만성 B형 간염에서 라미부딘 치료중 발생한 Viral Breakthrough 예의 임상 결과

안수현,장윤정,오성남,최도원,백수정,정원석,최창원,김경오,임형준,조남영,박종재,김재선,박영태,이명석,연종은,변관수,이창홍 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.4

목적: 만성 B형 간염의 치료 중 발생하는 약제 내성 변이종은 임상적으로는 치료 중 음전되었던 혈청 HBV DNA가 다시 양전되는 viral breakthrough 로 진단할 수 있다. 현재 약제 내성 변이종이 발생했을 경우라도 라미부딘 치료를 계속 유지하는 것을 권장하고 있으나, viral breakthrough 발생 예들의 장기적 임상경과가 아직도 불명확하여 이것을 일반화하기는 어려운 상황이다. 이에 라미부딘 사용 중 viral breakthrough 가 발생한 예들을 대상으로 그 임상경과를 알아보고자 하였다. 대상과 방법: 9개월 이상 라미부딘을 투약한 만성 B형 간염 환자로 viral breakthrough가 발생한 74명을 대상으로 하였다(남/여 54/20, 평균연령 42세). Viral breakthrough 후 혈청 ALT치, 총 빌리루빈치, HBV DNA 역가, HBeAg, anti-HBe를 정기적으로 검사하면서 임상경과를 관찰하였다. Viral breakthrough 후 라미부딘의 투약기간은 평균 13개 월(1-41개월)이었다. 결과: Viral breakthrough 발생후 혈청 ALT치가 정상으로 유지되었던 환자는 8예(11%)에 불과했고 나머지 66예(89%)에서는 ALT치가 증가하였으며, 이중 30예(41%)에서 급성 악화(ALT 정상 상한치의 5배 이상 상승)를 보였다. 급성악화는 viral breakthrough 후 3개월 내에 19예 (63%)에서 발생하여 3개월 내에 발생한 예가 많았으나 12개월 이상 지나서 나타나는 예도 약 20%에서 있었다. 비대상성 악화는 6예에서 관찰되었다. Viral breakthrough 후 급성악화가 일어난 예와 없었던 예의 비교에서 급성악화를 예측할 수 있는 인자는 발견할 수 없었다. Viral breakthrough 후 발견할 수 없었다. Viral breakthrough 후 HBeAg이 음전된 예는 8예(11%)였으나 그 임상경과는 양호하지 않았다. 결론: 만성 B형 간염 환자 에서 라미부딘 투여 중 발생한 viral breakthrough 예 중 상당수에서 급성악화가 발생하였으며, HBeAg 이 소실되더라도 그 임상경과는 양호하지만은 않았다. Viral breakthrough 발생 후 주의 깊은 임상경과 의 관찰이 요구되며, 앞으로 viral breakthrough 후 급성악화 예에 대한 대규모 연구와 적절한 치료방향의 제시가 이루어져야 할 것으로 생각된다. Background/Aims: Long-term lamivudine therapy can induce the emergence of lamivudine resistant hepatitis B virus (HBV) mutants. Clinically emergence of the mutant is expressed by the reappearance of disappeared HBV DNA in serum. Continued lamivudine treatment has been usually recommended in cases of viral breakthrough. However, the clinical outcome in patients with viral breakthrough is not clear. The aim of this study was to investigate the clinical course of chronic hepatitis B patients after viral breakthrough during lamivudine therapy. Methods: A total of 74 patients with chronic hepatitis B who showed viral breakthrough after at least 6 months of lamivudine treatment were included in this study. They had positive HBeAg and HBV DNA before treatment. The median follow-up duration after breakthrough was 13 months. Results: After viral breakthrough, only 8 patients (11%) maintained normal ALT levels and 66 patients (89%) showed elevation of ALT. 30 patients (41%) showed acute exacerbation of hepatitis (ALT increase over five-times upper normal limit). These acute exacerbations occurred within three months after breakthrough in 19 patients (63%). In the cases of acute exacerbation, 6 patients showed decompensated progression such as elevation of serum total bilirubin. One of them died of hepatic failure. A predictive factor for acute exacerbation was not found. HBeAg seroconversion occurred in 8 patients after viral breakthrough but their clinical course was highly variable. Conclusions: Chronic hepatitis B patients who had viral breakthrough during lamivudine therapy should be followed carefully and regularly in mind of potential clinical deterioration. New strategies are needed to manage the cases of acute exacerbation after viral breakthrough.(Korean J Hepatol 2002;8:389-396)

국가예방접종전산등록체계 개발을 위한 민간의료 기관 하부구조 및 환경 조사연구

이무식,김은영,이건세,이석구,홍지영,김건엽,김대경,신의철,이연경,기몽서,나백주,김영택 한국모자보건학회 2003 한국모자보건학회지 Vol.7 No.2

頭痛에 관한 精神醫學的 硏究

羅澈,李吉弘,李在光,奇柏錫,李在禹,兪英植,李永植 서울醫大 1990 精神醫學 Vol.15 No.3

The Direct Comparison between 7th AJCC Staging System and 8th AJCC Staging System for Prediction of Survival with Korean Multicenter HCC Patients

( Young-sun Lee ),( Sung Won Chang ),( Ha Seok Lee ),( Haein Bak ),( Sehwa Kim ),( Min-jin Lee ),( Chan Uk Lee ),( Young Kul Jung ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: AJCC staging is the most commonly used staging system in most solid tumors, and recent AASLD hepatocellular carcinoma (HCC) guideline also endorsed this AJCC staging system based on status of tumor, node, and metastasis. Recently, 8th edition of AJCC staging system was released in December 2016. This study aimed to compare prediction of survival in HCC patients between 7th AJCC staging system and 8th AJCC staging system. Methods: From 2004 to 2013, 2211 newly diagnosed HCC patients were consecutively enrolled in three Korea University medical centers and the medical records of patients were retrospectively reviewed. Each patients were classified following both of 7th AJCC staging system and 8th AJCC staging system. Results: Chronic hepatitis B (1523, 68.9%) was main attributable factor in development of HCC, followed by chronic hepatitis C (256, 11.6 %) and alcohol consumption (241, 10.9%). 1514 patients (68.5%) died during study period and median overall survival (OS) was 24.7 months. According to 7th AJCC staging system, 894 (40.4%) patients were included into stage I; 459 patients (20.8%) into stage II; 180 patients (8.1%) into stage IIIa; 354 patients (16.0%) into stage IIIb; 3 patients (0.1%) into stage IIIc; 119 patients (5.4%) into stage IVa; and 202 patients (9.1%) into stage IVb. According to 8th AJCC staging system, 400 (18.1%) patients were categorized into stage IA; 498 patients (22.5%) into stage IB; 442 patients (20.2%) into stage II; 193 patients (8.7%) into stage IIIa; 357 patients (16.1%) into stage IIIb; 119 patients (5.4%) into stage IVa; and 202 patients (9.1%) into stage IVb. Both 7th staging system and 8th staging system show distinct survival outcomes according to each stage. Although 7th AJCC staging system significantly well predicted 1 year of survival than 8th AJCC staging system (AUROC; 0.796 vs 0.784, P=0.013), AUROCs of 3 year and 5 year were similar in 7th and 8th AJCC staging system (0.754 vs 0.752 in 3 year, P=0.601; 0.744 vs 0.742 in 5 year, P=0.643). Conclusions: Both 7th and 8th AJCC staging system show distinct survival outcome according to each stage. Moreover, both 7th and 8th AJCC staging system are similar in prediction of survival outcomes.

NAFLD Is Associated with High Prevalence and High Recurrence Rate in Patients with Breast Cancer

( Young-sun Lee ),( Sung Won Chang ),( Ha Seok Lee ),( Haein Bak ),( Sehwa Kim ),( Min-jin Lee ),( Chan Uk Lee ),( Young Kul Jung ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Breast cancer is most common cancer in women worldwide. The incidence of breast cancer is correlated with metabolic component including diabetes, hypertension, and obesity. Likewise breast cancer, metabolic components are important risk factors for development of NAFLD. In this study, we analyzed the prevalence of NAFLD in patients with breast cancer and the effect of NAFLD on the prognosis of breast cancer. Methods: Patients with breast cancer were enrolled from January 2007 to June 2017. Patients who had other chronic liver were excluded. Hepatic steatosis was evaluated by non-enhanced CT scan. We diagnosed NAFLD when the mean attenuation of the liver is lower than 40 HU or 10 HU lower than that of the spleen. 123 healthy controls who took non-enhanced CT scan were also analyzed. Results: Total 1587 patients were enrolled from January 2007 to June 2017. The prevalence of NAFLD in patients with breast cancer was 15.8% (251/1587) and it was significantly higher comparing with healthy control (8.9%, 11/123)(P=0.036). After propensity score matching, the difference of NAFLD prevalence was still significant between control group (8.9%, 11/123) and breast cancer patients (17.9%, 22/123) (P=0.040). In breast cancer patients, overall survival did not showed significant difference between NAFLD group and non-NAFLD group (P=0.304) (Figure A). However, recurrence-free survival was significantly higher in patients without NAFLD comparing with those with NAFLD (P=0.009) (Figure B). Among breast cancer patients received endocrine treatment, NAFLD group showed higher cumulative incidence of significant liver injury comparing with non-NAFLD group (P<0.001). Conclusions: The prevalence of NAFLD in patients with breast cancer is significantly high compared to healthy control group. Moreover, breast cancer patients with NAFLD showed poor prognosis in terms of recurrence. Therefore, diagnostic evaluation to determine whether or not NAFLD is present would be important in managing patients with breast cancer.

Role of tenofovir disoproxil fumarate in prevention of perinatal transmission of hepatitis B virus from mother to child: a systematic review and meta-analysis

( Young-sun Lee ),( Ha Seok Lee ),( Ji Hoon Kim ),( Sung Won Chang ),( Myung Han Hyun ),( Haein Bak ),( Sehwa Kim ),( Min-jin Lee ),( Chan Uk Lee ),( Young Kul Jung ),( Yeon Seok Seo ),( Hyung Joon Yi 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.1

Background/Aims: To prevent the perinatal transmission of hepatitis B virus (HBV) from mother to child, administration of an antiviral agent during pregnancy has been attempted in women who are either hepatitis B e antigen positive or have a high viral load. In this systematic review and meta-analysis with randomized controlled trials, we analyzed the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing the perinatal transmission of HBV in pregnant women who have high HBV DNA titers. Methods: Multiple comprehensive databases (PubMed, EMBASE, and Cochrane databases) were searched for studies evaluating the efficacy of TDF for the prevention of perinatal transmission of HBV. Results: Two studies (one open label study and one double blind study) were included and analyzed. Intention-to-treat analysis (527 pregnancies) showed that the preventive effect of TDF was not significant (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.13 to 2.17; p = 0.38, I² = 81%). However, the per-protocol analysis showed that TDF significantly reduced perinatal transmission (OR, 0.10; 95% CI, 0.01 to 0.77; p = 0.03, I² = 0%). There was no significant difference between the TDF group and the control group with respect to maternal and fetal safety outcomes. Conclusions: In pregnant women who have high HBV DNA titers, TDF can reduce the perinatal transmission from mother to child without significant adverse events.

Effects of Inlet Turbulence Conditions and Near-wall Treatment Methods on Heat Transfer Prediction over Gas Turbine Vanes

Bak, Jeong-Gyu,Cho, Jinsoo,Lee, Seawook,Kang, Young Seok The Korean Society for Aeronautical and Space Scie 2016 International Journal of Aeronautical and Space Sc Vol.17 No.1

This paper investigates the effects of inlet turbulence conditions and near-wall treatment methods on the heat transfer prediction of gas turbine vanes within the range of engine relevant turbulence conditions. The two near-wall treatment methods, the wall-function and low-Reynolds number method, were combined with the SST and ${\omega}RSM$ turbulence model. Additionally, the RNG $k-{\varepsilon}$, SSG RSM, and $SST_+{\gamma}-Re_{\theta}$ transition model were adopted for the purpose of comparison. All computations were conducted using a commercial CFD code, CFX, considering a three-dimensional, steady, compressible flow. The conjugate heat transfer method was applied to all simulation cases with internally cooled NASA turbine vanes. The CFD results at mid-span were compared with the measured data under different inlet turbulence conditions. In the SST solutions, on the pressure side, both the wall-function and low-Reynolds number method exhibited a reasonable agreement with the measured data. On the suction side, however, both wall-function and low-Reynolds number method failed to predict the variations of heat transfer coefficient and temperature caused by boundary layer flow transition. In the ${\omega}RSM$ results, the wall-function showed reasonable predictions for both the heat transfer coefficient and temperature variations including flow transition onset on suction side, but, low-Reynolds methods did not properly capture the variation of the heat transfer coefficient. The $SST_+{\gamma}-Re_{\theta}$ transition model showed variation of the heat transfer coefficient on the transition regions, but did not capture the proper transition onset location, and was found to be much more sensitive to the inlet turbulence length scale. Overall, the Reynolds stress model and wall function configuration showed the reasonable predictions in presented cases.

Serum miRNA as a Useful Diagnostic Biomarker for Diagnosis of NASH and a Clue for Disease Progression Pathway in NAFLD Patients

( Young-sun Lee ),( Jeong-an Gim ),( Haein Bak ),( Sehwa Kim ),( Young Kul Jung ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon ),( Soon Ho Um ),( Kwan Soo Byun ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Non-alcoholic steatohepatitis (NASH), as subtype of non-alcoholic fatty liver disease (NAFLD), is progressive disease that can result in advanced fibrosis and cirrhosis. The aim of this study was to evaluate diagnostic value using serum miRNA to For distinguish ing NASH from simple steatosis (SS). Methods: RNA extraction and small RNA sequencing were done using sera from 24 patients who were diagnosed with NAFLD by biopsy. miRNA expression levels were compared between 12 SS patients and 12 NASH patients. After selecting miRNAs showing significantly increased expression in NASH group comparing to SS group, diagnostic accuracies of each miRNA and a combination of miRNAs were analysed. For functional relationship between specific signalling pathway and miRNAs that were significantly elevated in sera of NASH patients compared to those in sera of SS patients, miEAA database was used. Results: A total of 2,588 mature miRNA reads were obtained from miRDeep2 Quantifier module. Expression levels of 26 miRNAs were significantly increased in NASH group than in SS group, whereas those of 12 miRNAs were significantly decreased in NASH group than in SS group. Among 38 significant miRNAs, eight miRNAs that showed high expression within the top 25% of all miRNAs were selected and compared. Only four miRNAs showed meaningful area under receiver operating characteristic (AUROC) values for NASH diagnosis (P<0.05). When AUROC values for diagnosis of NASH were compared between a combination of 8 miRNAs (AUROC: 0.924; 95% CI: 0.739-0.992) and a combination of 4 miRNAs (AUROC: 0.875; 95% CI: 0.676-0.973), there was no significant difference (P=0.26). Among 26 miRNAs that showed significantly increased expression in NASH group, 10 miRNAs were included in 17 miRNA group, such as adipocytokine signalling pathway and thyroid hormone signalling pathway (Figure). Conclusions: Combination of serum circulating miRNAs could be used as novel biomarker for diagnosis of NASH. The expression of circulating miRNAs is correlated with specific signalling pathway.

MR-Based Non-Alcoholic Steato Hepatitis (MASH) Score in Patients with Non-Alcoholic Fatty Liver Disease

( Young-sun Lee ),( Ji Eun Lee ),( Haein Bak ),( Sehwa Kim ),( Young Kul Jung ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Baekhui Kim ),( Jeong Woo Kim ),( Chang Hee Lee ),( Jong Eun Yeon 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: As prevalence of NAFLD accounts for up to 30% of the general population worldwide, non-invasive evaluation of disease severity of NAFLD and non-invasive diagnosis of NASH are important issues. The objective of this prospective cross-sectional study was to develop a diagnostic scoring system that could improve the accuracy of NASH diagnosis by combining multiparametric MR and clinical indicators. Methods: This study included 130 patients who were diagnosed NAFLD by liver biopsy from October 2016 to July 2019. All patients were examined for medical history, laboratory tests, and multiparametric MR consisting of MRI proton density fat fraction, MR spectroscopy, T1 mapping, and MR elastography (MRE). Scoring model was developed using logistic regression. Internal validation was performed using bootstrapping. Results: NASH patients were older (59 years vs. 46 years, P<0.001) and had lower BMI (28.23 kg/㎡ vs. 31.19 kg/㎡, P=0.032) than nonalcoholic fatty liver (NAFL) patients. NASH group showed higher prevalence of diabetes/impaired fasting glucose, hypertension, and dyslipidemia. Four categorical variables and 19 continuous variables were evaluated for NASH diagnostic model. Diabetes/IFG and hypertension among categorical variables and age, BMI, hemoglobin, platelet count, T1 mapping, and MRE among continuous variables met the criterion of P-value ≤ 0.1. Variable interactions were identified between BMI and hemoglobin, between platelet count and diabetes/IFG, and between platelet count and MRE. Finally, equation for MR-based NASH (MASH) score was obtained using four demographic factors, two laboratory variables, and two MRI parameters (Figure 1). MASH score showed satisfactory accuracy for NASH diagnosis (C-statistics: 0.892; 95% CI: 0.834-0.950; P<0.001). When MASH score of 0.73 was set as a cut-off for NASH diagnosis, its sensitivity was 0.67 and its specificity was 0.90 (PPV = 0.89, 47/53). When MASH score of 0.37 was set as a cut-off for NASH exclusion, its sensitivity was 0.90 and its specificity was 0.78 (NPV = 0.87, 47/54). Only 17% (22/130) of patients were located in the gray zone (Table 1). Internal validation using 1000 bootstrapping also showed satisfactory accuracy for NASH diagnosis (C-statistics: 0.909; 95% CI: 0.855-0.964; P<0.001). Conclusions: MASH score is a novel non-invasive biomarker for the diagnosis of NASH in patients with NAFLD. Further external validation is required for its clinical application.

식량작물 상품 포장디자인 개선을 위한 현황조사 분석

유영석(Young-Seok Yu),김웅(Woong Kim),김홍기(Hong-Gi Kim),백윤금(Youn-Kum Bak),진혜련(Hye-Ryeon Jin) 한국디자인학회 2017 한국디자인학회 학술발표대회 논문집 Vol.2017 No.11