Publications by authors named "Jihyun An"

64 Publications

On-treatment gamma-glutamyl transferase predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.

Liver Int 2021 Oct 23. Epub 2021 Oct 23.

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background &aims: Gamma-glutamyl transferase (GGT) has been predictive of chronic hepatitis C-related hepatocellular carcinoma (HCC) development. Its role in the risk of HCC in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs) is elusive.

Methods: A total of 2,172 CHB patients from East Asia were randomized into development and validation groups in a 1:2 ratio. Serum GGT levels before and 6 months (M6) after initiating NAs and the potential risk factors were measured. The primary endpoint was HCC development 12 months after NA initiation.

Results: The annual incidence of HCC was 1.4/100 person-years in a follow-up period of 11370.7 person-years. The strongest factor associated with HCC development was high M6-GGT levels (>25 U/L; hazard ratio [HR]/95% confidence interval [CI]:3.31/2.02-5.42, P<0.001), followed by cirrhosis (HR/CI: 2.06/1.39-3.06, P<0.001), male sex (HR/CI: 2.01/1.29-3.13, P=0.002), and age (HR/CI: 1.05/1.03-1.17, P<0.001). Among cirrhotic patients, the incidence of HCC did not differ between those with high or low M6-GGT levels (P=0.09). In contrast, among non-cirrhotic patients, the incidence of HCC was significantly higher for those with M6-GGT level >25 U/L than for their counterparts (P<0.001). Cox regression analysis revealed that the strongest factor associated with HCC development in non-cirrhotic patients was high M6-GGT levels (HR/CI: 5.05/2.52-10.16, P<0.001), followed by age (HR/CI: 1.07/1.04-1.09, P<0.001). Non-cirrhotic elderly patients with high M6-GGT levels had a similarly high HCC risk as cirrhotic patients did (P=0.29).

Conclusions: On-treatment serum GGT levels strongly predicted HCC development in CHB patients, particularly non-cirrhotic patients, treated with NAs.
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http://dx.doi.org/10.1111/liv.15085DOI Listing
October 2021

Cervicocerebral atherosclerosis and its hepatic and coronary risk factors in patients with liver cirrhosis.

Clin Mol Hepatol 2021 Oct 12. Epub 2021 Oct 12.

Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background/aims: This study aimed to investigate the silent atherosclerotic burden of cervicocephalic vessels in cirrhotic patients compared with the general population, and the relevant risk factors including coronary parameters.

Methods: The study population consisted of 993 stroke-free subjects with LC who were screened by magnetic resonance angiography (MRA) of the head and neck as a pre-liver transplant workup, and 6,099 health checkup participants who underwent MRA examination. The two cohorts were matched for cerebrovascular risk factors, and the prevalence rates of atherosclerosis in the major intracranial and extracranial arteries were compared in 755 matched pairs. Also, traditional, hepatic and coronary variables related to the cerebral atherosclerosis were assessed in cirrhotics.

Results: Overall, intracranial atherosclerosis was significantly less prevalent in the LC samples than the matched controls (2.3% vs. 5.4%; P=0.002), whereas the prevalence of extracranial atherosclerosis were similar (4.4% vs. 5.8%; P=0.242). These results were maintained in multivariate analyses in the pooled samples, with the corresponding adjusted odds ratios (ORs) for LC of 0.56 and 0.77 (95% CIs, 0.36-0.88 and 0.55-1.09), respectively. In the cirrhotic series, lower platelet count was inversely correlated with intracranial atherosclerosis (adjusted OR, 0.31; 95% CI, 0.13-0.76). Coronary artery calcium (CAC) score ≥100 was the only factor predicting both intra- and extra-cranial atherosclerosis (adjusted ORs, 4.06 and 5.43; 95% CIs, 1.45-11.41 and 2.68-11.00, respectively).

Conclusions: Our data suggest that LC confers protection against intracranial atherosclerosis, and that thrombocytopenia may be involved in this protection. High CAC score could serve as a potential surrogate for cervicocerebral vascular screening in asymptomatic cirrhotics.
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http://dx.doi.org/10.3350/cmh.2021.0202DOI Listing
October 2021

Integrated prognostic and histogenomic justification of stage-directed therapy for single large hepatocellular carcinoma: a Korean nationwide registry study.

Gut 2021 Sep 7. Epub 2021 Sep 7.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, The Republic of Korea

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http://dx.doi.org/10.1136/gutjnl-2021-325844DOI Listing
September 2021

Comprehensive characterization of viral integrations and genomic aberrations in HBV-infected intrahepatic cholangiocarcinomas.

Hepatology 2021 Sep 3. Epub 2021 Sep 3.

Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background And Aims: Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV-infected iCCA tumors.

Approach And Results: We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, deep sequencing, and RNA sequencing, together with pre-constructed datasets of HBV-infected hepatocellular carcinoma (HBV-HCC; n=167) and combined hepatocellular cholangiocarcinoma (HBV-cHCC/CCA; n=59), and conventional (n=154) and fluke-related iCCAs (n=16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at 9 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2, and were associated with enrichment of epithelial-mesenchymal transition-related genes. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV-iCCA was closer to that of nonviral conventional iCCA, than to HBV-HCC and HBV-cHCC/CCA.

Conclusions: Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.
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http://dx.doi.org/10.1002/hep.32135DOI Listing
September 2021

Clinicopathological and molecular characterization of chromophobe hepatocellular carcinoma.

Liver Int 2021 Oct 15;41(10):2499-2510. Epub 2021 Jun 15.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background And Aims: Chromophobe hepatocellular carcinoma (HCC) is a newly included subtype of HCC in the 5th edition of the WHO classification with distinctive histological features (chromophobic cytoplasm with anaplastic nuclei and pseudocyst formation) and is strongly associated with the alternative lengthening of telomeres (ALT) phenotype. However, the clinicopathologic characterization and molecular features of chromophobe HCC are unknown.

Methods: To comprehensively characterize chromophobe HCC, whole exome sequencing, copy number variation, and transcriptomic analyses were performed in 224 surgically resected HCC cases. Additionally, telomere-specific fluorescence in situ hybridization was used to assess ALT. These genomic profiles and ALT status were compared with clinicopathological features among subtypes of HCC, particularly chromophobe HCC and conventional HCC.

Results: Chromophobe HCC was observed in 10.3% (23/224) cases and, compared to conventional HCC, was more frequent in females (P = .023). The overall and recurrence-free survival outcomes were similar between patients with chromophobe HCC and conventional HCC. However, chromophobe HCC displayed significantly more upregulated genes involving cell cycle progression and DNA repair. Additionally, ALT was significantly enriched in chromophobe HCC (87%; 20/23) compared to conventional HCC (2.2%, 4/178; P < .001). Somatic mutations in ALT-associated genes, including ATRX, SMARCAL1, FANCG, FANCM, SP100, TSPYL5, and RAD52 were more frequent in chromophobe HCC (30.4%, 7/23 cases) compared to conventional HCC (11.8%, 21/178 cases; P = .024).

Conclusions: Chromophobe HCC is a unique subtype of HCC with a prevalence of ~10%. Compared to conventional HCC, chromophobe HCC is associated with female predominance and ALT, although overall and recurrence-free outcomes are similar to conventional HCC.
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http://dx.doi.org/10.1111/liv.14975DOI Listing
October 2021

Antifibrosis treatment by inhibition of VEGF, FGF, and PDGF receptors improves bladder wall remodeling and detrusor overactivity in association with modulation of C-fiber afferent activity in mice with spinal cord injury.

Neurourol Urodyn 2021 08 20;40(6):1460-1469. Epub 2021 May 20.

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Aims: Spinal cord injury (SCI) above the sacral level causes bladder dysfunction and remodeling with fibrosis. This study examined the antifibrotic effects using nintedanib, an inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors, on detrusor overactivity (DO) and bladder fibrosis, as well as the modulation mechanisms of C-fiber afferent pathways.

Methods: Thirty female C57BL/6 mice were divided into group A (spinal intact), group B (SCI with vehicle), and group C (SCI with nintedanib). At 2 weeks after SCI, vehicle or 50 mg/kg nintedanib was administered subcutaneously for 2 weeks. Then, cystometry was conducted, followed by RT-PCR measurements of fibrosis-related molecules, muscarinic, β-adrenergic, TRP and purinergic receptors in the bladder or L6-S1 dorsal root ganglia (DRG). Trichrome stain and Western blot analysis of transforming growth factor-beta and fibronectin were performed in the bladder. TRPV1 expression in L6 DRG was measured by immunohistochemistry.

Results: In cystometry, intercontraction intervals, nonvoiding contractions, voided volume, and voiding efficiency were significantly improved in group C versus group B. RT-PCR, Western blotting, and trichrome staining revealed the fibrotic changes in the bladder of group B, which was improved in group C. Increased messenger RNA levels of TRPV1, TRPA1, P2X , and P2X in DRG of group B were significantly decreased in group C. TRPV1 immunoreactivity in DRG was increased in group B, but decreased in group C.

Conclusions: Nintedanib improves storage and voiding dysfunctions and bladder fibrosis in SCI mice. Also, nintedanib-induced improvement of DO is associated with reduced expression of C-fiber afferent markers, suggesting the modulation of bladder C-fiber afferent activity.
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http://dx.doi.org/10.1002/nau.24704DOI Listing
August 2021

Prognostic Molecular Indices of Resectable Hepatocellular Carcinoma: Implications of S100P for Early Recurrence.

Ann Surg Oncol 2021 Oct 30;28(11):6466-6478. Epub 2021 Mar 30.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Although hepatocellular carcinomas (HCCs) often recur in patients undergoing hepatectomy, there are no reliable biomarkers of this undesirable event. Recent RNA-based efforts have developed valuable genetic indices prognostic of cancer outcomes. We aimed to identify molecular predictors of early recurrence after resection of HCC, and reveal the genomolecular structure of the resected tumors.

Method: Based on the transcriptomic and genomic datasets of 206 HCC samples surgically resected in the Asan Medical Center (AMC), we performed a differential gene expression analysis to identify quantitative markers associated with early recurrence and used the unsupervised clustering method to classify genomolecular subtypes.

Results: Differential gene expression profiling revealed that S100P was the highest-ranked overexpressed gene in HCCs that recurred within 2 years of surgery. This trend was reproduced in immunohistochemical studies of the original cohort and an independent AMC cohort. S100P expression also independently predicted HCC-specific mortality post-resection (adjusted hazard ratio 1.09, 95% confidence interval 1.01-1.19; p = 0.042). Validation in a Chinese cohort and in in vitro experiments confirmed the prognostic value of S100P in HCC. We further identified five discrete molecular subtypes of HCC; a subtype with stem cell features ('AMC-C4') was associated with the worst prognosis, both in our series and another two Asian datasets, and S100P was most strongly upregulated in that subtype.

Conclusion: We identified a promising prognostic biomolecule, S100P, associated with early recurrence after HCC resection, and established the genomolecular architecture of tumors affecting clinical outcomes, particularly in Asian patients. These new insights into molecular mediators should contribute to effective care for affected patients.
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http://dx.doi.org/10.1245/s10434-021-09825-yDOI Listing
October 2021

Variceal bleeding is aggravated by portal venous invasion of hepatocellular carcinoma: a matched nested case-control study.

BMC Cancer 2021 Jan 5;21(1):11. Epub 2021 Jan 5.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Background: We hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis.

Methods: This study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored.

Results: In the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios [95% CIs], 1.662 [1.151-2.401]; 0.985 [0.978-0.993]; 4.240 [1.783-10.084]; and 3.345 [1.457-7.680], respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios [95% CIs], 26.432 [3.230-216.289]; and 5.676 [1.273-25.300], respectively; Ps < 0.05).

Conclusions: PVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.
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http://dx.doi.org/10.1186/s12885-020-07708-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786454PMC
January 2021

Continued value of the serum alpha-fetoprotein test in surveilling at-risk populations for hepatocellular carcinoma.

PLoS One 2020 26;15(8):e0238078. Epub 2020 Aug 26.

Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Backgrounds And Aims: Because of the known limitations of ultrasonography (US) alone, we re-evaluated whether complimentary testing for serum alpha-fetoprotein (AFP) is helpful in surveilling for hepatocellular carcinoma (HCC) in high-risk populations.

Methods: We included, from a hospital-based cancer registry, 1,776 asymptomatic adults who were surveilled biannually with the AFP test and US and eventually diagnosed with HCC between 2007 and 2015. Based on the screening results, these patients were divided into three groups: AFP (positive for AFP only; n = 298 [16.8%]), US (positive for US only; n = 978 [55.0%]), and AFP+US (positive for both; n = 500 [28.2%]). We compared the outcomes of the three groups, calculating the survival of the AFP group both as observed survival and as survival corrected for lead-time.

Results: In terms of tumor-related factors, the separate AFP and US groups were more likely to have early stage HCC and to receive curative treatments than the combined AFP+US group (Ps<0.05). The AFP group had significantly better overall and cancer-specific survival than the AFP+US group after adjusting for covariates (adjusted hazard ratios [HRs] 0.68 and 0.62, respectively). In analyses correcting for lead-time in the AFP group (doubling time 120 days), the respective adjusted HRs for the AFP group were unchanged (0.74 and 0.67), but they were no longer significant after additional adjustment for tumor stage and curative treatment (0.87 and 0.81).

Conclusions: HCC cases detected by the AFP test without abnormal ultrasonic findings appear to have better survival, possibly as a result of stage migration and the resulting cures. Complementary AFP surveillance, together with US, could be helpful for at-risk patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238078PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449471PMC
October 2020

Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial.

Clin Mol Hepatol 2020 10 10;26(4):506-515. Epub 2020 Jul 10.

Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs.

Methods: A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria.

Results: Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9-70.6). Patients' age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7-3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events.

Conclusion: SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.
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http://dx.doi.org/10.3350/cmh.2020.0038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641557PMC
October 2020

Consensus recommendations of three-dimensional visualization for diagnosis and management of liver diseases.

Hepatol Int 2020 Jul 7;14(4):437-453. Epub 2020 Jul 7.

Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases. Over the last decade, it has been proven safe and effective to use 3D simulation software for pre-hepatectomy assessment, virtual hepatectomy, and measurement of liver volumes in blood flow areas of the portal vein; meanwhile, the use of 3D models in combination with hydrodynamic analysis has become a novel non-invasive method for diagnosis and detection of portal hypertension. We herein describe the progress of research on 3D visualization, its workflow, current situation, challenges, opportunities, and its capacity to improve clinical decision-making, emphasizing its utility for patients with liver diseases. Current advances in modern imaging technologies have promised a further increase in diagnostic efficacy of liver diseases. For example, complex internal anatomy of the liver and detailed morphological features of liver lesions can be reflected from CT-based 3D models. A meta-analysis reported that the application of 3D visualization technology in the diagnosis and management of primary hepatocellular carcinoma has significant or extremely significant differences over the control group in terms of intraoperative blood loss, postoperative complications, recovery of postoperative liver function, operation time, hospitalization time, and tumor recurrence on short-term follow-up. However, the acquisition of high-quality CT images and the use of these images for 3D visualization processing lack a unified standard, quality control system, and homogeneity, which might hinder the evaluation of application efficacy in different clinical centers, causing enormous inconvenience to clinical practice and scientific research. Therefore, rigorous operating guidelines and quality control systems need to be established for 3D visualization of liver to develop it to become a mature technology. Herein, we provide recommendations for the research on diagnosis and management of 3D visualization in liver diseases to meet this urgent need in this research field.
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http://dx.doi.org/10.1007/s12072-020-10052-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366600PMC
July 2020

Infection control of operating room and anesthesia for cesarean section during the COVID-19 outbreak in Daegu, the Republic of Korea -a case series.

Korean J Anesthesiol 2021 04 5;74(2):169-174. Epub 2020 Jun 5.

Department of Anesthesiology and Pain Medicine, Daegu Fatimal Hospital, Daegu, Korea.

Background: The coronavirus disease-19 (COVID-19) was first reported in Wuhan, China, with Korea being subsequently exposed. In Korea, COVID-19 screening guidelines have been established in every hospital as an attempt to prevent its spread. There has been a previous report of a successful cesarean section of a confirmed mother; however, there remain no guidelines for suspected mothers. Cesarean section is often urgently operated without sufficient infection evaluations. We would like to suggest anesthetic management guidelines for cesarean section patients suspected of COVID-19.

Case: Our hospital, which is located in Daegu, Korea, was designated as a quarantine and delivery facility for suspected mothers. We performed the cesarean section on seven suspected mothers and one confirmed mother.

Conclusions: This case report presents guidelines for infection control during surgery and anesthesia for cesarean section of mothers with suspected COVID-19 involving operating room preparation and protection strategy.
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http://dx.doi.org/10.4097/kja.20204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024212PMC
April 2021

Emergency cesarean section performed in a patient with confirmed severe acute respiratory syndrome Coronavirus-2 -a case report.

Korean J Anesthesiol 2020 08 31;73(4):347-351. Epub 2020 Mar 31.

Department of Anesthesiology and Pain Medicine, Daegu Fatimal Hospital, Daegu, Korea.

Background: Since the first case of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) occurred in Wuhan in December 2019, the virus has spread globally. The World Health Organization declared the virus outbreak a pandemic on March 11, 2020. On January 19, 2020, a 35-year-old woman who returned from China was confirmed as the first SARS-CoV-2 infected case in Korea. Since then, it has spread all over Korea.

Case: We report the first case of a SARS-CoV-2 positive woman delivering a baby through cesarean section at 37+6 weeks of pregnancy in the Republic of Korea.

Conclusions: This case suggested that negative pressure operating room, skillful medical team, and enhanced personal protective equipment including N95 masks, surgical cap, double gown, double gloves, shoe covers, and powered air-purifying respirator are required at the hospital for safe delivery in such a case.
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http://dx.doi.org/10.4097/kja.20116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403113PMC
August 2020

Comparison of sugammadex and pyridostigmine bromide for reversal of rocuronium-induced neuromuscular blockade in short-term pediatric surgery: A prospective randomized study.

Medicine (Baltimore) 2020 Feb;99(7):e19130

Department of Anesthesiology and Pain Medicine, Daegu Fatima Hospital, Daegu, Korea.

Background: Sugammadex reverses rocuronium-induced neuromuscular blockade quickly and effectively. This study compared efficacy of sugammadex and pyridostigmine for reversal of rocuronium-induced light block or minimal block in children scheduled for elective entropion surgery.

Methods: A prospective randomized study was conducted on 60 pediatric patients aged 1 to 11 years and scheduled for entropion surgery under sevoflurane anesthesia. Neuromuscular blockade was achieved by administration of 0.6 mg/kg rocuronium and assessed using train-of-four (TOF) ulnar nerve stimulation. Patients were randomly assigned to 2 groups receiving sugammadex 2 mg/kg or pyridostigmine 0.2 mg/kg plus glycopyrrolate 0.01 mg/kg. Primary outcomes were time from reversal agents administration to TOF ratio 0.9 and time from reversal agent administration to TOF ratio 1.0. Time from TOF ratio 0.9 to extubation, time from TOF ratio 1.0 to extubation, and postoperative adverse events were also recorded.

Results: There were no substantial differences in demographic variables. Time from reversal agents administration to TOF ratio 0.9 and time from reversal agents to TOF ratio 1.0 were significantly faster in sugammadex group: 1.30 ± 0.84 versus 3.53 ± 2.73 minutes (P < .001) and 2.75 ± 1.00 versus 5.73 ± 2.83 minutes (P < .001). Extubation time was shorter in sugammadex group. Incidence of skin rash, nausea, vomiting, and postoperative residual neuromuscular blockade (airway obstruction) was not statistically different between groups. Incidence of patients agitation in recovery room was lower in sugammadex group.

Conclusion: Sugammadex provided more rapid reversal of rocuronium-induced neuromuscular blockade in pediatric patients undergoing surgery lasting 30 to 60 minutes than did pyridostigmine plus glycopyrrolate, with no differences in incidence of adverse events between groups.
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http://dx.doi.org/10.1097/MD.0000000000019130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035047PMC
February 2020

Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: Comparison with ultrasound.

J Hepatol 2020 04 10;72(4):718-724. Epub 2019 Dec 10.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background & Aims: Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that patients with inadequate ultrasonography be assessed by alternative imaging modalities. Non-enhanced MRI has potential as a surveillance tool based on the short scan times required and the absence of contrast agent-associated risks. This study compared the performance of non-enhanced MRI and ultrasonography for HCC surveillance in high-risk patients.

Methods: We included 382 high-risk patients in a prospective cohort who underwent 1 to 3 rounds of paired gadoxetic acid-enhanced MRI and ultrasonography. Non-enhanced MRI, consisting of diffusion-weighted imaging (DWI) and T2-weighted imaging, was simulated and retrospectively analyzed, with results considered positive when lesion(s) ≥1 cm showed diffusion restriction or mild-moderate T2 hyperintensity. Ultrasonography results were retrieved from patient records. HCC was diagnosed histologically and/or radiologically. Sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were evaluated using generalized estimating equations.

Results: Forty-eight HCCs were diagnosed in 43 patients. Per-lesion and per-exam sensitivities of non-enhanced MRI were 77.1% and 79.1%, respectively, which were higher than those achieved with ultrasonography (25.0% and 27.9%, respectively, p <0.001). Specificities of non-enhanced MRI (97.9%) and ultrasonography (94.5%) differed significantly (p <0.001). NPV was higher for non-enhanced MRI (99.1%) than ultrasonography (96.9%). Per-lesion and per-exam PPVs were higher for non-enhanced MRI (56.9% and 61.8%, respectively) than for ultrasonography (16.7% and 17.7%, respectively). The estimated scan time of non-enhanced MRI was <6 min.

Conclusion: Based on its good performance, short scan times, and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients.

Lay Summary: Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that selected patients with inadequate surveillance on ultrasonography be assessed by alternative imaging modalities such as computed tomography or magnetic resonance imaging (MRI). Herein, we show that MRI without contrast agents performed significantly better than ultrasonography for HCC surveillance in high-risk patients. Given this good performance, as well as short scan times and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients.
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http://dx.doi.org/10.1016/j.jhep.2019.12.001DOI Listing
April 2020

Hepatocyte-Specific Magnetic Resonance Imaging-Based Assessment of Indeterminate Hepatic Nodules in the Liver Transplant Evaluation of Patients With Cirrhosis.

Liver Transpl 2020 03;26(3):359-369

Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, South Korea.

We aimed to determine the identities in explants of indeterminate hepatic nodules (IDNs) that had been scanned by dynamic magnetic resonance imaging (MRI) to establish clinicoradiological parameters predicting which IDNs were hepatocellular carcinomas (HCCs). This study included 88 patients with cirrhosis who underwent gadoxetic acid-enhanced MRI in pre-liver transplantation (LT) workup followed within 90 days by primary LT. The MRI detected 168 hepatic nodules that were classified into 6 benign tumors, 49 HCCs, and 113 IDNs, in 5, 34, and 72 patients, respectively. We compared these pre-LT radiologic diagnoses and stagings with explant pathology on a per-lesion basis to enable us to identify features of IDNs related to malignancy. Of the 168 nodules seen on MRI, 119 that were classified radiologically as consisting of 1 benign nodule (33.3%), 46 HCCs (93.9%), and 72 IDNs (63.7%) all turned out to be pathological HCCs. Of 32 patients inside Milan and 54 without HCC staged by MRI, 11 progressed beyond the criteria after LT. High serum alpha-fetoprotein level (≥20 ng/mL) was the only per-patient factor significantly associated with malignant IDNs. Per-tumor analysis of the MRI signals revealed that arterial hyperintensity, hepatobiliary hypointensity, T -weighted mild-to-moderate intensity, and restricted diffusion-weighted images were significantly correlated with malignant IDN. A model combining these 4 MRI factors with alpha-fetoprotein level had the best performance in predicting the identification of IDNs as HCCs in explanted livers. Over 60% of the IDNs seen on dynamic images of cirrhotic livers proved to be HCCs when explanted livers were examined. It may therefore be possible to identify HCCs with reasonable accuracy by means of their hepatocyte-specific MRI features when patients are being assessed for LT.
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http://dx.doi.org/10.1002/lt.25684DOI Listing
March 2020

Neuromuscular blockade reversal with sugammadex versus pyridostigmine/glycopyrrolate in laparoscopic cholecystectomy: a randomized trial of effects on postoperative gastrointestinal motility.

Korean J Anesthesiol 2020 04 22;73(2):137-144. Epub 2019 Oct 22.

Department of Anesthesiology and Pain Medicine, Daegu Fatima Hospital, Daegu, Korea.

Background: Acetylcholinesterase inhibitors (e.g., pyridostigmine bromide) are used for neuromuscular blockade (NMB) reversal in patients undergoing surgery under general anesthesia (GA). Concurrent use of anticholinergic agents (e.g., glycopyrrolate) decreases cholinergic side effects but can impede bowel movements. Sugammadex has no cholinergic effects; its use modifies recovery of gastrointestinal (GI) motility following laparoscopic cholecystectomy compared to pyridostigmine/glycopyrrolate. This study evaluated the contribution of sugammadex to the recovery of GI motility compared with pyridostigmine and glycopyrrolate.

Methods: We conducted a prospective study of patients who underwent laparoscopic cholecystectomy. Patients were randomly allocated to the experimental group (sugammadex, Group S) or control group (pyridostigmine-glycopyrrolate, Group P). After anesthesia (propofol and rocuronium, and 2% sevoflurane), recovery was induced by injection of sugammadex or a pyridostigmine-glycopyrrolate mixture. As a primary outcome, patients recorded the time of their first passage of flatus ('gas-out time') and defecation. The secondary outcome was stool types.

Results: One-hundred and two patients participated (Group S, 49; Group P, 53). Mean time from injection of NMB reversal agents to gas-out time was 15.03 (6.36-20.25) h in Group S and 20.85 (16.34-25.86) h in Group P (P = 0.001). Inter-group differences were significant. Time until the first defecation as well as types of stools was not significantly different.

Conclusions: Sugammadex after laparoscopic cholecystectomy under GA resulted in an earlier first postoperative passage of flatus compared with the use of a mixture of pyridostigmine and glycopyrrolate. These findings suggest that the use of sugammadex has positive effects on the recovery of GI motility.
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http://dx.doi.org/10.4097/kja.19360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113156PMC
April 2020

The clinical behavior and survival of patients with hepatocellular carcinoma and a family history of the disease.

Cancer Med 2019 11 18;8(15):6624-6633. Epub 2019 Sep 18.

Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Familial clustering is a common feature of hepatocellular carcinoma (HCC) as well as a risk factor for the disease. We aimed to assess whether such a family history affected prognostic outcomes in patients with HCC diagnosed at different stages of the disease.

Materials/methods: This hospital registry-based cohort study included 5484 patients initially diagnosed with HCC. Individual family histories of cancer were obtained by interview and reported by trained nurses who constructed three-generation pedigrees. Overall survival data were compared between cases with and without first-degree relatives affected by HCC, with adjustment for other potential predictors.

Results: Of 5484 patients, 845 (15.4%) had first-degree relatives with a history of HCC. Family history was associated with longer survival in the entire cohort (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = .025). A significant trend for reduced risk of death with increasing number of affected family members was also observed (P for trend = 0.018). The stage-stratified analysis showed that the presence of family history was especially associated with a reduced risk of death in the subset of patients with HCC at a (very) early stage (adjusted HR 0.83, 95% CI 0.69-0.99; P = .042). The proportion of cases receiving curative treatment was also higher in early-stage patients with a family history (72.6% vs 63.3%; P < .001).

Conclusions: A first-degree family history of the disease is a prognostic factor for improved survival in patients with HCC, especially in those whose tumors can be cured by radical treatments.
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http://dx.doi.org/10.1002/cam4.2543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825981PMC
November 2019

A Prospective Evaluation of the Reliability and Utility of Quality of Life Measures in Patients With Hepatocellular Carcinoma.

Am J Clin Oncol 2019 07;42(7):555-563

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul.

Objectives: Little is known about how quality of life (QOL) can assist clinical decision-making for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the reliability and validity of QOL as well as its prognostic value and utility.

Materials And Methods: A prospective cohort of 300 HCC patients at various stages was recruited from 2015 to 2017 in Korea. The subjects answered the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and QLQ-HCC18 and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Prognostic nomograms including the QOL scales were developed. The prediction performance of the Barcelona Clinic Liver Cancer (BCLC) and the American Joint Committee on Cancer (AJCC) staging systems when they were incorporated with QOL was investigated.

Results: The EORTC QLQ-C30 and QLQ-HCC18 subscales showed higher reliability than FACT-Hep subscales. With regard to the validity, both questionnaires discriminated the patients by stages, treatment modalities, and performance status effectively. Multivariable analysis revealed that EORTC role functioning and EORTC appetite loss subscales were statistically associated with overall survival and disease progression. The developed nomograms accurately estimated the 1-year overall survival and disease progression-free rates. Incorporating the EORTC role functioning subscale or Hepatobiliary Cancer Subscale of FACT-Hep with the BCLC and AJCC systems improved the prognostic classification. Incorporating QOL into the AJCC system showed better predictive accuracy than incorporating performance status into it did.

Conclusions: The findings suggest that QOL data can serve as a reliable predictive factor and assist prognostic calculation for HCC patients.
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http://dx.doi.org/10.1097/COC.0000000000000555DOI Listing
July 2019

Immunogenomic landscape of hepatocellular carcinoma with immune cell stroma and EBV-positive tumor-infiltrating lymphocytes.

J Hepatol 2019 07 29;71(1):91-103. Epub 2019 Mar 29.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background & Aims: The immunogenomic characteristics of hepatocellular carcinomas (HCCs) with immune cell stroma (HCC-IS), defined histologically, have not been clarified. We investigated the clinical and molecular features of HCC-IS and the prognostic impact of Epstein-Barr virus (EBV) infection.

Methods: We evaluated 219 patients with conventional HCC (C-HCC) and 47 with HCC-IS using in situ hybridization for EBV, immunohistochemistry, multiplex immunofluorescence staining, and whole exome and transcriptome sequencing. Human leukocyte antigen types were also extracted from the sequencing data. Genomic and prognostic parameters were compared between HCC-IS and C-HCC.

Results: CD8 T cell infiltration was more frequent in HCC-IS than C-HCC (mean fraction/sample, 22.6% vs. 8.9%, false discovery rate q <0.001), as was EBV positivity in CD20-positive tumor-infiltrating lymphocytes (TILs) (74.5% vs. 4.6%, p <0.001). CTNNB1 mutations were not identified in any HCC-IS, while they were present in 24.1% of C-HCC (p = 0.016). Inhibitory and stimulatory immune modulators were expressed at similar levels in HCC-IS and EBV-positive C-HCC. Global hypermethylation, and expression of PD-1 and PD-L1 in TILs, and PD-L1 in tumors, were also associated with HCC-IS (p <0.001), whereas human leukocyte antigen type did not differ according to HCC type or EBV positivity. HCC-IS was an independent factor for favorable recurrence-free survival (adjusted hazard ratio [aHR] 0.23; p = 0.002). However, a subgroup of tumors with a high density of EBV-positive TILs had poorer recurrence-free (aHR 25.48; p <0.001) and overall (aHR 9.6; p = 0.003) survival, and significant enrichment of CD8 T cell exhaustion signatures (q = 0.0296).

Conclusions: HCC-IS is a distinct HCC subtype associated with a good prognosis and frequent EBV-positive TILs. However, paradoxically, a high density of EBV-positive TILs in tumors is associated with inferior prognostic outcomes. Patients with HCC-IS could be candidates for immunotherapy.

Lay Summary: Hepatocellular carcinomas with histologic evidence of abundant immune cell infiltration are characterized by frequent activation of Epstein-Barr virus in tumor-infiltrating lymphocytes and less aggressive clinical behavior. However, a high density of Epstein-Barr virus-positive tumor-infiltrating lymphocytes is associated with inferior prognostic outcomes, possibly as a result of immune escape due to significant CD8 T cell exhaustion.
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http://dx.doi.org/10.1016/j.jhep.2019.03.018DOI Listing
July 2019

Characterization of Hepatocellular Carcinoma Patients with Amplification Assessed by Fluorescence in situ Hybridization: A Large Cohort Study.

Liver Cancer 2019 Feb 22;8(1):12-23. Epub 2018 May 22.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: amplification is a relatively novel type of genetic aberration that has been proposed to be a driver of hepatocarcinogenesis. Selective inhibitors of , a receptor of , have been developed as targeted therapies for hepatocellular carcinoma (HCC). Despite the role of in mediating HCC progression, the clinicopathological characterization of patients exhibiting amplification remains unclear. Immunohistochemical staining is the simplest and most widely used method of identifying aberrations in the gene, although its specificity is very low.

Methods: This study investigated the prognostic significance of amplification in a large cohort of 989 HCC patients using fluorescence in situ hybridization (FISH), which has a high degree of specificity. In addition, FISH data from formalin-fixed, paraffin-embedded sections were compared with copy number variation (CNV) data obtained from fresh frozen sections to validate the use of FISH as a diagnostic tool.

Results: amplifications were detected by FISH in 51 (5.15%) of the 989 patients, and were independently associated with poor survival and a higher risk of tumor recurrence, as well as with poor prognostic factors such as a high α-fetoprotein level, hepatitis B or C virus infection, a large tumor size, microvascular invasion, and necrosis. In addition, amplification was associated with mutation, and was mutually exclusive with mutation. The results of the FISH and CNV analyses exhibited a significant concordance rate of 96% (κ = 0.618, < 0.001).

Conclusions: These data indicate that amplification represents a unique molecular subtype associated with poor prognostic characteristics, which supports the hypothesis that the signaling pathway plays an important role in hepatocarcinogenesis. We have also demonstrated that FISH is a viable alternative to CNV analysis, offering a number of advantages in the clinical setting.
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http://dx.doi.org/10.1159/000488541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388559PMC
February 2019

High Throughput Bar-Coating Processed Organic-Inorganic Hybrid Multi-Layers for Gas Barrier Thin-Films.

J Nanosci Nanotechnol 2019 07;19(7):4299-4304

Department of Chemistry, Chung-Ang University, Seoul 06974, Republic of Korea.

Herein, we demonstrate the preparation of a scalable bar-coated nanocomposite organic-inorganic hybrid film and developed robust barrier films for general purpose packaging. Using combinatory printing of polymers and nanocomposites by bar coating, a facile and effective barrier film fabrication method was developed. Based on a preliminary survey with several material combinations, a rationalized two-fold nanocomposite film was fabricated. The number of layers in the barrier film significantly modified oxygen barrier performance such that, for the 1 wt% ethylene vinyl alcohol (EVOH) intercalated film, the oxygen transmission rate (OTR) of the 5-layer sample was reduced to 31.69% of the OTR of the 3-layer sample (112.8 vs. 35.75 cc/(m² · day)). In addition, fine tuning the amount of EVOH polymer enabled further improvement of oxygen barrier performance. Intercalation of 2 wt% EVOH resulted an OTR improvement from 35.75 in the 1 wt% sample to 11.90 cc/(m² ·day), which is a 4.25-fold enhancement. Overall barrier characteristics proved that our approach could be used for large-area deposited, oxygen resistant, general purpose packaging applications.
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http://dx.doi.org/10.1166/jnn.2019.16333DOI Listing
July 2019

Magnetic Resonance Imaging Is Cost-Effective for Hepatocellular Carcinoma Surveillance in High-Risk Patients With Cirrhosis.

Hepatology 2019 04 25;69(4):1599-1613. Epub 2019 Feb 25.

School of Pharmacy, Sungkyunkwan University, Gyeonggi-do, Korea.

Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, surveillance using magnetic resonance imaging (MRI) with liver-specific contrast showed markedly higher sensitivity in detecting early-stage HCC than US. This study aimed to compare the cost-effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost-effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality-adjusted life-years (QALYs), between MRI and US, with a 20-year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus-associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost-effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost-effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life-years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost-effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver-specific contrast may be more cost-effective than US in patients with virus-associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.
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http://dx.doi.org/10.1002/hep.30330DOI Listing
April 2019

The effectiveness of transarterial chemoembolization in recurrent hepatocellular-cholangiocarcinoma after resection.

PLoS One 2018 7;13(6):e0198138. Epub 2018 Jun 7.

Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) can present as a hypervascular or peripherally enhancing tumor in dynamic imaging. We evaluated the effect of transarterial chemoembolization (TACE) on prognosis according to post-operative recurrence imaging patterns.

Methods: We retrospectively analyzed 42 cHCC-CC and 59 hepatocellular carcinoma (HCC-control) patients at the Asan Medical Center. We classified recurrent cHCC-CC according to enhancement pattern (globally enhancing: GE cHCC-CC, peripherally enhancing: PE cHCC-CC) and evaluated tumor response, time-to-local progression (TTPlocal), and overall survival (OS).

Results: The GE cHCC-CC group had a significantly higher best objective response rate (complete remission + partial response) than the PE cHCC-CC group (36% vs 0%, P = 0.005), and it was comparable to that of the HCC-control group (35.6%, P = 0.97). TTPlocal in the GE cHCC-CC group was significantly shorter than in the HCC-control group (6.6 vs 27.1 months, P < 0.001), and was not significantly different from that in the PE cHCC-CC group (5.3 months, P = 0.12). OS was 12.4 months, 52.8 months, and 67.5 months in the PE cHCC-CC, GE cHCC-CC, and HCC-control groups, respectively (Ps < 0.05). The adjusted hazard ratios (HRs) for TTPlocal and OS revealed an independent association with enhancement pattern of recurrent cHCC-CC (TTPlocal: HR 2.46; 95% CI 1.10-5.46; P = 0.03; OS: HR 5.97; 95% CI 2.38-14.96; P < 0.001).

Conclusions: The GE cHCC-CC group showed better response and prognosis after TACE than the PE cHCC-CC group, but poorer response and prognosis than the HCC-control group. Enhancement patterns at recurrence were crucially associated with tumor response and overall survival.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198138PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991684PMC
January 2019

Comparison of surgical resection versus transarterial chemoembolization with additional radiation therapy in patients with hepatocellular carcinoma with portal vein invasion.

Clin Mol Hepatol 2018 06 16;24(2):144-150. Epub 2018 Jan 16.

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: Portal vein invasion (PVI) is a poor prognostic factor in patients with hepatocellular carcinoma (HCC). We intended to compare the effects of surgical resection and transarterial chemoembolization (TACE) with additional radiation therapy (RT) in HCC patients with PVI.

Methods: The subjects comprised 43 patients who underwent surgical resection for HCC with PVI without previous treatment and another 43 patients who received TACE followed by RT (TACE+RT) as initial treatment who were matched for Child-Pugh class, tumor size, and extent of PVI. Disease progression and death after the treatment were examined, and progression-free survival (PFS) and overall survival (OS) were compared between groups. Predisposing factors affecting OS were analyzed using univariate and multivariate analyses in HCC patients with PVI.

Results: The subjects (Age [51, 24-74; median, range], Sex [81/13; male/female], Etiology [78/1/15; hepatitis B virus {HBV}/ hepatitis C virus {HCV}/non-HBV and non-HCV]) were followed for a median of 17 (2-68) months. There were no differences in clinical or tumor characteristics between the resection and TACE+RT groups. The cumulative PFS was not significantly different between groups. The median PFS was 5.6 and 4.0 months in the resection and TACE+RT groups, respectively. However, the cumulative OS was significantly longer in patients treated with resection than in those treated with TACE+RT (P=0.04). The median OS was 26.9 and 14.2 months in the resection and TACE+RT groups, respectively. Univariate and multivariate analyses revealed that surgical resection was an independent predictive factor for better survival outcome.

Conclusions: Surgical resection might be an effective treatment in HCC patients with PVI.
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http://dx.doi.org/10.3350/cmh.2017.0041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038940PMC
June 2018

Chronic hepatitis B infection and non-hepatocellular cancers: A hospital registry-based, case-control study.

PLoS One 2018 15;13(3):e0193232. Epub 2018 Mar 15.

Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Prior epidemiological evidences suggest that hepatitis B virus (HBV) infection is linked to cancers other than hepatocellular carcinoma. This prospective hospital registry-based case-control study aimed to investigate the sero-epidemiological association between chronic HBV infection and various types of cancer.

Methods: 95,034 patients with first-diagnosed non-hepatocellular malignancy in a tertiary hospital between 2007 and 2014; and 118,891 non-cancer individuals as controls from a health promotion center were included. Cases and controls were compared for HBV surface antigen (HBsAg) positivity by conditional regression with adjustment for age, hypertension, diabetes, body mass index, alcohol consumption, smoking status and cholesterol level in both genders.

Results: An analysis of matched data indicated significant associations of HBV infection with lymphoma (adjusted odds ratio[AOR] 1.53 [95% CI 1.12-2.09] in men and 3.04 [1.92-4.82] in women) and biliary cancer (2.59[1.98-3.39] in men and 1.71[1.16-2.51] in women). Cervical (1.49[1.11-2.00]), uterine (1.69[1.09-2.61]), breast (1.16[1.02-1.32]), thyroid (1.49[1.28-1.74]), and lung cancers (1.79[1.32-2.44]) in women; and skin cancer (5.33[1.55-18.30]) in men were also significantly related to HBV infection.

Conclusions: Chronic HBV infection is associated with several malignant disorders including lymphoma, and biliary, cervical, uterine, breast, thyroid, lung, and skin cancers. Our findings may offer additional insights into the development of these neoplasms and may suggest the need to consider HBV screening in cancer patients and cancer surveillance in HBV-infected subjects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193232PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854295PMC
June 2018

Histological expression of methionine adenosyl transferase (MAT) 2A as a post-surgical prognostic surrogate in patients with hepatocellular carcinoma.

J Surg Oncol 2018 Apr 15;117(5):892-901. Epub 2018 Feb 15.

Department of Pathology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background And Objectives: Deregulation of methionine adenosyltransferase (MAT) is involved in hepatocarcinogenesis. This study aimed to investigate the prognostic implications of the level of histological MAT1A and MAT2A in patients with resected hepatocellular carcinoma (HCC).

Methods: A total of 210 patients with HCC who underwent curative resection between 2004 and 2011 were included. The levels of MAT proteins were immunohistochemically measured.

Results: MAT1A and MAT2A were over-expressed in 134 (63.8%) and 124 (59.1%) of the 210 tumor tissues, respectively. Up-regulation of tumoral MAT1A was independently associated with male gender, and inversely related to tumors >5 cm (adjusted odds ratios [OR] 2.59, P = 0.008, and OR 0.44, P = 0.012, respectively). Enhanced MAT2A expression was significantly related to age ≥60 years and serum AFP >200 ng/mL (OR 0.51, P = 0.030; and OR 2.65, P = 0.003; respectively). Tumoral MAT2A over-expression independently predicted an increased rate of recurrence within 1 year after hepatectomy (adjusted hazard ratio [HR] 2.45, P = 0.012), but that was not the case for MAT1A expression (HR 0.90, P = 0.744). High MAT2A was also an independent predictor of early recurrence (HR 2.54, P = 0.034) in the subset of patients without microvascular invasion (n = 155).

Conclusions: Over-expression of MAT2A in HCC may be a useful biomarker for predicting and monitoring tumor recurrence, especially early after hepatic resection.
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http://dx.doi.org/10.1002/jso.24994DOI Listing
April 2018

Association between non-alcoholic fatty liver disease and cancer incidence rate.

J Hepatol 2017 Nov 2. Epub 2017 Nov 2.

Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background & Aims: Little is known about the association between non-alcoholic fatty liver disease (NAFLD) and cancer development. This study investigated the cancer incidence rates in NAFLD and analysed the association between NAFLD and cancer development.

Methods: This historical cohort study included subjects who were followed up for >1 year after having a heath checkup at a tertiary hospital in Korea from September 1, 2004 to December 31, 2005. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other known liver disease, including alcoholic or viral hepatitis. Cox proportional hazards regression model was conducted to assess the association between NAFLD and cancer development.

Results: Of 25,947 subjects, 8,721 (33.6%) had NAFLD. During the total follow-up of 164,671 person-years (median 7.5 years), the cancer incidence rate of the NAFLD group was higher than that of the non-NAFLD group (782.9 vs. 592.8 per 100,000 person-years; hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.17-1.49; p <0.001). When demographic and metabolic factors were adjusted for, NAFLD showed a strong association with three cancers: hepatocellular carcinoma ([HCC]; HR 16.73; 95% CI 2.09-133.85; p = 0.008), colorectal cancer in males (HR 2.01; 95% CI 1.10-3.68; p = 0.02), and breast cancer in females (HR 1.92; 95% CI 1.15-3.20; p = 0.01). A high NAFLD fibrosis score (NFS) and a high fibrosis-4 (FIB-4) score were associated with the development of all cancers and HCC.

Conclusion: NAFLD was associated with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NFS and a high FIB-4 score showed a strong association with the development of all cancers and HCC.

Lay Summary: Non-alcoholic fatty liver disease (NAFLD) is associated with developing hepatocellular carcinoma (HCC). There have been limited data on the association between NAFLD and extrahepatic cancers. This study demonstrated that patients with NAFLD showed a higher association with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NAFLD fibrosis score and a high fibrosis-4 score showed a strong association with the development of all cancers and HCC.
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http://dx.doi.org/10.1016/j.jhep.2017.09.012DOI Listing
November 2017

Correction to: Tumor Volume Doubling Time as a Dynamic Prognostic Marker for Patients with Hepatocellular Carcinoma.

Dig Dis Sci 2017 11;62(11):3259

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, 05505, South Korea.

The original version of this article unfortunately contained an error in corresponding author e-mail. It was submitted and published as [email protected] instead of [email protected]
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http://dx.doi.org/10.1007/s10620-017-4785-6DOI Listing
November 2017

Current status and strategies for hepatitis B control in Korea.

Clin Mol Hepatol 2017 Sep 19;23(3):205-211. Epub 2017 Sep 19.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.
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http://dx.doi.org/10.3350/cmh.2017.0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628005PMC
September 2017
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