Genetics and epigenetics of NAFLD and NASH: Clinical impact

Eslam, Mohammed; Valenti, Luca; Romeo, Stefano

doi:10.1016/j.jhep.2017.09.003

Cited by 705 publications

(619 citation statements)

References 134 publications

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“…NAFLD is a complex metabolic disease that is closely associated with visceral adiposity and insulin resistance [34,35]. Most researchers consider that lipid accumulation in the liver is the first step but alone may not be enough to induce progressive liver injury.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, the treatment of NAFLD is divided into three main categories: one is lifestyle changes, such as dietary adjustments, and increased physical activity; the second is control by clinical drugs; and the third is surgical intervention [3,12,34]. For the patient as a whole, changes in diet, energy intake control and increased exercise are still the first-line choice.…”

Section: Discussionmentioning

confidence: 99%

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Cangju Qinggan Jiangzhi Decoction Reduces the Development of NonAlcoholic Steatohepatitis and Activation of Kupffer Cells

Cheng

Chen

Jian

et al. 2018

Cell Physiol Biochem

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Background/Aims: Nonalcoholic steatohepatitis (NASH) is defined as lipid accumulation with hepatic injury, inflammation and early to moderate fibrosis. Kupffer cells play a crucial role in promoting hepatic inflammation, which further facilitates the development of NASH. Here we investigated the effects of Cangju Qinggan Jiangzhi decoction (CQJD) on high fat diet (HFD) and methionine-choline deficient (MCD) induced mouse NASH pathogenesis. Methods: Mouse NASH models were developed by HFD and MCD diet. The treated mice were divided into three groups: the control group (n = 10), the low-dose CQJD treatment group (n = 10) and the high-dose CQJD treatment group (n = 10). The hepatic injury, inflammation, and apoptotic molecules were evaluated by H&E staining, immunohistochemistry and real-time PCR. Kupffer cells were isolated from control mice and CQJD-treated mice after stimulation by lipopolysaccharide (LPS) and/or palmitic acid. The level of the inflammatory cytokines TNFα, IL1β, and CCL2 was measured by ELISA. Results: The HFD-fed mice displayed significant metabolic, inflammatory, and oxidative stress-related alterations due to hepatic lipid accumulation. CQJD treatment largely normalized the hepatic injury, lowered the ALT/AST level, and reduced the severity of liver inflammation, as revealed by the decreased inflammatory cytokines levels. In vitro, CQJD blocked the activation of LPS- or palmitic acid-primed Kupffer cells in a dose-dependent manner. In the MCD diet-induced NASH mice, similar therapeutic effects of CQJD were also observed. Conclusion: CQJD ameliorates mouse nonalcoholic steatohepatitis. The reduction in liver injury and inflammation induced by CQJD is associated with reduced activation of Kupffer cells. Our results suggest that CQJD is a promising therapeutic strategy in clinical steatohepatitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cangju Qinggan Jiangzhi Decoction Reduces the Development of NonAlcoholic Steatohepatitis and Activation of Kupffer Cells

Cheng

Chen

Jian

et al. 2018

Cell Physiol Biochem

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“…A cohort study showed that this TM6SF2 variant is a risk factor for fibrosis in the liver and is associated with a 1.9-fold increase in advanced fibrosis. [174] Methylation patterns have been found to act on the HSC activation-related gene, which protects against fibrosis. The E167K form seems to cause a 40% reduction in cardiovascular events and a 50% reduction in atherosclerotic carotid plaques.…”

Section: Geneticsmentioning

confidence: 99%

Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases

et al. 2018

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease which affects ≈25% of the adult population worldwide, placing a tremendous burden on human health. The disease spectrum ranges from simple steatosis to steatohepatitis, fibrosis, and ultimately, cirrhosis and carcinoma, which are becoming leading reasons for liver transplantation. NAFLD is a complex multifactorial disease involving myriad genetic, metabolic, and environmental factors; it is closely associated with insulin resistance, metabolic syndrome, obesity, diabetes, and many other diseases. Over the past few decades, countless studies focusing on the investigation of noninvasive diagnosis, pathogenesis, and therapeutics have revealed different aspects of the mechanism and progression of NAFLD. However, effective pharmaceuticals are still in development. Here, the current epidemiology, diagnosis, animal models, pathogenesis, and treatment strategies for NAFLD are comprehensively reviewed, emphasizing the outstanding breakthroughs in the above fields and promising medications in and beyond phase II.

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“…Genome-wide association studies suggest that variation in several genes [e.g., PNPLA3 (patatin-like phospholipase domain-containing protein 3), TM6SP2 (transmembrane 6 superfamily member 2), and FADS (fatty acid desaturase)] related to hepatic lipid metabolism are associated with increased hepatic steatosis in human NAFLD subjects (14–16). A more detailed discussion regarding the contribution of genetic (or epigenetic) factors to the pathogenesis of NASH has been recently reviewed elsewhere (17). Thus, various risk factors contribute to the development of hepatic steatosis and NALFD/NASH by affecting hepatic lipid metabolism through multiple pathways (Figure 1).…”

Section: “Multiple-parallel Hit” Pathogenesis Of Nashmentioning

confidence: 99%

Pathogenesis of Nonalcoholic Steatohepatitis and Hormone-Based Therapeutic Approaches

Kim

Lee

2018

Front. Endocrinol.

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Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for type 2 diabetes, cardiovascular disease, and chronic kidney disease. Nonalcoholic steatohepatitis (NASH), an advanced form of NAFLD, is a predisposing factor for development of cirrhosis and hepatocellular carcinoma. The increasing prevalence of NASH emphasizes the need for novel therapeutic approaches. Although therapeutic drugs against NASH are not yet available, fundamental insights into the pathogenesis of NASH have been made during the past few decades. Multiple therapeutic strategies have been developed and are currently being explored in clinical trials or preclinical testing. The pathogenesis of NASH involves multiple intracellular/extracellular events in various cell types in the liver or crosstalk events between the liver and other organs. Here, we review current findings and knowledge regarding the pathogenesis of NASH, focusing on the most recent advances. We also highlight hormone-based therapeutic approaches for treatment of NASH.

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Genetics and epigenetics of NAFLD and NASH: Clinical impact

Cited by 705 publications

References 134 publications

Cangju Qinggan Jiangzhi Decoction Reduces the Development of NonAlcoholic Steatohepatitis and Activation of Kupffer Cells

Cangju Qinggan Jiangzhi Decoction Reduces the Development of NonAlcoholic Steatohepatitis and Activation of Kupffer Cells

Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases

Pathogenesis of Nonalcoholic Steatohepatitis and Hormone-Based Therapeutic Approaches

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