• Genomics & Informatics
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• 제21권4호
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• pp.45.1-45.11
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• 2023

Nonalcoholic fatty liver disease (NAFLD) is a common type of chronic liver disease, with severity levels ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). The extent of liver fibrosis indicates the severity of NASH and the risk of liver cancer. However, the mechanism underlying NASH development, which is important for early screening and intervention, remains unclear. Weighted gene co-expression network analysis (WGCNA) is a useful method for identifying hub genes and screening specific targets for diseases. In this study, we utilized an mRNA dataset of the liver tissues of patients with NASH and conducted WGCNA for various stages of liver fibrosis. Subsequently, we employed two additional mRNA datasets for validation purposes. Gene set enrichment analysis (GSEA) was conducted to analyze gene function enrichment. Through WGCNA and subsequent analyses, complemented by validation using two additional datasets, we identified five genes (BICC1, C7, EFEMP1, LUM, and STMN2) as hub genes. GSEA analysis indicated that gene sets associated with liver metabolism and cholesterol homeostasis were uniformly downregulated. BICC1, C7, EFEMP1, LUM, and STMN2 were identified as hub genes of NASH, and were all related to liver metabolism, NAFLD, NASH, and related diseases. These hub genes might serve as potential targets for the early screening and treatment of NASH.

• Laboraroty Animal Research
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• 제34권4호
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• pp.133-139
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• 2018

Nonalcoholic steatohepatitis (NASH) is becoming common chronic liver disease because of the increasing global prevalence of obesity and consequently Nonalcoholic fatty liver disease (NAFLD). However, the mechanism for progression of NAFLD to NASH and then cirrhosis is not completely understood, yet. The triggering of these hepatic diseases is thought from hepatocyte injury caused by over-accumulated lipid toxicity. Injured hepatocytes release damage-associated molecular patterns (DAMPs), which can stimulate the Kupffer cells (KCs), liver-resident macrophages, to release pro-inflammatory cytokines and chemokines, and recruit monocyte-derived macrophages (MDMs). The increased activation of KCs and recruitment of MDMs accelerate the progression of NAFLD to NASH and cirrhosis. Therefore, characterization for activation of hepatic macrophages, both KCs and MDMs, is a baseline to figure out the progression of hepatic diseases. The purpose of this review is to discuss the current understanding of mechanisms of NAFLD and NASH, mainly focusing on characterization and function of hepatic macrophages and suggests the regulators of hepatic macrophages as the therapeutic target in hepatic diseases.

• Journal of Ginseng Research
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• 제48권2호
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• pp.122-128
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• 2024

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation, while nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by hepatic inflammation, fibrosis, and liver injury, resulting in liver cirrhosis and hepatocellular carcinoma (HCC). Given the evidence that ginseng and its major bioactive components, ginsenosides, have potent anti-adipogenic, anti-inflammatory, anti-oxidative, and anti-fibrogenic effects, the pharmacological effect of ginseng and ginsenosides on NAFLD and NASH is noteworthy. Furthermore, numerous studies have successfully demonstrated the protective effect of ginseng on these diseases, as well as the underlying mechanisms in animal disease models and cells, such as hepatocytes and macrophages. This review discusses recent studies that explore the pharmacological roles of ginseng and ginsenosides in NAFLD and NASH and highlights their potential as agents to prevent and treat NAFLD, NASH, and liver diseases caused by hepatic steatosis and inflammation.

• IMMUNE NETWORK
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• 제16권3호
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• pp.147-158
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• 2016

The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

• Journal of Ginseng Research
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• 제45권2호
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• pp.316-324
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• 2021

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

• Journal of Ginseng Research
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• 제41권4호
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• pp.450-455
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• 2017

Chronic liver disease, one of the most common diseases, typically arises from nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, or hepatocellular carcinoma. Therefore, there is a pressing need for improved treatment strategies. Korean Red Ginseng has been known to have positive effects on liver disease and liver function. In this paper, we summarize the current knowledge on the beneficial effects of Korean Red Ginseng on chronic liver disease, a condition encompassing nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, and hepatocellular carcinoma, as supported by experimental evaluation and clinical investigation.

• Clinical and Experimental Pediatrics
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• 제48권1호
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• pp.13-20
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• 2005

목 적 : 비만증은 대사성증후군과 더불어 비알코올성 지방간염과 밀접한 관계가 있다. 본 연구는 비만증으로 진단된 학생을 대상으로 비알코올성 지방간염 및 그에 관련된 인자를 알아보고자 하였다. 방 법 : 초 중학교 신체검사상 체질량지수 95 백분위수 이상의 비만아 중 279명을 대상으로 설문지, 신체계측, 혈액검사, 복부지방 초음파 검사를 실시하였다. 결 과 : 전체 연구 대상자 279명 중 비알코올성 지방간염이 있는 사람은 27명으로 9.7%였다. 이중 비만도 30% 이하인 경도비만아 135명 중 5명(3.7%)에서 비알코올성 지방간염이 나타났으며 비만도 30% 이상인 중증도 이상의 비만아에서 비알코올성 지방간염의 유병률은 144명 중 22명(15.2%)으로 비만정도가 심할수록 지방간염의 유병률은 증가하였다. 또한 대사성증후군과 밀접한 연관성이 있다고 알려진 복부 내장지방두께와 허리/엉덩이 둘레비가 클수록 비알코올성 지방간염이 잘 반영되는 것으로 나타났다. 결 론 : 본 연구의 결과는 소아 비만아에서 비알코올성 지방간염의 유병률은 9.7%였으며 비만정도가 심할수록 비알코올성 지방간염의 유병률은 증가하였다. 또한 대사성 증후군의 구성인자와 비알코올성 지방간염은 상당한 연관성이 있으며 이들의 공통적인 특징인 인슐린 저항성의 지표는 치료효과 판정 및 통합적인 위험인자 관리에 도움이 될 것이라 생각된다.

• 한국방사선학회논문지
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• 제16권7호
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• pp.943-952
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• 2022

지방간 진단을 위한 검사로, 최근 초음파 검사와 혈액검사를 동시에 병행하여 시행하고 있다. 특히 혈액검사 중 hs-CRP의 경우, 심혈관 질환 뿐 아닌, 인체의 다양한 부위에 대한 염증 수치를 나타내는 지표로 사용되고 있다. 따라서 본 연구를 통해 비알콜성 지방간 정도에 따른 대사증후군 구성 요소와 간 기능 및 hs-CRP수치 등의 연관성을 분석해 지방간 진단 임상 지표로 활용하고자 연구를 진행하였다. 2021년 3월~2021년 8월 한국 건강관리 협회 광주 전남지부에서 복부 초음파 검사를 실시하여 비알콜 지방간이 관찰된 환자 중 대사증후군 구성요소와 간 기능 및 hs-CRP 검사를 모두 실시한 만 20세 이상, 남녀 총 1,139명의 피검사 수치 데이터를 대상으로 하였다. 남녀 전체를 대상으로 분석한 경우 경도 지방간 환자의 간 검사 수치가 AST 30 U/L, ALT 32.1 U/L hs-CRP 0.14 mg/dL로 중등도 지방간 환자의 혈액 검사 수치 AST 38 U/L, ALT 47.6 U/L, 54.9 IU/L, hs-CRP 0.22 mg/dL보다 낮았으며 통계적으로 유의했다(P<0.001). hs-CRP 검사의 경우 경도 지방간 환자보다 중등도 지방간 환자에서 통계적으로 유의할 만큼 높은 수치 차이를 나타낸 것으로 보아 hs-CRP 검사가 지방간 예방과 관리를 위한 임상적 데이터로도 활용될 수 있을 것으로 사료된다.

• 한국식품영양학회지
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• 제35권5호
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• pp.332-342
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• 2022

Nonalcoholic fatty liver disease (NAFLD) is recognized one of the leading metabolic diseases globally, and the younger age population with the disease is rapidly growing, especially in developed countries. Since there has been no approved medicine, losing weight is known to be the only best remedy to control or reverse the disease. Recently, the field of microbiome has attracted much attention to offer more practical choices for patients. Here, we provide experimental evidence that Streptococcus thermophilus LM1012 (LM1012), a safe probiotic strain, is effective for improving NAFLD indexes. In the methionine-choline deficient (MCD) diet induced C57BL/6 mouse model, administration of LM1012 promoted marked reductions of aspartate transaminase (23.8%), total bilirubin (27.8%), hydroxycholesterol (64.2%), triglyceride (29.7%) and IL-1β (68.3%) compared to the MCD diet alone group. Also, the histopathological data imply that LM1012 inhibited fat accumulation and inflammation in the liver, which are the key biomarkers for progression of the disease. Together, these findings suggest that human consumption of LM1012 as a healthy nutritional supplement, may be helpful in reducing the risk of liver damages in NAFLD patients.

• Clinical and Experimental Pediatrics
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• 제56권1호
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• pp.19-25
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• 2013

Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.