• Journal of Life Science
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• v.32 no.2
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• pp.94-100
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• 2022

Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

• Journal of Life Science
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• v.33 no.2
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• pp.183-190
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• 2023

Red yeast rice, also known as Hong Qu and red Koji, has been used for a long time in Asian functional food and traditional medicine. It consists of multiple bioactive substances, which can potentially be used as nutraceuticals. Alcoholic liver disease (ALD) can range from simple steatosis or inflammation to fibrosis and cirrhosis, possibly through leaky gut and systemic endotoxemia. This study examined the liver and gut effects of red yeast rice (RYR) (Monascus purpureus) ethanol extract against binge ethanol-induced liver injury in mice. RYR extract was orally administered to C57BL/6N mice at a concentration of 200 mg/kg body weight per day for 10 days. Then, mice were administered binge alcohol (5 g/kg/dose) three times at 12 hr intervals. Binge alcohol exposure significantly elevated the endotoxin, aspartate aminotransferase (AST), and alanine transaminase (ALT) activity of plasma, as well as hepatic triglyceride levels; however, RYR treatments reduced these levels. In addition, RYR pretreatment significantly reduced the alcohol-induced oxidative maker protein and apoptosis maker in binge alcohol-induced gut and liver injuries. These results suggest that RYR may prevent alcohol-induced acute leaky gut and liver damage.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.253-262
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• 2021

Objective: To determine whether the values of hepatic apparent diffusion coefficient (ADC) can differentiate biliary atresia (BA) from non-BA or be correlated with the grade of hepatic fibrosis in infants with cholestasis. Materials and Methods: This retrospective cohort study included infants who received liver MRI examinations to evaluate cholestasis from July 2009 to October 2017. Liver ADC, ADC ratio of liver/spleen, aspartate aminotransferase to platelet ratio index (APRI), and spleen size were compared between the BA and non-BA groups. The diagnostic performances of all parameters for significant fibrosis (F3-4) were obtained by receiver-operating characteristics (ROCs) curve analysis. Results: Altogether, 227 infants (98 males and 129 females, mean age = 57.2 ± 36.3 days) including 125 BA patients were analyzed. The absolute ADC difference between two reviewers was 0.10 mm²/s for both liver and spleen. Liver ADC value was specific (80.4%) and ADC ratio was sensitive (88.0%) for the diagnosis of BA with comparable performance. There were 33 patients with F0, 15 with F1, 71 with F2, 35 with F3, and 11 with F4. All four parameters of APRI (τ = 0.296), spleen size (τ = 0.312), liver ADC (τ = -0.206), and ADC ratio (τ = -0.288) showed significant correlation with fibrosis grade (all, p < 0.001). The cutoff values for significant fibrosis (F3-4) were 0.783 for APRI (area under the ROC curve [AUC], 0.721), 5.9 cm for spleen size (AUC, 0.719), 1.044 x 10^-3 mm²/s for liver ADC (AUC, 0.673), and 1.22 for ADC ratio (AUC, 0.651). Conclusion: Liver ADC values and ADC ratio of liver/spleen showed limited additional diagnostic performance for differentiating BA from non-BA and predicting significant hepatic fibrosis in infants with cholestasis.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.705-711
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• 2022

A 46-year-old male with alcoholic liver cirrhosis underwent a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites. On the 9th day after the procedure, he presented with melena and decreasing hemoglobin levels. Hemobilia due to fistula formation between the right intrahepatic bile duct and right hepatic artery was suspected on computed tomography. Angiography revealed a fistula of the small branches of the hepatic segmental arteries, and right intrahepatic bile duct was confirmed; embolization was successfully performed with a coil for the eighth segmental hepatic artery, a glue-lipiodol mixture for the fifth segmental hepatic artery, and gelfoam slurry for the right anterior hepatic artery. However, 2 days after embolization, the patient died owing to aggravated disseminated intravascular coagulopathy. When gastrointestinal bleeding occurs after TIPS, careful evaluation is immediately required, and hemobilia should be considered.

• Korean Journal of Radiology
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• v.23 no.12
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• pp.1269-1280
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• 2022

Objective: This study aimed to evaluate the usefulness of quantitative indices obtained from deep learning analysis of gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and their longitudinal changes in predicting decompensation and death in patients with advanced chronic liver disease (ACLD). Materials and Methods: We included patients who underwent baseline and 1-year follow-up MRI from a prospective cohort that underwent gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance between November 2011 and August 2012 at a tertiary medical center. Baseline liver condition was categorized as non-ACLD, compensated ACLD, and decompensated ACLD. The liver-to-spleen signal intensity ratio (LS-SIR) and liver-to-spleen volume ratio (LS-VR) were automatically measured on the HBP images using a deep learning algorithm, and their percentage changes at the 1-year follow-up (ΔLS-SIR and ΔLS-VR) were calculated. The associations of the MRI indices with hepatic decompensation and a composite endpoint of liver-related death or transplantation were evaluated using a competing risk analysis with multivariable Fine and Gray regression models, including baseline parameters alone and both baseline and follow-up parameters. Results: Our study included 280 patients (153 male; mean age ± standard deviation, 57 ± 7.95 years) with non-ACLD, compensated ACLD, and decompensated ACLD in 32, 186, and 62 patients, respectively. Patients were followed for 11-117 months (median, 104 months). In patients with compensated ACLD, baseline LS-SIR (sub-distribution hazard ratio [sHR], 0.81; p = 0.034) and LS-VR (sHR, 0.71; p = 0.01) were independently associated with hepatic decompensation. The ΔLS-VR (sHR, 0.54; p = 0.002) was predictive of hepatic decompensation after adjusting for baseline variables. ΔLS-VR was an independent predictor of liver-related death or transplantation in patients with compensated ACLD (sHR, 0.46; p = 0.026) and decompensated ACLD (sHR, 0.61; p = 0.023). Conclusion: MRI indices automatically derived from the deep learning analysis of gadoxetic acid-enhanced HBP MRI can be used as prognostic markers in patients with ACLD.

• Korean Journal of Radiology
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• v.21 no.8
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• pp.987-997
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• 2020

Objective: Measurement of the liver and spleen volumes has clinical implications. Although computed tomography (CT) volumetry is considered to be the most reliable noninvasive method for liver and spleen volume measurement, it has limited application in clinical practice due to its time-consuming segmentation process. We aimed to develop and validate a deep learning algorithm (DLA) for fully automated liver and spleen segmentation using portal venous phase CT images in various liver conditions. Materials and Methods: A DLA for liver and spleen segmentation was trained using a development dataset of portal venous CT images from 813 patients. Performance of the DLA was evaluated in two separate test datasets: dataset-1 which included 150 CT examinations in patients with various liver conditions (i.e., healthy liver, fatty liver, chronic liver disease, cirrhosis, and post-hepatectomy) and dataset-2 which included 50 pairs of CT examinations performed at ours and other institutions. The performance of the DLA was evaluated using the dice similarity score (DSS) for segmentation and Bland-Altman 95% limits of agreement (LOA) for measurement of the volumetric indices, which was compared with that of ground truth manual segmentation. Results: In test dataset-1, the DLA achieved a mean DSS of 0.973 and 0.974 for liver and spleen segmentation, respectively, with no significant difference in DSS across different liver conditions (p = 0.60 and 0.26 for the liver and spleen, respectively). For the measurement of volumetric indices, the Bland-Altman 95% LOA was -0.17 ± 3.07% for liver volume and -0.56 ± 3.78% for spleen volume. In test dataset-2, DLA performance using CT images obtained at outside institutions and our institution was comparable for liver (DSS, 0.982 vs. 0.983; p = 0.28) and spleen (DSS, 0.969 vs. 0.968; p = 0.41) segmentation. Conclusion: The DLA enabled highly accurate segmentation and volume measurement of the liver and spleen using portal venous phase CT images of patients with various liver conditions.

• Korean Journal of Radiology
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• v.21 no.12
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• pp.1317-1325
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• 2020

Objective: The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by two-dimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. Materials and Methods: We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0-F4) and necroinflammatory activity grade (A0-A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value. The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. Results: Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. Conclusion: The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

• Journal of the Korean Society of Radiology
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• v.84 no.3
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• pp.666-675
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• 2023

Purpose This study aimed to determine whether the attenuation coefficient (AC) from attenuation imaging (ATI) was correlated with visual US assessment in patients with hepatic steatosis. Moreover, it aimed to assess whether the patient's blood chemistry results and CT attenuation were correlated with AC. Materials and Methods Patients who underwent abdominal US with ATI between April 2018 and December 2018 were included in this study. Patients with chronic liver disease or cirrhosis were excluded. The correlation between AC and other parameters, such as visual US assessment, blood chemistry results, liver attenuation, and liver-to-spleen (L/S) ratio, were analyzed. AC values according to visual US assessment grades were compared using analysis of variance. Results A total of 161 patients were included in this study. The correlation coefficient between US assessment and AC was 0.814 (p < 0.001). The mean AC values for the normal, mild, moderate, and severe grades were 0.56, 0.66, 0.74, and 0.85, respectively (p < 0.001). Alanine aminotransferase levels were significantly correlated with AC (r = 0.317, p < 0.001). The correlation coefficients between liver attenuation and AC and between L/S ratio and AC were -0.702 and -0.626, respectively (p < 0.001). Conclusion Visual US assessment and AC showed a strong positive correlation with the discriminative value between the groups. Computed tomography attenuation and AC showed a strong negative correlation.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.4
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• pp.386-394
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• 2022

Splenic artery steal syndrome (SASS) is a cause of graft hypoperfusion leading to the development of biliary tract complications, graft failure, and in some cases to retransplantation. Its management is still controversial since there is no universal consensus about its prophylaxis and consequently treatment. We present a case of SASS that occurred 48 hours after orthotopic liver transplantation (OLTx) in a 56-year-old male patient with alcoholic cirrhosis and severe portal hypertension, and who was successfully treated by splenic artery embolization. A literature search was performed using the PubMed database, and a total of 22 studies including 4,789 patients who underwent OLTx were relevant to this review. A prophylactic treatment was performed in 260 cases (6.2%) through splenic artery ligation in 98 patients (37.7%) and splenic artery banding in 102 (39.2%). In the patients who did not receive prophylaxis, SASS occurred after OLTx in 266 (5.5%) and was mainly treated by splenic artery embolization (78.9%). Splenic artery ligation and splenectomies were performed, respectively, in 6 and 20 patients (2.3% and 7.5%). The higher rate of complications registered was represented by biliary tract complications (9.7% in patients who received prophylaxis and 11.6% in patients who developed SASS), portal vein thrombosis (respectively, 7.3% and 6.9%), splenectomy (4.8% and 20.9%), and death from sepsis (4.8% and 30.2%). Whenever possible, prevention is the best way to approach SASS, considering all the potential damage arising from an arterial graft hypoperfusion. Where clinical conditions do not permit prophylaxis, an accurate risk assessment and postoperative monitoring are mandatory.

• Clinical and Experimental Pediatrics
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• v.50 no.1
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• pp.28-32
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• 2007

Purpose : Human angiotensin converting enzyme (ACE) gene shows an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by whether a 287 bp fragment of the DNA is present or not; II, ID and DD genotype. DD genotype has been suggested as a risk factor of chronic nephrotic disease such as IgA nephropathy and diabetic nephropathy, various cardiovascular diseases and several other diseases. ACE activity increases in acute hepatitis, chronic persistent hepatitis, chronic active hepatitis and cirrhosis. On the other hand, patients with fatty livers have normal ACE activity. This study was designed to find out the relation between polymorphsims of the ACE genes and neonatal hyperbilirubinemia in Koreans. Methods : The genomic DNA was isolated from 110 full-term Korean neonates who had hyperbilirubinemia with no obvious causes (serum bilirubin$${\geq_-}12mg/dL$$) and 164 neonates of a control population (serum bilirubin <12 mg/dL). We performed polymerase chain reaction (PCR) to see the allele of the ACE gene. Electrophoresis was done in the PCR products in 1.5 percent agarose gel, and then DNA patterns were directly visualized under ethidium bromide staining. Results : ACE genotypes in the hyperbilirubinemia group are as follows; 26.36 percent for II, 53.64 percent for ID, 20.00 percent for DD, 0.532 for I allele and 0.468 for D allele. These distributions were not significantly different from those in the control group; 24.39 percent for II, 51.83 percent for DI, 23.78 percent for DD, 0.503 for I allele and 0.497 for D allele. Conclusion : In this study, ACE gene polymorphism was detected in the neonatal hyperbilirubinemia and control group. The most frequent genotype was ID. Our results indicate that the ACE gene polymorphism is not associated with the prevalence of neonatal hyperbilirubinemia in Koreans.