• Toxicological Research
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• 제33권1호
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• pp.31-41
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• 2017

Side stream cigarette smoke (SSCS) is known to be as harmful and hazardous to human health as is active smoking. In this study, we investigated the relationship between the exposure to SSCS and its stimulatory and subacute effects on the progression of non-alcoholic steatohepatitis (NASH). A methionine and choline-deficient plus high fat (MCDHF) diet was administered to C57BL/6 mice for 6 weeks. During the first three weeks of MCDHF diet feeding, each diet group was exposed to SSCS (0, 20, $40{\mu}g/L$) or fresh air for 2 hrs per day and 5 days per week. Additional experiments were performed by increasing the concentration (0, 30, $60{\mu}g/L$) and exposure time (6 hours per day) of SSCS. According to histopathologic analysis and serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), there were no differences in hepatic fat deposition, fibrosis, apoptosis or liver damage in MCDHF-fed mice based on SSCS exposure. There were also no differences in the expression of inflammation-, oxidative stress- or fibrosis-related genes between MCDHF-fed mice with or without SSCS exposure. Therefore, it is concluded that SSCS with current exposure amounts does not have additive detrimental effects on the early stage of NASH.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제25권3호
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• pp.240-250
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• 2022

Purpose: This study aimed to examine the advantages and usefulness of transient elastography (Fibroscan^®) in diagnosing non-alcoholic steatohepatitis in children and adolescents compared to those of abdominal computed tomography and liver ultrasonography. Methods: Forty-six children and adolescent participants aged between 6 and 16 years who underwent transient elastography (Fibroscan^®) as well as liver ultrasonography or abdominal computed tomography were included. Thirty-nine participants underwent liver ultrasonography and 11 underwent computed tomography. The physical measurements, blood test results, presence of metabolic syndrome, and the degree of liver steatosis and liver fibrosis were analyzed, and their correlations with transient elastography (Fibroscan^®), abdominal computed tomography, and liver ultrasonography, as well as the correlations between examinations, were analyzed. Results: Thirty-six participants (78.3%) were boys, and the mean age was 12.29±2.57 years, with a mean body mass index of 27.88±4.28. In the 46 participants, the mean values for aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 89.87±118.69 IU/L, 138.54±141.79 IU/L, and 0.77±0.61 mg/dL, respectively. Although transient elastography (Fibroscan^®) and abdominal computed tomography grading had a statistically significant positive correlation with aspartate aminotransferase and alanine aminotransferase values, the correlations between the results of grading performed by transient elastography (Fibroscan^®), abdominal computed tomography, and liver ultrasonography were not statistically. Conclusion: We confirmed that each examination was correlated with the results of some blood tests, suggesting the usefulness and possibility of diagnosis and treatment of steatohepatitis mediated by transient elastography (Fibroscan^®) in the department of pediatrics.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권2호
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• pp.204-209
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• 2008

저자들은 뇌하수체저하증을 동반한 조기에 발병된 소아 비만 환자에서 비알코올성 지방간질환의 진행으로 인한 간경화를 경험하였기에 이를 보고하는 바이며, 향후 뇌하수체저하증이 동반된 비만 환자에서 비알코올성 지방간질환의 발생 및 진행에 대한 주의 깊은 관찰이 필요할 것으로 사료된다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제10권2호
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• pp.185-192
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• 2007

목 적: 본 연구에서는 소아 비만 환자에서 발생하는 비알코올성 지방간 질환의 발병에 TNF-${\alpha}$, adiponectin, leptin 등의 adipokine들이 미치는 영향을 알아보며, 이들 adipokine과 체지방분포 및 인슐린 저항성과의 연관성을 함께 살펴보고자 하였다. 방 법: 2004년 3월에서 2005년 6월까지 분당서울대병원 소아과에 내원한 비만한 소아 61명을 대상으로 하여 비알코올성 지방간 질환의 상태에 따라 대상 환자들을 지방간 질환이 없는 소아 비만 환자(n=23), 단순 지방간(n=20), 그리고 비알코올성 지방간염(n=18)의 세군으로 나누고, 각 환자에서 혈중 TNF-${\alpha}$, leptin, adiponectin 농도를 측정하고 인슐린 저항성의 지표로서 HOMA-IR을 계산하였으며 복부 전산화단층촬영에서 VSR (visceral-subcutaneous fat ratio)을 산출하였다. 결 과: 총 61명(남 : 여=42 : 19, 평균 연령 11.2${\pm}$1.3세)의 환아를 대상으로 지방간 질환에 따라 세 군으로 나누었을 때, 세 군 간의 성별, 연령별 차이는 없었다(p=0.422, p=0.119). 각 군의 혈중 TNF-${\alpha}$ 농도는 유의한 차이가 없었고(22.13${\pm}$6.37 vs. 21.35${\pm}$6.95 vs. 25.17${\pm}$9.30; p=0.342), leptin 농도에도 유의한 차이가 없었으나 (20.29${\pm}$8.57 vs. 16.42${\pm}$6.85 vs. 20.10${\pm}$7.86; p=0.330), adiponectin은 유의한 차이를 보여 비알코올성 지방간염에서 혈중농도가 의미 있게 감소하였다 (6.08${\pm}$1.38 vs. 5.69${\pm}$0.79 vs. 4.93${\pm}$1.75; p=0.026). 복부 전산화단층 촬영에서 산출한 VSR도 지방간염군에서 유의하게 증가된 소견을 보였다(0.31${\pm}$0.08 vs. 0.32${\pm}$0.11 vs. 0.47${\pm}$0.14; p=0.001). HOMA-IR도 세 군에서 유의한 차이를 보였다(4.77${\pm}$3.67 vs. 6.89${\pm}$7.05 vs. 10.42${\pm}$6.73; p=0.000). 그러나 adiponectin과 HOMA-IR 또는 VSR간에 유의한 상관관계는 보이지 않았다(r=-0.117; p=0.450 & r=-0.106; p=0.499). 결 론: 인슐린 저항성은 비만한 소아에서 간 내 지방 축적과 지방간염으로의 진행과정에 모두 영향을 미칠 것으로 추정되며, 비만한 소아의 지방조직에서 분비되는 adipokine 중에서 adiponectin이 단순지방간에서 지방간염으로의 이행하는 기전에 관여할 것으로 여겨진다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8377-8382
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• 2016

Background: The aim of this study was to evaluate any association between a single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409, C>G) and the development and prognosis in patients with hepatocellular carcinoma (HCC). Materials and Methods: Two hundred heathy controls and 388 HCC cases were included: 211 with HBV, 98 patients with HCV, 29 with alcoholic steatohepatitis (ASH) and 52 with non-alcoholic steatohepatitis (NASH). The SNP was determined by real-time PCR based on TaqMan assays. Results: The prevalence of rs738409 genotypes CC, CG and GG in controls was 91 (45.5%), 88 (44.0%), and 21 (10.5%), respectively, while the corresponding genotypes in all patients with HCC was 158 (40.7%), 178 (45.9%), and 52 (13.4%). The GG genotype had significantly higher distribution in patients with ASH/NASH-related HCC compared with controls (OR=2.34, 95% CI=1.16-4.71, P=0.018), and viral-related HCC cases (OR=2.15, 95% CI=1.13-4.08, P=0.020). However, the frequency of the GG genotype was similar between controls and patients with viral-related HCC. At initial diagnosis, HBV-related HCC were larger and at more advanced BCLC stage than the other HCC groups. There were no significant differences between the GG and non-GG groups regarding clinical characteristics, tumor stage and overall survival. Conclusions: These data suggest an influence of the PNPLA3 polymorphism on the occurrence of HCC in patients with ASH/NASH but not among those with chronic viral hepatitis. However, the polymorphism was not associated with the prognosis of HCC.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제18권3호
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• pp.168-174
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• 2015

Purpose: Recent studies have suggested that decreased serum potassium level may contribute to various metabolic disorders in adult patients including nonalcoholic fatty liver disease (NAFLD). We aimed to study the correlation between serum potassium levels and the histologic severity of NAFLD in children. Methods: Pediatric patients with biopsy-proven NAFLD were included in this study. Demographic, clinical, and histopathological data were obtained. Multivariable logistic regression analysis was used to assess whether potassium levels are associated with the presence of nonalcoholic steatohepatitis (NASH) or fibrosis after adjusting for possible confounders. A p-value <0.05 was considered statistically significant. Results: Among 125 biopsies, 49.6% (62) had evidence of NASH while 66.4% (83) had some degree of fibrosis (stage 1-3). Mean serum potassium was significantly lower in NASH group as compared to non-NASH group ($4.4{\pm}0.42mmoL/L$ vs. $4.8{\pm}0.21$, p<0.001). Higher potassium level had negative correlation with presence of steatosis, ballooning, lobular inflammation, fibrosis and NAFLD activity score (p<0.05). On multivariable analysis and after adjusting for the metabolic syndrome and insulin resistance, higher potassium level was significantly associated with lower likelihood of having a histological diagnosis of NASH on biopsy (odds ratio [OR], 0.12; 95% confidence interval [95% CI], 0.05-0.28; p<0.001). Similarly, the likelihood of having fibrosis decreases by 76% for every 0.5 mmoL/L increase in potassium (OR, 0.24; 95% CI, 0.11-0.54; p<0.001). Conclusion: Our study shows an inverse relationship between serum potassium levels and the presence of aggressive disease (NASH and fibrosis) in children with NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권3호
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• pp.276-285
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• 2020

Purpose: Non-alcoholic fatty liver disease (NAFLD) ranges in severity from simple steatosis to steatohepatitis. Early detection of NAFLD is important for preventing the disease from progressing to become an irreversible end-stage liver disease. We developed a nomogram that allows for non-invasive screening for NAFLD in obese children. Methods: Anthropometric and laboratory data of 180 patients from our pediatric obesity clinic were collected. Diagnoses of NAFLD were based on abdominal ultrasonographic findings. The nomogram was constructed using predictors from a multivariate analysis of NAFLD risk factors. Results: The subjects were divided into non-NAFLD (n=67) and NAFLD groups (n=113). Factors, including sex, body mass index, abdominal circumference, blood pressure, insulin resistance, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γGT), uric acid, triglycerides, and insulin, were significantly different between the two groups (all p<0.05) as determined using homeostatis model assessment of insulin resistance (HOMA-IR). In our multivariate logistic regression analysis, elevated serum ALT, γGT, and triglyceride levels were significantly related to NAFLD development. The nomogram was established using γGT, uric acid, triglycerides, HOMA-IR, and ALT as predictors of NAFLD probability. Conclusion: The newly developed nomogram may help predict NAFLD risk in obese children. The nomogram may also allow for early NAFLD diagnosis without the need for invasive liver biopsy or expensive liver imaging, and may also allow clinicians to intervene early to prevent the progression of NAFLD to become a more advanced liver disease.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권1호
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• pp.44-51
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• 2012

Purpose: Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-${\alpha}$ promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M:F=74:37; mean age, $11.1{\pm}2.0$ yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-${\alpha}$ levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-${\alpha}$ -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-${\alpha}$ polymorphism at the -308 or the -238 loci between group I and group II + III ($p$=0.134 and $p$=0.133). The medians of HOMA-IR were significantly different between group I and group II + III ($p$=0.001), with significant difference between group II and group III ($p$=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus ($p$=0.061) or the -238 locus ($p$=0.207) in obese children. Conclusion: TNF-${\alpha}$ promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제22권5호
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• pp.470-478
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• 2019

Purpose: The incidence of non-alcoholic fatty liver disease (NAFLD) in children is gradually increasing. The aim of this study was to investigate the use of serum adiponectin and soluble adiponectin receptor 2 (soluble Adipo R2) levels for the diagnosis of fatty liver disease in obese and overweight children. Methods: The study included 51 obese and overweight children between the ages of 6 and 18 years diagnosed with NAFLD using ultrasonography and 20 children without fatty liver disease. Patients whose alanine transaminase level was two times higher than normal (${\geq}80U/L$) were included in the non-alcoholic steatohepatitis (NASH) group. Results: NASH was observed in 11 (21.6%) of the patients with NAFLD. The incidence of obesity was higher in patients with NASH (80% and 45%, p=0.021). While the adiponectin levels were similar in patients with NAFLD and those without, they were below the normal level in the whole study group. Adiponectin and soluble Adipo R2 levels of patients with NASH were lower than those in patients without NASH; however, this difference was not statistically significant (p=0.064 and p=0.463). Soluble Adipo R2 levels in obese patients with NAFLD were higher than those in obese children without NAFLD (p<0.001). Conclusion: Soluble adiponectin receptor 2 level is a noninvasive marker that can be used for the diagnosis of NAFLD in obese children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권2호
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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.