• Clinical and Molecular Hepatology
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• v.24 no.4
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• pp.384-391
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• 2018

Backgrounds/Aims: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. Methods: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ${\geq}7.9kPa$. Results: A total of 214 patients were included in the analysis, and 62% of them had a BMI ${\geq}25kg/m^2$. During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ${\geq}25kg/m^2$ versus 56% of patients without SF (P<0.05). Conclusions: In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.

• Korean Journal of Veterinary Research
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• v.49 no.3
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• pp.249-252
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• 2009

A 6-year-old, neutered male, Schnauzer was presented with a one year history of weight loss and exercise intolerance. Physical examination revealed abdominal distention and ecchymosis on the abdominal skin. CBC and serum chemistry profiles revealed anemia and increased serum liver enzymes. Ultrasonography revealed a large liver mass which was characterized by multiple hypoechoic lesions. Postmortem examination revealed primary hepatic hemangiosarcoma. The tumor had extended to the mesentery and diaphragm, but distant metastasis was not found. This case report describes primary hepatic hemangiosarcoma which is very rare in a dog.

• 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.

• Archives of Obesity and Metabolism
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• v.2 no.2
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• pp.71-75
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• 2023

Obesity is closely related to chronic diseases and cancer. The present case report aims to discuss the anti-obesity treatment strategy and the evaluation of the clinical progress in a patient with obesity and concurrent fatty liver disease. Following five months of treatment with liraglutide and rosuvastatin, the patient had a weight reduction of 3 kg (4.7%), a decrease in fasting blood sugar by 42 mg/dl (26.6%), a decrease in low-density lipoprotein cholesterol by 82 mg/dl (60.2%), and decrease in alanine transaminase. This case report documented the treatment of a patient with common chronic diseases encountered in the outpatient setting. Based on the therapeutic effects documented in clinical and laboratory indices, the anti-obesity treatment plan significantly aided in managing chronic diseases.

• The Korean Journal of Nuclear Medicine
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• v.16 no.1
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• pp.63-72
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• 1982

Hepatoscintigram has been a useful diagnostic method for the liver diseases since 1953, but reasonable diagnostic criteria for parenchymal liver diseases are not yet accurately established. For the purpose of searching for more advanced diagnostic criteria for various types of live disease by the liver scan, a retrospective study was made of 272 cases who underwent both hepatoscintigram with 198 Au colloid and liver biopsy in Hanynag University Hospital from Jan., 1978 to Dec., 1981. The results were as follows: 1. Fuzzy margin (irregular indentation of the liver margin) in the hepatoscintigram was noted in 226 cases (97.79%). 2. Of 35 cases with fuzzy margin only, 28 cases (80%) revealed mild parenchymal liver disease, such as acute hepatitis or chronic persistent hepatitis by the liver biopsy. 3. Mottling change (209 cases) was always accompanied by fuzzy margin except only one case, and 31 cases (86.1%) of fuzzy and mottling cases (36 cases) showed mild parenchymal liver disease. 4. Configuration change (193 cases) was usually accompanied with other changes and espicially 104 cases had configuration change with fuzzy and mottling changes. 73 cases (88.44%) of 86 cases with severe configuration change revealed advanced parenchymal liver disease on biopsy. If liver scan showed mild configuration change, we could not decide the type of liver disease only liver scan, and so further studies are needed. 5. Splenic uptake was noted in 34 cases (40.48%) of 84 cases with advanced parenchymal liver disease, and the degree of splenic uptake was for the most part morderate or severe; whereas splenic uptake was noted in 18 cases (16.51%) of the mild parenchymal liver disease (109 cases), and the degree of splenic uptake was largely mild.

• Korean Journal of Exercise Nutrition
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• v.23 no.1
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• pp.21-27
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• 2019

[Purpose] In the present pilot study, we aimed to investigate the effects of the Silverrobics exercise program, which is similar to aerobic dance, on the factors related to glucose metabolism and liver enzymes. [Methods] Eight elderly women with obesity and impaired fasting glucose participated in the Silverrobics exercise program (60 minutes per session for five times a week for 8 weeks). The program was conducted at 50-60% of the heart rate reserve at 1 to 2 weeks and at 60-80% of the heart rate reserve at 3 to 8 weeks. To verify the effect of this 8-week exercise program on glucose metabolism and liver enzymes, blood analysis at pre- and post-training was performed. [Results] After the Silverrobics exercise program, there were significant decreases in the glucose (p<0.05), glycated hemoglobin A1c (p<0.05), 1,5-anhydroglucitol (p<0.05), and insulin levels (p<0.01) and homeostatic model assessment of insulin resistance score (p<0.05). However, there were no significant effects on the liver enzymes, except for alkaline phosphatase. The alkaline phosphatase level increased after the Silverrobics exercise program (p<0.05). [Conclusion] Although the Silverrobics exercise program had no beneficial effects on the liver enzymes, it may play an important role in preventing liver diseases considering the effects on glucose metabolism.

• The Korean Journal of Nuclear Medicine
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• v.5 no.2
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• pp.7-18
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• 1971

The liver function test was performed by means of two radioisotope tracer techniques in 20 normal subjects and in 63 patients with hepatobiliary diseases. The blood disappearance rates of $^{131}I$-rose bengal and of $^{198}Au$ colloid were determined by external counting method. The hepatocellular function and the hepatic blood flow were estimated from the observed data and the results were compared with those of the conventional liver function tests. The results obtained were as follows: 1. The mean blood disappearance half time of $^{131}I$-rose bengal was $6.6{\pm}0.63$ minutes in normal control, $17.7{\pm}6.93$ in cirrhosis of the liver, $16.6{\pm}4.80$ in acute hepatitis, and $14.7{\pm}3.46$ in obstructive jaundice. It was markedly prolonged in the hepatobiliary diseases as compared with the normal control, but there was no significant difference among the hepatobiliary diseases. 2. The mean blood disappearance half time of $^{198}Au$ colloid was $4.0{\pm}0.66$ minutes in normal control, $9.8{\pm}3.42$ in cirrhosis of the liver, $4.4{\pm}0.82$ in acute hepatitis, and $5.0{\pm}1.42$ in obstructive jaundice. The difference between cirrhosis of the liver and normal control Was statistically significant. However, there was no definite difference among acute hepatitis, obstructive jaundice, and normal control. The mean blood disappearance rate constant (K value) was $0.177{\pm}0.028/minute$ in normal control. In cirrhosis of the liver, it was markedly decreased which was suggestive of the reduced hepatic blood flow. 3. The ratio of $^{131}I$-rose bengal blood disappearance half time to $^{198}Au$ colloid disappearance half time was $1.68{\pm}0.20$ in normal control, $1.82{\pm}0.31$ in cirrhosis of the liver, $3.80{\pm}0.82$ in acute hepatitis, and $3.01{\pm}0.54$ in obstructive jaundice. The ratios in acute hepatitis and obstructive jaundice were remarkably higher than those in normal control and cirrhosis of the liver. 4. There was a significant correlation between the blood disappearance half time of $^{131}I$-rose bengal and that of $^{198}Au$ colloid in cirrhosis of the liver. 5. In cirrhosis of the liver, the blood disappearance half times of $^{131}I$-rose bengal and of $^{198}Au$ colloid were inversely correlated to the serum albumin level. In acute hepatitis, there was a good positive correlation between the blood disappearance half time of $^{131}I$-rose bengal and the serum transaminase activities. In obstructive jaundice, the blood disappearance half time of $^{131}I$-rose bengal was correlated to the serum bilirubin level.

• Herbal Formula Science
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• v.24 no.4
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• pp.311-321
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• 2016

Chronic or acute alcohol abuse often leads to liver injury associated with alcoholic hepatitis, liver fibrosis, cirrhosis, and liver cancer. In addition to the liver, alcohol abuse also induces a variety of other tissue injuries including pancreatitis, cardiomyopathy, neurotoxicity and muscle loss. Chronic skeletal muscle myopathy, independent of peripheral neuropathy, is well recognised in alcoholic patients. Several mechanisms may be involved in the pathogenesis of alcoholic myopathy. Ethanol is a potent inhibitor of muscle protein synthesis. Gastrocnemius and plantaris muscles are Type II fiber-predominant and usually considered representative of the musculature as a whole. Whereas, soleus muscle is Type I fiber predominant. Shihosogan-san is a traditional Korean medicine that is widely employed to treat indigestion and liver diseases. Muscle diseases are often related to liver diseases and conditions. We therefore tested the hypothesis that treatment with Shihosogan-san could ameliorate the ethanol-induced changes in muscle protein synthesis. Young male Sprague-Dawley rats were orally given 25% ethanol (5ml/kg, body weight) daily with Ethanol for 28 days. Normal group was similarly administrated with saline. In Shihosogan-san treated group, rats were orally administrated Shihosogan-san extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. For comparative purposes, liver function was also investigated. The muscles from rats of EtOH group displayed a significant reduction in average cross section area compared to Normal group. Shihosogan-san treated group had increased fiber compared to the EtOH group. Moreover, Shihosogan-san treated group compared with EtOH group showed significantly decreased pro-apoptotic BAX expression and increased anti-apoptotic Bcl-2 expression. In conclusion, Shihosogan-san extract showed ameliorating effects on chronic alcohol toxicity in skeletal muscle.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.534-542
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• 2023

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

• International Journal of Stem Cells
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• v.16 no.1
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• pp.1-15
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• 2023

Liver organoids have gained much attention in recent years for their potential applications to liver disease modeling and pharmacologic drug screening. Liver organoids produced in vitro reflect some aspects of the in vivo physiological and pathological conditions of the liver. However, the generation of liver organoids with perfusable luminal vasculature remains a major challenge, hindering precise and effective modeling of liver diseases. Furthermore, vascularization is required for large organoids or assembloids to closely mimic the complexity of tissue architecture without cell death in the core region. A few studies have successfully generated liver organoids with endothelial cell networks, but most of these vascular networks produced luminal structures after being transplanted into tissues of host animals. Therefore, formation of luminal vasculature is an unmet need to overcome the limitation of liver organoids as an in vitro model investigating different acute and chronic liver diseases. Here, we provide an overview of the unique features of hepatic vasculature under pathophysiological conditions and summarize the biochemical and biophysical cues that drive vasculogenesis and angiogenesis in vitro. We also highlight recent progress in generating vascularized liver organoids in vitro and discuss potential strategies that may enable the generation of perfusable luminal vasculature in liver organoids.