Efficacy of Long-Term Tenofovir-Based Therapy in Chronic Hepatitis B Patients with Previous Nucleos(t)ide Analogues Treatment Experience

( Na Eun Lee ),( Hong Seon Son ),( Sung Hoon Choi ),( Chang Hun Lee ),( Seung Young Seo ),( Seong Hun Kim ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ),( In Hee Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Tenofovir disoproxil fumarate (TDF) is considered as the preferred treatment option for chronic hepatitis B (CHB) patients with treatment failure or resistance to prior nucleos(t)ide analogues (NAs) treatment. We investigated the efficacy of long-term TDF-based therapy in CHB patients with previous NAs-experience. Methods: This study included total 251 patients who had previous history of NAs therapy and were treated with TDF mono (n=173) or TDF combined with other NA (n=78) from August 2012 to March 2017. Virologic response (VR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL). Results: Mean age of patients was 49.3 years, median duration of TDF therapy was 27.2 months, 75.7% were HBeAg-positive, and median HBV DNA was 3.7 log10IU/mL. The cumulative rates of VR were 188/244 (77.0%), 180/211 (85.3%), and 146/161 (90.7%) at 12, 24, and 36 months, respectively. Multivariate analysis showed that body mass index (OR 0.77, 95% CI 0.61-0.95, p=0.0189) and duration of TDF therapy (OR 1.09, 95% CI 1.02-1.18, p=0.0221) was significantly associated with VR. TDF monotherapy, HBeAg-positivity, platelet count, serum albumin was associated with VR in the univariate analysis, but not significant in the multivariate analysis. In relation to renal safety, patients showed renal impairment (7, 3.0%), mild hypophosphatemia (15, 7.2%), severe hypophosphatemia (1, 0.4%). Conclusions: Long-term TDF-based therapy demonstrated highly effective in viral suppression and relatively favorable renal safety in CHB patients with previous NA-experience. The body mass index and duration of TDF therapy was independent factors associated with VR.

Original Articles : Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer Lines

( Hyun Ju Lee ),( Ja Sung Rho ),( Shao Ran Gui ),( Mi Kyung Kim ),( Yu Kyoung Lee ),( Yeon Sook Lee ),( Jeong Eun Kim ),( Eu Na Cho ),( Mong Cho ),( Tae Ho Hwang ) 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3

Background/Aims: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. Methods: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. Results: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na+/H+-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. Conclusions: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H+ gradient. (Korean J Hepatol 2011;17:213-219)

Comparison of Virologic Response and Renal Safety of Long-Term Antiviral Therapy with Tenofovir and Entecavir in Naive Patient with Chronic Hepatitis B

( Hong Seon Son ),( Sung Hoon Choi ),( Na Eun Lee ),( Chang Hun Lee ),( Seung Young Seo ),( Seong Hun Kim ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ),( In Hee Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Tenofovir (TDF) entecavir (ETV) are considered as the preferred treatment options for treatment-naïve chronic hepatitis B (CHB) patients. We compared the virologic response and renal safety of long-term TDF versus ETV therapy in naïve CHB patients. Methods: This retrospective study included total 432 patients who were treated with TDF (n=205) or ETV (n=227) from August 2012 to March 2017. Virologic response (VR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL). Results: Mean age of patients, sex, baseline serum levels of AST, ALT, creatinine, and HBV DNA were not significantly different between TDF and ETV groups. The cumulative rates of VR between TDF and ETV groups were 71.6% vs. 61.8% (p=0.477), 88.1% vs. 79.6% (p=0.058), and 84.8% vs. 83.7% (p=0.966) at 1, 2, and 3 years, respectively. The cumulative rates of genotypic resistance between TDF and ETV groups were 0% vs. 0%, 0% vs. 1.5% (p=0.404), and 0% vs. 2.2% (p=0.447) at 1, 2, and 3 years, respectively. Incidences of renal impairment and hypophosphatemia during treatment up to 3 years were not significantly different between two groups. Multivariate analysis showed that HBeAg-positivity (OR 0.27, 95% CI 0.12-0.58, p=0.0012) and serum HBV DNA at 1 year 2000 IU/mL (OR 0.09, 95% CI 0.03-0.25, p<0.0001) were significantly associated with VR. Conclusions: Long-term TDF and ETV treatments appear to have similar virologic response and renal safety in naïve CHB patient. However, long-term ETV therapy might to be associated with genotypic resistance in 2.2% up to 3 years, while none of patients on TDF therapy did.

Rebuilding a Support System for Vulnerable Populations in Disasters - Lessons from USA and Japan -

Sung Soo Byun,Do Hyeong Kim,Jae Eun Lee,Jeong Il Na,Seong Cho,Ga Hee Kim 위기관리 이론과 실천 2018 Crisisonomy Vol.14 No.5

재난약자 및 재난 특성에 따라 여성가족부, 보건복지부, 행정안전부 등 소관 부처에 따라 개별적 정책 수립 및 지원이 이루어지고 있다. 또한 재난발생시 대응 및 복구 과정에서의 재난약자에 대한 지원 대책도 갖추고 있지 않다. 이에 이 연구는 재난약자에 대한 지원체계 개선 방안 제시를 목적으로 하고 있다. 또한 연구 목적 달성을 위해, 미국, 일본 등 재난관리 선진국의 재난약자 보호 및 지원을 위한 제도 및 체계를 비교분석하여 그 시사점을 찾고자 한다. 연구의 목적을 달성하기 위해, 이 연구는 우리나라의 재난약자 지원 현황을 분석하였으며, 외국의 재난약자 지원체계 사례를 분석하여 시사점 을 도출하였다. 이 연구는 해외사례에서 도출된 시사점을 바탕으로 우리나라의 재난약자 지원체계 개선을 위한 3가지 방안을 제시하였다. 첫째 법령체계 개선과 관련하여 재난약자 관련 대상 및 업무의 명확화와 지방자치단체의 재난약자 지원 관련 조례의 개선을 제시하였다. 둘째, 재난약자 피해경감을 위하여, 재난약자 신속 대피지원 강화, 재난약자 지원을 위한 공공 및 민간 조직간 협력 강화 등이 요구된다. 셋째, 노인, 장애인, 영유아 등에 따라 주관하는 부처 및 부서가 다르기 때문에 통합적 지원체계 구축에는 어려움이 있다. 이에 재난약자 지원체계는 재난약자 지원관련 계획 수립 및 교육은 각 개별기관에서 진행하며, 지원에 필요한 인력⋅예산⋅장비 등은 총괄기관에서 담당하는 방향으로 구축하는 것이 효율적일 것으로 판단된다. The policy design and implementation processes for vulnerable populations in disasters are scattered across various governmental agencies in Korea including the Ministry of Gender Equality and Family, the Ministry of Health and Welfare and the Ministry of Public Administration and Security, depending on the type of the vulnerable and the nature of the disaster. Moreover, there is no effective strategy to assist the vulnerable during the processes of disaster response and recovery. Therefore, this study aims to improve the support system for the victims of disasters in Korea by analyzing and comparing the U.S. and Japanese systems of protecting and supporting the vulnerable. Based on the lessons from the two countries, we analyze the current status of disaster support system in Korea and draw implications for policymakers and practitioners in Korea. In conclusion, the study suggests several measures to improve the support system for the vulnerable in Korea, including legal reform, organizational reconstruction, and clear identification of tasks and responsibilities among relevant government agencies.

EC-SOD Suppresses Contact Hypersensitivity in Mouse Skin by Impairing Langerhans Cell Migration

Na, Kwangmin,Kim, Kyoung-Eun,Park, Sang-Tae,Kim, Tae-Yoon The Society for Investigative Dermatology, Inc 2007 The Journal of investigative dermatology Vol.127 No.8

Extracellular superoxide dismutase (EC-SOD) is primarily a tissue enzyme and has been implicated in the modulation of inflammatory response. The biological role of EC-SOD in skin, however, has rarely been investigated. In this study, we aim to explore the effects of EC-SOD on the inflammatory response in skin by evaluating the contact hypersensitivity response (CHS) in EC-SOD transgenic mice. Transgenic mice with skin-specific expression of EC-SOD were sensitized and challenged with 2,4,6-trinitro-1-chlorobenzene (TNCB), followed by measurement of ear swelling. EC-SOD transgenic mice showed significantly reduced CHS responses compared with wild-type mice. Histological evaluation of the challenged ears of EC-SOD transgenic mice revealed diminished infiltration of inflammatory cells with a failure to induce expression of inflammatory cytokines, such as tumor necrosis factor-α and IFN-γ, on sensitization and challenge with TNCB. Furthermore, Langerhans cell migration to lymph nodes was impaired in EC-SOD transgenic mice. These results indicate that EC-SOD downregulates CHS through inhibition of the inflammatory response, suggesting a possible therapeutic regimen in inflammatory skin diseases.Journal of Investigative Dermatology (2007) 127, 1930–1937; doi:10.1038/sj.jid.5700802; published online 29 March 2007

Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma

Na, Keun,Lee, Eun-Young,Lee, Hyoung-Joo,Kim, Kwang-Youl,Lee, Hanna,Jeong, Seul-Ki,Jeong, An-Sung,Cho, Sang Yun,Kim, Sun A.,Song, Si Young,Kim, Kyung Sik,Cho, Sung Won,Kim, Hoguen,Paik, Young-Ki WILEY-VCH Verlag 2009 Proteomics Vol.9 No.16

<P>To identify and characterize a serologic glycoprotein biomarker for hepatocellular carcinoma (HCC), multi-lectin affinity chromatography was used to isolate intracellular N-linked glycoprotein fractions from five paired non-tumor and tumor tissues. From the series of 2-D DIGE targeted differentially expressed N-linked glycoproteins, we identified human liver carboxylesterase 1 (hCE1), which was remarkably down-regulated in tumor tissues, a finding confirmed by Western blot, a quantitative real-time RT-PCR, and immunohistochemical staining of non-tumor and tumor tissues from total 58 HCC patients. To investigate whether hCE1 is also present in human plasma, we employed a magnetic bead-based immunoprecipitation followed by nano-LC-MS/MS analysis, and we found for the first time that hCE1 is present in human plasma as opposed to that in liver tissues. That is, from normalization of hCE1 signal by the immunoprecipitation and Western blot analysis, hCE1 levels were increased in plasma specimens from HCC patients than in plasma from other disease patient groups (e.g. liver cirrhosis, chronic hepatitis, cholangiocarcinoma, stomach cancer, and pancreatic cancer). From the receiver operating characteristic analysis in HCC, both sensitivity and specificity were shown to be greater than 70.0 and 85.0%, respectively. Thus, the high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC.</P>

The Association Between Tachycardia and Mortality in Septic Shock Patients According to Serum Lactate Level: A Nationwide Multicenter Cohort Study

Na Soo Jin,Oh Dong Kyu,Park Sunghoon,Lee Yeon Joo,Hong Sang-Bum,Park Mi Hyeon,Ko Ryoung-Eun,Lim Chae-Man,Jeon Kyeongman 대한의학회 2023 Journal of Korean medical science Vol.38 No.40

Background: This study aimed to evaluate whether the effect of tachycardia varies according to the degree of tissue perfusion in septic shock. Methods: Patients with septic shock admitted to the intensive care units were categorized into the tachycardia (heart rate > 100 beats/min) and non-tachycardia (≤ 100 beats/min) groups. The association of tachycardia with hospital mortality was evaluated in each subgroup with low and high lactate levels, which were identified through a subpopulation treatment effect pattern plot analysis. Results: In overall patients, hospital mortality did not differ between the two groups (44.6% vs. 41.8%, P = 0.441), however, tachycardia was associated with reduced hospital mortality rates in patients with a lactate level ≥ 5.3 mmol/L (48.7% vs. 60.3%, P = 0.030; adjusted odds ratio [OR], 0.59, 95% confidence interval [CI], 0.35–0.99, P = 0.045), not in patients with a lactate level < 5.3 mmol/L (36.5% vs. 29.7%, P = 0.156; adjusted OR, 1.39, 95% CI, 0.82–2.35, P = 0.227). Conclusion: In septic shock patients, the effect of tachycardia on hospital mortality differed by serum lactate level. Tachycardia was associated with better survival in patients with significantly elevated lactate levels.

Indeterminate leprosy presented as a hypoaesthetic ill-defined whitish patch

( Sang Hyun Park ),( Ga Hye Na ),( Soo Hyun Noh ),( Jin Kyung Chae ),( Eun Jung Kim ),( Kun Park ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which primarily affects the skin and peripheral nerves. Indeterminate leprosy is the early phase of Hansen disease before the host makes a definitive immunologic commitment. A 23-year old male patient from Sri-Lanka presented with a hypoaestheticskin lesion on his right elbow which had been present for 2 years. It had started as a small whitish macule but progressed to an ill-defined large scaly whitish patch (5cm x 5 cm). There was no thickening and/or tenderness of ulnar and radial nerve. There was no family history of leprosy or any apparent preceding immune suppression or trauma prior to development of the skin lesion. Lepromin test was negative. Histopathological examination of a biopsy taken from the lesion showed patchy lymphohistiocytic infiltrate around the skin appendage and dermal nerve and perivascular area. No epithelioid granulomatous infiltration was found and no acid-fast bacilli (AFB) were detected in the section after Fite-AFB staining. Polymerase chain reaction testing for M. leprae was negative. PGL-1 antibody test was also performed but the result was negative. We clinically diagnosed indeterminate leprosy and administered rifampin 600mg, ofloxacin 400mg, and minocycline 100mg daily for 6 months. At present, the skin lesion shows partial improvement and sensory anomaly has subsided.

Case Report : Two cases of telbivudine-induced myopathy in siblings with chronic hepatitis B

( Eun Hye Kim ),( Ha Na Park ),( Kun Ho Lee ),( Sang Hoon Ahn ),( Seung Min Kim ),( Kwang Hyub Han ) 대한간학회 2013 Clinical and Molecular Hepatology(대한간학회지) Vol.19 No.1

Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine has a more potent and sustained antiviral activity with a lower frequency of viral resistance than lamivudine. Although there are several reports concerning the safety profile of telbivudine, most adverse events are described as mild and transient in nature. Here we report two cases of telbivudine-induced myopathy in patients with chronic hepatitis B who were siblings. (Clin Mol Hepatol 2013;19:82-86)

Critically Ill Patients with Pandemic Influenza A/H1N1 2009 at a Medical Center in Korea

( Eun Young Choi ),( Jin Won Huh ),( Chae Man Lim ),( Youn Suck Koh ),( Sung Han Kim ),( Sang Ho Choi ),( Won Young Kim ),( Won Kim ),( Mi Na Kim ),( Sang Bum Hong ) 대한결핵 및 호흡기학회 2011 Tuberculosis and Respiratory Diseases Vol.70 No.1

Background: The aim of the study was to describe the characteristics, treatments, and outcomes of critically ill patients with pandemic Influenza A/H1N1 2009 at a major medical center in Korea. Methods: This retrospective observational study examined critically ill adult patients with pandemic Influenza A/H1N1 2009, who were admitted to the AMC between August and December 2009. Results: 27 patients with confirmed pandemic Influenza A/H1N1 2009 were admitted to the intensive care unit (ICU) at the Asan Medical Center (AMC). The median age (IQR) was 59 years (41∼67), and 66.7% of the patients were older than 51 years. A total of 81.5% of the patients had 2 or more co-morbidities. The median time (IQR) from symptom onset to presentation was 2 days (1∼4), and the median time from presentation to ICU admission was 0 days (0∼1.5). All patients received oseltamivir (300 mg/day) and 13 patients received triple combination therapy (oseltamivir, amantadine, ribavirin). Twelve patients required mechanical ventilation on the first day of ICU admission. A total of 6 patients (22.2%) died within 28 days of admission. The patients who died had significantly higher acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores at presentation. There were no significant differences in age, co-morbidities, or antiviral regimens between survivors and non-survivors. Conclusion: Critical illness related to pandemic Influenza A/H1N1 2009 was common in elderly patients with chronic co-morbidities. All patients were given high-dose oseltamivir or triple combination antiviral therapy. Nonetheless, patients with critical illnesses associated with pandemic Influenza A/H1N1 2009 had a death rate of 22.2%.