이황화탄소 중독과 심박동수 변이와의 관련성

전형준,임상혁,백도명 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

목적: 1980년대 말에 레이온 섬유를 생산하는 업체에서 대규모 이황화탄소 중독 사례가 발생하였으며 1998년까지 사망자 38명을 포함하여 830명의 근로자들이 이황화탄소 중독으로 진단되었다. 이황화탄소 중독으로 진단 받았던 환자들과 정상인들의 심박동수 변이를 측정하여 이황화탄소 노출이 중단된 상태에서의 건강영향에 대해 조사하였다. 아울러 환자군을 대상으로 이황화탄소 노출량과 심박동수 변이와의 사이에 양-반응 관계가 있는 지를 조사하였다. 방법: 이황화탄소 중독으로 진단된 71명의 남성 퇴직 근로자들을 환자군으로, 이황화탄소를 포함한 유기용제에 직업적으로 노출된 적이 없고 심혈관계질환이 없는 환자군과 같은 연령대의 남성 127명을 대조군으로 선정하였다. 두 군에서 자기 기입식 설문지를 이용하여 연령, 흡연, 음주, 규칙적인 운동, 과거의 직업력 및 질병력 등에 대한 정보를 수집하였다. 건강검진을 통해 신장, 체중, 혈압을 측정하고 심전도 검사, 흉부 방사선 촬영 등을 실시하였다. 심박동수 변이의 지표로서 시간 영역(maximum, average, minimum RR interval)과 주파수 영역(low frequency - LF, high frequency - HF, total power spectrum - TPS, LF/HF ratio)을 측정하였다. 환자군에서 과거의 이황화탄소 노출에 대한 지표들(근무기간, 근무부서별 노출량, 누적노출지수, 퇴사기간)을 조사하여 심박동수 변이와 양-반을 관계가 있는 지를 평가하였다. 결과: 단변량 분석에서 두 군의 시간 영역 측정치에는 유의한 차이가 없었다. 이에 비해 고주파 영역을 제외한 주파수 영역 측정치들은 환자군들이 대조군에 비해 유의하게 낮았다. 다중선형분석에서 이황화탄소 중독의 과거력은 모든 주파수 영역 변수들과 음의 관계를 나타냈으며, 특히 저주파 영역(p<0.05)과 저주파/고주파 비(p<0.05)에 유의한 영향을 나타냈다. 환자군에서 이황화탄소 노출 지표들과 심박동수 변이와의 양-반응 관계를 조사하였으나 유의한 관계는 나타나지 않았다. 결론: 환자군에서 이황화탄소와 심박동수 변이와의 사이에 양-반응관계를 확인할 수는 없었으나 환자군과 정상인을 비교했을 때 저주파 영역과 저주파/고주파 비 등에서 심박동수 변이의 감소가 있었다. 이황화탄소의 노출이 중단된 상태에서도 심혈관계 건강영향이 있을 가능성에 대한 연구가 더 필요하다. Objectives: Mass poisoning by carbon disulfide (CS_(2)) occurred in a viscose rayon factory in Korea. Up until 1998, 830 employees, including 38 who had died, were diagnosed with CS_(2) poisoning. Among the CS_(2) poisoned subjects, heart rate variability (HRV) was evaluated to investigate whether the toxic effect of CS_(2) persists after the exposure has ceased. The dose-response relationship between carbon disulfide exposure and HRV was also evaluated. Methods: The case group was comprised of 71 retired male workers diagnosed as being CS_(2) poisoned. The control group was comprised of 127 males of same age-range who had no history of CS_(2) exposure and cardiovascular diseases. Information on individual age, height, weight, weight, cigarette smoking, alcohol drinking, regular exercise, medical and occupational history, chest x-ray, and ECG recording of the two groups were collected through a self-administered questionnaire and with a medical examination, Time (maximum, average, minimum RR interval) and frequency domain measures (low frequency - LF, high frequency - HF, total power spectrum TPS, and LF/HF ratio) of the two groups were analyzed. CS_(2) exposure indices of the case group (duration of employment, exposure level per work department, cumulative exposure index and duration of retirement) were investigated. Results: Using a univariate analysis, the frequency domain measures for the case group were significantly lower than those in the control group, except for HF. In the multivariate analysis, previous history of CS_(2) poisoning was inversely related to all frequency domain parameters and it significantly affected the LF(p<0.05). There was no significant dose-response relationship between CS_(2) exposure indices and HRV parameters in the case group. Conclusion: This study suggests that further studies are necessary to evaluate the residual effects of CS_(2) poisoning even after the CS_(2) exposure has ceased.

이황화탄소 중독자들의 노출중단 이후의 심박동수 변이

이상윤,조성일,백도명,변창범,김미정,박경근,임상혁,양길승,황창국,전형준 大韓産業醫學會 2006 대한직업환경의학회지 Vol.18 No.2

목적: 2000년도에 이황화탄소 중독증 환자들과 대조군의 심박동수 변이를 비교하여 이황화탄소 중독증 환자들의 심박동수 변이가 대조군에 비해 유의하게 낮다는 연구보고가 있었다. 당시의 연구가 이황화탄소 노출이 중단된 상태에서 이황화탄소 중독자들의 건강 문제를 연구했다는 점에 의의가 있으나 연구 결과를 해석하는데 있어 제한점들이 있었다. 이 연구는 2000년도에 수행하였던 연구의 제한점을 극복하고 이황화탄소 노출이 중단된 이후의 이황화탄소 중독자들의 심혈관계 상태를 심박동수 변이를 이용하여 평가해보고자 하였다. 방법: 이황화탄소 중독증으로 진단받은 환자 122명과 환자군의 연령대와 성별 빈도에 따라 무작위 추출한 112명을 대조군으로 선정하였다. 자기 기입식 설문지와 건강검진을 통해 연령, 성별, 신장, 체중, 흡연, 음주, 규칙적 운동, 질병력, 직업력, 흉부 방사선 촬영, 심전도 측정을 실시하였다. 연구 대상자들은 의자에 앉힌 상태에서 5분 동안 심박동수 변이를 측정하였다. 이 연구에서 측정한 심박동수 변이 지표들은 정상 RR간격의 표준편차(standard deviation of all norma-to-normal intervals, SDNN), 인접한 RR간격들의 차이를 제곱의 합의 평균의 제곱근(square root of the mean of the sum of squares of differences between adjacent normal-to-normal intervals, RMSSD). 저주파영역(low frequency power, LF: 0.04~0.15Hz), 고주파 영역 (high frequency power, HF:0.15~0.4Hz), 전체 주파수 강도(total power, TP), 저주파/고주파 비 (LF/HF ratio)이다. 결과: 단변량 분석에서 이황화탄소 중독자들의 모든 심박동수 변이 지표들이 대조군에 비하여 낮았다. 다중선형회귀분석에서 이황화탄소 중독은 RMSSD를 유의하게 감소시키는 것으로 나타났다.(P<0.05). 결론: 이 연구는 이황화탄소 노출이 중단된 상태에서도 이황화탄소 중독자들에게 심혈관계와 관련된 건강문제가 있을 수 있음을 시사한다. Objectives: A previous study conducted in 2000 measuring the heart rate variability (HRV) of carbon disulfide (CS_(2))-poisoned subjected suggested that their HRV was reduced after exposure cessation. However, the study was limited by the following procedural limitations: (1) only 71 CS_(2)-poisoned subjects participated, (2) no females participated, and (3) the CS_(2)-poisoned subjects were older than the controls. This study was therefore conducted to overcome these limitations of the earlier study. Methods: The study subjects comprised 122 retired workers with CS_(2) poisoning and the same number of age- and sex-matched controls. Information on individual age, sex, height, wight, smoking history, alcohol drinking, regular exercise, medical and occupational history, chest x-ray, and ECG recording of the two groups was collected though a self-administered questionnaire and a medical examination. Standard Deviation of NN intervals (SDNN), Root-Mean-Square of Successive Differences (RMSSD), Total Power (TP), Low Frequency (LF), High Frequency (HF), and LF/HF ratio were measured as HRV indices for 5 minutes in the sitting position. Results: Univariate analysis revealed that all HRV indices of CS_(2)-poisoned subjected were lower than those of the controls. Multiple linear regression analysis showed that CS_(2) poisoning had negative association with all HRV indices and that its association with RMSSD was statistically significant(P<0.05). Conclusions: This study suggests that CS_(2)-poisoned subjects continue to have reduced HRV, even though the exposure has ceased.

Adding adefovir compared with switching to entecavir in patients with Lamivudine-resistant chronic hepatitis B (ACE study) -A multicenter prospective randomized study: One-year interim analysis (초)

( Hyung Joon Yim ),( Jeong Han Kim ),( Yeon Seok Seo ),( Chang Wook Kim ),( Chang Don Lee ),( Sang Hoon Park ),( Myung Seok Lee ),( Choong Kee Park ),( Hee Bok Chae ),( Moon Young Kim ),( Soon Koo Bai 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3(S)

대한간학회 학술연구기금 지원과제 결과 보고 : 클레부딘 내성 만성 B형간염의 치료에 대한 다기관 후향 및 전향 연구

( Hyung Joon Yim ),( Eun Young Cho ),( Eileen L. Yoon ),( Yeon Seok Seo ),( Ji Hoon Kim ),( Hong Soo Kim ),( Se Hwan Lee ),( Sang Hoon Ahn ),( Sook Hyang Jeong ),( Jin Wook Kim ),( Jeong Il Lee ),( Ji 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.5(S)

Evolution of Multi-Drug Resistant Hepatitis B Virus: Implications on Rescue Therapy

( Hyung Joon Yim ),( Munira Hussain ),( Ying Liu ),( Stephen N. Wong ),( Scott K. Fung ),( Anna S. F. Lok ) 대한간학회 2006 Clinical and Molecular Hepatology(대한간학회지) Vol.12 No.3(S)

Comments on Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Reply

Yim Hyung Joon,Ahn Young Eun,Kim Tae Hyung,Jung Young Kul 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Establishment of Full Genomic Length Resistance-Associated Variant Genotype 2 Hepatitis C Viruses and Applications for Future Therapeutic Strategies

( Hyung Joon Yim ),( Billy Lin ),( Shanshan He ),( Zongyi Hu ),( T. Jake Liang ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Several directly acting antiviral agents (DAA) were currently approvedfor the treatment of chronic hepatitis C (CHC). AlthoughDAA therapies are associated with better tolerability and improvedresponse rates, occurrence of drug resistance has been the drawback.The aim of the present study is to develop full-length resistance associatedvariants (RAV) HCV culture systems to evaluate the efficacyand the cross resistance of current antiviral drugs for future therapeuticstrategies.Methods: Resistance associated substitutions on NS3 (A156T, D168V),NS5A (L31V, Y93H, L31V+Y93H), and NS5B (S282T) domains weregenerated by site directed mutagenesis and cloned into genotype2a J6/JFH1 HCV plasmid with or without luciferase gene. After In vitro RNA transcription, RNAs of RAV were transfected into Huh 7.5.1cells. HCVcc in the supernatants were collected and used for thereinfection and treatment experiment to confirm drug susceptibility.We performed HCV core staining and Renilla luciferease assays toassess treatment response to multiple DAAs and other antiviral drugswith different mechanism of action after transfection or infectionof RAVs.Results: DAAs in the same classes shared cross resistance to correspondingRAVs: boceprevir, telaprevir, simeprevir, and asunaprevirto NS3 RAVs; daclatasvir and ledipasvir to NS5A RAVs; sofosbuvirto NS5B RAV. However, DAAs of the other classes effectively suppressedRAVs as well as wild type. All the RAVs were sensitive todrugs with different action of mechanism including interferon alfa,ribavirin, cyclosporine (cyclophilin inhibitor) or chlorcyclizine (entry inhibitors).Conclusions: We developed full-length RAV HCV culture systemsbased on genotype 2a strain. This system will be useful to assessantiviral response of drugs with different action of mechanisms.Combination of different classes of DAA or new drugs with differentaction mechanisms (e.g. cyclophilin inhibitor or entry inhibitors) shouldbe a future therapeutic strategy for overcoming drug resistance inthe treatment of CHC.

Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop

Hyung Joon Yim,Ji Hoon Kim,Jun Yong Park,Eileen L. Yoon,Hana Park,Jung Hyun Kwon,Dong Hyun Sinn,Sae Hwan Lee,Jeong-Hoon Lee,Hyun Woong Lee 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.4

Clinical practice guidelines are important for guiding the management of specific diseases by medical practitioners, trainees, and nurses. In some cases, the guidelines are utilized as a reference for health policymakers in controlling diseases with a large public impact. With this in mind, practice guidelines for the management of chronic hepatitis B (CHB) have been developed in the United States, Europe, and Asian-Pacific regions to suggest the best-fit recommendations for each social and medical circumstance. Recently, the Korean Association for the Study of the Liver published a revised version of its clinical practice guidelines for the management of CHB. The guidelines included updated information based on newly available antiviral agents, the most recent opinion on the initiation and cessation of treatment, and updates for the management of drug resistance, partial virological response, and side effects. Additionally, CHB management in specific situations was comprehensively revised. This review compares the similarities and differences among the various practice guidelines to identify unmet needs and improve future recommendations.

When Should We Consider Systemic Therapy in BCLC Stage B Hepatocellular Carcinoma?

( Hyung Joon Yim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

The Barcelona Clinic Liver Cancer (BCLC) classification includes 5 disease stages (0, A-D). The BCLC stage B consists of patients with cirrhosis with 1) underlying liver function of Child-Pugh class A or B, 2) multiple tumors beyond Milan criteria, but no vascular invasion, no extrahepatic lesions, and 3) tolerable performance status for anti-cancer therapy. As the definition of BCLC stage B is broad, it includes a heterogeneous population. Hence, response to transarterial chemoembolization (TACE) which is the standard treatment for BCLC B may not be uniform. In some instances, patients who are not suitable for TACE can exist in this stage. If the tumor is not controlled by an initial TACE, the same therapy can be repeated. However, if repeated TACEs do not achieve complete necrosis of tumors, it should be considered as TACE failure or refractoriness, which requires alternative therapies for HCC. If the tumor is localized and the underlying liver function is good, surgical resection may be an option. If there is no vascular invasion and no extrahepatic lesions, extended criteria for liver transplantation could be applied. However, most of the patients experiencing TACE failure are not the candidate for such surgical therapies, mainly due to its nature of the BCLC B stage. Currently, there are new pharmacologic therapeutic agents for unresectable or advanced HCCs (BCLC C stage); sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab, nivolumab, and atezolizumab plus bevacizumab. Hence, timely adjustment of treatment strategy should be undertaken for the best outcomes. Previously, Raoul et al. suggested that patients who show progression after two cycles of TACE need switching therapy to sorafenib. Likewise, Japan Society of Hepatology defined the TACE failure as follows and recommended modifying therapies to molecular targeting agents (MTTs); 1) Intrahepatic lesion with two or more consecutive insufficient responses (viable lesion >50%) or those with two or more consecutive progressions in the liver (tumor number increases as compared with tumor number before the previous TACE procedure) even after having changed the chemotherapeutic agents and/or reanalysis of the feeding artery seen on response evaluation CT/MRI at 1-3 months after having adequately performed selective TACE, 2) Continuous elevation of tumor makers immediately after TACE even though a slight transient decrease in observed, 3) Appearance of vascular invasion, and 4) Appearance of extrahepatic spread. A recent survey conducted in Korea indicated that nearly half of Korean clinicians prefer to consider TACE failure after more than three times of repeated TACEs, and sorafenib and radiotherapy were subsequent choices in that situation. So far, there is no concrete definition of TACE failures, but 2 or 3 times of TACE session would be the reasonable limit for deciding the next treatment. A single-center study also suggested no objective response after two consecutive TACEs is related to poorer survival. Well-designed clinical trials and further discussions should be warranted to improve the patients’ survival in patients with TACE failures. Recently, a proof of concept study compared lenvatinib and TACE in BCLC stage B patients with Child A liver function and multiple tumors exceeding up-to-7 criteria.8 The lenvatinib group showed a significantly better objective response rate and significantly longer progression-free survival as well as overall survival than the TACE group. Hence, the early application of an MTT agent could be a better choice for patients with BCLC stage B patients. Combination of immunotherapeutics and MTT is a promising strategy in patients with TACE failure considering results of atezolizumab plus bevacizumab clinical trial which included treatment-experienced patients up to 52%. In the future, choosing an appropriate time point of treatment modification and the best next option will lead to the improvement of clinical outcomes.

Free Paper Session : Hepatitis B ; Adding adefovir compared with switching to entecavir in patients with Lamivudine-resistant chronic hepatitis B (ACE study) - a multicenter prospective randomized study: final results (초)

( Hyung Joon Yim ),( Ei Leen Yoon ),( Yeon Seok Seo ),( Chang Wook Kim ),( Chang Don Lee ),( Sang Hoon Park ),( Myung Seok Lee ),( Choong Kee Park ),( Hee Bok Chae ),( Moon Young Kim ),( Soon Koo Baik 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3(S)