Clinical and Molecular Hepatology

"Baek Gyu Jun"

Review

Impact of diabetes, obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases: Hwang Sik Shin, Baek Gyu Jun, Sang-Wook Yi; Clin Mol Hepatol 2022;28(4):773-789.
Published online August 8, 2022; DOI: https://doi.org/10.3350/cmh.2021.0383

Abstract
PDF

Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.

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Original Articles

Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study: Ji Hyun Kim, Baek Gyu Jun, Minjong Lee, Hye Ah Lee, Tae Suk Kim, Jeong Won Heo, Da Hye Moon, Seong Hee Kang, Ki Tae Suk, Moon Young Kim, Young Don Kim, Gab Jin Cheon, Soon Koo Baik, Dong Joon Kim, Dae Hee Choi; Clin Mol Hepatol 2022;28(3):540-552.
Published online May 6, 2022; DOI: https://doi.org/10.3350/cmh.2021.0169

Background/Aims
Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections.
Methods
A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated.
Results
The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, P<0.001) and qSOFA (AUROC, 0.67; 95% CI, 0.64–0.70; P<0.001) score. The CLIF-SOFA, CLIF-C-AD scores, Sepsis-3 criteria, septic shock, and qSOFA positivity were significantly associated with in-hospital mortality (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.19–1.28; aHR, 1.13; 95% CI, 1.09–1.17; aHR, 1.19; 95% CI, 1.15–1.24; aHR, 1.88; 95% CI, 1.42–2.48; aHR, 2.06; 95% CI, 1.55–2.72; respectively; all P<0.001). For CLIF-SOFA scores ≥6, in-hospital mortality was >10%; this is the cutoff point for the definition of sepsis.
Conclusions
Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.

Citations

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Do Seon Song, Hee Yeon Kim, Young Kul Jung, Tae Hyung Kim, Hyung Joon Yim, Eileen L Yoon, Ki Tae Suk, Jeong-ju Yoo, Sang Gyune Kim, Moon Young Kim, Young Chang, Soung Won Jeong, Jae Young Jang, Sung-Eun Kim, Jung-Hee Kim, Jung Gil Park, Won Kim, Jin Mo Ya
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Liver fibrosis, cirrhosis, and portal hypertension

Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis: Yoon Ok Jang, Baek Gyu Jun, Soon Koo Baik, Moon Young Kim, Sang Ok Kwon; Clin Mol Hepatol 2015;21(2):141-149.
Published online June 26, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.2.141

Abstract
PDF

Background/Aims

Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.

Methods

We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.

Results

The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.

Conclusions

These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

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Antifibrotic Effects of Kangxian Ruangan Capsule on Rats with Nonalcoholic Fatty Liver Fibrosis and Hepatic Stellate Cells through Regulation of TGF-β and TLR4 Signaling Pathways
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Evidence-Based Complementary and Alternative Medicine.2021; 2021: 1. CrossRef
Mesenchymal stem cells attenuate liver fibrosis by targeting Ly6Chi/lo macrophages through activating the cytokine-paracrine and apoptotic pathways
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Ultrasound-targeted microbubble destruction optimized HGF-overexpressing bone marrow stem cells to repair fibrotic liver in rats
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Mesenchymal stem cells suppress hepatic fibrosis accompanied by expanded intrahepatic natural killer cells in rat fibrosis model
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Molecular Biology Reports.2019; 46(3): 2997. CrossRef
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Current Transplantation Reports.2019; 6(2): 119. CrossRef
Response-Related Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis
Haripriya Gupta, Gi Soo Youn, Sang Hak Han, Min Jea Shin, Sang Jun Yoon, Dae Hee Han, Na Young Lee, Dong Joon Kim, Soon Koo Baik, Ki Tae Suk
Journal of Clinical Medicine.2019; 8(6): 862. CrossRef
Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?
Irina V. Kholodenko, Leonid K. Kurbatov, Roman V. Kholodenko, Garik V. Manukyan, Konstantin N. Yarygin
Cells.2019; 8(10): 1127. CrossRef
Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases
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Mechanisms Underlying Cell Therapy in Liver Fibrosis: An Overview
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Cells.2019; 8(11): 1339. CrossRef
Possible Mechanisms and Prospects of Stem Cell Therapy for Keloids
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J Qiao
Archives of Hepatitis Research.2019; 5(1): 022. CrossRef
Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon
Seong Hee Kang, Moon Young Kim, Soon Koo Baik
Hepatology International.2018; 12(S1): 112. CrossRef
Mammalian MSC from selected species: Features and applications
Christiane Uder, Sandra Brückner, Sandra Winkler, Hans‐Michael Tautenhahn, Bruno Christ
Cytometry Part A.2018; 93(1): 32. CrossRef
Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis
Yoon Ok Jang, Sung Hoon Kim, Mee-Yon Cho, Kyung Sik Kim, Kyu-Sang Park, Seung-Kuy Cha, Moon Young Kim, Sei Jin Chang, Soon Koo Baik
Biochemical and Biophysical Research Communications.2018; 497(1): 264. CrossRef
Nonintegrating Direct Conversion Using mRNA into Hepatocyte-Like Cells
Sangtae Yoon, Kyojin Kang, Young-duck Cho, Yohan Kim, Elina Maria Buisson, Ji-Hye Yim, Seung Bum Lee, Ki-Young Ryu, Jaemin Jeong, Dongho Choi
BioMed Research International.2018; 2018: 1. CrossRef
Measuring Intrahepatic Vascular Changes Using Contrast-Enhanced Ultrasonography to Predict the Prognosis of Alcoholic Hepatitis Combined with Cirrhosis: A Prospective Pilot Study
Min Sun Park, Soonchang Hong, Yoo Li Lim, Seong Hee Kang, Soon Koo Baik, Moon Young Kim
Gut and Liver.2018; 12(5): 555. CrossRef
Antifibrotic potential of bone marrow‑derived mesenchymal stem cells in biliary atresia mice
Jun Lei, Yong Chai, Juhua Xiao, Huakun Hu, Zhiqiang Liu, Yu Xiao, Lijun Yi, Jinshi Huang, Tianxin Xiang, Shouhua Zhang
Molecular Medicine Reports.2018;[Epub] CrossRef
Platelet-Rich Plasma and Bone Marrow-Derived Mesenchymal Stromal Cells Prevent TGF-β1-Induced Myofibroblast Generation but Are Not Synergistic when Combined: Morphological in vitro Analysis
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Cells Tissues Organs.2018; 206(6): 283. CrossRef
Relative Adrenal Insufficiency in Patients with Cirrhosis: A Systematic Review and Meta-Analysis
Gaeun Kim, Ji Hye Huh, Kyong Joo Lee, Moon Young Kim, Kwang Yong Shim, Soon Koo Baik
Digestive Diseases and Sciences.2017; 62(4): 1067. CrossRef
Diagnostic Accuracy of Hepatic Vein Arrival Time Performed with Contrast-Enhanced Ultrasonography for Cirrhosis: A Systematic Review and Meta-Analysis
Gaeun Kim, Kwang Yong Shim, Soon Koo Baik
Gut and Liver.2017; 11(1): 93. CrossRef
Anti-fibrotic potential of human umbilical cord mononuclear cells and mouse bone marrow cells in CCl4- induced liver fibrosis in mice
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Biomedicine & Pharmacotherapy.2017; 89: 1378. CrossRef
Transient elastography versus hepatic venous pressure gradient for diagnosing portal hypertension: a systematic review and meta-analysis
Gaeun Kim, Moon Young Kim, Soon Koo Baik
Clinical and Molecular Hepatology.2017; 23(1): 34. CrossRef
Long-Term Follow-Up of Patients after Autologous Bone Marrow Cell Infusion for Decompensated Liver Cirrhosis
Ja Kyung Kim, Soo-Jeong Kim, Yuri Kim, Yong Eun Chung, Young Nyun Park, Hyun Ok Kim, Jin Seok Kim, Mi-Suk Park, Isao Sakaida, Do Young Kim, Jung Il Lee, Sang Hoon Ahn, Kwan Sik Lee, Kwang-Hyub Han
Cell Transplantation.2017; 26(6): 1059. CrossRef
Improvement of portal venous pressure in cirrhotic rat livers by systemic treatment with adipose tissue–derived mesenchymal stromal cells
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Cytotherapy.2017; 19(12): 1462. CrossRef
Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress
Veruska Cintia Alexandrino de Souza, Thiago Almeida Pereira, Valéria Wanderley Teixeira, Helotonio Carvalho, Maria Carolina Accioly Brelaz de Castro, Carolline Guimarães D’assunção, Andréia Ferreira de Barros, Camila Lima Carvalho, Virgínia Maria Barros d
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Current Understanding of Stem Cell and Secretome Therapies in Liver Diseases
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Tissue Engineering and Regenerative Medicine.2017; 14(6): 653. CrossRef
1-Methyl-L-tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS
Ji Eun Oh, Kwang Yong Shim, Jong In Lee, Soo In Choi, Soon Koo Baik, Young Woo Eom
International Journal of Molecular Medicine.2017; 40(2): 576. CrossRef
3D Spheroid Culture Enhances the Expression of Antifibrotic Factors in Human Adipose‐Derived MSCs and Improves Their Therapeutic Effects on Hepatic Fibrosis
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Stem Cells International.2016;[Epub] CrossRef
Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells
Yi Feng, Hai-yan Ying, Ying Qu, Xiao-bo Cai, Ming-yi Xu, Lun-gen Lu
Protein & Cell.2016; 7(9): 662. CrossRef
Transplantation with autologous bone marrow‐derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial
Ki Tae Suk, Jung‐Hwan Yoon, Moon Young Kim, Chang Wook Kim, Ja Kyung Kim, Hana Park, Seong Gyu Hwang, Dong Joon Kim, Byung Seok Lee, Sae Hwan Lee, Hong Soo Kim, Jae Young Jang, Chang‐Hyeong Lee, Byung Seok Kim, Yoon Ok Jang, Mee Yon Cho, Eun Sun Jung, Yon
Hepatology.2016; 64(6): 2185. CrossRef
Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis
Yoon Ok Jang, Mee-Yon Cho, Chae-Ok Yun, Soon Koo Baik, Kyu-Sang Park, Seung-Kuy Cha, Sei Jin Chang, Moon Young Kim, Yoo Li Lim, Sang Ok Kwon
Stem Cells Translational Medicine.2016; 5(9): 1247. CrossRef
MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells
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Scientific Reports.2015;[Epub] CrossRef