Publications by authors named "In Hee Kim"

114 Publications

Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in South Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.

Epidemiol Health 2021 Oct 6:e2021077. Epub 2021 Oct 6.

Seoul National University Bundang Hospital , Seongnam, Korea.

Objectives: Injection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data are available in South Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).

Methods: We used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of the questionnaire survey focused on the lifetime risk factors for HCV infection were analyzed based on the self-reported history of injection drug use.

Results: Among the 2,468 patients, 166 (6.7%) had a history of injection drug use (PWID group). In the PWID group, the patients were younger (50.68.2 vs. 58.213.1 years) and the proportion of males was higher (81.9% vs. 48.8%) than in the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not differ between the groups.

Conclusion: By 2019, PWID were a minority among the HCV-infected people in Korea. The epidemiological characteristics were different between the groups, but not the treatment uptake and outcomes. Therefore, active screening and treatment should be offered to PWID in Korea.
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http://dx.doi.org/10.4178/epih.e2021077DOI Listing
October 2021

Direct Hyperbilirubinemia as a Predictor of Mortality in Patients with Liver Cirrhosis.

Gut Liver 2021 07;15(4):490-491

Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.

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http://dx.doi.org/10.5009/gnl210296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283295PMC
July 2021

Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study.

J Hepatocell Carcinoma 2021 18;8:613-623. Epub 2021 Jun 18.

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

Background/aim: Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment.

Methods: This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles.

Results: The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P < 0.001), hand-foot skin reaction (aHR = 1.688; P = 0.003), and concomitant treatment with chemoembolization or radiotherapy (aHR = 2.766; P < 0.001). Poor prognostic factors of long-term survival were a Child-Pugh score of B (HR = 0.422; P < 0.001), the presence of extrahepatic metastasis (HR = 0.639; P = 0.005), main portal vein invasion (HR = 0.502; P = 0.001), and elevated alpha-fetoprotein (>1,000 ng/mL; HR = 0.361; P < 0.001).

Conclusion: This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.
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http://dx.doi.org/10.2147/JHC.S304439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219232PMC
June 2021

Direct-Acting Antiviral Therapy and Risk of Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C.

Gut Liver 2021 05;15(3):327-328

Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.

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http://dx.doi.org/10.5009/gnl210191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129652PMC
May 2021

Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro.

Mar Drugs 2021 Apr 15;19(4). Epub 2021 Apr 15.

Marine Biotechnology Research Center, Jeonnam Bioindustry Foundation, 21-7, Nonggongdanji 4Gil, Wando-eup, Wando-gun, Jeollanam-do 59108, Korea.

Much attention is being devoted to the potential of marine sulfated polysaccharides as antiviral agents in preventing COVID-19. In this study, sulfated fucoidan and crude polysaccharides, extracted from six seaweed species (Undaria pinnatifida sporophyll, Laminaria japonica, Hizikia fusiforme, Sargassum horneri, Codium fragile, Porphyra tenera) and Haliotis discus hannai (abalone viscera), were screened for their inhibitory activity against SARS-CoV-2 virus entry. Most of them showed significant antiviral activities at an IC50 of 12~289 μg/mL against SARS-CoV-2 pseudovirus in HEK293/ACE2, except for P. tenera (IC50 > 1000 μg/mL). The crude polysaccharide of S. horneri showed the strongest antiviral activity, with an IC50 of 12 μg/mL, to prevent COVID-19 entry, and abalone viscera and H. fusiforme could also inhibit SARS-CoV-2 infection with an IC50 of 33 μg/mL and 47 μg/mL, respectively. The common properties of these crude polysaccharides, which have strong antiviral activity, are high molecular weight (>800 kDa), high total carbohydrate (62.7~99.1%), high fucose content (37.3~66.2%), and highly branched polysaccharides. These results indicated that the crude polysaccharides from seaweeds and abalone viscera can effectively inhibit SARS-CoV-2 entry.
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http://dx.doi.org/10.3390/md19040219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071526PMC
April 2021

The Superoxide Dismutase Mimetic M40403, Improves 5-Fluorouracil-induced Small Intestinal Mucositis in a Mouse Model.

In Vivo 2021 May-Jun;35(3):1485-1497

Department of Internal Medicine, Jeonbuk National University Medical School and Hospital, Jeollabukdo, Republic of Korea;

Background/aim: Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea.

Materials And Methods: BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated.

Results: M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment.

Conclusion: M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.
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http://dx.doi.org/10.21873/invivo.12401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193283PMC
June 2021

Maximal diameter of liver abscess independently predicts prolonged hospitalization and poor prognosis in patients with pyogenic liver abscess.

BMC Infect Dis 2021 Feb 11;21(1):171. Epub 2021 Feb 11.

Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School and Research Institute of Clinical Medicine of Jeonbuk National University Hospital-Jeonbuk National University Medical School, 20 Geonjiro, Dukjingu, Jeonju, Jeonbuk, 54907, South Korea.

Background/aims: This study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess.

Methods: We retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days.

Results: A total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality.

Conclusions: A large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses.
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http://dx.doi.org/10.1186/s12879-021-05873-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879520PMC
February 2021

Addition of liver stiffness enhances the predictive accuracy of the PAGE-B model for hepatitis B-related hepatocellular carcinoma.

Aliment Pharmacol Ther 2021 04 19;53(8):919-927. Epub 2021 Jan 19.

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

Background: The modified PAGE-B (mPAGE-B) and PAGE-B models reliably predict the risk of developing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC).

Aim(s): To investigate whether the addition of liver stiffness (LS) value, assessed using transient elastography, enhanced the predictive accuracies of these models METHODS: Patients with CHB who started anti-viral therapy (AVT) between 2007 and 2017 were enrolled. The training (Yonsei University Hospital) and validation (seven Korean referral institutes) cohorts contained 1211 and 973 patients, respectively.

Results: Based on multivariate analysis, older age (hazard ratio [HR] = 1.051, 95% confidence interval [CI] = 1.031-1.071), male sex (HR = 2.265, 95% CI = 1.463-3.506), lower platelet count (HR = 0.993, 95% CI = 0.989-0.997) and greater LS values (HR = 1.015, 95% CI = 1.002-1.028) were independently associated with an increased risk of HCC development (all P < 0.05). Thus, we developed a modified PAGE -B model (maximum score 34) that included age, male sex, platelet count and LS value. The integrated area under the curve of the modified PAGE model was greater than those of the PAGE-B and mPAGE-B models (0.760 vs 0.714 and 0.716, respectively) in the derivation dataset. The cumulative HCC incidence was significantly higher in the high-risk (modified PAGE-B score ≥ 24) group than in the intermediate-risk (modified PAGE -B score 12-24) or low-risk (modified PAGE -B score < 12) group (all P < 0.001). Similar results were observed in the validation cohort.

Conclusions: The predictive accuracies of the PAGE-B and mPAGE-B models were validated in Korean patients with CHB receiving AVT. However, the modified PAGE -B model featuring the addition of LS value showed higher predictability than the PAGE-B and mPAGE-B models.
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http://dx.doi.org/10.1111/apt.16267DOI Listing
April 2021

Addition of probiotics to antibiotics improves the clinical course of pneumonia in young people without comorbidities: a randomized controlled trial.

Sci Rep 2021 01 13;11(1):926. Epub 2021 Jan 13.

Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea.

This study was aimed at investigating the clinical efficacy of probiotics in pneumonia patients. To this end, we enrolled 80 participants diagnosed with pneumonia at Naval Pohang Hospital, Pohang, Korea, from May 2016 to January 2017. The participants were randomly assigned to the control and probiotic groups depending on whether they received probiotics. All participants clinically improved but 22.6% of the participants complained of abnormal stool habits after pneumonia treatment. In comparison, fever duration was significantly shorter in the probiotic group, and the group exhibited an improved general condition. The probiotic group also showed better stool characteristics according to the Bristol stool scale (P = 0.009). Notably, the serum hs-CRP levels were significantly lower in the probiotic group at 2 weeks of treatment (P = 0.015), and all participants in the probiotic group achieved their levels within the normal range. Flow cytometry was used to analyze T-helper 17 (Th17) cells and regulatory T cells (Tregs). Tregs were promoted and the Th17 cell/Treg ratio was suppressed after 2 weeks of treatment in the probiotic group (P = 0.007 and 0.037, respectively). This study demonstrated that probiotics improved clinical symptoms and normalized inflammatory biomarker levels in patients with pneumonia. Early infection and inflammation recovery may be due to the immunomodulatory effects of probiotics by facilitating the subset of Tregs and suppressing the Th17 cell/Treg ratio.
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http://dx.doi.org/10.1038/s41598-020-79630-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806890PMC
January 2021

Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retrospective nested case-control study.

Clin Rheumatol 2021 May 19;40(5):2037-2045. Epub 2020 Oct 19.

Division of Rheumatology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, South Korea.

Objective: We aimed to determine whether methotrexate (MTX) treatment in patients with rheumatoid arthritis (RA) leads to the development of non-alcoholic fatty liver (NAFL).

Method: Data were derived from records of all patients with RA who underwent abdominal ultrasonography at the Jeonbuk National University Hospital. Patients with ultrasound-proven NAFL were identified, and those without NAFL were matched by age and sex using the propensity score matching method at 1:3 ratio. We also analyzed the Health Insurance Review and Assessment Service-National Patient Samples, a nationwide cohort database, to determine the association between MTX use and NAFL in a large number of patients (n = 24,653).

Results: In the hospital cohort, 92 patients with NAFL did not show significant differences in the cumulative MTX dose when compared with the no-NAFL group (n = 276) (1908.5 ± 1757.5 vs. 1948.6 ± 2118.8 mg, p = 0.911). The prevalence of NAFL was not significantly different across strata of cumulative MTX dose. Multiple logistic analyses identified hypertriglyceridemia (OR, 4.88 [95% CI, 1.13-20.93]) and higher body mass index (OR, 1.22 [95% CI, 1.05-1.41]) as being associated with an increased risk of NAFL. In the nationwide cohort, the MTX exposure rate between the NAFL and no-NAFL groups was not significantly different.

Conclusions: Collectively, no significant association between NAFL development and administration of MTX was detected in this study. Our results suggest that it is more efficient to adjust for individualized risk factors for NAFL prevention rather than discontinuation of MTX in patients with RA. Key Points • NAFLD has been highlighted with increasing prevalence worldwide and possible progression to end-stage liver disease. • Cumulative dose or exposure history of MTX does not show a significant association with NAFLD prevalence. • Modifying well-established risk factors is more efficient in NAFLD prevention rather than discontinuation of MTX.
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http://dx.doi.org/10.1007/s10067-020-05456-yDOI Listing
May 2021

Tenofovir-based combination therapy or monotherapy for multidrug-resistant chronic hepatitis B: Long-term data from a multicenter cohort study.

J Viral Hepat 2020 12 20;27(12):1306-1318. Epub 2020 Aug 20.

Department of Internal Medicine, Yonsei University Medical College, Seoul, Korea.

The treatment of multidrug-resistant (MDR) chronic hepatitis B (CHB) is challenging. Herein, we report a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)-based therapy for MDR CHB in a real-life setting. The inclusion criteria comprised patients with resistance to more than two nucleos(t)ide analogue (NA) classes and hepatitis B virus (HBV) DNA level of ≥200 IU/mL. The primary end-point was virologic response (VR), defined as undetectable HBV DNA (<20 IU/mL) after 60 months. A total of 236 patients met the inclusion criteria. The mean HBV DNA level was 4.16 ± 1.44 log IU/mL; 26.7% of patients had liver cirrhosis. Before the initiation of TDF, 33.5%, 44.9% and 21.6% of patients had mutations resistant to L-NA + adefovir, L-NA + entecavir (ETV) and L-NA + adefovir + ETV, respectively. A total of 184 patients received TDF-based combination therapy [TDF + ETV (n = 178) or TDF + L-NA (n = 6)], and 52 patients received TDF monotherapy. In the entire cohort, the VR rates were 77.2%, 89.9% and 92.2% at 12, 36 and 60 months, respectively. The VR rates were not significantly different between the combination therapy and the monotherapy group after 12 (76.2% vs 80.4%, P = .533), 36 (89.8% vs 90.3%, P = 1.000) or 60 (92.9% vs 87.5%, P = .499) months. Also, there was no significant difference in the cumulative VR rates for 5 years between the treatment groups (P = .910). Newly developed antiviral resistance was not observed. TDF-based therapy was effective for the treatment of MDR CHB. The efficacy of TDF monotherapy was not different from that of the TDF-based combination therapy.
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http://dx.doi.org/10.1111/jvh.13363DOI Listing
December 2020

An unusual complication of pyloric ring obstruction caused by flange of lumen apposing metal stent in endoscopic ultrasound-guided gallbladder drainage: A case report.

Medicine (Baltimore) 2020 Jul;99(27):e21017

Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.

Introduction: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative treatment option for patients with acute cholecystitis, especially for those who are unsuitable for cholecystectomy. Recently used luminal apposing metal stents (LAMS) in EUS-GBD has several advantages over standard metal stents. However, there is no current guideline on where to locate the LAMS when transgastric approach is required. This study reports a case of gastric outlet obstruction (GOO) by placing LAMS too close to the pyloric ring.

Patient Concerns: A 79-year-old female patient was referred to our department for evaluation of a large hepatic mass on abdominal ultrasound. Abdominal pain on right upper quadrant and spiking fever up to 38 °C appeared after liver biopsy. Abdominal ultrasound showed thickened GB wall and positive sonographic Murphy sign.

Diagnoses: Intrahepatic cholangiocarcinoma with multiple lung and intrahepatic metastasis, acute cholecystitis, and pyloric ring obstruction caused by flange of LAMS in EUS-GBD.

Interventions: EUS-GBD via transgastric approach was performed with LAMS. After complete deployment of stent, esophagogastroduodenoscopy showed complete GOO by flange of LAMS. A gastroduodenal metal stent was inserted to relieve the GOO.

Outcomes: The patient recovered well. She did not complain about obstruction induced symptom such as vomiting or abdominal fullness after gastroduodenal stent insertion.

Conclusion: To the best of our knowledge, this is the first case report of EUS-GBD induced GOO. If physicians use LAMS as a transgastric approach in EUS-GBD, the puncture site should be carefully selected considering the size of the flange.
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http://dx.doi.org/10.1097/MD.0000000000021017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337471PMC
July 2020

Dynamics of liver stiffness-based risk prediction model during antiviral therapy in patients with chronic hepatitis B.

Eur J Gastroenterol Hepatol 2021 06;33(6):885-893

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

Objective: The liver stiffness-based risk prediction models predict hepatocellular carcinoma (HCC) development. We investigated the influence of antiviral therapy (AVT) on liver stiffness-based risk prediction model in patients with chronic hepatitis B (CHB).

Methods: Patients with CHB who initiated AVT were retrospectively recruited from 13 referral Korean institutes. The modified risk estimation for hepatocellular carcinoma in chronic hepatitis B (mREACH-B) model was selected for the analysis.

Results: Between 2007 and 2015, 1034 patients with CHB were recruited. The mean age of the study population (639 men and 395 women) was 46.8 years. During AVT, the mREACH-B score significantly decreased from the baseline to 3 years of AVT (mean 9.21 → 7.46, P < 0.05) and was maintained until 5 years of AVT (mean 7.23, P > 0.05). The proportion of high-risk patients (mREACH-B score ≥11) was significantly reduced from the baseline to 2 years of AVT (36.4% → 16.4%, P < 0.001) and was maintained until 5 years of AVT (12.2%, P > 0.05). The mREACH-B scores at baseline and 1 year of AVT independently predicted HCC development (hazard ratio = 1.209-1.224) (all P < 0.05). The cumulative incidence rate of HCC was significantly different at 5 years of AVT among risk groups (high vs. high-intermediate vs. low-intermediate vs. low) from baseline (4.5% vs. 3.2% vs. 1.5% vs. 0.8%) and 1 year (11.8% vs. 4.6% vs. 1.8% vs. 0.6%) (all P < 0.05, log-rank tests).

Conclusions: The mREACH-B score was dynamically changed during AVT. Thus, repeated assessment of the mREACH-B score is required to predict the changing risk of HCC development in patients with CHB undergoing AVT.
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http://dx.doi.org/10.1097/MEG.0000000000001794DOI Listing
June 2021

Effectiveness and safety of elbasvir/grazoprevir in Korean patients with hepatitis C virus infection: a nationwide real-world study.

Korean J Intern Med 2021 03 17;36(Suppl 1):S1-S8. Epub 2020 Jun 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aim: This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea.

Methods: A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted.

Results: The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naïve and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event.

Conclusion: EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.
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http://dx.doi.org/10.3904/kjim.2019.357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009154PMC
March 2021

Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response.

Clin Mol Hepatol 2020 07 28;26(3):352-363. Epub 2020 May 28.

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

Background/aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.

Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.

Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.

Conclusion: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).
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http://dx.doi.org/10.3350/cmh.2019.0044nDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364362PMC
July 2020

Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase.

Aliment Pharmacol Ther 2020 07 26;52(1):196-204. Epub 2020 May 26.

Yonsei University College of Medicine, Seoul, Korea.

Background: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase.

Aims: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase.

Methods: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes.

Results: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >10  IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001).

Conclusions: The criterion of HBV-DNA level > 10  IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.
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http://dx.doi.org/10.1111/apt.15741DOI Listing
July 2020

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.

Nutrients 2020 May 15;12(5). Epub 2020 May 15.

Medical Research Collabration Center in KNUH and School of Medicine, Kyungpook National University, Daegu 41944, Korea.

Background And Aims: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease.

Methods: Liver cirrhosis patients with Child-Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months.

Results: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score ( = 0.009) and CP score ( = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221-0.684, < 0.001).

Conclusion: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.
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http://dx.doi.org/10.3390/nu12051429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284598PMC
May 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

Effect of Cancer Awareness on Treatment Decision for Pancreatic Cancer Patients.

Korean J Gastroenterol 2020 04;75(4):198-206

Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea.

Background/aims: With recent changes in the treatment of pancreatic cancer, patients' active decision-making has become more important. Nevertheless, it is difficult to give patients proper insights into the disease. The purpose of this study was to determine associated factors between pancreatic cancer awareness and treatment decisions as well as how cancer awareness affects the timing of treatment decisions and the desired treatment method.

Methods: This is a retrospective study that reviewed and analyzed the electronic medical records of 110 patients who were diagnosed with pancreatic cancer from January 2013 to April 2016. A "patient with pancreatic cancer awareness" means that the patient was informed of their disease state before making the first treatment decision.

Results: Of all, only 63.6% of patients (n=70) were shown to have pancreatic cancer awareness before making their first treatment decision. Compared to patients without pancreatic cancer awareness, patients with pancreatic cancer awareness were younger (65.00 vs. 76.98, t=6.70, p<0.001), were more likely to have presented their spouse as legal guardians (42.9% vs. 10.0%, χ=31.70, p<0.001), and spent a shorter time for treatment decision-making (1.6 vs. 10.5 days, t=4.26, p<0.001). The patients without pancreatic cancer awareness were more likely to opt for best supportive care compared to the patients with pancreatic cancer awareness (79.5% vs. 28.6%, χ=31.70, p<0.001).

Conclusions: This study provides insights into cancer awareness. Since cancer awareness appears to influence treatment decision, it is necessary to develop guidelines to improve cancer awareness of patients.
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http://dx.doi.org/10.4166/kjg.2020.75.4.198DOI Listing
April 2020

Multiparametric MR Is a Valuable Modality for Evaluating Disease Severity of Nonalcoholic Fatty Liver Disease.

Clin Transl Gastroenterol 2020 04;11(4):e00157

Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.

Introduction: Because nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease, noninvasive evaluations of its severity are immediately needed. This prospective cross-sectional study evaluated the effectiveness of noninvasive assessments of hepatic steatosis, fibrosis, and steatohepatitis.

Methods: Patients underwent laboratory tests, liver biopsy, transient elastography, and MRI. Multiparametric MR was used to measure MRI proton density fat fraction, MR spectroscopy, T1 mapping, and MR elastography (MRE).

Results: We enrolled 130 patients between October 2016 and July 2019. For the diagnosis of moderate-to-severe steatosis (grade ≥ 2), the area under the receiver operating characteristic curve (AUROC) was lower in controlled attenuation parameter (0.69; 95% confidence interval [CI], 0.60-0.76) than MRI proton density fat fraction (0.82; 95% CI, 0.75-0.89; P = 0.008) and MR spectroscopy (0.83; 95% CI, 0.75-0.89; P = 0.006). For the diagnosis of advanced fibrosis (stage ≥ 3), the AUROC of MRE (0.89; 95% CI, 0.83-0.94) was superior compared with those of the Fibrosis-4 index (0.77; 95% CI, 0.69-0.84; P = 0.010), NAFLD fibrosis score (0.81; 95% CI, 0.73-0.87; P = 0.043), and transient elastography (0.82; 95% CI, 0.74-0.88; P = 0.062). For detecting advanced fibrosis or nonalcoholic steatohepatitis, the AUROC of MRE (0.86; 95% CI, 0.79-0.91) was higher than that of TE (0.76; 95% CI, 0.68-0.83) with statistical significance (P = 0.018).

Discussion: Multiparametric MR accurately identified a severe form of NAFLD. Multiparametric MR can be a valuable noninvasive method for evaluating the severity of NAFLD.
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http://dx.doi.org/10.14309/ctg.0000000000000157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263657PMC
April 2020

Patterns and Outcomes in Hepatocellular Carcinoma Patients with Portal Vein Invasion: A Multicenter Prospective Cohort Study.

Dig Dis Sci 2021 01 13;66(1):315-324. Epub 2020 Feb 13.

Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.

Background And Aims: Sorafenib is a proven first-line treatment recommended for hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). However, multiple treatment modalities are used in clinical practice as a first-line option. This study is a prospective, observational, multicenter, cohort study evaluating patterns of treatment modalities and outcomes for HCC patients with PVI.

Methods: The baseline characteristics, treatment modalities, and outcomes were prospectively collected for 287 newly diagnosed HCC patients with PVI between August 2015 and July 2016 from 16 sites in Korea.

Results: During a median 7.8 months of follow-up (range 0.3-24.6 months), mortality was observed in 123 (42.9%) patients. Decision tree analysis classified patients into five subgroups with different outcomes. The patterns of treatment were very heterogeneous, and there was no dominant treatment modality. The most commonly used treatment modality was transarterial chemoembolization (TACE) (20.2%) followed by TACE plus external beam radiation therapy (17.8%) and sorafenib (12.5%). When stratified according to the extent of PVI, sorafenib treatment showed comparable outcomes when the PVI extent was lobal or main/bilateral, yet showed worse outcomes when the PVI extent was limited to the segmental level compared to those who received treatment other than sorafenib.

Conclusions: HCC patients with PVI comprise a heterogeneous population and are treated with various treatment modalities with diverse clinical outcomes in clinical practice. Subclassification of HCC patients with PVI is required to minimize heterogeneity and should be considered for the selection of treatment modalities and future clinical trials.
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http://dx.doi.org/10.1007/s10620-020-06134-4DOI Listing
January 2021

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose.

Gut Liver 2020 11;14(6):775-782

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection.

Methods: From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention- to-treat (ITT) and per-protocol (PP) analyses.

Results: The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber's discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea.

Conclusions: SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.
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http://dx.doi.org/10.5009/gnl19260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667937PMC
November 2020

Sciatic neuropathy after normal vaginal delivery: A case report.

J Clin Neurosci 2020 Feb 9;72:480-482. Epub 2019 Dec 9.

Department of Rehabilitation Medicine, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea. Electronic address:

Postpartum neuropathies of the lower extremities are possible complications after delivery, with an estimated incidence of 1%. There are a few case reports about sciatic neuropathy after a caesarean section. However, a sciatic neuropathy after normal vaginal delivery has not been reported till date. This is a case report of a 30-year-old woman who visited our department with a chief complaint of left lower extremity weakness after normal vaginal delivery (at gestational age of 38 + 5 weeks) one month prior. The delivery took place under epidural anesthesia for about 6 h, with no dystocia or perinatal complications. She was primiparous, with a medical history of gestational diabetes. Physical examination revealed a lower extremity we;2akness (MRC grade III of left ankle plantar flexor) and a paresthesia at the left posterior calf and sole. Magnetic resonance imaging, nerve conduction studies, and electromyography were performed, and a diagnosis of left sciatic neuropathy proximal to the branch to the biceps femoris muscle was made. After 3 months, her motor weakness and paresthesia resolved spontaneously. In addition, the follow-up nerve conduction studies and electromyography confirmed a near complete recovery of the left sciatic neuropathy. In conclusion, sciatic neuropathy can occur after normal vaginal delivery even without dystocia and perinatal complications. The sciatic neuropathy in the case presented here had a good prognosis.
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http://dx.doi.org/10.1016/j.jocn.2019.11.031DOI Listing
February 2020

Biofilm Formation by Clinical Isolates is Differentially Affected by Glucose and Sodium Chloride Supplemented Culture Media.

J Clin Med 2019 Nov 2;8(11). Epub 2019 Nov 2.

Department of Laboratory Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Korea.

() causes persistent biofilm-related infections. Biofilm formation by is affected by the culture conditions and is associated with certain genotypic characteristics. Here, we show that glucose and sodium chloride (NaCl) supplementation of culture media, a common practice in studies of biofilms , influences both biofilm formation by 40 clinical isolates (methicillin-resistant and methicillin-sensitive ) and causes variations in biofilm quantification. Methicillin-resistant strains formed more robust biofilms than methicillin-sensitive strains in tryptic soy broth (TSB). However, glucose supplementation in TSB greatly promoted and stabilized biofilm formation of all strains, while additional NaCl was less efficient in this respect and resulted in significant variation in biofilm measurements. In addition, we observed that the ST239-SCC (Staphylococcal Cassette Chromosome ) type III lineage formed strong biofilms in TSB supplemented with glucose and NaCl. Links between biofilm formation and accessory gene regulator () status, as assessed by δ-toxin production, and with mannitol fermentation were not found. Our results show that TSB supplemented with 1.0% glucose supports robust biofilm production and reproducible quantification of biofilm formation , whereas additional NaCl results in major variations in measurements of biofilm formation.
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http://dx.doi.org/10.3390/jcm8111853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912320PMC
November 2019

Real-life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance-associated substitution test.

J Med Virol 2019 12 9;91(12):2158-2165. Epub 2019 Sep 9.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.

This study aimed to investigate the real-life effectiveness and safety of daclatasvir (DCV) and asunaprevir (ASV) combination therapy in Korean patients. We consecutively enrolled patients with genotype 1b hepatitis C virus (HCV) infection treated with at least one dose of DCV/ASV combination therapy in seven tertiary hospitals of South Korea. The sustained virologic response (SVR) rates and safety according to intention-to-treat (ITT) and per-protocol (PP) analyses were evaluated. Among the 526 enrolled patients, 91% showed negative (87%) or "undetermined" (4%) resistance-associated substitution (RAS); 9% did not undergo RAS testing. The SVR rates for ITT and PP were 89.3% and 95.0% in treatment-naive patients and 93.2% and 95.6% in treatment-experienced patients, respectively. In PP analysis, negative RAS was associated with higher SVR (96.3%) than with "undetermined RAS" (85.7%) or "not tested for RAS" (84.4%). Adverse events were reported in 185 (35.4%) patients, and events leading to discontinuation were observed in 4.3% of the study population. Forty-two (8.0%) patients developed transaminase elevation (≥2 × upper normal limit), resulting in treatment discontinuation in six (1.1%) patients. DCV/ASV combination therapy showed acceptable efficacy in genotype 1b compensated HCV-infected patients with negative pretreatment RAS. Although most adverse events were tolerable to continue antiviral treatment, adequate monitoring for transaminase elevation is warranted.
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http://dx.doi.org/10.1002/jmv.25575DOI Listing
December 2019

Parthenolide inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in colorectal cancer cells.

Intest Res 2019 Oct 23;17(4):527-536. Epub 2019 Aug 23.

Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University, and Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.

Background/aims: Transforming growth factor-β1 (TGF-β1) induction of epithelial-mesenchymal transition (EMT) is one of the mechanisms by which colorectal cancer (CRC) cells acquire migratory and invasive capacities, and subsequently metastasize. Parthenolide (PT) expresses multiple anti-cancer and anti-inflammatory activities that inhibit nuclear factor κB by targeting the IκB kinase complex. In the present study, we aimed to investigate whether PT can inhibit TGF-β1-induced EMT in CRC cell lines.

Methods: HT-29 and SW480 cell lines were used in the experiment. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sub-G1 analysis was measured by flow cytometry. The induction of EMT by TGF-β1 and inhibition of the process by PT was analyzed by phase contrast microscopy, wounding healing, cellular migration and invasion assays, and Western blotting.

Results: TGF-β1 inhibits HT-29 cell proliferation, but has no effect on SW480 cell proliferation; different concentrations of TGF-β1 did not induce apoptosis in HT-29 and SW480 cells. PT attenuates TGF-β1-induced elongated, fibroblast-like shape changing in cells. PT inhibits TGF-β1-induced cell migration and cell invasion. In addition, other EMT markers such as β-catenin, Vimentin, Snail, and Slug were suppressed by PT, while E-cadherin was increased by PT.

Conclusions: Our findings show that PT inhibits TGF-β1-induced EMT by suppressing the expression of the mesenchymal protein and increasing expression of the epithelial protein. These findings suggest a novel approach for CRC treatment by suppression of TGF-β1-induced EMT.
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http://dx.doi.org/10.5217/ir.2019.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821947PMC
October 2019

A comparative evaluation of BACT/ALERT FA PLUS and FN PLUS blood culture bottles and BD BACTEC Plus Aerobic and Anaerobic blood culture bottles for antimicrobial neutralization.

Eur J Clin Microbiol Infect Dis 2019 Dec 2;38(12):2229-2233. Epub 2019 Aug 2.

Department of Laboratory Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 150 Sungan-ro, Kangdong-gu, Seoul, 05355, South Korea.

The performance of BACT/ALERT FA and FN PLUS (FA PLUS and FN PLUS) blood culture bottles with the BACT/ALERT VIRTUO (bioMérieux, Inc., Durham, NC) and BD BACTEC Plus Aerobic and Anaerobic (BD Aerobic and BD Anaerobic) blood culture bottles with the BD BACTEC FX (BD Diagnostics, Sparks, MD) for antimicrobial neutralization at peak serum concentration was evaluated. The following antibiotic agents and microbial strains were used: ampicillin, cefepime, cefotaxime, gentamicin, levofloxacin, meropenem, piperacillin-tazobactam, and vancomycin; methicillin-sensitive Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis. The detection rate of FA PLUS bottles was 69.1% (259/375) and that of BD Aerobic bottles was 75.5% (283/375) (p = 0.050). In the case of anaerobic culture, the overall detection rate of FN PLUS bottles was 77.0% (231/300) and that of BD Anaerobic bottles was 71.3% (214/300) (p = 0.113). The time to detection (TTD) from aerobic culture was 2.8 h shorter in FA PLUS bottles (12.4 h) compared to BD Aerobic bottles (15.2 h) (p < 0.001). And the TTD from anaerobic culture was 1.6 h shorter in FN PLUS bottles (18.1 h) compared to BD Anaerobic bottles (19.7 h) (p = 0.061). The FA PLUS bottles exhibited a lower detection rate compared to BD Aerobic bottles, while FN PLUS bottles showed a higher detection rate compared to BD Anaerobic bottles. The BACT/ALERT VIRTUO system exhibited shorter TTD compared to the BD BACTEC FX system for both aerobic and anaerobic cultures.
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http://dx.doi.org/10.1007/s10096-019-03663-3DOI Listing
December 2019

Epidemiological and Clinical Characteristics of Hepatitis C Virus Infection in South Korea from 2007 to 2017: A Prospective Multicenter Cohort Study.

Gut Liver 2020 03;14(2):207-217

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: This study aimed to elucidate the epidemiological and clinical characteristics of chronic hepatitis C (CHC) patients in South Korea from 2007 to 2017 and to compare the treatment patterns between two periods before and after the first approval of direct-acting antivirals (DAA) in South Korea in 2015.

Methods: This prospective, multicenter cohort enrolled 2,758 patients with hepatitis C virus (HCV) viremia at seven tertiary centers, and clinical data were prospectively collected with questionnaire surveys focused on lifetime risk factors related to HCV infection.

Results: The HCV patients had a mean age of 57.3 years (50.8% male). Among them, 14.3% showed a positive history of transfusion before HCV screening and 5.6% reported intravenous drug use (IVDU), with significant differences in these risk factors between men and women. The proportions of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) were 69.5%, 18.9%, and 11.5%, respectively. The mean alanine aminotransaminase level was within the upper normal limit at 49.9%, and the major genotypes were 1b (48.2%) and 2 (46.4%). The overall treatment rate was 53.8%, showing a rapid transition from interferon-based therapy to DAA therapy. In the post-DAA-approval era, the untreated group was older, had a higher prevalence of HCC, and had less education than the treated group.

Conclusions: More than 90% of CHC patients were over 40 years old, the major genotypes were 1b and 2, and IVDU was observed in less than 6% of CHC patients. Approximately half of the patients underwent antiviral therapy even in the DAA era, showing an unmet need with regard to HCV elimination.
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http://dx.doi.org/10.5009/gnl19005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096238PMC
March 2020

Down-regulation of miR-9 promotes epithelial mesenchymal transition via regulating anoctamin-1 (ANO1) in CRC cells.

Cancer Genet 2019 02 27;231-232:22-31. Epub 2018 Dec 27.

Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk 54907, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea. Electronic address:

MicroRNA-9 (miR-9) has been reported to play a suppressive or promoting role according to cancer type. In this study, we investigated the effects of anoctamin-1 (ANO1) and miR-9 on colorectal cancer (CRC) cell proliferation, migration, and invasion and determined the underlying molecular mechanisms. Thirty-two paired CRC tissues and adjacent normal tissues were analyzed for ANO1 expression using quantitative real-time PCR (qRT-PCR). HCT116 cells were transiently transfected with miR-9 mimic, miR-9 inhibitor, or si-ANO1. Cell proliferation was determined by MTT, and flow cytometric analysis, while cell migration and invasion were assayed by trans-well migration and invasion assay in HCT116 cells. ANO1 was validated as a target of miR-9 using luciferase reporter assay and bioinformatics algorithms. We found that ANO1 expression was up-regulated in CRC tissues compared with adjacent normal tissues. ANO1 expression was associated with advanced tumor stage and lymph node metastasis, and there was an inverse relationship between miR-9 and ANO1 mRNA expression in CRC specimens, but no significant difference was found between miR-9 and ANO1 expression. ANO1 is a direct target of miR-9, and overexpression of miR-9 suppressed both mRNA and protein expression of ANO1 and inhibited cell proliferation, migration, and invasion of HCT116 cells. We also showed that overexpression of miR-9 suppressed expression of p-AKT, cyclin D1, and p-ERK in HCT116 cells. We conclude that miR-9 inhibits CRC cell proliferation, migration, and invasion by directly targeting ANO1, and miR-9/ANO1 could be a potential therapeutic target for CRC.
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http://dx.doi.org/10.1016/j.cancergen.2018.12.004DOI Listing
February 2019

Treatment Outcome and Renal Safety of 3-Year Tenofovir Disoproxil Fumarate Therapy in Chronic Hepatitis B Patients with Preserved Glomerular Filtration Rate.

Gut Liver 2019 01;13(1):93-103

Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.

Background/aims: To investigate the treatment efficacy and renal safety of long-term tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients with preserved renal function.

Methods: The medical records of 919 CHB patients who were treated with TDF therapy were reviewed. All patients had preserved renal function with an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m².

Results: A total of 426 patients (184 treatment-naïve and 242 treatment-experienced) were included for analysis. A virologic response (VR) was defined as achieving an undetectable serum hepatitis B virus (HBV) DNA level, and the overall VR was 74.9%, 86.7%, and 89.4% at the 1, 2, and 3-year follow-ups, respectively. Achieving a VR was not influenced by previous treatment experience, TDF combination therapy, or antiviral resistance. In a multivariate analysis, being hepatitis B e antigen positive at baseline and having a serum HBV DNA level ≥2,000 IU/mL at 12 months were associated with lower VR rates during the long-term TDF therapy. The overall renal impairment was 2.9%, 1.8%, and 1.7% at the 1, 2, and 3-year follow-ups, respectively. With regard to renal safety, underlying diabetes mellitus (DM) and an initial eGFR of 60 to 89 mL/min/1.73 m² were significant independent predictors of renal impairment.

Conclusions: TDF therapy appears to be an effective treatment option for CHB patients with a preserved GFR. However, patients with underlying DM and initial mild renal dysfunction (eGFR, 60 to 89 mL/min/1.73 m²) have an increased risk of renal impairment.
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http://dx.doi.org/10.5009/gnl18183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347000PMC
January 2019
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