contraceptive discontinuation and body weight control are recommended as first measures, unless β-catenin mutations are present.…”

Section: Sex Differences In Benign Liver Lesions and Their Neoplastic...mentioning

confidence: 99%

“…HCAs with β-catenin mutations are overrepresented in men relative to women, and about half of such cases receive the final histological diagnosis of HCC 42 . Thus, the clinical course of HCA is more often benign in women than in men 43–45 …”

Section: Sex Differences In Benign Liver Lesions and Their Neoplastic...mentioning

confidence: 99%

Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review

et al. 2023

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Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient's sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sexrelated inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender

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“…Liver tumors include both benign (non-cancerous) and malignant (cancerous) varieties [ 1 ], and the latter tumors are further classified into tumors that originated in the liver (primary liver cancer) and tumors that spread from extrahepatic primary tumors (metastatic liver cancer). Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the two major malignant primary liver tumors [ 2 ], whereas colorectal, lung, and pancreatic cancers are the major extrahepatic primary tumors causing liver metastasis.…”

mentioning

confidence: 99%