• 센서학회지
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• 제20권2호
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• pp.71-76
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• 2011

To characterize the relationship between the stage of hepatic fibrosis and bioimpedance, several electric parameters were estimated in rats with $CCl_4$-induced liver fibrosis. Thirty three Sprague-Dawley rats were intraperitoneally injected with a $CCl_4$-mineral oil mixture (1:1, 0.2 mL/100 g) twice a week for 8 weeks. The resistance(R), reactance(X), impedance(Z), and dissipation factor(D) between 1 kHz and 100 kHz were then evaluated in the livers of the rats under pentobarbital anesthesia using an HP4294A Impedance Analyzer. The rats were killed 2, 4, 6, and 8 weeks later, and their livers were classified in accordance with Ishak's scoring system. R, X, and Z changed in accordance with the progression of hepatic fibrosis and the changes were greater at lower frequencies than at higher frequencies. In comparison, the D spectrum was biphasic; D increased initially then decreased with increasing frequency. All of the parameters(R, X, Z, and D) changed in accordance with the stage of fibrosis in the livers, but D changed specifically with the progression of fibrosis. These results indicate that hepatic fibrosis may be evaluated by determining the changes in D.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제27권4호
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• pp.236-245
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• 2024

Purpose: The prevalence of nonalcoholic steatohepatitis (NASH) is increasing with the increasing prevalence of childhood obesity. Although NASH has a high risk of progression to liver fibrosis and cirrhosis, few studies have reported noninvasive markers for predicting hepatic fibrosis in children. This study aimed to evaluate and compare the diagnostic accuracies of serologic biomarkers and scoring systems for hepatic fibrosis in obese children with NASH. Methods: A total of 96 children were diagnosed with NASH based on liver biopsy findings and divided into two groups according to the degree of liver fibrosis: mild (stage 0-1) or advanced (stage 2-4). Clinical and laboratory parameters and serum levels of hyaluronic acid and type IV collagen were measured. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) score were calculated. Results: Among the noninvasive markers, only serum type IV collagen level and FIB-4 were significantly different between the two groups. The area under the receiver operating curve of each biomarker and scoring system was 0.80 (95% confidence interval [CI]: 0.70-0.90) for type IV collagen at an optimal cutoff of 148 ng/mL (sensitivity 69.8%, specificity 84.6%), followed by 0.69 (95% CI: 0.57-0.83) for APRI, 0.68 (95% CI: 0.56-0.80) for FIB-4, and 0.65 (95% CI: 0.53-0.77) for hyaluronic acid. Conclusion: Type IV collagen as a single noninvasive serologic biomarker for hepatic fibrosis and FIB-4 as a hepatic fibrosis score are beneficial in predicting advanced hepatic fibrosis and determining proper diagnosis and treatment strategies before fibrosis progresses in obese children with NASH.

• 대한방사선기술학회지:방사선기술과학
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• 제42권3호
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• pp.187-194
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• 2019

The purpose of this study was to evaluate the pathologic results of hepatic parenchyma parameters such as liver parenchyma, liver surface, liver margin and liver, portal vein, spleen size, And to evaluate the usefulness of fibrosis progression and hepatic ultrasonography. The sensitivity, specificity, positive predictive value, and prognostic value according to the stage of fibrosis and grade of inflammation were divided into two groups according to the morphologic variable "A" through ultrasound and "B" We evaluated the predictive value and predicted the variables to evaluate fibrosis in clinical diagnosis and treatment of patients with chronic liver disease. The sensitivity and specificity of hepatic fibrosis in hepatic morphologic variables and other size variables were highest in liver surface and edge. The morphologic parameters used in the evaluation of fibrosis were clinically relevant in distinguishing the fibrosis stage from the results of liver biopsy.

• Korean Journal of Radiology
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• 제23권2호
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• pp.180-188
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• 2022

Objective: To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard. Materials and Methods: This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0-F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal-Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. Results: Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97-0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0-F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97-0.98 (sensitivity 91.2%-95.9%, specificity 90.7%-99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0-F3 stages. Conclusion: The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.320-327
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• 2020

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3879-3884
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• 2014

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

• 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.

• 대한한의학회지
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• 제37권4호
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• pp.36-44
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• 2016

Objectives: Granulocyte-colony-stimulating factor (G-CSF) mobilized bone marrow (BM)-derived hematopoietic stem cells could contribute to improvement of liver function. In addition, liver fibrosis can reportedly be prevented by the Rg 1 component of red ginseng. This study investigated the combined effect of G-CSF and red ginseng on decompensated liver cirrhosis. Methods: Four patients with decompensated liver cirrhosis were injected with G-CSF to proliferate BM stem cells for 4 days ($5{\mu}g/kg$ bid subcutaneously) and followed-up for 3 months. The patients also received red ginseng for 4 days (2 tablets tid per os). We analyzed Child-Pugh scores, Model for End-Stage Liver Disease (MELD) scores and cirrhotic complications. Results: All patients showed marked increases in White blood cell (WBC) and CD34+ cells in the peripheral blood, with a peak time of 4 days after G-CSF injection. Spleen size also increased after G-CSF injection, but not severely. At end of the study, 2 patients showed improvement in Child-Pugh scores, hepatic encephalopathy, and refractory ascites. During the clinical trial period, none of the 4 patients showed any other adverse events or deterioration of liver function. Conclusions: We conclude that G-CSF/red ginseng combination therapy is relatively effective in improving liver function and major complications of decompensated liver cirrhosis without adverse effects. Further clinical trials are warranted to assess the clinical effects of G-CSF for decompensated liver cirrhosis.

• Journal of Korean Medical Science
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• 제33권51호
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• pp.324.1-324.6
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• 2018

Oxysterol $7{\alpha}$-hydroxylase deficiency is a very rare liver disease categorized as inborn errors of bile acid synthesis, caused by CYP7B1 mutations. As it may cause rapid progression to end-stage liver disease even in early infancy, a high index of suspicion is required to prevent fatal outcomes. We describe the case of a 3-month-old boy with progressive cholestatic hepatitis and severe hepatic fibrosis. After excluding other etiologies for his early liver failure, we found that he had profuse urinary excretion of $3{\beta}$-monohydroxy-${\Delta}^5$-bile acid derivatives by gas chromatography/mass spectrometry analysis with dried urine spots on filter paper. He was confirmed to have a compound heterozygous mutation (p.Arg388Ter and p.Tyr469IlefsX5) of the CYP7B1 gene. After undergoing liver transplantation (LT) from his mother at 4 months of age, his deteriorated liver function completely normalized, and he had normal growth and development until the current follow-up at 33 months of age. We report the first Korean case of oxysterol $7{\alpha}$-hydroxylase deficiency in the youngest infant reported to undergo successful living donor LT to date.

• 보험의학회지
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• 제2권1호
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• pp.34-36
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• 1985

Korea is an endemic area of chronic hepatitis in the world. Liver cirrhosis and liver cell carcinoma, presumed to be related to such chronic hepatitis, are the major causes of death in this country. The purpose of this study is disclosing the sources of chronic hepatitis in Korea establishing its histologic characteristics, disclosing the patterns of progression in chronic hepatitis, delineating its prognosis and finally speculating its etiology. The study group was composed of 183 patients with biopsy-proven acute icteric viral hepaticis, 32 patients with biopsy- proven anicteric hepatitis and 260 patients with biopsy- proven chronic hepatitis. These patients submitted to long-term follow-up by means of liver needle biopsy and/or clinicolaboratory evaluation. The period of follow-up ranged from two months to 18 years. The histological features of the initial biopsy specimens of chronic hepatitis permitted a division of the cases cases into the following five types: Type I. Persisting portal hepatitis : so called persisting hepatitis 43 Type II. Chronic inactive hepatitis with incomplete strand septal fibrosis. This type has thin fibrotic septation in addition to Type I with portal sclerosis 38 Type III. Chronic active periportal hepatitis(CAPH) : so called aggressive hepatitis, characterized by marked piecemeal necrosis. This type has been subdivided further into three groups: AB and C on the basis of histologic features. A CAPH without cirrhosis 15 B CAPH with cirrhosis 99 C CAPH with diffuse acinus type parenchymal nodules; characterized by rosette-forming micronodules 21 Type IV. Subacute hepatic necrosis; characterized by multilobular and/or bridging necrosis. 14 Type V. Persisting lobular hepatitis; characterized by spotty necrosis, which looks very similar to acute viral hepatitis. Such histologic changes should be persisted for more than six months 30 In Korea the main source of chronic hepatitis is the anicteric type. Of the chronic hepatitis observed in the hospital, Type IIIb was the most frequent in its incidence and occasionally exhibited development of hepatocellular carcinoma, but the mortality was highest in Type IIIc during the period of follow-up. Histologic characteristics of these five types suggest a spectrum of chronic hepatitis in Korea from an early and mild stage to advanced and fatal cirrhosis, which is occasionally associated with primary hepatic cell carcinoma. It seems that Type IV can be followed by flare-up of various stages of acute and chronic hepatitis with HBsAg and that many cases of liver cirrhosis prevalent in Korea occur through such an active process of Type IV. The etiology is not established, but in Korea it is mainly related to HBsAg.