scholarly journals Two Differentially Methylated Region (DMR) Networks in Nonalcoholic Fatty Liver Disease, Viral Hepatitis, and Hepatocellular Carcinoma

2022 ◽  
Author(s):  
Suguru Kurokawa ◽  
Masato Yoneda ◽  
Yuji Ogawa ◽  
Yasushi Honda ◽  
Takaomi Kessoku ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
The Other ◽  
Differentially Methylated Region ◽  
Nonalcoholic Fatty Liver ◽  
Hcc Cells

Abstract Background We previously reported that two differentially methylated region (DMR) networks identified by DMR, and co-methylation analyses are strongly correlated with the fibrosis stages of nonalcoholic fatty liver disease (NAFLD). In the current study, we examined these DMR networks in viral hepatitis and hepatocellular carcinoma (HCC). Methods We performed co-methylation analysis of DMRs using a normal dataset (GSE48325), two NAFLD datasets (JGAS000059 and GSE31803), and two HCC datasets (GSE89852 and GSE56588). Results One DMR network was clearly observed in viral hepatitis and two HCC populations. Methylation levels of genes in this network were higher in viral hepatitis and lower in HCC. Fatty acid binding protein 1 (FABP1), serum/glucocorticoid regulated kinase 2 (SGK2), and hepatocyte nuclear factor 4 α (HNF4A) were potential hub genes in this network. Increased methylation levels of the FABP1 gene deteriorated the protection capacity of hepatocytes from oxidative metabolites in NAFLD and viral hepatitis. The decreased methylation levels of SGK2 facilitated the growth and proliferation of HCC cells. Decreased methylation levels of HNF4A in HCC cells were associated with tumorigenesis. The other DMR network was observed in NAFLD, but not in viral hepatitis or HCC. This second network-included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation, which are specifically related to fibrosis and/or tumorigenesis in NAFLD. Conclusions Our results suggest that one DMR network was associated with fibrosis and tumorigenesis in both NAFLD and viral hepatitis, while the other network was specifically associated with NAFLD progression. FABP1, SGK2, and HNF4A could be possible candidate targets for the prevention and treatment of HCC.

scholarly journals The Current View of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 516
Author(s):  
Tomomi Kogiso ◽  
Katsutoshi Tokushige
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Current View ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes ◽  
Life Threatening ◽  
Lifestyle Related Diseases

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.

scholarly journals Improved survival after treatments of patients with nonalcoholic fatty liver disease associated hepatocellular carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jihane N. Benhammou ◽  
Elizabeth S. Aby ◽  
Gayaneh Shirvanian ◽  
Kohlett Manansala ◽  
Shehnaz K. Hussain ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis

2019 ◽  
Vol 35 (5) ◽  
pp. 862-869 ◽  
Author(s):  
Maki Tobari ◽  
Etsuko Hashimoto ◽  
Makiko Taniai ◽  
Kazuhisa Kodama ◽  
Tomomi Kogiso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 579 ◽  
Author(s):  
Yoshio Sumida ◽  
Masashi Yoneda ◽  
Yuya Seko ◽  
Hiroshi Ishiba ◽  
Tasuku Hara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
High Sensitivity ◽  
Cost Effective ◽  
Abdominal Ultrasound ◽  
Screening Tests ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability.

Genetics of Nonalcoholic Fatty Liver Disease: A 2018 Update

2019 ◽  
Vol 24 (38) ◽  
pp. 4566-4573 ◽  
Author(s):  
Luca V.C. Valenti ◽  
Guido A. Baselli
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Rare Variants ◽  
Pharmacological Therapy ◽  
Full Spectrum ◽  
Nonalcoholic Fatty Liver ◽  
Disease Predisposition

Nonalcoholic fatty liver disease (NAFLD), now the leading cause of liver damage worldwide, is epidemiologically associated with obesity, insulin resistance and type 2 diabetes, and is a potentially progressive condition to advanced liver fibrosis and hepatocellular carcinoma. However, there is huge interindividual variability in liver disease susceptibility. Inherited factors also play an important role in determining disease predisposition. During the last years, common variants in PNPLA3, TM6SF2, MBOAT7 and GCKR have been demonstrated to predispose to the full spectrum of NAFLD pathology by facilitating hepatic fat accumulation in the presence of environmental triggers. Other variants regulating inflammation and fibrogenesis then modulate liver disease progression in those at higher risk. Evidence is also accumulating that rare variants are involved in disease predisposition. In the future, evaluation of genetic risk factors may be exploited to stratify the risk of liver-related complications of the disease, and to guide hepatocellular carcinoma surveillance and choose pharmacological therapy.

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