• BMB Reports
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• v.56 no.4
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• pp.225-233
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• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

• Journal of Ginseng Research
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• v.48 no.2
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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.

• The Journal of the Korean life insurance medical association
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• v.2 no.1
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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.

• The Journal of Internal Korean Medicine
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• v.26 no.4
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• pp.853-863
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• 2005

Object : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba(ACH) on cultured rat hepatic stellate cells. Methods : Hepatic Stellate Cells were obtained from a 350gm Sprague-Dawley rat by tissue perfusion system, and the cells for the study were selected after 3 passages of culture on non-coated plastic culture dishes which enable the cells to activate, thus producing collagens in the cell media. Cells were treated with various concentrations of Artemisia Capillaris Herba(ACH) extract powder for 24 or 48 hours. After the treatment, Soluble collagen, procollagen levels and the mRNA of the procollagen type I C were measured by using assay kit and RT-PCR method. Results : Procollagen production by the hepatic stellate cells decreased after the treatment in a time-dependent dose-dependent manner. The mRNA expression decreased consistently with the volume of the secreted procollagen which indicates the herb hat inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. Conclusion : These results suggest that ACH is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.743-747
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• 2001

Hepatic encephalopathy is caused by disorders affecting the liver. The exact cause of the disorder is unknown. It occurs changes in mental state, consciousness, behavior, personality and changes in mood include forgetfulness, confusion, disorientation, delirium, dementia, decreased alertness, daytime sleepiness, decreased responsiveness, progressive stupor, coma. As 3 admission patients into oriental hospital of daejeon university include 2 cases of cerebral infarction, 1 case of liver cirrhosis, we found those are all hepatic encephalopathy. But until the diagnosis is made, we have many mistakes to find correct. Among the mistackes, specialy mixed thing is to compare hepatic encephalopathy and cerebral infarction. So, we report these cases with a brief review of related literatures.

• Natural Product Sciences
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• v.17 no.3
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• pp.216-220
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• 2011

Activation of hepatic stellate cells (HSCs) characterized by increased proliferation and extracellular matrix deposition is identified as the major pathological feature of hepatic cirrhosis. Therefore, suppression of HSC activation has been proposed as an important antifibrotic therapeutic strategy. In the present study, we investigated the antiproliferative activity of root barks of Ulmus davidiana var. japonica (Ulmaceae) by employing HSC-T6 hepatic stellate cells as an in vitro assay system. Further investigation of the n-hexane and $CHCl_3$ fractions of root barks of U. davidiana var japonica led to the isolation of six triterpenoids: friedelin (1), epifridelanol (2), oleanolic acid (3), maslinic acid (4), ${\beta}$-amyrin (5) and ${\alpha}$-amyrin (6), together with ${\beta}$-sitosterol (7) and daucosterol (8). Among these compounds, 2, 3 and 4 significantly inhibited HSC proliferation. In addition, 4 inhibited HSC proliferation in time- and concentration-related manners, via a partially direct toxic effect, as assessed by morphological changes and release of lactate dehydrogenase.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.120-126
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• 2003

Object : This study was done to evaluate the inhibitory effect of Samul-tang (Siwu-tang) on collagen production by cultured murine hepatic non-parenchymal cells. Methods : Hepatic non-parenchymal cells were cultured from normal Sprague-Dawley rats and established in a primary cell culture on uncoated plastic culture plates. The Samul-tang (Siwu-tang) was treated into the cell culture media for 72 hours and the cells were harvested for analysis. Analyses were done on cell proliferation, [3H]thymidine incorporation assay and procollagen type IC-peptide. Results : The cultured cells resembled fibroblasts in shape and produced procollagen which is consistent to fibrogenesis in vivo. Proliferation of the non-parenchymal cells was inhibited slightly and the [3H]thymidine incorporation assay showed a dose-dependent decrease by Samul-tang (Siwu-tang) treatment. Production of procollagen type I C-peptide was decreased by low-concentration treatment of the Samul-tang (Siwu-tang), but increased by high-concentration treatment. Conclusion : It seemed that the cells were responding to the Samul-tang (Siwu-tang) in low-concentration, thus producing less collagen. However, when the drug was administered with high enough concentration to cause excessive stimulation of cells, it seemed that the activated cells might overly produce procollagen, the precursor of collagen, thus aggravating fibrosis of the liver. So, it is considered that the proper concentration of Samul-tang (Siwu-tang) is important when treating patients with liver cirrhosis based on the patients' status.

• Investigative Magnetic Resonance Imaging
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• v.12 no.2
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• pp.115-122
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• 2008

Purpose : To evaluate the correlation between the radiological non-invasive hepatic fibrosis index (RNHFI), as determined by SPIO-enhanced MRI, and the laboratory non-invasive hepatic fibrosis index. Materials and Methods : Patients (99 total: 61 men and 38 women; mean age: 58 years) who underwent SPIO-enhanced MRI (1.5T) during 5 years included. These patients were subdivided into a liver cirrhosis group (LCG) and a non-liver cirrhosis group (non-LCG). Using PACS view, we measured the RNHFI (mean standard deviation of hepatic signal intensity (SD), noise-corrected coefficient of variation (CV)) of three ROIs in the liver parenchyma by SPIO-enhanced MRI. The laboratory non-invasive hepatic fibrosis index (AST-platelet ratio index (APRI)) of all patients was calculated from the laboratory data. We compared the RNHFI and APRI of LCG with those of non-LC group using Student's t-test. A bivariate correlation was performed to investigate the relationship between the RNHFI and APRI in the LCG. Results : For the LCG, mean values of SD and CV by SPIO-enhanced MRI were $10.3{\pm}3.7$ and $0.19{\pm}0.08$, respectively. For the non-LCG, mean values of SD and CV were $6.5{\pm}1.6$ and $0.08{\pm}0.05$, respectively. The mean APRI of the LCG and the non- LCG were $2.04{\pm}1.7$ and $0.32{\pm}0.32$, respectively. The RNHFI and APRI were significantly different between both groups (p<0.05). For the LCG, the bivariate correlation between SD and APRI revealed a statistically significant positive correlation (r=0.5, p<0.001). In both groups, there was no statistically significant correlation between CV and APRI. Conclusion: A measurement of SD can be a simple and useful method for the evaluation of hepatic fibrosis.

• BMB Reports
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• v.40 no.5
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• pp.814-824
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• 2007

Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

• Journal of Yeungnam Medical Science
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• v.34 no.2
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• pp.265-269
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• 2017

Chylothorax or chylous ascites are rare manifestations of liver cirrhosis. We report a rare case of simultaneous chylothorax and chylous ascites in a patient with hepatitis B virus-related liver cirrhosis. A 76-year-old woman was referred to our hospital with a pleural effusion on her right side. She had no history of recent medical procedures, trauma or tumor. There was no evidence of mass or thoracic duct obstruction in a computed tomography scan. Pleural fluid and ascites were confirmed as chylothorax and chylous ascites by chemistry analysis. Despite thorough conservative care, there was no improvement. Pleurodesis was planned, but hepatic encephalopathy developed suddenly and she did not recover.