Differences in Cognitive Function between Patie nts with Viral and Alcoholic Compensated Liver Cirrhosis

( Meegun Hong ),( Ki Tae Suk ),( Yunhyeong Lee ),( Chulho Kim ),( Hui Chul Choi ),( Chang Seok Bang ),( Jai Hoon Yoon ),( Gwang Ho Baik ),( Dong Joon Kim ),( Min Uk Jang ),( Jong Hee Sohn ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. Methods: From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n=1,000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. Results: In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1±3.6 and 17.8±4.8, p=0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0±2.6 and 17.3±4.0, p=0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1±6.9 and 12.7±6.9, p=0.004), and the Korea-Mini Mental Status Examination (27.5±1.9 and 26.2±3.1, p=0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p=0.033). Conclusions: Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.

Anti-Fibrosis Effect of Urushiol (Rhus Verniciflua Stokes) in Mice with Thioaceamide Induced Liver Fibrosis

( Meegun Hong ),( Heesun Hong ),( Sangyeol Kim ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Liver fibrosis leads to cirrhosis, organ failure, and even cancer. However, there is no effective medicinal treatment for liver fibrosis. Urushiol (Rhus verniciflua Stokes) has inhibitive effects against the growths of ovarian cancer, mouse leukemia, and human adenocarcinoma. We investigated the effect of urushiol on liver fibrosis induced by thioacetamide (TAA). Methods: Thirty C57BL/6 mice were equally divided into 3 treatment groups for 6 weeks i.e., TAA (intra-peritoneal injection of saline (3 times/week) intra-peritoneal injection of TAA (300 mg/kg/day, 3 times/week), and TAA + urushiol (TAA groups with intra-gastric urushiol (0.128 mg/mL/day, 28 times). Urushiol captains 6 compounds, of which C₂₁H₃₀O₂ and C₂₁H₃₄O₂ are the 2 major compounds. Results: The TAA + Urushiol group decreased the deposition of fibrillary collagen (Sirius Red (%) 1.63 ± 0.76 vs. 3.04 ± 1.39 TAA, p < 0.01) as well as the mRNA expression collagen I (0.36-fold change vs. TAA, p < 0.05). The analysis of mRNA expression demonstrated that Socs2, JAK pathway signal transduction adaptor activity gene (0.15-fold change vs. TAA, p < 0.001) and cyp2b9, oxidation-reduction process gene (0.38-fold change vs. TAA, p < 0.001), downregulated significantly. On microarray analysis shows downregulation of Serpina4-ps1 (6.40-fold change vs. TAA, p < 0.001), Chka, lipid metabolic process gene (2.21-fold change vs. TAA, p < 0.001), Onecut1, negative regulation of transforming growth factor beta receptor signaling gene (3.00-fold change vs. TAA, p < 0.001), however, Orm2, regulation of immune system process gene (2.28-fold change vs. TAA, p < 0.001), Kcnk5, potassium channel activity gene (2.4-fold change vs. TAA, p < 0.001) upregulated, significantly. Conclusions: Urushiol is effective in the treatment of TAA-induced hepatic fibrosis in mice. (NRF- 2016R1C1B2011223 and NRF-2015R1C1A1A01053232)

Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with nonalcoholic fatty liver disease

Hong, Meegun,Lee, Yoon Hyeong,Kim, Seungwoo,Suk, Ki Tae,Bang, Chang Seok,Yoon, Jai Hoon,Baik, Gwang Ho,Kim, Dong Joon,Kim, Myong Jo The Korean Society of Ginseng 2016 Journal of Ginseng Research Vol.40 No.3

Background: Korean Red Ginseng (KRG) is a well-known natural product with anticarcinogenic and antioxidant effects. We evaluated the antifatigue effect of KRG in patients with nonalcoholic fatty liver disease (NAFLD). Methods: Eighty patients with NAFLD were prospectively randomized to receive 3 wk of KRG or placebo in addition to counseling on healthy eating and regular exercise. Liver function test, proinflammatory cytokines, adiponectin, antioxidant activity, and fatigue score were measured and compared according to the body mass index between the KRG and placebo groups. Results: The liver function tests were significantly improved after 3 wk of treatment in both groups. The mean levels (at baseline and after treatment) of tumor necrosis factor-${\alpha}$ were $108.0pg/mL{\pm}54.8pg/mL$ and $92.7pg/mL{\pm}39.0pg/mL$ (p = 0.018) in the KRG group and $123.1pg/mL{\pm}42.1pg/mL$ and $127.5pg/mL{\pm}62.2pg/mL$ (p = 0.694) in the placebo group, respectively. There was a significant difference in change of adiponectin levels between the KRG ($7,751.2pg/mL{\pm}3,108.1pg/mL$ and $8,197.3pg/mL{\pm}2,714.5pg/mL$) and placebo groups ($7,711.6pg/mL{\pm}3,041.3pg/mL$ and $7,286.1pg/mL{\pm}5,188.7pg/mL$, p = 0.027). In patients with overweight, the fatigue score was significantly decreased in the KRG group ($35.0{\pm}13.2$ and $24.5{\pm}8.9$, p = 0.019). Conclusion: Our results show that KRG might be effective in reducing proinflammatory cytokine and fatigue in overweight patients with NAFLD, in addition to improvements in adiponectin levels.

Profiling of Secretory Proteins from Human Bone Marrow- Derived Mesenchymal Stem Cells in Liver Repair by cDNA Microarray

( Heesun Hong ),( Sang Yeol Kim ),( Meegun Hong ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Background & Aim: Cirrhosis is the end stage of chronic liver disease, which may lead to severe hepatic dysfunction and even life-threatening conditions. The beneficial impact of mesenchymal stem cells (MSCs) transplantation on liver diseases has been confirmed on several studies which have shown the ability of MSCs to reduce liver fibrosis and improve liver function, although the secreted gene and/or proteins and molecular mechanisms behind it remain elusive. We aimed to identify secreted factors by undifferentiated bone marrow-derived mesenchymal stem cells (BM-MSCs) in order to describe related pathways potentially targeted gene by MSC in liver cirrhosis. Methods: Human bone marrow-derived mesenchymal stem cells (BM-MSCs) from normal and BM-MSCs transplanted patients who had liver cirrhosis and cultured specific medium condition for mesenchymal stem cells. We evaluated the differentiation potential to osteoblast and adipocytes, and morphological changes, cell proliferation and immunophenotyping assay were tested with trypan blue exclusion assay and CD34, CD45, CD45 and CD105. At passage 4-5 of BM-MSCs were used for cDNA microarrays to identify secreted genes and related pathway that differentially expressed in specific stem cell population in liver cirrhosis and identified by biomathmatical analysis. Results: BM MSCs secreted different factors normal and patients with liver cirrhosis. We found 2968 genomes of 15 maps in KEGG pathway, include Metabolic pathways, TGF-beta signaling pathway, Wnt signaling pathway, Cytokine-cytokine receptor interaction, HIF-1 signaling pathway, Ras signaling pathway, Natural killer cell mediated cytotoxicity and Antigen processing and presentation. Within these pathways, functionally up-regulated genes were 7 genes and down-regulated genes were 9 genes. In particular, we were able to identify potential specific genes for regulation of liver fibrosis (FBN2, P4HA1 and STC1), and KIR3DL2, which is gene for regulation of immune system process. Conclusion: Application of MSCs might target a widespread pattern of biological, cellular compositional and molecular functional event in the liver. MSC secreted genes and proteins can be differ depending on pathways and molecular mechanisms. Genes involved liver fibrosis are able to release hepatotropic factors from transplanted MSCs, also potentially supporting liver regenerations.

Effects of Probiotics (Lactobacillus Rhamnosus R0011 and Lactobacillus Acidophilus R0052) in the Treatment of Mild Alcoholic Liver Disease

( Heesun Hong ),( Meegun Hong ),( Sang Yeol Kim ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Backgroud and Aim: Alcohol cause abnormal bowel overgrowth of gram-negative bacteria and disruption the gut barrier, consequently, promotes the translocation of lipopolysaccharide(LPS). Probiotics might restore bowel flora by reducing gut-derived microbial lipopolysaccharide( LPS) in patients with alcoholic hepatitis (AH). We evaluated the therapeutic effects of probiotics in patients with mild AH. Methods: Between September 2013 and September 2015, 101 patients (probiotics: 53 and placebo: 48) and normal control patients were prospectively randomized to receive the 7 days of Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052 (120mg/day) or placebo. All patients, except normal control patients were hospitalized and were not permitted to consume alcohol. Liver function and LPS level were evaluated by enzyme-linked immunosorbent assay (ELISA), and to determine the relative importance of gut bacterial changes for patients with alcoholic liver disease were screening using PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with 16S rRNA detection was performed, analyzed and compared for the evaluation of microbial species between before and after probiotics treatment for 7 days. Results: In both groups, liver function were significantly improved after 7 days of abstinence and dominant types of bacteria were gram negative at baseline. In patients with cirrhosis with probiotics treatment (baseline and after), the mean level of alanine aminotransferase (64+117 and 27+24, p=0.049), Child-Pugh score (79+2.5 and 7.2+2.1, p<0.001), and LPS (p<0.001) significantly improved compared with control group. In the probiotics treatment group, quantitative and qualitative changes in the density of gram-negative bacteria, E-coli and Enterobacteria were decreased after 7 days. At the phylum level, proportion of the gut microbiota between before and after 7-day treatment with probiotics shown that firmicutes (45.66→66.81) and actinobacteria (0.06→0.08) were increased, however bacteroidetes (37.64→22.15), proteobacteria (24.36→9.76) and fusobacterial (4.76→2.31) were decreased, respectively. Conclusions: Seven-day of supplementation with Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052 was associated with restoration of bowel flora and probiotics might be effective in the treatment of alcoholic hepatitis by regulation gut-liver axis. And, indicating that a short-term administration of probiotics can change the gut microbiota, leading to the amelioration of liver injury induced by chronic alcohol consumption.

Effect of Korean Red Ginseng in chronic liver disease

Park, Tae Young,Hong, Meegun,Sung, Hotaik,Kim, Sangyeol,Suk, Ki Tae The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4

Chronic liver disease, one of the most common diseases, typically arises from nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, or hepatocellular carcinoma. Therefore, there is a pressing need for improved treatment strategies. Korean Red Ginseng has been known to have positive effects on liver disease and liver function. In this paper, we summarize the current knowledge on the beneficial effects of Korean Red Ginseng on chronic liver disease, a condition encompassing nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, and hepatocellular carcinoma, as supported by experimental evaluation and clinical investigation.

Effect of Korean Red Ginseng in chronic liver disease

Tae Young Park,Meegun Hong,Hotaik Sung,Sangyeol Kim,Ki Tae Suk 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4

Chronic liver disease, one of the most common diseases, typically arises from nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, or hepatocellular carcinoma. Therefore, there is a pressing need for improved treatment strategies. Korean Red Ginseng has been known to have positive effects on liver disease and liver function. In this paper, we summarize the current knowledge on the beneficial effects of Korean Red Ginseng on chronic liver disease, a condition encompassing nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, and hepatocellular carcinoma, as supported by experimental evaluation and clinical investigation.