The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

Chen, Yuguang; Yang, Chih‐Wei; Chung, Chi‐Hsiang; Ho, Ching‐Liang; Chen, Wei‐Liang; Chien, Wu-Chien

doi:10.1007/s12072-021-10281-9

Cited by 23 publications

(22 citation statements)

References 37 publications

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“…Non-alcoholic fatty liver disease (NAFLD) describes several related pathological states associated with excessive fat accumulation in the liver (hepatosteatosis) and in the absence of excessive alcohol consumption; NAFLD is a manifestation of obesity and metabolic syndrome and has been positively associated with risk/development of HCC [ 56 , 57 ]. The noted increase in liver weights of both male and female mice null for KLF9 initially suggested the possibility of greater steatosis in the livers of the Klf9 −/− mice; however, Oil Red O and H&E staining as well as triglyceride assay did not show any significant differences between genotypes.…”

Section: Discussionmentioning

confidence: 99%

Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet

Brown

Alhallak

Simmen

et al. 2022

Cancers

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Obesity, oxidative stress, and inflammation are risk factors for hepatocellular carcinoma (HCC). We examined, in mice, the effects of Krüppel-like factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9+/+ (wild type, WT) and Klf9−/− (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum adiponectin and leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9−/− mice of either sex did not exhibit significant alterations in weight gain, adipocyte size, adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9−/− mice of both sexes had increased liver weight/size (hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH/GSSG ratio and increased homocysteine, 3-nitrotyrosine, 3-chlorotyrosine, and 4HNE content. Decreased GSH to GSSG ratio and a trend toward increased homocysteine levels were observed in the corresponding Klf9−/− mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9−/− mice. KLF9 suppresses hepatic oxidative stress and inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps cancers of other tissues.

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Section: Discussionmentioning

confidence: 99%

Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet

Brown

Alhallak

Simmen

et al. 2022

Cancers

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“… 101 Chen et al has shown in a nationwide cohort that while metabolic syndrome alone without NAFLD does not increase the risk of HCC, it significantly increases the risk of hepatocarcinogenesis in patients with NAFLD. 102 …”

Section: Overview Of Risk Factorsmentioning

confidence: 99%

Hepatocellular Carcinoma Due to Nonalcoholic Fatty Liver Disease: Current Concepts and Future Challenges

Ahmad¹,

Khan²,

Kodali³

et al. 2022

JHC

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Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.

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“…An interesting observation of the current study [ 7 ] was the further 2.5-fold increase in liver cancer development in fatty liver disease in the context of the metabolic syndrome defined by the ATPIII diagnostic criteria. This is to be expected given that those with the “full-house” are likely to have a worse metabolic milieu than those with only some of the diagnostic risk components.…”

mentioning

confidence: 90%

“…In this issue of the journal, Chen et al [ 7 ] use a longitudinal nationwide cohort from Taiwan to assess the risk of incident liver cancer in patients with metabolic syndrome (MetS) alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The primary cohort comprised individuals with both NAFLD and MetS based on ICD-CM-9 codes while the comparator groups (MetS alone, NAFLD alone, overlap NAFLD/MAFLD and individuals without MetS and NAFLD [control population]) were selected by propensity matching one to one by age, sex, index date and case number with no consideration to hepatitis virology status or other risk factors.…”

mentioning

confidence: 99%

“…In the Asian Pacific, NAFLD prevalence was estimated in a meta-analysis to be 27% [ 8 ], while the prevalence of MAFLD in those who are overweight or obese is about 50% [ 9 ]. As the paper by Chen et al [ 7 ] highlights, for patients with NAFLD alone without concomitant MetS, the risk for liver cancer development increased ~ sixfold likely because they had one or more risk factors for metabolic dysregulation without meeting the MetS definition. Thus, the presence of metabolic dysfunction should be investigated at the time of diagnosis of liver cancer in any patient with fatty liver.…”

mentioning

confidence: 99%

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Liver fat and a perturbed metabolic milieu: a consilience of factors driving liver cancer development

George

Kawaguchi

2022

Hepatol Int

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The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

Cited by 23 publications

References 37 publications

Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet

Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet

Hepatocellular Carcinoma Due to Nonalcoholic Fatty Liver Disease: Current Concepts and Future Challenges

Liver fat and a perturbed metabolic milieu: a consilience of factors driving liver cancer development

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