• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• Journal of radiological science and technology
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• v.42 no.5
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• pp.345-350
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• 2019

Liver biopsy is the gold standard for diagnosing liver fibrosis, but it is invasive and has a risk for complications. For this reason, recently, study has been actively conducted on non-invasive liver fibrosis evaluation method. But, there is no established standard for the type of diffuse liver disease. Therefore, this study was suggest the usefulness and cut-off values of Fibroscan, FIB-4, APRI and AAR of patients with hepatitis C in Korea. According to the diagnosis, 240 people in hepatitis C are classified into fatty liver, chronic hepatitis, and liver cirrhosis. The statistical analysis was performed by ANOVA to verify difference between groups. The ROC curve was analyzed to determine the usefulness and practical cut-off value. As a result, for all diseases, the AUC value for Fibroscan was 0.8 over and the APRI was 0.7 over. Cut-off value of serum based liver fibrosis markers was increased in order of fatty liver, chronic hepatitis and liver cirrhosis. If Fibroscan and serological liver fibrosis markers are applied to predict liver fibrosis, it is expected that excessive liver biopsy can be reduced.

• Journal of Korean Biological Nursing Science
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• v.8 no.2
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• pp.41-59
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• 2006

Chronic liver diseases and hepatic cancer have been reported as 10% of cause of death in Koreans. Regardless of various causes, chronic liver disease accompanies commonly hepatic fibrosis. But still the mechanism of hepatic fibrosis remains poorly understood. Using the dimethylnitrosamine(DMN)-induced hepatic fibrosis rat model, We performed to evaluate the possible therapeutic effect of RIP(extracts of Phellodendron amurense and Patrinia scabiosaefolia) and to investigate the changes in referential connective tissue proteins($TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin, and vimentin) as a marker of fibrogenesis. For these purposes, liver tissues were stained with H & E, and Azan staining for estimation of developing fibrosis. In the DMN-treated rat liver tissue, fibrosis were developed forming incomplete septal fibrosis. Whereas, in the RIP-treated rat liver tissues, the fibrosis were decreased recovering to normal morphology. The expressions of $TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin($\alpha-SMA$), and vimetin were increased in the DMN-treated rat liver tissues, but decreased in the various areas of RIP-treated rat liver tissues. According to these results, RIP could be a possible therapeutic agent to reduce hepatic fibrosis, and the $TGF-{\beta}_1$, ${\alpha}$-SMA, and vimentin could be possible indicative markers of hepatic fibrosis development and recovery.

• The Korea Journal of Herbology
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• v.37 no.6
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• pp.9-17
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• 2022

Objective : In modern society, liver diseases such as liver fibrosis are on the rise as inflammation and wound healing processes of the liver are repeated due to factors such as drinking, smoking, and stress. This study was conducted to evaluate the effect of Saenggangeonbi-tang (SGGBT) on thioacetamide (TAA)-induced liver fibrosis. Methods : The mice were divided into 4 groups for examination (n=6): Normal group (Nor), distilled water-treated liver fibrosis mice (Con), silymarin 50 mg/kg-treated liver fibrosis mice (Sily), SGGBT 200 mg/kg-treated liver fibrosis mice (S200). Liver fibrosis was established in the mice via TAA for 8 weeks (1 week 100 mg/kg, 2,3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg, three times a week, intraperitoneal injection) and they were administered silymarin and SGGBT (every day, oral administration) with the TAA. Results : SGGBT significantly decreased the levels of aspartate aminotransferase, alanine aminotransferanse, ammonia, and myeloperoxidase in serum increased by liver fibrosis. As a result of confirming H&E and MT staining, it was confirmed that SGGBT reduced damage and inflammatory cell infiltration in liver tissue, and alleviated changes in collagen fiber deposition and histological fibrosis. Also, it was confirmed through PAS staining that it reduced glycogen deposition in liver tissue. In addition, SGGBT significantly decreased the NADPH oxidases as well as significantly modulated the expression of MMP-2 and TIMP-2. Conclusions : These results suggest that SGGBT regulates the expression of MMP/TIMP protein through inhibition of oxidative stress and alleviates liver fibrosis by reducing collagen and glycogen deposition in liver tissue.

• Journal of the Korean Society of Radiology
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• v.13 no.4
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• pp.547-555
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• 2019

The purpose of this study was to evaluate the usefulness of routine liver ultrasonography on the basis of the scoring system according to the morphological parameters of liver ultrasound images and the histopathological results of liver biopsy. The morphological parameters of the liver through ultrasonography were divided into liver surface, liver edge and liver parenchyma. Pathologic results of liver biopsy were classified as mild fibrosis(F1), significant fibrosis(F2), severe fibrosis(F3), and cirrhosis(F4). In conclusion, routine ultrasound examination showed a sensitive predictive factor for fibrosis with mild fibrosis (F1) to severe fibrosis (F3) were liver edge>liver parenchyma>liver surface. However, the predictive factors for detecting cirrhosis (F4) were liver parenchyma>liver surface>liver edge. The use of three variable combinations rather than individual variables in routine ultrasonography may be useful in evaluating the degree and progress of liver fibrosis.

• Journal of the Korean Society of Radiology
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• v.13 no.4
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• pp.539-546
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• 2019

Liver biopsy is invasive and it is a risk of complications. Nevertheless, liver biopsy is gold standard for predicting liver fibrosis. To compensate for these shortcomings, in this study, the liver fibrosis stage was divided using Fibroscan(R) in 200 chronic hepatitis C patients. And, the usefulness and cut-off values of fibrosis index based on four factors(FIB-4), AST to platelet ratio index(APRI) and AST/ALT ratio(AAR) calculated as serum tests were investigated by analyzing ROC curve. As a result, using FIB-4 and APRI rather than AAR is appropriate for evaluation of liver fibrosis. And using APRI to predict significant Fibrosis(F2) and FIB-4 is considered useful for predicting cirrhosis(F4). By applying the advantages of the serum based liver fibrosis marker, which are convenient and repeatable, liver fibrosis follow-up term can be reduced, and furthermore, the prevalence of liver cirrhosis and hepatocellular carcinoma(HCC) can be reduced.

• Journal of radiological science and technology
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• v.42 no.3
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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.

• Journal of Biomedical Engineering Research
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• v.41 no.1
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• pp.48-54
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• 2020

In this paper, we deal with a liver fibrosis classification problem using ultrasound B-mode images. Commonly representative methods for classifying the stages of liver fibrosis include liver biopsy and diagnosis based on ultrasound images. The overall liver shape and the smoothness and roughness of speckle pattern represented in ultrasound images are used for determining the fibrosis stages. Although the ultrasound image based classification is used frequently as an alternative or complementary method of the invasive biopsy, it also has the limitations that liver fibrosis stage decision depends on the image quality and the doctor's experience. With the rapid development of deep learning algorithms, several studies using deep learning methods have been carried out for automated liver fibrosis classification and showed superior performance of high accuracy. The performance of those deep learning methods depends closely on the amount of datasets. We propose an enhanced U-net architecture to maximize the classification accuracy with limited small amount of image datasets. U-net is well known as a neural network for fast and precise segmentation of medical images. We design it newly for the purpose of classifying liver fibrosis stages. In order to assess the performance of the proposed architecture, numerical experiments are conducted on a total of 118 ultrasound B-mode images acquired from 78 patients with liver fibrosis symptoms of F0~F4 stages. The experimental results support that the performance of the proposed architecture is much better compared to the transfer learning using the pre-trained model of VGGNet.

• BMB Reports
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• v.56 no.2
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• pp.114-119
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• 2023

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

• Toxicological Research
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• v.34 no.3
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• pp.241-247
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• 2018

Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes ($Col1{\alpha}1$, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.