1.Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien TSAI ; Chung-Feng HUANG ; Ming-Lun YEH ; Meng-Hsuan HSIEH ; Hsing-Tao KUO ; Chao-Hung HUNG ; Kuo-Chih TSENG ; Hsueh-Chou LAI ; Cheng-Yuan PENG ; Jing-Houng WANG ; Jyh-Jou CHEN ; Pei-Lun LEE ; Rong-Nan CHIEN ; Chi-Chieh YANG ; Gin-Ho LO ; Jia-Horng KAO ; Chun-Jen LIU ; Chen-Hua LIU ; Sheng-Lei YAN ; Chun-Yen LIN ; Wei-Wen SU ; Cheng-Hsin CHU ; Chih-Jen CHEN ; Shui-Yi TUNG ; Chi‐Ming TAI ; Chih-Wen LIN ; Ching-Chu LO ; Pin-Nan CHENG ; Yen-Cheng CHIU ; Chia-Chi WANG ; Jin-Shiung CHENG ; Wei-Lun TSAI ; Han-Chieh LIN ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Jee-Fu HUANG ; Chia-Yen DAI ; Wan-Long CHUNG ; Ming-Jong BAIR ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(3):468-486
Background/Aims:
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods:
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results:
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
2.Transarterial chemoembolization for hepatocellular carcinoma: 2023 Expert consensus-based practical recommendations of the Korean Liver Cancer Association
Yuri CHO ; Jin Woo CHOI ; Hoon KWON ; Kun Yung KIM ; Byung Chan LEE ; Hee Ho CHU ; Dong Hyeon LEE ; Han Ah LEE ; Gyoung Min KIM ; Jung Suk OH ; Dongho HYUN ; In Joon LEE ; Hyunchul RHIM ;
Clinical and Molecular Hepatology 2023;29(3):521-541
Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.
3.Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association
Yuri CHO ; Jin Woo CHOI ; Hoon KWON ; Kun Yung KIM ; Byung Chan LEE ; Hee Ho CHU ; Dong Hyeon LEE ; Han Ah LEE ; Gyoung Min KIM ; Jung Suk OH ; Dongho HYUN ; In Joon LEE ; Hyunchul RHIM ;
Journal of Liver Cancer 2023;23(2):241-261
Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.
4.Change of Dendritic Cell Subsets Involved in Protection Against Listeria monocytogenes Infection in ShortTerm-Fasted Mice
Young-Jun JU ; Kyung-Min LEE ; Girak KIM ; Yoon-Chul KYE ; Han Wool KIM ; Hyuk CHU ; Byung-Chul PARK ; Jae-Ho CHO ; Pahn-Shick CHANG ; Seung Hyun HAN ; Cheol-Heui YUN
Immune Network 2022;22(2):e16-
The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes(LM). Fasting induced an increased number of CD103 + CD11b − DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103 + CD11b − DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103 + CD11b - DCs in mice infected with LM might affect to increase of Foxp3 + regulatory T cells. Changes of major subset of DCs from CD103 + to CD103 - may induce the increase of IFN-γ–producing cells with forming Th1-biased environment.Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.
5.Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia
Kee Hyung PARK ; YoungSoon YANG ; Christopher CHEN ; Yong S. SHIM ; Jacqueline C. DOMINGUEZ ; Chan-Nyoung LEE ; Kyunghun KANG ; Hee-Jin KIM ; Seul-Ki JEONG ; Jee Hyang JEONG ; Zhen HONG ; Soo Jin YOON ; Zhen-Xin ZHANG ; Eun-Joo KIM ; Jae-Won JANG ; Yansheng LI ; Yun XU ; Yu-Te LIN ; Qiumin QU ; Chaur-Jong HU ; Chih-Ho CHOU ; Dongsheng FAN ; Nagaendran KANDIAH ; Yuan-Han YANG ; Chi-ieong LAU ; Leung-Wing CHU ; Huali WANG ; San JUNG ; Seong Hye CHOI ; SangYun KIM
Journal of Clinical Neurology 2021;17(3):376-384
Background:
and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia.
Methods:
This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS).
Results:
Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS.
Conclusions
In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
6.Prospective Multi-Center Korean Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolics for Nodular Hepatocellular Carcinoma: A Two-Year Outcome Analysis
Myungsu LEE ; Jin Wook CHUNG ; Kwang-Hun LEE ; Jong Yun WON ; Ho Jong CHUN ; Han Chu LEE ; Jin Hyoung KIM ; In Joon LEE ; Saebeom HUR ; Hyo-Cheol KIM ; Yoon Jun KIM ; Gyoung Min KIM ; Seung-Moon JOO ; Jung Suk OH
Korean Journal of Radiology 2021;22(10):1658-1670
Objective:
To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC).
Materials and Methods:
This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed.
Results:
The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%).
Conclusion
DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.
7.Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia
Kee Hyung PARK ; YoungSoon YANG ; Christopher CHEN ; Yong S. SHIM ; Jacqueline C. DOMINGUEZ ; Chan-Nyoung LEE ; Kyunghun KANG ; Hee-Jin KIM ; Seul-Ki JEONG ; Jee Hyang JEONG ; Zhen HONG ; Soo Jin YOON ; Zhen-Xin ZHANG ; Eun-Joo KIM ; Jae-Won JANG ; Yansheng LI ; Yun XU ; Yu-Te LIN ; Qiumin QU ; Chaur-Jong HU ; Chih-Ho CHOU ; Dongsheng FAN ; Nagaendran KANDIAH ; Yuan-Han YANG ; Chi-ieong LAU ; Leung-Wing CHU ; Huali WANG ; San JUNG ; Seong Hye CHOI ; SangYun KIM
Journal of Clinical Neurology 2021;17(3):376-384
Background:
and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia.
Methods:
This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS).
Results:
Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS.
Conclusions
In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
8.Prospective Multi-Center Korean Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolics for Nodular Hepatocellular Carcinoma: A Two-Year Outcome Analysis
Myungsu LEE ; Jin Wook CHUNG ; Kwang-Hun LEE ; Jong Yun WON ; Ho Jong CHUN ; Han Chu LEE ; Jin Hyoung KIM ; In Joon LEE ; Saebeom HUR ; Hyo-Cheol KIM ; Yoon Jun KIM ; Gyoung Min KIM ; Seung-Moon JOO ; Jung Suk OH
Korean Journal of Radiology 2021;22(10):1658-1670
Objective:
To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC).
Materials and Methods:
This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed.
Results:
The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%).
Conclusion
DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.
9.Current Status of Patient Education in the Management of Atopic Dermatitis in Korea
Min Kyung LEE ; Ju Hee SEO ; Howard CHU ; Hyunjung KIM ; Yong Hyun JANG ; Jae Won JEONG ; Hye Yung YUM ; Man Yong HAN ; Ho Joo YOON ; Sang Heon CHO ; Yeong Ho RHA ; Jin Tack KIM ; Young Lip PARK ; Seong Jun SEO ; Kwang Hoon LEE ; Chang Ook PARK
Yonsei Medical Journal 2019;60(7):694-699
Patient education is important for successful management of atopic dermatitis; however, due to limited time and resources, patient education remains insufficient. This study aimed to investigate the current state of education provided by Korean dermatologists, pediatric allergists, and allergists to patients with atopic dermatitis. A questionnaire survey consisting of items regarding educational programs for patients with atopic dermatitis was conducted via e-mail. In total, 153 participants responded to the questionnaires, and 26.8% indicated that they have had separate educational programs. The workforce involved in the educational program included nurses, residents or fellows, dieticians, pharmacists, and clinical psychologists. Most education protocols addressed the characteristics and natural course of atopic dermatitis and environmental management. Overall, 96.7% of the participants replied that an additional charge is needed for education; moreover, additional assistance from an academic society or association, in the form of medical staff, organized data, and advertisement, is required to develop and provide a well-structured educational program. A standardized education protocol will effectively provide appropriate education for patients with atopic dermatitis. Arrangement of education fees, covered by the National Health Insurance Service, will lead to the establishment of a structured educational program and participation of an additional medical workforce.
Dermatitis, Atopic
;
Education
;
Electronic Mail
;
Fees and Charges
;
Humans
;
Korea
;
Medical Staff
;
National Health Programs
;
Nutritionists
;
Patient Education as Topic
;
Pharmacists
;
Psychology
10.Methionine Adenosyltransferase 1: A Proteomic Surrogate Marker of Early Hepatocellular Carcinoma in Cirrhotic Patients
Joo Ho LEE ; Mi Jung JUN ; Ju Hyun SHIM ; Gi Won SONG ; Eunyoung TAK ; Bora OH ; Eunsil YU ; Sang Woon CHOI ; Jihyun AN ; Danbi LEE ; Kang Mo KIM ; Young Suk LIM ; Han Chu LEE ; Young Hwa CHUNG ; Yung Sang LEE
Journal of Liver Cancer 2018;18(1):33-43
BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase
;
Biomarkers
;
Blotting, Western
;
Carcinoma, Hepatocellular
;
Humans
;
Immunoblotting
;
Liver
;
Liver Cirrhosis
;
Mass Spectrometry
;
Methionine Adenosyltransferase
;
Methionine
;
Proteomics
;
Real-Time Polymerase Chain Reaction
;
RNA, Messenger
;
Two-Dimensional Difference Gel Electrophoresis

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