Publications by authors named "Soon Sun Kim"

102 Publications

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

Gut Liver 2021 Nov 23. Epub 2021 Nov 23.

Department of Radiology, Ajou University School of Medicine, Suwon, Korea.

Background/aims: Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model.

Methods: A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model.

Results: PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>-0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF.

Conclusions: Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.
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http://dx.doi.org/10.5009/gnl210130DOI Listing
November 2021

Diagnostic Yield of Transabdominal Ultrasonography for Evaluation of Pancreatic Cystic Lesions Compared with Endoscopic Ultrasonography.

J Clin Med 2021 Oct 8;10(19). Epub 2021 Oct 8.

Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon-si 443-380, Korea.

Detection rates of pancreatic cystic lesions (PCLs) have increased, resulting in greater requirements for regular monitoring using imaging modalities. We aimed to evaluate the capability of ultrasonography (US) for morphological characterization of PCLs as a reference standard using endoscopic ultrasonography (EUS). A retrospective analysis was conducted of 102 PCLs from 92 patients who underwent US immediately prior to EUS between January 2014 and May 2017. The intermodality reliability and agreement of the PCL morphologic findings of the two techniques were analyzed and compared using the intraclass correlation coefficient and κ values. The success rates of US for delineating PCLs in the head, body, and tail of the pancreas were 77.8%, 91.8%, and 70.6%, respectively. The intraclass correlation coefficient for US and the corresponding EUS lesion size showed very good reliability (0.978; < 0.001). The κ value between modalities was 0.882 for pancreatic duct dilation, indicating good agreement. The κ values for solid components and cystic wall and septal thickening were 0.481 and 0.395, respectively, indicating moderate agreement. US may be useful for monitoring PCL growth and changes in pancreatic duct dilation, but it has limited use in the diagnosis and surveillance of mural nodules or cystic wall thickness changes.
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http://dx.doi.org/10.3390/jcm10194616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509250PMC
October 2021

is the most suitable reference gene for RT-qPCR in human HCC tissues and blood samples.

Oncol Lett 2021 Nov 17;22(5):791. Epub 2021 Sep 17.

Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.

Reverse transcription-quantitative (RT-q) PCR is the most feasible and useful technique for identifying and evaluating cancer biomarkers; however, the method requires suitable reference genes for gene expression analysis. The aim of the present study was to identify the most suitable reference gene for the normalization of relative gene expression in human hepatocellular carcinoma (HCC) tissue and blood samples. First, 14 candidate reference genes were selected through a systematic literature search. The expression levels of these genes ( and ) were evaluated using human multistage HCC transcriptome data (dataset GSE114564), which included normal liver (n=15), chronic hepatitis (n=20), liver cirrhosis (n=10), and early (n=18) and advanced HCC (n=45). From the 14 selected genes, five genes, whose expression levels were stable in all liver disease statuses ( and ), were further assessed using RT-qPCR in 40 tissues (20 paired healthy tissues and 20 tissues from patients with HCC) and 40 blood samples (20 healthy controls and 20 samples from patients with HCC). BestKeeper statistical algorithms were used to identify the most stable reference genes, of which was found to be the most stable in both HCC tissues and blood samples. Therefore, the results of the present study suggest as a promising reference gene for the normalization of relative RT-qPCR techniques in HCC-related studies.
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http://dx.doi.org/10.3892/ol.2021.13052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461756PMC
November 2021

Assessment of medical students' clinical performance using high-fidelity simulation: comparison of peer and instructor assessment.

BMC Med Educ 2021 Sep 25;21(1):506. Epub 2021 Sep 25.

Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.

Background: High-fidelity simulators are highly useful in assessing clinical competency; they enable reliable and valid evaluation. Recently, the importance of peer assessment has been highlighted in healthcare education, and studies using peer assessment in healthcare, such as medicine, nursing, dentistry, and pharmacy, have examined the value of peer assessment. This study aimed to analyze inter-rater reliability between peers and instructors and examine differences in scores between peers and instructors in the assessment of high-fidelity-simulation-based clinical performance by medical students.

Methods: This study analyzed the results of two clinical performance assessments of 34 groups of fifth-year students at Ajou University School of Medicine in 2020. This study utilized a modified Queen's Simulation Assessment Tool to measure four categories: primary assessment, diagnostic actions, therapeutic actions, and communication. In order to estimate inter-rater reliability, this study calculated the intraclass correlation coefficient and used the Bland and Altman method to analyze agreement between raters. A t-test was conducted to analyze the differences in evaluation scores between colleagues and faculty members. Group differences in assessment scores between peers and instructors were analyzed using the independent t-test.

Results: Overall inter-rater reliability of clinical performance assessments was high. In addition, there were no significant differences in overall assessment scores between peers and instructors in the areas of primary assessment, diagnostic actions, therapeutic actions, and communication.

Conclusions: The results indicated that peer assessment can be used as a reliable assessment method compared to instructor assessment when evaluating clinical competency using high-fidelity simulators. Efforts should be made to enable medical students to actively participate in the evaluation process as fellow assessors in high-fidelity-simulation-based assessment of clinical performance in situations similar to real clinical settings.
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http://dx.doi.org/10.1186/s12909-021-02952-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467013PMC
September 2021

Update on liver disease management during the pandemic of coronavirus disease 2019 (COVID-19): 2021 KASL guideline.

Clin Mol Hepatol 2021 10 17;27(4):515-523. Epub 2021 Sep 17.

Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3350/cmh.2021.0293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524065PMC
October 2021

Overexpressed Proteins in HCC Cell-Derived Exosomes, CCT8, and Cofilin-1 Are Potential Biomarkers for Patients with HCC.

Diagnostics (Basel) 2021 Jul 6;11(7). Epub 2021 Jul 6.

Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Korea.

Protein markers of hepatocellular carcinoma (HCC)-derived exosomes (HEX) have not yet been fully evaluated. Here, we identified novel protein contents of HEX and their clinical significance as biomarkers. Exosomes were isolated from human HCC cell lines and an immortalized normal hepatocyte cell line. Proteomic analyses revealed 15 markedly overexpressed proteins in HEX. The clinical relevance of the 15 proteins was analyzed in public RNA-sequencing datasets, and 6 proteins were selected as candidate of potential biomarkers. Serum CCT8 and CFL1 were markedly overexpressed in test cohort ( = 8). In the validation cohort ( = 224), the area under the curve (AUC) of serum CCT8 and CFL1 for HCC diagnosis was calculated as 0.698 and 0.677, respectively, whereas that of serum alpha-fetoprotein (AFP) was 0.628. The combination of three serum markers (CCT8, CFL1, and AFP) demonstrated the highest AUC for HCC diagnosis. (AUC = 0.838, 95% confidence interval = 0.773-0.876) Furthermore, higher serum CCT8 and CFL1 concentrations were significantly associated with the presence of vascular invasion, advanced tumor stage, poor disease-free survival, and poor overall survival. Cofilin-1 and CCT8, enriched proteins in HEX, were identified as potential diagnostic and prognostic serum biomarkers for HCC patients.
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http://dx.doi.org/10.3390/diagnostics11071221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307801PMC
July 2021

Early detection of hepatocellular carcinoma via liquid biopsy: panel of small extracellular vesicle-derived long noncoding RNAs identified as markers.

Mol Oncol 2021 Oct 12;15(10):2715-2731. Epub 2021 Jul 12.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.

This study investigated the diagnostic potential of serum small extracellular vesicle-derived long noncoding RNAs (EV-lncRNAs) for hepatocellular carcinoma (HCC). Driver oncogenic lncRNA candidates were selected by a comparative analysis of lncRNA expression profiles from two whole transcriptome human HCC datasets (Catholic_LIHC and TCGA_LIHC). Expression of selected lncRNAs in serum and small EVs was evaluated using quantitative reverse transcription PCR. Diagnostic power of serum EV-lncRNAs for HCC was determined in the test (n = 44) and validation (n = 139) cohorts. Of the six promising driver onco-lncRNAs, DLEU2, HOTTIP, MALAT1, and SNHG1 exhibited favorable performance in the test cohort. In the validation cohort, serum EV-MALAT1 displayed excellent discriminant ability, while EV-DLEU2, EV-HOTTIP, and EV-SNHG1 showed good discriminant ability between HCC and non-HCC. Furthermore, a panel combining EV-MALAT1 and EV-SNHG1 achieved the best area under the curve (AUC; 0.899, 95% CI = 0.816-0.982) for very early HCC, whereas a panel with EV-DLEU2 and alpha-fetoprotein exhibited the best positivity (96%) in very early HCC. Serum small EV-MALAT1, EV-DLEU2, EV-HOTTIP, and EV-SNHG1 may represent promising diagnostic markers for very early-stage HCC.
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http://dx.doi.org/10.1002/1878-0261.13049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486572PMC
October 2021

Outcomes and Loop Pattern Analysis of a Road-Map Technique for ERCP with Side-Viewing Duodenoscope in Patients with Billroth II Gastrectomy (with Video).

J Pers Med 2021 May 12;11(5). Epub 2021 May 12.

Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients who have undergone a Billroth II gastrectomy is a major challenge. This study aimed to evaluate the outcomes of the road-map technique for duodenal intubation using a side-viewing duodenoscope for ERCP in Billroth II gastrectomy patients with naïve papilla, and to analyze the formation and release patterns of common bowel loops that occur when the duodenoscope navigates the afferent limb. The duodenoscopy approach success rate was 85.8% (97/113). In successful duodenoscopy approach patients, there were five bowel looping patterns that occurred when the preceding catheter-connected duodenoscope was advanced into the duodenum: (1) reverse ɣ-loop (29.9%), (2) fixed reverse ɣ-loop (5.2%), (3) simple U-loop (22.7%), (4) N-loop (28.9%), and (5) reverse alpha loop (13.4%). The duodenoscopy cannulation and duodenoscopy therapeutic success rates were 81.4% (92/113) and 80.5% (91/113), respectively, while the overall cannulation and therapeutic success rates were 92.0% (104/113) and 87.6% (99/113), respectively. Bowel perforation occurred in three patients (2.7%). The road-map technique may benefit duodenoscope-based ERCP in Billroth II gastrectomy patients by minimizing the tangential axis alignment between the duodenoscopic tip and driving of the afferent limb, and by predicting and counteracting bowel loops that occur when the duodenoscope navigates the afferent limb.
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http://dx.doi.org/10.3390/jpm11050404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150314PMC
May 2021

Effects of high-fidelity simulation education on medical students' anxiety and confidence.

PLoS One 2021 13;16(5):e0251078. Epub 2021 May 13.

Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.

Introduction: Psychological factors such as anxiety and confidence that students have in the patient care situation are important in that this affects the actual clinical performance. Students who are just starting clinical practice have a lack of clinical knowledge, skill proficiency, and patient communication skills, so they experience anxiety and lack of confidence in clinical setting. Practice in a safe environment, such as simulation education, can help students perform more settled and competently in patient care. The purpose of this study was to analyze the effect of high-fidelity simulation experience on anxiety and confidence in medical students.

Materials And Methods: This study enrolled 37 5th-year students at Ajou University School of Medicine in 2020. Two simulation trainings were implemented, and a survey was conducted to measure students' level of anxiety and confidence before and after each simulation. Based on the research data, a paired t-test was conducted to compare these variables before and after the simulation, and whether this was their first or second simulation experience.

Results: Students had a significantly lower level of anxiety and a significantly higher level of confidence after the simulation than before. In addition, after one simulation experience, students had less anxiety and more confidence before the second simulation compared to those without simulation experience.

Conclusions: We confirmed that medical students need to be repeatedly exposed to simulation education experiences in order to have a sense of psychological stability and to competently deliver medical treatment in a clinical setting. There is a practical limitation in that medical students do not have enough opportunities to meet the patients during clinical practice in hospitals. Therefore, in order to produce excellent doctors, students should have the expanded opportunities to experience simulation education so they can experience real-world medical conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251078PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118241PMC
October 2021

Bioelectrical impedance analysis for predicting postoperative complications and survival after liver resection for hepatocellular carcinoma.

Ann Transl Med 2021 Feb;9(3):190

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.

Background: Bioelectrical impedance analysis provides information on body composition and nutritional status. However, it's unclear whether the preoperative edema index or phase angle predicts postoperative complication or mortality in patients with hepatocellular carcinoma (HCC). Thus, we investigated whether preoperative bioelectrical impedance analysis could predict postoperative complications and survival in patients with HCC.

Methods: Seventy-nine patients who underwent hepatectomy for hepatocellular carcinoma were prospectively enrolled and bioelectrical impedance analysis was performed before surgery. Postoperative ascites or acute kidney injury and patients' survival were monitored after surgery.

Results: Among 79 patients, 35 (44.3%) developed ascites or acute kidney injury after hepatectomy. In multivariate analysis, a high preoperative edema index (extracellular water/total body water) (>0.384) (odds ratio 3.96; 95% confidence interval: 1.03-15.17; P=0.045) and higher fluid infusion during surgery (odds ratio 1.36; 95% confidence interval: 1.04-1.79; P=0.026) were identified as significant risk factors for ascites or acute kidney injury after hepatectomy. Subgroup analyses showed that the edema index was a significant predictor of ascites or acute kidney injury in patients with cirrhosis. Tumor size was the only significant predictive factor for short-term survival after hepatectomy.

Conclusions: The preoperative edema index using bioelectrical impedance analysis can be used as a predictor of post-hepatectomy complication, especially in patients with liver cirrhosis.
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http://dx.doi.org/10.21037/atm-20-5194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940938PMC
February 2021

Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma.

Yonsei Med J 2021 Jan;62(1):12-20

Liver Center, Pusan National University Yangsan Hospital, Yangsan, Korea.

Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC.

Materials And Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR.

Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all =0.001).

Conclusion: High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.
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http://dx.doi.org/10.3349/ymj.2021.62.1.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820452PMC
January 2021

Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma.

Cancers (Basel) 2020 Dec 18;12(12). Epub 2020 Dec 18.

Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Korea.

Exosomal microRNAs (exo-miRs) contribute to cancer metastasis. To identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients with HCC (eight non-metastatic and six with metastasis within 1 year of follow-up) were analyzed. Sixty-one miRs were significantly overexpressed among patients with metastatic HCC. Candidate miRs were selected through integrative analyses of two different public expression datasets, GSE67140 and The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC). Integrative analyses revealed 3 of 61 miRs (miR-106b-5p, miR-1307-5p, and miR-340-5p) commonly overexpressed both in metastasis and vascular invasion groups, with prognostic implications. Validation was performed using stored blood samples of 150 patients with HCC. Validation analysis showed that circulating exo-miR-1307-5p was significantly overexpressed in the metastasis group ( = 0.04), as well as in the vascular invasion and tumor recurrence groups. Circulating exo-miR-1307-5p expression was significantly correlated with tumor stage progression ( < 0.0001). Downstream signaling pathways of miR-1307 were predicted using TargetScan and Ingenuity Pathway Analysis. On comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, promoting epithelial-mesenchymal transition (EMT), showed SEC14L2 and ENG downregulation. Our results show that circulating exo-miR-1307-5p promotes metastasis and helps predict metastasis in HCC, and SEC14L2 and ENG are target tumor suppressor genes of miR-1307 that promote EMT.
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http://dx.doi.org/10.3390/cancers12123819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766543PMC
December 2020

Microbiome as a potential diagnostic and predictive biomarker in severe alcoholic hepatitis.

Aliment Pharmacol Ther 2021 02 2;53(4):540-551. Epub 2020 Dec 2.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.

Background: Severe alcoholic hepatitis (AH) is the most aggressive form of alcohol-related liver disease with high mortality. The microbiome is an emerging therapeutic target in alcohol-related liver disease.

Aims: To investigate the microbiome composition in patients with severe AH, and to determine microbiome recovery after rifaximin treatment in gut bacteria and bacteria derived-extracellular vesicles.

Methods: We enrolled 24 patients with severe AH and 24 healthy controls. Additional faecal samples were collected after 4 weeks in 8 patients with severe AH who completed rifaximin treatment. Treatment response was defined based on Lille score model after 7 days of treatment. Metagenomic profiling was performed using 16S ribosomal RNA amplicon sequencing.

Results: Faecal microbiomes of patients with severe AH had lower alpha diversity and higher beta diversity than those of healthy controls in both gut bacteria and extracellular vesicles. Bacilli, Lactobacillales and Veillonella were significantly increased in the gut bacteria of patients with severe AH, and Veillonella, Veillonella parvula group and Lactobacillales were significantly increased in the extracellular vesicles of patients with severe AH. Eubacterium_g23, Oscillibacter and Clostridiales decreased in the gut bacteria of patients with severe AH, and Eubacterium_g23, Oscillibacter and Christensenellaceae decreased in the extracellular vesicles of patients with severe AH. After rifaximin treatment, 17 taxa in the gut bacteria and 23 taxa in extracellular vesicles were significantly restored in patients with severe AH. In common, Veillonella and Veillonella parvula group increased in patients with severe AH and decreased after rifaximin treatment, and Prevotella and Prevotellaceae decreased in patients with severe AH and increased after rifaximin treatment. Treatment non-responders showed a significantly lower abundance of Prevotella at baseline than did treatment responders.

Conclusion: Dysbiosis was confirmed in severe AH but was alleviated by rifaximin treatment. Taxa associated with severe AH can be candidate biomarkers or therapeutic targets.
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http://dx.doi.org/10.1111/apt.16200DOI Listing
February 2021

MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma.

Sci Rep 2020 10 20;10(1):17862. Epub 2020 Oct 20.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.

Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confirmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC.
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http://dx.doi.org/10.1038/s41598-020-74494-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576198PMC
October 2020

Liver stiffness in magnetic resonance elastography is prognostic for sorafenib-treated advanced hepatocellular carcinoma.

Eur Radiol 2021 Apr 8;31(4):2507-2517. Epub 2020 Oct 8.

Department of Gastroenterology, School of Medicine, Ajou University, 164 Worldcup-ro, Yeongtong-Gu, Suwon, 16499, South Korea.

Objective: We investigated whether liver stiffness (LS) quantified using magnetic resonance elastography (MRE) could predict the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib.

Methods: We selected 50 sorafenib-treated advanced HCC patients who underwent MRE within 3 months before drug administration from a prospectively maintained cohort of chronic liver disease patients, according to the inclusion and exclusion criteria. Univariate and multivariate analyses were performed to evaluate the prognostic role of laboratory data, tumor characteristics, and MRE-assessed LS for overall survival (OS), progression-free survival (PFS), and significant liver injury (grade ≥ 3) after sorafenib administration.

Results: High MRE-assessed LS either as continuous (per kPa, hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.23-1.92, p < 0.001) or categorical (> 7.5 kPa, HR 4.06, 95% CI 1.40-11.79, p < 0.01) variable was significantly associated with poor OS along with higher serum alpha-fetoprotein (AFP, ≥ 400 ng/mL) and advanced tumor stage (modified Union for International Cancer Control (mUICC) IVb). Higher MRE-assessed LS was also significantly associated with the development of significant liver injury after sorafenib administration (per kPa, HR 1.62, 95% CI 1.21-2.17, p = 0.001; > 7.5 kPa, HR 10.11, 95% CI 2.41-42.46, p = 0.002). PFS analysis identified higher serum AFP (≥ 400 ng/mL) and advanced tumor stage (mUICC IVb) as significant risk factors for early disease progression, whereas LS was not associated with PFS CONCLUSION: Higher MRE-assessed LS is a potential biomarker for predicting poor OS and significant liver injury in advanced HCC patients treated with sorafenib.

Key Points: • Higher pretreatment LS by MRE (> 7.5 kPa), higher AFP (≥ 400 ng/mL), and advanced tumor stage (mUICC IVb) were associated with poor OS in advanced HCC patients treated with sorafenib. • Higher pretreatment LS by MRE was associated with developing significant (grade ≥ 3) liver injury during sorafenib treatment, which required termination of the therapy. • Patients with high pretreatment LS by MRE should be monitored carefully for potential liver injury during sorafenib treatment.
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http://dx.doi.org/10.1007/s00330-020-07357-9DOI Listing
April 2021

Pathway-Based Integrative Analysis of Metabolome and Microbiome Data from Hepatocellular Carcinoma and Liver Cirrhosis Patients.

Cancers (Basel) 2020 Sep 21;12(9). Epub 2020 Sep 21.

Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, Korea.

Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host's phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.
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http://dx.doi.org/10.3390/cancers12092705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563418PMC
September 2020

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C.

Gut Liver 2021 05;15(3):410-419

Departments of Gastroenterology, Ajou Research Institute for Innovative Medicine, Ajou University School of Medicine, Suwon, Korea.

Background/aims: This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence.

Methods: A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results.

Results: Among the 100 patients, 88% achieved a sustained virological response (SVR) 12 weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR 3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively).

Conclusions: DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.
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http://dx.doi.org/10.5009/gnl20151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129654PMC
May 2021

Direct-Acting Antivirals Improve Treatment Outcomes in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Nationwide, Multi-center, Retrospective Cohort Study.

Dig Dis Sci 2021 07 28;66(7):2427-2438. Epub 2020 Aug 28.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background And Aims: The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE).

Methods: This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison.

Results: A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411-0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042).

Conclusions: DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment.
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http://dx.doi.org/10.1007/s10620-020-06533-7DOI Listing
July 2021

Management of liver diseases during the pandemic of coronavirus disease-19.

Clin Mol Hepatol 2020 07 23;26(3):243-250. Epub 2020 Jun 23.

Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3350/cmh.2020.0111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364349PMC
July 2020

Exosomal microRNA-4661-5p-based serum panel as a potential diagnostic biomarker for early-stage hepatocellular carcinoma.

Cancer Med 2020 08 14;9(15):5459-5472. Epub 2020 Jun 14.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.

Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early-stage HCC (single tumor < 2 cm). We aimed to investigate diagnostic serum exosomal microRNA (exo-miR) panel for early-stage HCC. Driver oncogenic miR (onco-miR) candidates were selected by integrative analysis of miR expression profiles from three different RNA sequencing datasets of human HCC. Expressions of selected onco-miRs in serum exosome were measured using quantitative real-time PCR. Diagnostic performances of serum exo-miRs for HCC were evaluated in the test cohort (N = 24) and validation cohort (N = 144). Serum exo-miR panels were developed using a logistic regression model, and their diagnostic performance was evaluated. Six promising driver onco-miRs, including miR-25-3p, miR-140-3p, miR-423-3p, miR-1269a, miR-4661-5p, and miR-4746-5p, were identified by integrative analysis of three different RNA sequencing datasets. Among the six candidates, four serum exo-miRs (miR-25-3p, miR-1269a, miR-4661-5p, and miR-4746-5p) showed promising performance in the test cohort with area under the receiving operator curve (AUROC) >0.8. In our validation study, serum exo-miR-4661-5p could diagnose HCC in all stages (AUROC = 0.917), even in early stage (AUROC = 0.923), with a greater accuracy than other candidate serum exo-miRs and serum AFP. The panel composed of exo-miR-4661-5p and exo-miR-4746-5p was identified as the most accurate biomarker for early-stage HCC (AUROC = 0.947, 95% confidence interval = 0.889-0.980, sensitivity = 81.8%, and specificity = 91.7%). In conclusion, exo-miR-4661-5p-based serum panel is a promising diagnostic marker for early-stage HCC.
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http://dx.doi.org/10.1002/cam4.3230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402848PMC
August 2020

Serum small extracellular vesicle-derived LINC00853 as a novel diagnostic marker for early hepatocellular carcinoma.

Mol Oncol 2020 10 13;14(10):2646-2659. Epub 2020 Jul 13.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.

This study aimed to identify novel long noncoding RNA (lncRNA) biomarkers for hepatocellular carcinoma (HCC) using publicly available tissue genomic datasets and validate their diagnostic utility for early-stage HCC. Differentially expressed lncRNAs between 371 HCC and 50 nontumor tissues were obtained from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC) project. Subsequently, the expression of the serum- and extracellular vesicle (EV)-derived lncRNA was assessed in 10 patients with HCC and 10 healthy controls using RT-qPCR. The candidate lncRNAs were validated in 90 HCC and 92 non-HCC (29 healthy control, 28 chronic hepatitis, 35 liver cirrhosis) patients. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for the candidate lncRNAs and the current HCC biomarker, alpha-fetoprotein (AFP). SFTA1P, HOTTIP, HAGLROS, LINC01419, HAGLR, CRNDE, and LINC00853 were markedly upregulated in HCC in TCGA_LIHC dataset. Among them, LINC00853 has not been reported in relation to HCC before. In patients with HCC, only expression of small EV-derived LINC00853 (EV-LINC00853) was increased. EV-LINC00853 showed excellent discriminatory ability in the diagnosis of all-stage HCC (AUC = 0.934, 95% confidence interval = 0.887-0.966). Moreover, using a 14-fold increase and 20 ng·mL as cutoffs for EV-LINC00853 expression and AFP level, respectively, EV-LINC00853 was found to have a sensitivity of 93.75% and specificity of 89.77%, while AFP showed only 9.38% sensitivity and 72.73% specificity for the diagnosis of early-stage HCC (mUICC stage I). EV-LINC00853 had a positivity of 97% and 67% in AFP-negative and AFP-positive early HCC, respectively. Serum EV-derived LINC00853 may be a novel potential diagnostic biomarker for early HCC, especially for AFP-negative HCC.
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http://dx.doi.org/10.1002/1878-0261.12745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530776PMC
October 2020

Predictive score for hepatocellular carcinoma after hepatitis B e antigen loss in patients treated with entecavir or tenofovir.

J Viral Hepat 2020 10 28;27(10):1052-1060. Epub 2020 May 28.

Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

The risk of developing hepatocellular carcinoma (HCC) after hepatitis B e antigen seroclearance (ESC) remains unclear. We established and validated a new risk prediction model for HCC development after ESC in patients with chronic hepatitis B (CHB) receiving antiviral therapy (AVT). Between 2006 and 2016, 769 patients (training cohort) and 1,061 patients (validation cohort) with CHB who experienced ESC during AVT using entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were recruited. In the multivariate analysis, male sex (hazard ratio [HR] = 2.092; 95% confidence interval [CI] = 1.152-3.800), cirrhosis (HR = 5.141; 95% CI = 2.367-11.167) and fibrosis-4 index (FIB-4) of >3.25 (HR = 2.070; 95% CI = 1.184-3.620) were the independent risk factors for HCC development (all P < .05). Accordingly, a novel HCC-ESC model was developed (1x[sex: male = 1, female = 0] + 3x(cirrhosis = 1, noncirrhosis = 0) + 1x(FIB-4: >3.25 = 1, ≤3.25 = 0). The cumulative risk for HCC development was significantly different among the risk groups based on the HCC-ESC category (0-1, 2-4 and 5 for the low-, intermediate- and high-risk groups, respectively) (overall P < .001, log-rank test). The area under the receiver operating characteristic curve (AUC) for predicting HCC development 3, 5 and 10 years after ESC was 0.791, 0.771 and 0.790, respectively (all P < .05). The predictive value of the HCC-ESC model was similar in the validation cohort (AUC = 0.802, 0.774 and 0.776 at 3, 5 and 10 years, respectively; all P < .05). Hence, we have developed and validated a new HCC-ESC model for HCC development, which includes male sex, cirrhosis and FIB-4 of >3.25 as constituent variables.
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http://dx.doi.org/10.1111/jvh.13316DOI Listing
October 2020

The αC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases.

Biomaterials 2020 07 17;245:119974. Epub 2020 Mar 17.

Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea. Electronic address:

Despite being crucial for combating microbes, paradoxical Toll-like receptors (TLRs) signaling have been associated with the aggravation of multiple immune disorders such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, and nonalcoholic steatohepatitis. The stoichiometry and precise arrangement of the interaction of adapters (via their Toll/interleukin-1 receptor [TIR] domains) are indispensable for the activation of TLRs and of downstream signaling cascades. Among adapters, plasma membrane-anchored MyD88 adaptor-like (MAL) has the potential for BB-loop-mediated self-oligomerization and interacts with other TIR domain-containing adaptors through αC and αD helices. Here, we used information on the MAL-αC interface to exploit its pharmacophores and to design a decoy peptide (MIP2) with broad-range TLR-inhibitory abilities. MIP2 abrogated MyD88- and TRIF-dependent lipopolysaccharide (LPS)-induced TLR4 signaling in murine and human cell lines and manifested a therapeutic potential in models of psoriasis, systemic lupus erythematosus, nonalcoholic steatohepatitis, and sepsis. Levels of hallmark serological and histological biomarkers were significantly restored and the disease symptoms were substantially ameliorated by MIP2 treatment of the animals. Collectively, our biophysical, in vitro, and in vivo findings suggest that MIP2 has broad specificity for TLRs and may be effective in modulating autoimmune complications caused by microbial or environmental factors.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119974DOI Listing
July 2020

Liver stiffness measured by MR elastography is a predictor of early HCC recurrence after treatment.

Eur Radiol 2020 Aug 18;30(8):4182-4192. Epub 2020 Mar 18.

Department of Gastroenterology, Ajou University School of Medicine, Worldcup-ro 164, Yeongtong-Gu, Suwon, 443-380, South Korea.

Objectives: Magnetic resonance elastography (MRE) is a non-invasive tool for measuring liver stiffness (LS) with high diagnostic accuracy. This study investigated whether quantified LS by MRE could predict early recurrence of patients with hepatocellular carcinoma (HCC) within the Milan criteria.

Methods: A prospectively collected cohort, which included the HCC patients who underwent MRE before treatment (an HCC-MRE cohort), was analyzed. In the HCC-MRE cohort, only patients under the Milan criteria, who underwent hepatic resection, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE), were reviewed. We investigated whether LS assessed by MRE was an independent predictor of early recurrence using Cox regressions and Kaplan-Meier analyses.

Results: A total of 192 HCC patients under the Milan criteria who underwent hepatic resection (n = 96), RFA (n = 23), or TACE (n = 73) were included. Higher LS ratings (kPa; hazard ratio [HR] = 1.12; 95% confidence interval [CI] = 1.01-1.25; p = 0.040) emerged as an independent risk factor for early tumor recurrence. In the subgroup analysis, higher LS ratings were associated with higher risks of early HCC recurrence in both the resection/RFA group (> 4.5 kPa; HR = 2.95; 95% CI = 1.26-6.94; p = 0.013) and the TACE group (> 6 kPa; HR = 2.94; 95% CI = 1.27-6.83; p = 0.012).

Conclusion: LS assessed by MRE was an independent predictor of early recurrence among HCC patients under the Milan criteria after achieving a complete response.

Key Points: • Liver parenchymal stiffness measured by MRE predicts early recurrence of treated HCC under Milan criteria. • A liver stiffness > 5.5 kPa was associated with worse recurrence-free survival. • Patients with high pre-treatment LS may benefit from stringent follow-up.
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http://dx.doi.org/10.1007/s00330-020-06792-yDOI Listing
August 2020

Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma.

J Clin Med 2020 Jan 20;9(1). Epub 2020 Jan 20.

Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Korea.

Exosomal microRNAs (exo-miRs) have been promising cancer biomarkers. MiRs in hepatocellular carcinoma (HCC) cell-derived exosomes (HEX) were analyzed to identify reliable serum biomarkers for HCC. To detect overexpressed miRs in HEX, extracted exosomal small RNAs from human HCC cell lines and normal hepatocytes were sequenced and analyzed. Clinical significance of the overexpressed miRs in HEX was evaluated using quantitative real-time PCR (qRT-PCR) on serum samples of a validation cohort consisting of 28 healthy individuals, 60 with chronic liver disease, and 90 with HCC. We found 49 significantly overexpressed miRs in HEX compared to a normal hepatocyte. Among them, miR-10b-5p, miR-18a-5p, miR-215-5p, and miR-940 were overexpressed in HCC tissues and also associated with prognosis of HCC in the analysis of a public omics database. qRT-PCR analysis of the four serum exo-miRs in the validation cohort revealed serum exo-miR-10b-5p as a promising biomarker for early-stage HCC with 0.934 area under the curve (AUC) (sensitivity, 90.7%; specificity, 75.0%; cutoff value, 1.8-fold). Overexpression of serum exo-miR-215-5p was found to be significantly associated with poor disease-free survival in patients with HCC. Serum exo-miR-10b-5p is a potential biomarker for early-stage HCC, while serum exo-miR-215-5p can be used as prognostic biomarker for HCC.
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http://dx.doi.org/10.3390/jcm9010281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019940PMC
January 2020

Treatment and prognosis of hepatic epithelioid hemangioendothelioma based on SEER data analysis from 1973 to 2014.

Hepatobiliary Pancreat Dis Int 2020 Feb 29;19(1):29-35. Epub 2019 Nov 29.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

Background: Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor of vascular origin with an unknown etiology, a low incidence, and a variable natural course. We evaluated the management and prognosis of HEH from the Surveillance, Epidemiology and End Results (SEER) program and changes in treatment modalities of HEH over 30 years.

Methods: From 1973 to 2014 in the SEER database, we selected patients diagnosed with HEH. We analyzed the clinical characteristics, patterns of management, and clinical outcomes of patients with HEH.

Results: We identified 79 patients with HEH (median age: 54.0 years; male to female ratio: 1:2.6). The initial extent of disease was local in 22 (27.8%) patients, regional metastasis in 22 (27.8%), distant metastasis in 31 (39.2%) and unknown in 4 (5.1%). The median size of primary tumor was 3.85 cm (interquartile range, 2.50-7.93 cm). Among 74 patients with available management data, the most common management was no treatment (29/74, 39.2%), followed by chemotherapy only (22/74, 29.7%), liver resection-based (13/74, 17.6%), and transplantation-based therapy (6/74, 8.1%). The 5-year cancer-specific survival rate was 57.8%. Patients who underwent surgical treatment had significantly higher survival than those who underwent non-surgical treatment (5-year survival; 88% vs. 49%, P = 0.019). Multivariate analysis revealed that surgical therapy was the only independent prognostic factor for survival (hazard ratio: 0.20, P = 0.040).

Conclusions: Resection or liver transplantation is worth considering for treatment of patients with HEH.
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http://dx.doi.org/10.1016/j.hbpd.2019.11.006DOI Listing
February 2020

Staged partial hepatectomy versus transarterial chemoembolization for the treatment of spontaneous hepatocellular carcinoma rupture: a multicenter analysis in Korea.

Ann Surg Treat Res 2019 Jun 29;96(6):275-282. Epub 2019 May 29.

Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

Purpose: The aim of this study was to identify the prognostic factors and compare the long-term outcomes of staged hepatectomy and transarterial chemoembolization (TACE) for patients with spontaneous rupture of hepatocellular carcinoma (HCC).

Methods: This study is a multicenter, retrospective analysis of patients with newly diagnosed ruptured HCC. To compare overall survival between staged hepatectomy group and TACE alone group, we performed propensity score-matching to adjust for significant differences in patient characteristics. To identify prognostic factors, the clinical characteristics at the time of diagnosis of tumor rupture were investigated using Cox-regression analysis.

Results: From 2000 to 2014, 172 consecutive patients with newly diagnosed ruptured HCC were treated in 6 Korean centers. One hundred seventeen patients with Child-Pugh class A disease were identified; of which 112 were initially treated with transcatheter arterial embolization (TAE) for hemostasis and five underwent emergency surgery for bleeder ligation. Of the 112 patients treated with TAE, 44 underwent staged hepatectomy, 61 received TACE alone, and 7 received conservative treatment after TAE. Those that underwent staged hepatectomy had significantly higher overall survival than those that underwent TACE alone before matching (P < 0.001) and after propensity score-matching (P = 0.006). Multivariate analysis showed that type of treatment, presence of portal vein thrombosis, pretreatment transfusion >1,200 mL, and tumor size >5 cm were associated with poor overall survival.

Conclusion: Staged hepatectomy may offer better long-term survival than TACE alone for spontaneous rupture of HCC. Staged hepatectomy should be considered in spontaneous rupture of HCC with resectable tumor and preserved liver function.
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http://dx.doi.org/10.4174/astr.2019.96.6.275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543054PMC
June 2019

Circulating Microbiota-Based Metagenomic Signature for Detection of Hepatocellular Carcinoma.

Sci Rep 2019 05 17;9(1):7536. Epub 2019 May 17.

Department of Statistics, Seoul National University, Seoul, Korea.

Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3-V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.
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http://dx.doi.org/10.1038/s41598-019-44012-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525191PMC
May 2019

A Proposal for Modification of the Barcelona Clinic Liver Cancer Staging System Considering the Prognostic Implication of Performance Status.

Gut Liver 2019 09;13(5):557-568

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

Background/aims: Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1-2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS.

Methods: A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS.

Results: As a result, the BCLC C stage, which includes patients with PS 1-2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001).

Conclusions: An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.
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http://dx.doi.org/10.5009/gnl18444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743810PMC
September 2019

Improvement of Nonalcoholic Fatty Liver Disease Reduces the Risk of Type 2 Diabetes Mellitus.

Gut Liver 2019 04;13(4):440-449

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

Background/aims: Little evidence is available about the effect of change in nonalcoholic fatty liver disease (NAFLD) status on risk of diabetes mellitus (DM) development. In this study, we tried to analyze the DM risk according to change in NAFLD status over time.

Methods: Among a total of 10,141 individuals for whom routine healthcare assessment was performed, 2,726 subjects were selected according to the inclusion/exclusion criteria. NAFLD status change was determined by using serial abdominal ultrasonography and fatty liver index (FLI) during the follow-up period.

Results: Subjects were categorized according to change in NAFLD status as follows: 670 subjects in the persistent NAFLD group, 155 subjects in the resolved NAFLD group, 498 subjects in the incident NAFLD group, and 1,403 subjects in the no NAFLD group. Multivariate Cox regression analysis revealed that incident NAFLD (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.08 to 3.50; p=0.026) and persistent NAFLD (HR, 3.59; 95% CI, 2.05 to 6.27; p<0.001) were independent risk factors for predicting DM development, whereas the risk with resolved NAFLD was not significantly different from that with no NAFLD. FLI could reproduce the results acquired by ultrasonography.

Conclusions: This study demonstrated that future DM risk could be influenced by changes in NAFLD status over time. Resolution of NAFLD could reduce the risk of future DM development, while the development of new NAFLD could increase the risk of DM development.
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http://dx.doi.org/10.5009/gnl18382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622569PMC
April 2019
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