청소년의 식이행태 조사 : 서울·양평 두 지역간 비교 The Comparison of Urban and Rural Areas

최준호,안동현,최보율,강윤주,백영석,조연규,고복자,남정현 漢陽大學校 精神健康硏究 1998 精神健康硏究 Vol.17 No.-

PI3Kγ Inhibition Enhances the Anti-Cancer Effect of Cytokine-Induced Killer or Natural Killer Cell

( Joon Yeul Nam ),( Young Chang ),( Hyo Young Lee ),( Yun Bin Lee ),( Eunju Cho ),( Jeong-hoon Lee ),( Su Jong Yu ),( Yoon Jun Kim ),( Jung-hwan Yoon ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Phosphoinositide 3-kinase (PI3Kγ) signaling through the Akt and mTOR pathways promotes immunosuppression by inhibiting activation of nuclear factor kappaB and stimulating CCAAT/enhancer-binding protein β activation. In contrast, inactivation of macrophage-elicited PI3Kγ activates immunostimulatory signals that restore CD8+ T cell activation and cytotoxicity. Cytokine-induced killer (CIK) or natural killer cell (NK) infusion therapy alone is insufficient for treating advanced cancers. Thus, this study evaluated whether inhibiting PI3Kγ enhances the anti-cancer effects of CIK and NK cell therapy in a mouse hepatocellular carcinoma (HCC) model. Methods: CIK and NK cells were generated from mouse splenocytes using interferon gamma, a CD3 monoclonal antibody (CIK cells), and interleukin 2 (CIK and NK cells). The potential synergistic effect of CIK or NK cell therapy with a PI3Kγ inhibitor was evaluated in a mouse HCC model. Results: A synergistic anti-cancer effect was observed by measuring tumor volume following treatment with CIK or NK cells and/or a PI3K-γ inhibitor. Relative tumor volume increased to 41.49 ± 14.41 in the control group, whereas that in the CIK plus PI3K-γ inhibitor group increased to only 16.48 ± 8.58 (P=0.004). Relative tumor volume in the NK plus PI3K-γ inhibitor group increased to 20.30 ± 3.98, whereas that in the control group was 47.63 ± 7.38 (P=0.016). TUNEL assays revealed that the combined treatment group (CIK or NK cells plus the PI3Kγ inhibitor) demonstrated significant increases in the proportion of apoptotic cells compared to the control (both P<0.05). Conclusions: This study demonstrates that inhibiting PI3Kγ enhances the anti-cancer effect of CIK and NK cell therapy in a mouse model of HCC; therefore, PI3Kγ may be a potential immunotherapeutic target for HCC.

Body Mass Index and FIB-4 Score Are Risk Factors for Development of Hepatocellular Carcinoma in Liver Cirrhosis on Entecavir Therapy

( Joon Yeul Nam ),( Jong Ho Lee ),( Hee Yoon Jang ),( Kanghyug Choi ),( In-gyoon Ha ),( Eun Sun Jang ),( Jin-wook Kim ),( Sook-hyang Jeong ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Prediction of development of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-related cirrhosis patients on potent antiviral therapy is not well defined. This study aimed to investigate the incidence and predictors of HCC development in cirrhosis patients on entecavir therapy. Methods: This single center, retrospective cohort study included 424 consecutive patients with HBV-related cirrhosis who underwent entecavir therapy from 2007 to 2013. Surveillance for HCC was based on semiannual ultrasonography and serum alpha fetoprotein (AFP) measurement. HCC incidence and the related factors were analyzed. Results: The subjects showed a median age of 52.7±10.1 years with 63.5% of male, mean body mass index (BMI) of 24.2±3.1 kg/㎡, HBeAg positivity in 41.5%, baseline HBV DNA level of 1.39x10⁸ IU/mL, and mostly Child-Pugh class A (80.9%). During median follow-up of 62.0 months (interquartile range, 29.0-83.0), 90.8% (385/424) reached complete virologic response of entecavir therapy. The overall incidence of HCC was 86 out of 424 patients (20.3%); incidence rate of 2.54/100 person-yr at 1 yr, 8.07/100 at 3 yr, and 8.37/100 at 5 years of follow-up. The multivariate analysis showed that the independent factors related to HCC development were BMI ≥23 (hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.23-3.39; P=0.006), and high FIB-4 (≥3.25; HR, 5.65; 95% CI, 1.35-23.72; P=0.018) or intermediate FIB-4 (≥1.45 and <3.25; HR, 4.58; 95% CI, 1.08-19.41; P=0.039). Conclusions: HCC incidence rate among HBV-related liver cirrhosis on entecavir therapy was 2.54/100, 8.07/100, and 8.37/100 person-yr at 1, 3 and 5 yr, respectively. High BMI and high to intermediate FIB-4 score were independent factors for HCC development.

New Prediction Model of Convolutional Neural Network for Hepatocellular Carcinoma in Patients of Hepatitis B Virus-Related Cirrhosis on Potent Antiviral Therapy with Comparison of Preexisting Models

( Joon Yeul Nam ),( Jong Ho Lee ),( Hee Yoon Jang ),( Kanghyug Choi ),( In-gyoon Ha ),( Eun Sun Jang ),( Jin-wook Kim ),( Sook-hyang Jeong ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Although there are several prediction models for hepatocellular carcinoma (HCC) development in chronic hepatitis B virus (HBV) infection including various proportion of liver cirrhosis, they are not based on the entirely cirrhotic patients on antiviral therapy. This study aimed to develop a new model of convolutional neural network (CNN) using deep learning technique for the prediction of HCC among HBV-related cirrhosis on the potent antivirals. Methods: The subjects were 424 patients with HBV-related cirrhosis on entecavir therapy and followed for median 62.0 months at a single tertiary hospital in Korea. Four existing models (PAGE-B, CU-HCC, HCC-RESCUE and ADRESS-HCC) were applied to our subjects and, compared for the accuracy of each model at 5 years using Harrell’s c-index. A New model using CNN was developed, and accuracy of the new model was calculated. Results: During the follow-up period, HCC developed in 86 out of 424 patients (20.3%) with 5 year cumulative incidence of 22%. In discrimination assessment, PAGE-B (c-index= 0.612), HCC-RESCUE (c-index=0.613), and ADRESS-HCC (c-index=0.606) showed a better discriminatory power compared to CU-HCC (c-index=0.563). The predicted 5 year cumulative HCC incidence among PAGE-B, CU-HCC, and HCC-RESCUE using the reported cutoff of each model were 16.0%, 21.1%, and 41.2%, respectively. However, application of the PAGE-B, CU-HCC, and HCC-RESCUE for our cohort showed a predicted 5 year HCC incidence of 23.6%, 17.2%, and 21.7%, respectively, suggesting an underestimation in PAGE-B, but overestimation in CU-HCC, and HCC-RESCUE. Accuracy of new model using CNN was 79.7 %, which seems to be a better performance. Conclusions: Our new model of CNN may present better prediction than the preexisting 4 models for HBV-related cirrhosis on potent antivirals. Further validation study is warranted.

S-135 Delay in viral suppression increases Hepatocellular carcinoma risk in chronic hepa titis B.

( Joon Yeul Nam ),( Yoon Jun Kim ),( Young Chang ),( Hyeki Cho ),( Seong Hee Kang ),( Young Youn Cho ),( Eunju Cho ),( Jeong-hoon Lee ),( Su Jong Yu ),( Jung-hwan Yoon ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

Background/Aims: Response rate of antiviral therapy is variable among individual chronic hepatitis B (CHB) patients. This study investigated the development of hepatocellular carcinoma (HCC) or liver cirrhosis in hepatitis B envelope antigen (HBeAg) positive CHB patients, according to the time needed to achieve complete viral suppression. Methods: A total of 401 HBeAg positive CHB patients who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were categorized into 2 groups with 4 separated criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3, or 4 years of therapy initiation. The measured outcomes were development of HCC and liver cirrhosis. Results: Cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.95; 95% confidence interval (CI), 1.15-21.28; p=0.032) or 2 years (HR, 3.10; 95% CI, 1.26-7.62; p=0.013), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of liver cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.94; 95% CI, 1.05-3.59; p=0.033) or 2 years (HR ratio, 2.17; 95% CI, 1.31-3.59; p=0.003). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or liver cirrhosis was not different regardless of viral suppression. Baseline fibrosis with adjusting aspartate amino transferase to platelet ratio index and Fibrosis-4 score did not differ based on the duration of achieving viral suppression. Conclusions: Complete hepatitis B virus suppression should be achieved within 2 years of antiviral therapy initiation to reduce the risk of liver cirrhosis or HCC development.

Delay in a Viral Suppression Increases Hepatocellular Carcinoma and Liver Cirrhosis Risk in HBeAg-Positive Chronic Hepatitis B Patients Treated with Antiviral Therapy

( Joon Yeul Nam ),( Young Chang ),( Hyeki Cho ),( Seong Hee Kang ),( Young Youn Cho ),( Eunju Cho ),( Jeong-hoon Lee ),( Su Jong Yu ),( Jung-hwan Yoon ),( Yoon Jun Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The treatment option in chronic hepatitis B (CHB) patients with persistent low-level of viremia despite of entecavir or tenofovir monotherapy is not clear yet. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B envelope antigen (HBeAg) positive CHB patients, according to the time needed to achieve complete viral suppression. Methods: A total of 401 HBeAg-positive CHB patients who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were categorized into 2 groups with 4 separated criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3, or 4 years of therapy initiation. The measured outcomes were development of HCC and cirrhosis. Results: Cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 5.42; 95% confidence interval (CI), 1.25-23.46; P=0.024) or 2 years (HR, 4.47; 95% CI, 1.70-11.73; P=0.020), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 2.09; 95% CI, 1.12-3.89; P=0.021) or 2 years (HR, 2.70; 95% CI, 1.59-4.59; P<0.001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Conclusions: Complete hepatitis B virus suppression should be achieved within 2 years of antiviral therapy initiation to reduce the risk of cirrhosis or HCC development.

Is it possible to predict the development of an entecavir resistance mutation in patients with chronic hepatitis B in clinical practice?

( Joon Yeul Nam ),( Jeong-hoon Lee ) 대한간학회 2017 Clinical and Molecular Hepatology(대한간학회지) Vol.23 No.4

Oral Medications Improve Overall Survival by Enhancing Adherence to Regular Surveillance for Hepatocellular Carcinoma: Results of Mediation Analysis

( Joon Yeul Nam ),( Jeong-hoon Lee ),( Jieun E Kim ),( Dong Hyeon Lee ),( Young Chang ),( Hongkeun Ahn ),( Hyeki Cho ),( Jung-ju Yoo ),( Minjong Lee ),( Young Youn Cho ),( Eunju Cho ),( Su Jong Yu ),( 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Regular surveillance for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients is essential to detect HCC earlier and to improve prognosis. This study investigated whether prescription of oral medication contributes to adherence to surveillance, early tumor detection, and overall survival (OS). Methods: A total of 401 CHB patients who were newly diagnosed with HCC were included: 134 patients received no medication (group 1), 151 received hepatoprotective agents such as ursodeoxycholic acid and silymarin (group 2), and 116 received antiviral agents (group at two years before HCC diagnosis. The primary endpoint was OS, and secondary endpoints were compliance to regular surveillance and HCC status at diagnosis. Results: Compared to group 1, both group 2 and 3 had higher rates of good compliance to regular surveillance (defined as participation >80% of imaging intervals being ≤6 months) (58.2%, 90.1%, and 97.4%, respectively; P<0.001), more HCC diagnosed at a very early stage (20.9%, 32.5%, and 36.2%; P=0.019) and smaller tumor size (2.8±2.4cm, 1.9±1.1cm, and 1.8±0.9cm; P<0.001). Finally, compared to group 1, both group 2 (hazard ratio, 0.63; 95% confidence interval, 0.41-0.97; P=0.035) and group 3 (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P=0.002) had significantly longer OS Figure 1). In mediation analysis, prolonged OS is resulted considerably from indirect effect mediated by shorter imaging interval (>100% in group 2 and 14.5% in group 3) rather than direct effect of medication itself (Figure 2). Conclusions: Prescription of oral medication improves compliance to surveillance and enables early detection of HCC, which is finally associated with enhanced survival.

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

( Joon Yeul Nam ),( Eun Sun Jang ),( Young Seok Kim ),( Youn Jae Lee ),( In Hee Kim ),( Sung Bum Cho ),( Han Chu Lee ),( Si Hyun Bae ),( Moran Ki ),( Hwa Young Choi ),( Eun Young Lee ),( Sook-hyang Je 대한간학회 2020 Gut and Liver Vol.14 No.2

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.

Clinical and Epidemiological Features of Hepatitis C Virus Infection in South Korea from 2007 to 2017: A Prospec-tive, Multicenter Cohort Study

( Joon Yeul Nam ),( Eun Sun Jang ),( Young Seok Kim ),( Youn Jae Lee ),( In Hee Kim ),( Sung Bum Cho ),( Han Chu Lee ),( Si Hyun Bae ),( Mo-ran Ki ),( Eun Young Lee ),( Sook-hyang Jeong ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: This study aimed to investigate the clinical and epidemiological features of chronic hepatitis C patients in South Korea from 2007 to 2017. Methods: The Korea hepatitis C virus (HCV) cohort is a prospective, multicenter cohort which enrolled 2,910 adult patients with anti-HCV positivity at 7 tertiary centers. A standardized questionnaire survey on the risk factor for HCV infection, and clinical data collection with patient follow-up were prospectively performed. Among them, clinical profiles of 2,758 patients with HCV RNA viremia were described. Results: The HCV cohort showed a mean age of 57.3 years with 50.7% men, current or past alcohol intake in 52.8%, obesity in 27.4%, and diabetes mellitus in 18.6%. Past history of transfusion before 1995 was in 14.4%, intravenous drug use (IVDU) in 5.6%, piercing in 33.4%, and tattooing in 37.4%. The diagnostic category consisted of chronic hepatitis (69.5%, n=1918), liver cirrhosis (18.9%, n=522), and hepatocellular carcinoma (HCC) (11.5%, n=318). The mean level of platelet count was 235K, ALT level over upper normal limit (UNL) in 50.1%, and HCV RNA level>600,000 IU/mL in 48.1%. The major HCV genotypes were genotype 1b (48.2%), genotype 2 (46.4%), genotype 3, 4, and 6 in 0.6%, 0.2%, and 0.5%, respectively. Liver biopsy was performed in 227 patients (8.2%), while FibroScan^® was performed in 289 patients. Antiviral treatment including interferon-based therapy and direct acting antivirals was undergone in 32.8%. Comparison of clinical profiles between the first half period (2007-2011) and second half (2012-2017) will be discussed. Conclusions: The current clinical profile of Korean chronic hepatitis C patients showed a mean age of 57 years with male to female ratio of 1, past history of transfusion and IVDU in less than 25%, genotype 1 and 2 in 95%, liver cirrhosis and HCC in 30%, and one third of the patients underwent antiviral therapy.