• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.3
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• pp.295-305
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• 2021

Purpose: Hepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels. Methods: This retrospective case series included 12 boys aged 6-17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity. Results: Serum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gamma-glutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count. Conclusion: There was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.

• The Journal of the Korea Contents Association
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• v.9 no.6
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• pp.237-246
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• 2009

This study was carried out to investigate of the associations of Alcoholic & Nonalcoholic fatty liver disease(AFLD & NAFLD) with metabolic syndrome(MS) defined by IDF criteria. We conducted a cross-sectional study of 799 adult males with alcohol consumption underwent laboratory investigation(control 297, alcoholic 206, nonalcoholic 296). The ultrasound scan of the liver was performed to determine the presence and the severity of FLD. We analyzed the association between the severity of AFLD & NAFLD and MS by logistic regression analysis. The distribution of metabolic syndrome was 7.4%, 48.8%, 34.9% in control, AFLD & NAFLD. The association of blood pressure, glucose, triglycerides, obesity were risk factor in AFLD & NAFLD. According to the severity of FLD, AFLD was significantly increased with MS, Obesity, low HDL-cholesterol. MS, High triglycerides was increased significantly in NAFLD(p<0.05). The prevalence of AFLD & NAFLD was increased with increasing the number of features of metabolic syndrome. This study shows that AFLD & NAFLD was closely associated with MS and its components. The patients of AFLD & NAFLD should managed and monitored to prevent metabolic abnormalities.

• Journal of radiological science and technology
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• v.40 no.2
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• pp.205-211
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• 2017

There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions.

• Toxicological Research
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• v.35 no.4
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• pp.403-410
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• 2019

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.74-78
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• 2012

With a markedly increased prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now becomes the most common cause of chronic liver disease in both adults and children. The etiology and pathogenesis of NAFLD are multifactorial and remain incompletely understood. According to the "two-hit" theory, inflammatory cytokines and adipokines are activated by oxidative stress and they are involved in insulin resistance, necroinflammatory steatohepatitis and fibrosis. This review discusses the latest updates on the role of some of important inflammatory adipokines and cytokines in the pathogenesis of NAFLD with an emphasis on their potential therapeutic implications.

• Health Policy and Management
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• v.31 no.4
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• pp.472-478
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• 2021

Background: Early identification of patients who are highly likely to develop severe illness among confirmed cases of coronavirus disease 19 (COVID-19) can be expected to lead to effective treatment. This study therefore aimed to determine whether the presence of nonalcoholic fatty liver disease (NAFLD) has an impact on the exacerbation of COVID-19 symptoms. Methods: The study used the Korean National Health Insurance claim data for treatment of COVID-19 patients in 2020. NAFLD includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The outcome variables used were hospitalization and the use of medical devices. Hospitalization was defined by a length of stay exceeding one day and the use of medical devices was defined as one or more uses of a ventilator or extracorporeal membrane oxygenation. Multivariable logistic regression analysis was performed to determine if there was a difference in the hospitalization and use of medical devices of COVID-19 patients depending on the presence of NAFLD. Results: The odds ratio of hospitalization was 1.059, indicating slightly higher odds of hospitalization for patients with NAFL or NASH compared to those without the conditions, but it was not statistically significant (0.969-1.156). On the other hand, the odds ratio of use of medical devices was high at 1.667 and was statistically significant (1.111-2.501). Conclusion: The study results found NAFLD to be a risk factor that can exacerbate symptoms in COVID-19 patients. Accordingly, it is necessary to identify NAFLD patients through preemptive screening and provide them with appropriate treatments.

• Journal of Ginseng Research
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• v.45 no.2
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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).

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.533-542
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• 2012

Objectives : We try to compared the efficacy of six herbal medicines, Rhizoma Alismatis (RA), Fructus Crataegi (FC), Fructus Lycii (FL), Radix Curcumae (RC), Radix Salviae Miltiorrhizae (RSM), and Herba Artemisiae Scopariae (HAS), constituting KHchunggan-tang which was previously proven to be hepatoprotective on non-alcoholic fatty liver disease with combined properties of cellular steatosis, ROS production, and cytoprotection. Methods : HepG2 cells were pretreated with aqueous extracts of the six herb medicines at concentrations of 1, 10, 50 and 100 ${\mu}g/ml$ each, and treated with 0.5 mM palmitate consecutively. After 21 hrs, cell viability was assessed using MTT assay, and the percentage of cells with sub-G1 DNA content was measured using fluorescence-activated cell sorting after propidium iodide staining. Results : The first three extracts, RA, FC, and FL restored cell viability reduced by palmitate in MTT assay, and RA, FC, FL and RC inhibited palmitate-induced apoptosis in sub-G1 analysis. FL showed relatively weak potential only at tested maximal dose, and RA showed the greatest higher efficacy on this experimental cellular model of nonalcoholic fatty liver disease. Conclusions : According to this comparative experiment, Rhizoma Alismatis seems to have the most powerful potential among the six herbs constituting KHchunggan-tang, and consecutive further study seems to be required for more standardized and effective clinical application of KHchunggan-tang for treatment of non-alcoholic fatty liver disease.

• Clinical and Experimental Pediatrics
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• v.59 no.9
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• pp.362-367
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• 2016

Purpose: This study aimed to investigate the clinical significance of serum alanine aminotransferase (ALT) levels in children with nonalcoholic fatty liver disease (NAFLD) and the effect of lifestyle intervention on NAFLD. Methods: The clinical data of 86 children diagnosed with NAFLD were reviewed retrospectively. Forty-six patients belonged to the elevated ALT group and 40 to the normal ALT group. The clinical parameters of patients with NAFLD were also compared based on the status of ALT levels after lifestyle intervention. Results: Patients with elevated ALT had significantly higher body mass index (BMI) scores than those with normal ALT (P<0.05). Of all the patients with elevated ALT, 89% exhibited moderate or severe degree of fatty change in the liver on ultrasonographic examination, whereas most patients with normal ALT exhibited mild or moderate degree changes. Liver biopsy was performed in 15 children with elevated ALT and all showed mild histological changes. Of all patients with elevated ALT, 49% achieved normal ALT levels after lifestyle intervention. Those with more severe histological changes tended to have continuously increasing ALT levels. There was no correlation between the normalization of posttreatment ALT level and BMI, as well as ultrasonographic findings at diagnosis. Conclusion: ALT elevation in NAFLD is highly associated with higher BMI scores and more severe degree of fatty changes on ultrasonographic examination. Lifestyle intervention can significantly improve ALT in children with NAFLD. The degree of histologic changes appears to be a predictor of the treatment response to NAFLD.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.350-361
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• 2020

Background: Black ginseng (BG) is a type of Korean ginseng prepared by steaming and drying raw ginseng to improve the saponin content. This study examined the effects of BG on nonalcoholic fatty liver disease (NAFLD) in HepG2 cells and diet-induced obese mice. Methods: HepG2 cells were treated with free fatty acids to induce lipid accumulation before supplementation with BG. NAFLD-induced mice were fed different doses (0.5%, 1%, and 2%) of BG for 8 weeks. Results: BG significantly reduced lipid accumulation and expression of lipogenic genes, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein-1c, and fatty acid synthase in HepG2 cells, and the livers of mice fed a 45% high-fat diet with 10% fructose in the drinking water (HFHF diet). BG supplementation caused a significant reduction in levels of aspartate aminotransferase and alanine aminotransferase, while antioxidant enzymes activities were significantly increased in 45% high-fat diet with 10% fructose in the drinking water diet-fed mice. Expression of proliferator-activated receptor alpha and carnitine palmitoyltransferase I were upregulated at the transcription and translation levels in both HepG2 cells and diet-induced obese mice. Furthermore, BG-induced phosphorylation of AMP-activated protein kinase and acetyl CoA carboxylase in both models, suggesting its role in AMP-activated protein kinase activation and the acetyl CoA carboxylase signaling pathway. Conclusion: Our results indicate that BG may be a potential therapeutic agent for the prevention of NAFLD.