초음파상 지방간 정도와 검사실 소견의 비교 : Correlation between the Sonographic Grades and Liver Function Tests

조영아,김현진,유정현,이정식 대한초음파의학회 1998 ULTRASONOGRAPHY Vol.17 No.4

Liver Tissue Engineering: Recent Advances in the Development of a Bio-artificial Liver

Jung Seung Lee,조승우 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.3

Orthotopic liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a donor shortage. Liver tissue engineering may offer a promising strategy to solve this problem by providing transplantable,bioartificial livers. Diverse types of cells, biomaterials, and growth factor delivery systems have been tested for efficient regeneration of liver tissues that possess hepatic functions comparable to native livers. This article reviews recent advances in liver tissue engineering and describes cell sources, biomaterial scaffolds, and growth factor delivery systems that are currently being used to improve the regenerative potential of tissue-engineered livers. Orthotopic liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a donor shortage. Liver tissue engineering may offer a promising strategy to solve this problem by providing transplantable,bioartificial livers. Diverse types of cells, biomaterials, and growth factor delivery systems have been tested for efficient regeneration of liver tissues that possess hepatic functions comparable to native livers. This article reviews recent advances in liver tissue engineering and describes cell sources, biomaterial scaffolds, and growth factor delivery systems that are currently being used to improve the regenerative potential of tissue-engineered livers.

Feasibility of Commercially Available, Fully Automated Hepatic CT Volumetry for Assessing Both Total and Territorial Liver Volumes in Liver Transplantation

신청일,김세형,임정효,이남준,서경석,이정민,한준구,최병인 대한영상의학회 2013 대한영상의학회지 Vol.68 No.2

Purpose: To assess the feasibility of commercially-available, fully automated hepatic CT volumetry for measuring both total and territorial liver volumes by comparing with interactive manual volumetry and measured ex-vivo liver volume. Materials and Methods: For the assessment of total and territorial liver volume, portal phase CT images of 77 recipients and 107 donors who donated right hemiliver were used. Liver volume was measured using both the fully automated and interactive manual methods with Advanced Liver Analysis® software. The quality of the automated segmentation was graded on a 4-point scale. Grading was performed by two radiologists in consensus. For the cases with excellent-to-good quality, the accuracy of automated volumetry was compared with interactive manual volumetry and measured ex-vivo liver volume which was converted from weight using analysis of variance test and Pearson’s or Spearman correlation test. Processing time for both automated and interactive manual methods was also compared. Results: Excellent-to-good quality of automated segmentation for total liver and right hemiliver was achieved in 57.1% (44/77) and 17.8% (19/107), respectively. For both total and right hemiliver volumes, there were no significant differences among automated, manual, and ex-vivo volumes except between automate volume and manual volume of the total liver (p = 0.011). There were good correlations between automate volume and ex-vivo liver volume (γ= 0.637 for total liver and γ= 0.767 for right hemiliver). Both correlation coefficients were higher than those with manual method. Fully automated volumetry required significantly less time than interactive manual method (total liver: 48.6 sec vs. 53.2 sec, right hemiliver: 182 sec vs. 244.5 sec). Conclusion: Fully automated hepatic CT volumetry is feasible and time-efficient for total liver volume measurement. However, its usefulness for territorial liver volumetry needs to be improved.

LT, Others : O-064 ; High prevalence of steatosis among liver donors who had no evidence of fatty liver on ultrasonography justifies pre-operative liver biopsy

( Joon Seong Ahn ),( Dong Hyun Sinn ),( Geum Youn Gwak ),( Jong Man Kim ),( Choon Hyuck Kwon ),( Jae Won Joh ),( Yong Han Paik ),( Moon Seok Choi ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: The degree of steatosis of donated liver is one of decisive factors that determine graft function in recipient and recovery of remnant liver in living donor. Hence, the assessment of hepatic steatosis is a critical element to judge donor compatibility. We evaluated the prevalence and predictors of steatosis among liver donors who had no evidence of fatty liver on screening ultrasonography (US-negative). Methods: Degree of hepatic steatosis was reviewed for 492 US-negative liver donors (age: 30.1 ± 9.9, male: 301 (61.2%)). Clinical and laboratory variables were analyzed to identify predictors for steatosis. Results: The prevalence of severe (≥ 60%), moderate (30 ~ 59%), mild (5 ~ 29%) and no steatosis (<5%) were 0.6% (3/ 492), 10.8% (53/492), 39.6% (195/492) and 49.0% (241/492), respectively. In multivariate analysis, BMI [kg/m2, OR (95% CI): 1.15, p = 0.021] and serum triglyceride level [mg/dl, OR (95% CI): 1.01, p = 0.004] were independent factors associated with steatosis ≥ 30%. The optimal cutoff for steatosis ≥ 30% by receiver operator curve analysis was 23 kg/m2 for BMI and 88 mg/dl for triglyceride. Steatosis ≥ 30% was significantly more prevalent for liver-donors with high BMI (15.2% vs. 9.0% for BMI ≥ 23 vs. < 23 kg/m2, p = 0.034) and with high serum triglyceride level (15.5% vs. 8.7% for triglyceride ≥ 88 vs. < 88 mg/dl, p = 0.021). Based on these two parameters, the prevalence of steatosis ≥ 30% was 6.6%, 13.0% and 28.6% for none, one and both risk factors, respectively. Conclusions: About a half of US-negative liver donors have steatosis ≥ mild degree and one-tenth of them has ≥ moderate degree. USG assessment is not sufficient to exclude donors with significant steatosis especially for those with high BMI and triglyceride level, and thus, pre-operative liver biopsy should be positively considered for them.

Liver Stem Cells

장주왕,Eric B. Richardson,박선후,이승범 한양대학교 의과대학 2014 Hanyang Medical Reviews Vol.34 No.4

Liver transplantation has been regarded as the definitive curative approach for pathologic liver conditions from the acute stage to the chronic end stage for decades. Recently, translational research has been focused on liver stem cell transplantation, using various cell therapies, due to the potential benefit of natural host liver regeneration. Many studies are ongoing utilizing and evaluating the use of either fetal-liver-derived stem cells or oval cells, however many obstacles still remain. Extensive research identifying and characterizimg stem/progenitor cells for potential application to in vitro cell therapy, whereas many questions remain concerning the isolation and identification of adult liver stem cells with adequate capacity for proliferation and the regeneration of injured liver. Recent approaches to liver regeneration include the production of hepatocyte-like cells from other stem cell sources such as mesenchymal stem cells and embryonic stems cells. Another major target for liver regeneration studies include the generation of liver stem cells from induced pluripotent stem cells (IPSC) We review the current data concerning characterization of stem cells and progenitor cells for their capacity to support their potential for re-population and regeneration of normal adult liver from liver damaged due to injury and/or disease.

Gd-BOPTA 조영증강 자기공명영상에서 간의 조영증강 양상: 경변성 간과 정상 간의 비교

신상수,정용연,강형근,임효순,윤웅,서정진,박진균,Sin, Sang-Su,Jeong, Yong-Yeon,Gang, Hyeong-Geun,Im, Hyo-Sun,Yun, Ung,Seo, Jeong-Jin,Park, Jin-Gyun 대한영상의학회 2004 대한영상의학회지 Vol.50 No.1

목적:Gd-BOPTA 조영증강 자기공명영상의 지연기 영상에서 간경변 환자군과 정상군 사이에 간실질의 조영증강 양상의 차이를 비교하고자 하였다. 대상과 방법:Gd-BOPTA 조영증강 자기공명영상을 시행한 60명(간경변 환자군 35명, 정상군 25명)을 대상으로 하였다.1.5T 자기공명영상 기기에서 위상배열 다중코일을 사용하여 조영전과 Gd-BOPTA를 일시에 정맥 주입하고 60분 후에 in-phase와 opposed-phase T1강조 경사에코 영상을 각각 얻었다. 모든 영상은 다음과 같이 분석하였다. 정량적 분석은 간실질의 신호잡음비 (signal to noise ratio,이하 SNR)와 조영증강값 (signal enhancement,이하 SE)을 구하여, 간경변 환자군과 정상군 사이에 차이를 비교하였다. 간경변 환자군에서는 Child-Pugh분류에 따른 SNR과 SE의 차이를 비교하였다. 정성적 분석은 간의 조영증강 양상을 두 명의 방사선과의사가 합의하에 균질성과 비균질성으로 분류하였다. 결과:간실질의 SNR은 간경변 환자군 (p<0.001)과 정상군 (p<0.001)모두가 지연기 영상에서 조영전과 비교하여 유의하게 증가하였고,Gd-BOPTA 조영증강 in-phase(p<0.001)와opposed-phase(p<0.001)T1강조 경사에코 영상에서 간경변 환자군이 정상군에 비해 유의하게 낮았다. 경변성 간의 SE는 정상 간에 비해 유의하게 낮았다 (in-phase:p=0.002,opposed-phase:p=0.011). 경변성 간에서 간실질의 SNR은 Child-Pugh A군(p<0.001)과 B군(p<0.001)모두가 지연기 영상에서 유의하게 증가하였고, Gd-BOPTA 조영증강 in-phase(p<0.001)와 opposed-phase(p=0.022)T1강조 경사에코 영상에서 Child-Pugh A군이 B군에 비해 유의하게 높았다.SE는 in-phase T1강조 경사에코 영상에서 Child-Pugh A군이 B군에 비해 유의하게 높았다 (p=0.004).간경변 환자군에서는 35명중 20명(57%)에서 비균질성의 조영증강 양상을 보였지만,정상군에서는 모든 예에서 균질성의 조영증강 양상을 보였다. 결론:Gd-BOPTA 조영증강 자기공명영상의 지연기 영상에서 경변성 간은 정상 간에 비해 조영증강의 정도가 낮았으며,간경변 환자에서 간기능이 떨어질수록 조영증강의 정도가 낮았다. 따라서 Gd-BOPTA 조영증강 자기공명영상의 지연기 영상은 간기능의 보존정도를 평가하는데 도움을 줄 수 있을 것으로 생각된다. Purpose: To compare the enhancement features of hepatic parenchyma between cirrhotic and normal liver, using Gd-BOPTA-enhanced delayed MR imaging. Materials and Methods: The 60 patients (35 with cirrhotic and 25 with normal liver) included in our study underwent Gd-BOPTA-enhanced MR imaging using a 1.5T system with a phase-array multicoil. In all cases, T1-weighted in-phase and opposed-phase gradient-echo MR imaging was performed before and 60 minutes after intravenous administration of a bolus of Gd-BOPTA. All images were quantitatively analysed by comparing the signal-to-noise ratio (SNR) and signal enhancement (SE) of cirrhotic and normal liver before and after contrast enhancement, and in cirrhotic patients, SNR and SE were also compared in terms of the Child-Pugh classification. For qualitative analysis, the hepatic enhancement patterns of cirrhotic and normal liver were classified as homogeneous or heterogeneous according to the consensual findings of two radiologists. Results: At contrast-enhanced imaging, both cirrhotic (p<0.001) and normal liver (p<0.001) showed substantially increased SNR relative to unenhanced images, and the SNR of cirrhotic liver was significantly lower than that of normal livers at both in-phase (p<0.001) and opposed-phase (p<0.001) imaging. The SE of cirrhotic liver was significantly lower than that of normal liver (in-phase: p=0.002; opposed phase: p=0.011). Both Child-Pugh class A (p<0.001) and B (p<0.001) cirrhotic liver showed a substantial increase in SNR at contrast-enhanced imaging relative to unenhanced imaging and the SNR of Child-Pugh class A was significantly higher than that of Child-Pugh class B at both in-phase (p<0.001) and opposed-phase (p=0.022) imaging. In addition, the SE of class A was significantly higher than that of class B at in-phase imaging (p=0.004). Cirrhotic liver showed heterogeneous enhancement in 20 of 35 patients (57%), whereas normal liver showed homogeneous enhancement in all patients. Conclusion: At Gd-BOPTA-enhanced delayed MR imaging, cirrhotic liver showed less enhancement than normal liver. In cirrhotic patients, hepatic enhancement and hepatic function decreased in tandem. Gd-BOPTAenhanced delayed MR imaging may be useful for evaluating the functional reserve of the liver.

Thermoneutral Housing Exacerbates Liver Fibrosis In Mice

( Nga Thi Ha ),( Ho Yeop Lee ),( Hyon-seung Yi ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Thermoneutral condition has been had a significant impact on metabolic studies. The roles of brown adipose tissue (BAT) on metabolic disease including obesity or fatty liver is receiving increasing attention. Here, we investigated the impact of thermoneutral condition on hepatic fibrosis as well as the contribution of BAT on regulation liver fibrosis in mice. Methods: In this study, we used carbon tetrachloride (CCl4) induced liver fibrosis mouse model and hepatic stellate cells isolated from mice in order to checked fibrotic marker in mice livers housed under room temperature and thermoneutral condition for three weeks. We also compared the changes in the population of hepatic immune cells and the deposition of collagen in mice livers between two kinds of housing conditions. Furthermore, we investigated the effect of secreted factors from brown adipocytes-conditioned media on hepatic stellate cells (HSC) activation process. Results: Serum levels of liver injury and the expression of Col1a1, Acta2 and inflammatory cytokines were up-regulated in the liver of mice under thermoneutral condition compared to room temperature. Moreover, inactivation of BAT by thermoneutrality aggravated hepatic collagen deposition as well as promoted the activation of hepatic stellate cells during CCl4-induced liver fibrogenesis. In consistent with these findings, we also found that the population of infiltrating liver immune cells and pro-inflammatory cytokine-producing T cells was significantly increased in thermoneutral housing mice livers. Treatment of brown adipocytes-conditioned media attenuated HSC activation through down-regulated expression of a-SMA at day 4, day 7 and day 10 cultured HSC. Conclusions: These results suggest that BAT inactivation by thermoneutrality contributes to the activation of pro-inflammatory and pro-fibrotic pathways in CCl4-induced liver fibrogenesis. Secreted factors released from BAT have potential roles on inhibiting HSC activation. Thus, BAT-liver axis may serve as a potential therapeutic target for liver fibrosis.

LT, Other : O-064 ; High prevalence of steatosis among liver donors who had no evidence of fatty liver on ultrasonography justifies pre-operative liver biopsy

( Joon Seong Ahn ),( Dong Hyun Sinn ),( Geum Youn Gwak ),( Jong Man Kim ),( Choon Hyuck Kwon ),( Jae Won Joh ),( Yong Han Paik ),( Moon Seok Choi ),( Joon Hyeok Lee ),( Kwang Cheol Koh ),( Seung Woon 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: The degree of steatosis of donated liver is one of decisive factors that determine graft function in recipient and recovery of remnant liver in living donor. Hence, the assessment of hepatic steatosis is a critical element to judge donor compatibility. We evaluated the prevalence and predictors of steatosis among liver donors who had no evidence of fatty liver on screening ultrasonography (US-negative). Methods: Degree of hepatic steatosis was reviewed for 492 US-negative liver donors (age: 30.1 ± 9.9, male: 301 (61.2%)). Clinical and laboratory variables were analyzed to identify predictors for steatosis. Results: The prevalence of severe (≥ 60%), moderate (30 ∼ 59%), mild (5 ∼ 29%) and no steatosis (<5%) were 0.6% (3/492), 10.8% (53/492), 39.6% (195/492) and 49.0% (241/492), respectively. In multivariate analysis, BMI [kg/㎡, OR (95% CI): 1.15, p = 0.021] and serum triglyceride level [mg/dl, OR (95% CI): 1.01, p = 0.004] were independent factors associated with steatosis ≥ 30%. The optimal cutoff for steatosis ≥ 30% by receiver operator curve analysis was 23 kg/㎡ for BMI and 88 mg/dl for triglyceride. Steatosis ≥ 30% was significantly more prevalent for liver-donors with high BMI (15.2% vs. 9.0% for BMI ≥ 23 vs. < 23 kg/m2, p = 0.034) and with high serum triglyceride level (15.5% vs. 8.7% for triglyceride ≥ 88 vs. < 88 mg/dl, p = 0.021). Based on these two parameters, the prevalence of steatosis ≥ 30% was 6.6%, 13.0% and 28.6% for none, one and both risk factors, respectively. Conclusions: About a half of US-negative liver donors have steatosis ≥ mild degree and one-tenth of them has ≥ moderate degree. USG assessment is not sufficient to exclude donors with significant steatosis especially for those with high BMI and triglyceride level, and thus, pre-operative liver biopsy should be positively considered for them.

Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl4)–Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation

Ning Dai,Yuan Zou,Lei Zhu,Hui-Fang Wang,Mu-Gen Dai 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.6

Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead tooxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties,we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride(CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. Wepre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastricallyadministering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical–generating CYP2E1 enzyme.

Gut-Liver Axis in Liver Disease

유수종 ( Su Jong Yu ) 대한간학회 2021 간학회 싱글토픽 심포지움 Vol.2021 No.1

The gut-liver axis denotes the reciprocal interaction between the gut and gut microbiota, and the liver, resulting from the incorporation of signals generated by dietary, genetic and environmental factors. This bidirectional relationship is established by the portal vein which allows transport of gut-derived products directly to the liver, and the hepatic feedback route of bile and antibody secretion to the gut. The intestinal mucosal and vascular barrier is the anatomical and functional structure that serves as a field for the interactions between the gut and the liver, limiting the systemic dissemination of gut microbiota and toxins while permitting nutrients to access the circulation and to reach the liver. The control of commensal communities is crucial to maintaining homeostasis of the gut-liver axis, and as part of this reciprocal communication the liver shapes gut commensal communities. The gut-liver axis is widely participated in the pathogenesis of liver diseases, where it is increasingly the attention of clinical research. Alcohol disturbs the gut-liver axis at multiple interrelated levels, including the gut micro-biota, mucus barrier, epithelial barrier and at the level of antimicrobial peptide production, which increases microbial exposure and the hepatic proinflammatory environment. Growing evidence shows the pathogenetic role of microbe-derived metabolites, such as secondary bile acids (BAs), trimethylamine, ethanol, and short-chain fatty acids, in the pathogenesis of non-alcoholic fatty liver disease. Liver cirrhosis by itself is linked with profound alterations in gut microbiota and damage at the different levels of defense of the intestinal barrier, including the epithelial, immune, and vascular barriers. The relevance of the severe disturbance of the intestinal barrier in liver cirrhosis has been linked to live bacterial translocation, bacterial infections and disease progression. Recent research has revealed the carcinogenic effects of small molecules including lipopolysaccharide (LPS), BAs, and lipoteichoic acid (LTA) produced by the gut microbiome that downregulate the immune system in the liver. LPS can activate Toll-like receptor (TLR) 4 to contribute to the pathogenesis of liver cancer. Secondary BAs regulate liver cancer via natural killer T (NKT) cells. A study by Ma et al. showed that gut microbiome composition in mice closely associates with liver cancer by influencing the immune system. This group provided evidence showing that changing commensal gut bacteria in mice affected the accumulation of hepatic C-X-C chemokine receptor type 6 (CXCR6)⁺ NKT cells through mediation of chemokine (C-X-C motif) ligand 16 (CXCL16) expression in liver sinusoidal endothelial cells. CXCL16 is the only ligand for the chemokine receptor CXCR6, which mediates NKT cell survival and accumulation in the liver. The accumulation of CXCR6 in hepatic NKT cells enhances the production of interferon-,upon antigen stimulation, which contributes to the inhibition of tumor growth. The accumulation of NKT cells is known to be mainly regulated by a type of Clostridium species that metabolizes primary BAs to secondary BAs because depletion of Clostridium by vancomycin increases hepatic NKT cells and colonization of C. scindens induces a rapid decrease in liver NKT cells. This evidence highlighted the significant contribution of the gut microbiome to regulating anti-tumor immunity in liver and hepatic cancers. LTA, a major constituent of the cell wall of gram-positive bacteria, has also been shown to accumulate in the livers of high-fat diet (HFD)-fed mice in the presence of DMBA (7,12- dimethylbenz(a)anthracene, a chemical carcinogen) that can give rise to HCC. Both deoxycholic acid and LTA cooperatively induce the senescence-associated secretory phenotype (SASP) of hepatic stellate cells to produce various inflammatory and pro-tumorigenic factors, including interleukin-6, growth-regulated oncogene-alpha, CXCL9, and prostaglandin E2 (PGE2), leading to a tumorigenic microenvironment that promotes liver cancer development in mice. The identification of the factors of the gut-liver axis primarily injured in each chronic liver disease provides possibilities for intervention. Beyond antibiotics, upcoming therapies centered on the gut include new generations of probiotics, postbiotics (bacterial metabo-lites), fecal microbial transplantation, and carbon nanoparticles. Farnesoid X receptor-agonists target both the gut and the liver and are presently being tested in various liver diseases. Finally, phages, synthetic biotic medicines that target specific bacteria or treatments that create physical barriers between the gut and the liver offer new therapeutic strategies. Considering these approaches, the armamentarium for targeting the gut-liver axis will keep expanding. Further clinical trials, translated from our up-to-date knowledge of the gut-liver axis, promise a thrilling future in the treatment of liver diseases.