Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the livers of patients without a history of alcohol abuse. It is classified as either simple steatosis (nonalcoholic fatty liver) or nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis a...
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MDPI AG
2023-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2761 |
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| author | Yoshihisa Takahashi Erdenetsogt Dungubat Hiroyuki Kusano Toshio Fukusato |
| author_facet | Yoshihisa Takahashi Erdenetsogt Dungubat Hiroyuki Kusano Toshio Fukusato |
| author_sort | Yoshihisa Takahashi |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the livers of patients without a history of alcohol abuse. It is classified as either simple steatosis (nonalcoholic fatty liver) or nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, it was suggested that the terms “metabolic dysfunction-associated steatotic liver disease (MASLD)” and “metabolic dysfunction-associated steatohepatitis (MASH)” should replace the terms “nonalcoholic fatty liver disease (NAFLD)” and “nonalcoholic steatohepatitis (NASH)”, respectively, with small changes in the definitions. MASLD, a hepatic manifestation of metabolic syndrome, is rapidly increasing in incidence globally, and is becoming an increasingly important cause of HCC. Steatohepatitic HCC, a histological variant of HCC, is characterized by its morphological features resembling non-neoplastic steatohepatitis and is closely associated with underlying steatohepatitis and metabolic syndrome. Variations in genes including patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) are associated with the natural history of MASLD, including HCC development. The mechanisms of HCC development in MASLD have not been fully elucidated; however, various factors, including lipotoxicity, inflammation, reactive oxygen species, insulin resistance, and alterations in the gut bacterial flora, are important in the pathogenesis of MASLD-associated HCC. Obesity and MASLD are also recognized as risk factors for hepatocellular adenomas, and recent meta-analyses have shown an association between MASLD and intrahepatic cholangiocarcinoma. In this review, we outline the pathology and pathogenesis of MASLD-associated liver tumors. |
| first_indexed | 2024-03-10T21:24:42Z |
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| language | English |
| last_indexed | 2024-03-10T21:24:42Z |
| publishDate | 2023-10-01 |
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| series | Biomedicines |
| spelling | doaj.art-a2e535bbdcb44053a9f77b91f29dc4832023-11-19T15:46:43ZengMDPI AGBiomedicines2227-90592023-10-011110276110.3390/biomedicines11102761Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic TumorsYoshihisa Takahashi0Erdenetsogt Dungubat1Hiroyuki Kusano2Toshio Fukusato3Department of Pathology, School of Medicine, International University of Health and Welfare, Narita 286-8686, JapanDepartment of Pathology, School of Medicine, International University of Health and Welfare, Narita 286-8686, JapanDepartment of Pathology, School of Medicine, International University of Health and Welfare, Narita 286-8686, JapanGeneral Medical Education and Research Center, Teikyo University, Tokyo 173-8605, JapanNonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the livers of patients without a history of alcohol abuse. It is classified as either simple steatosis (nonalcoholic fatty liver) or nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, it was suggested that the terms “metabolic dysfunction-associated steatotic liver disease (MASLD)” and “metabolic dysfunction-associated steatohepatitis (MASH)” should replace the terms “nonalcoholic fatty liver disease (NAFLD)” and “nonalcoholic steatohepatitis (NASH)”, respectively, with small changes in the definitions. MASLD, a hepatic manifestation of metabolic syndrome, is rapidly increasing in incidence globally, and is becoming an increasingly important cause of HCC. Steatohepatitic HCC, a histological variant of HCC, is characterized by its morphological features resembling non-neoplastic steatohepatitis and is closely associated with underlying steatohepatitis and metabolic syndrome. Variations in genes including patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) are associated with the natural history of MASLD, including HCC development. The mechanisms of HCC development in MASLD have not been fully elucidated; however, various factors, including lipotoxicity, inflammation, reactive oxygen species, insulin resistance, and alterations in the gut bacterial flora, are important in the pathogenesis of MASLD-associated HCC. Obesity and MASLD are also recognized as risk factors for hepatocellular adenomas, and recent meta-analyses have shown an association between MASLD and intrahepatic cholangiocarcinoma. In this review, we outline the pathology and pathogenesis of MASLD-associated liver tumors.https://www.mdpi.com/2227-9059/11/10/2761nonalcoholic fatty liver diseasenonalcoholic steatohepatitismetabolic dysfunction-associated steatotic liver diseasemetabolic dysfunction-associated steatohepatitishepatocellular carcinomasteatohepatitic hepatocellular carcinoma |
| spellingShingle | Yoshihisa Takahashi Erdenetsogt Dungubat Hiroyuki Kusano Toshio Fukusato Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors Biomedicines nonalcoholic fatty liver disease nonalcoholic steatohepatitis metabolic dysfunction-associated steatotic liver disease metabolic dysfunction-associated steatohepatitis hepatocellular carcinoma steatohepatitic hepatocellular carcinoma |
| title | Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors |
| title_full | Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors |
| title_fullStr | Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors |
| title_full_unstemmed | Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors |
| title_short | Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors |
| title_sort | pathology and pathogenesis of metabolic dysfunction associated steatotic liver disease associated hepatic tumors |
| topic | nonalcoholic fatty liver disease nonalcoholic steatohepatitis metabolic dysfunction-associated steatotic liver disease metabolic dysfunction-associated steatohepatitis hepatocellular carcinoma steatohepatitic hepatocellular carcinoma |
| url | https://www.mdpi.com/2227-9059/11/10/2761 |
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