Differences in the genetic backgrounds of patients with alcoholic liver disease and non‐alcoholic fatty liver disease

Yamamoto, Kaori; Kogiso, Tomomi; Taniai, Makiko; Hashimoto, Etsuko; Tokushige, Katsutoshi

doi:10.1002/jgh3.12097

Cited by 15 publications

(12 citation statements)

References 36 publications

(60 reference statements)

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“…As consequence of advanced liver disease, these patients are characterized by severely enhanced circulating ALT and AST levels ( p = 0.07 and p < 0.0001 at one-way ANOVA, respectively). In addition, according to literature evidence [ 30 , 31 ], HCC patients display an increased frequency distribution of PNPLA3 variant (29% MM vs. 16%; p < 0.0001 at one-way ANOVA) compared to NAFLD patients without cancer.…”

Section: Resultsmentioning

confidence: 78%

The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Meroni

Longo

Paolini

et al. 2021

Cancers

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Background and Aims: Dyslipidemia and cardiovascular diseases (CVD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 gene cluster, has been associated CVD, but its impact on metabolic traits and on the severity liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 had HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC), and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n = 125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p < 0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The minor G allele was associated with higher risk of HCC, independently of fibrosis severity (odds ratio (OR): 5.62; 95% c.i. 1.77–17.84, p = 0.003), poor prognosis and advanced tumor stage (p < 0.05) in the overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p < 0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p < 0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p < 0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p < 0.05). Conclusions: In sum, the rs599839 A>G variant is associated with protection against dyslipidemia and CVD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively.

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Section: Resultsmentioning

confidence: 78%

The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Meroni

Longo

Paolini

et al. 2021

Cancers

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“…53 We found that the prevalence of SNPs in ADH1B, ALDH2, and MTP differed significantly between ALD and NAFLD patients (p < 0.01). 54 It is clinically important to investigate how these SNPs, especially those in ADH1B, ALDH2, and P450IIE1, influence the progression of MetALD. These cumulative clinical and genomic data could lead to improved treatment methods for MetALD.…”

Section: Moderate Weekly Alcohol Intake and Masld (Metald)mentioning

confidence: 99%

New concept in fatty liver diseases

Tokushige

2024

Hepatology Research

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In 2023, the Nonalcoholic Fatty Liver Disease (NAFLD) Nomenclature Consensus group proposed a new name and concept for NAFLD/nonalcoholic steatohepatitis (NASH). The Japanese Society of Gastroenterology and the Japanese Society of Hepatology have accepted these new names and concepts. It was reported that the terms "nonalcoholic" and "fatty" are misleading and inappropriate, because NAFLD does not reflect the etiology. Thus, appropriate disease names are discussed, and new concepts are published. First, the concept of steatotic liver disease (SLD) was proposed to encompass fatty liver diseases of various etiologies, which are classified into five categories. The diagnostic criteria for metabolic dysfunction‐associated steatotic liver disease (MASLD) included fatty liver with at least one of the five cardiometabolic risk factors (body mass index or waist diameter, blood glucose or HbA1C, blood pressure, triglycerides, and HDL cholesterol) and the same restriction of alcohol consumption as NAFLD. A new fatty liver category was described, MetALD, to represent the intermediate drinker group (patients with MASLD with high weekly alcohol intake (140‐350 g/week in women and 210‐420 g/week in men)). The other five categories are alcohol‐associated liver disease (ALD), fatty liver with an identifiable specific cause, and other fatty livers of unknown cause. NASH is an important pathological concept (metabolic dysfunction‐associated steatohepatitis [MASH]); however, its definition, including hepatocellular balloon‐like degeneration, needs to be reassessed. In Japan, we should use these names and criteria to manage SLD, including hepatocellular carcinoma, which is markedly increasing.This article is protected by copyright. All rights reserved.

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“…Microsomal triglyceride transfer protein (MTP) regulates hepatic triglycerides and very low-density lipoproteins (VLDL) by exporting lipids from the liver. It has recently been shown that the MTP polymorphism genotype GG was associated with NAFLD [44].…”

Section: Genetics In Nafld and Aldmentioning

confidence: 99%

The Interplay between Alcoholic Liver Disease, Obesity, and the Metabolic Syndrome

Malnick

Maor

2020

Visc Med

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Background: Fatty liver may be the result of several factors. The two main contributors are nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Summary: NAFLD is the hepatic manifestation of the metabolic syndrome (MetS) and is the major cause of chronic liver disease worldwide as a result of the obesity epidemic. ALD is also a common cause of chronic liver disease. Obesity is a major contributory factor to MetS and is also common in individuals who consume large amounts of alcohol. There is a similar hepatic pathology and both can result in severe fibrosis, cirrhosis, and its complications including hepatocellular carcinoma. This review discusses the etiology, pathogenesis, and genetics of both NAFLD and ALD and their interaction. It is necessary to understand this better in order to prevent and treat these important causes of liver disease worldwide. Key Message: Obesity, MetS, and alcohol consumption are linked to the development and progression of fatty liver disease. The coexistence of these factors in many patients requires a reassessment of many aspects of treatment of fatty liver disease.

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Differences in the genetic backgrounds of patients with alcoholic liver disease and non‐alcoholic fatty liver disease

Cited by 15 publications

References 36 publications

The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

New concept in fatty liver diseases

The Interplay between Alcoholic Liver Disease, Obesity, and the Metabolic Syndrome

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