1.Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma
Jae Seung LEE ; Young Eun CHON ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Wonseok KANG ; Moon Seok CHOI ; Geum-Youn GWAK ; Yong-Han PAIK ; Joon Hyeok LEE ; Kwang Cheol KOH ; Seung Woon PAIK ; Hwi Young KIM ; Tae Hun KIM ; Kwon YOO ; Yeonjung HA ; Mi Na KIM ; Joo Ho LEE ; Seong Gyu HWANG ; Soon Sun KIM ; Hyo Jung CHO ; Jae Youn CHEONG ; Sung Won CHO ; Seung Ha PARK ; Nae-Yun HEO ; Young Mi HONG ; Ki Tae YOON ; Mong CHO ; Jung Gil PARK ; Min Kyu KANG ; Soo Young PARK ; Young Oh KWEON ; Won Young TAK ; Se Young JANG ; Dong Hyun SINN ; Seung Up KIM ;
Yonsei Medical Journal 2021;62(1):12-20
Purpose:
Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC.
Materials and Methods:
Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR.
Results:
Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001).
Conclusion
High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.
2.Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial
Do Seon SONG ; Won KIM ; Sang Hoon AHN ; Hyung Joon YIM ; Jae Young JANG ; Young Oh KWEON ; Yong Kyun CHO ; Yoon Jun KIM ; Gun Young HONG ; Dong Joon KIM ; Young Kul JUNG ; Joo Hyun SOHN ; Jin-Woo LEE ; Sung Jae PARK ; Byung Seok LEE ; Ju Hyun KIM ; Hong Soo KIM ; Seung Kew YOON ; Moon Young KIM ; Kwan Sik LEE ; Young Suk LIM ; Wan Sik LEE ; Jin Mo YANG ; Kyun-Hwan KIM ; Kwang-Hyub HAN ; Soon Ho UM
Clinical and Molecular Hepatology 2021;27(2):346-359
Background/Aims:
Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.
Methods:
Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV).
Results:
Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group.
Conclusions
BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
3.Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients
David Sooik KIM ; Soo Young PARK ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Kwang-Hyub HAN ; Yu Rim LEE ; Won Young TAK ; Young Oh KWEON ; Inkyung JUNG ; Minkyung HAN ; Eun Hwa KIM ; Sang Hoon AHN ; Seung Up KIM
Journal of Korean Medical Science 2021;36(16):e105-
Background:
Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.
Methods:
A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]).
Results:
Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).
Conclusion
The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.
4.Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial
Do Seon SONG ; Won KIM ; Sang Hoon AHN ; Hyung Joon YIM ; Jae Young JANG ; Young Oh KWEON ; Yong Kyun CHO ; Yoon Jun KIM ; Gun Young HONG ; Dong Joon KIM ; Young Kul JUNG ; Joo Hyun SOHN ; Jin-Woo LEE ; Sung Jae PARK ; Byung Seok LEE ; Ju Hyun KIM ; Hong Soo KIM ; Seung Kew YOON ; Moon Young KIM ; Kwan Sik LEE ; Young Suk LIM ; Wan Sik LEE ; Jin Mo YANG ; Kyun-Hwan KIM ; Kwang-Hyub HAN ; Soon Ho UM
Clinical and Molecular Hepatology 2021;27(2):346-359
Background/Aims:
Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.
Methods:
Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV).
Results:
Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group.
Conclusions
BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
5.Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients
David Sooik KIM ; Soo Young PARK ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Kwang-Hyub HAN ; Yu Rim LEE ; Won Young TAK ; Young Oh KWEON ; Inkyung JUNG ; Minkyung HAN ; Eun Hwa KIM ; Sang Hoon AHN ; Seung Up KIM
Journal of Korean Medical Science 2021;36(16):e105-
Background:
Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.
Methods:
A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]).
Results:
Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).
Conclusion
The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.
6.Multicenter Retrospective Risk Assessment of Esophageal Variceal Bleeding in Patients with Cirrhosis: An Acoustic Radiation Force Impulse Elastography-Based Prediction Model
Ja Yoon HEO ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Won Young TAK ; Young Oh KWEON ; Kwang Hyub HAN ; Soo Young PARK ; Seung Up KIM
Gut and Liver 2019;13(2):206-214
BACKGROUND/AIMS: Acoustic radiation force impulse (ARFI) elastography predicts the presence of esophageal varices (EVs). We investigated whether an ARFI-based prediction model can assess EV bleeding (EVB) risk in patients with cirrhosis. METHODS: The records of 262 patients with cirrhosis who underwent ARFI elastography and endoscopic surveillance at two institutions in 2008 to 2013 were retrospectively reviewed, and ARFI spleen diameter-to-platelet ratio scores (ASPS) were calculated. RESULTS: The median patient age (165 men, 97 women) was 56 years. The median ARFI velocity, spleen diameter, platelet count, and ASPS were 1.7 m/sec, 10.1 cm, 145×10⁹/L, and 1.16, respectively. During the median 38-month follow-up, 61 patients experienced EVB. Among all patients (179 without EVs and 83 with EVs), the cutoff value that maximized the sum of the sensitivity (73.1%) and specificity (78.4%) (area under receiver operating characteristic curve [AUROC], 0.824) for predicting EVB was 2.60. The cumulative EVB incidence was significantly higher in patients with ASPS ≥2.60 than in those with ASPS <2.60 (p<0.001). Among patients with EVs (n=83), 49 had high-risk EVs (HEVs), and 22 had EVB. The cumulative EVB incidence was significantly higher in HEV patients than in low-risk EV patients (p=0.037). At an ASPS of 4.50 (sensitivity, 66.7%; specificity, 70.6%; AUROC, 0.691), the cumulative EVB incidence was significantly higher in patients with a high ASPS than in those with a low ASPS (p=0.045). A higher ASPS independently predicted EVB (hazard ratio, 4.072; p=0.047). CONCLUSIONS: ASPS can assess EVB risk in patients with cirrhosis. Prophylactic management should be considered for patients with HEVs and ASPS ≥4.50.
Acoustics
;
Elasticity Imaging Techniques
;
Esophageal and Gastric Varices
;
Fibrosis
;
Follow-Up Studies
;
Hemorrhage
;
Humans
;
Incidence
;
Liver Cirrhosis
;
Male
;
Platelet Count
;
Retrospective Studies
;
Risk Assessment
;
ROC Curve
;
Sensitivity and Specificity
;
Spleen
;
Viperidae
7.Molecular Characterization of Enterotoxigenic Escherichia coli in Foodborne Outbreak.
Sang Hun PARK ; Hyun Jung SEUNG ; Hyo Won JEONG ; So Yun PARK ; Ji Hun JUNG ; Young Hee JIN ; Sung Hee HAN ; Hee Soon KIM ; Jin Seok KIM ; Joo Hyun PARK ; Ye Ji GONG ; Chae Kyu HONG ; Jib Ho LEE ; Il Young KIM ; Kweon JUNG
Journal of Bacteriology and Virology 2018;48(4):113-120
Diarrheagenic Escherichia coli (E. coli) is a main cause of diarrhea worldwide. This study reports the investigation on the occurrence of enterotoxigenic E. coli (ETEC) serotype O27:H7-associated foodborne gastrointestinal disease that occurred at two schools, one middle school and one high school, in Seoul, Korea in June 2015. The immediate government investigation in 1,216 students and 19 food handlers in these two schools revealed that 116 students, 32 students in the middle school and 84 students in the high school, and 2 food handlers, one from middle school and the other from high school, developed gastrointestinal illness symptoms including diarrhea. Following lab investigation identified 29 ETEC serotype O27:H7 strains, 27 from 116 students and 2 from 19 food handlers. Pattern of pulsed-field gel electrophoresis analysis of ETEC isolates suggested that ETEC serotype O27:H7 caused the diarrheal outbreak in June 2015 in Seoul, Korea was a specific clone. In addition, these ETEC serotype O27:H7 isolates were highly resistance to the several antibiotics. The results from the present study provide the evidence that ETEC serotype O27:H7 can be an important cause of domestic foodborne outbreak in Korea.
Anti-Bacterial Agents
;
Clone Cells
;
Diarrhea
;
Electrophoresis, Gel, Pulsed-Field
;
Enterotoxigenic Escherichia coli*
;
Escherichia coli
;
Gastrointestinal Diseases
;
Humans
;
Korea
;
Seoul
;
Serogroup
8.Factors Influencing the Diagnostic Accuracy of Acoustic Radiation Force Impulse Elastography in Patients with Chronic Hepatitis B.
Mi Sung PARK ; Sun Wook KIM ; Ki Tae YOON ; Seung Up KIM ; Soo Young PARK ; Won Young TAK ; Young Oh KWEON ; Mong CHO ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang Hyub HAN
Gut and Liver 2016;10(2):275-282
BACKGROUND/AIMS: To determine factors predictive of discordance in staging liver fibrosis using liver biopsy (LB) and acoustic radiation force impulse (ARFI) elastography in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with CHB who underwent LB and ARFI elastography on the same day from November 2010 to March 2013 were prospectively recruited from three tertiary hospitals. RESULTS: We analyzed 105 patients (median age of 47 years). The F0-1, F2, F3, and F4 fibrosis stages were identified in 27 (25.7%), 27 (25.7%), 21 (20.0%), and 30 (28.6%) patients, respectively. The areas under the receiver operating characteristics curves for ARFI elastography in assessing ≥F2, ≥F3, and F4 was 0.814, 0.848, and 0.752, respectively. The discordance of at least one stage between LB and ARFI was observed in 68 patients (64.8%) and of at least two stages in 16 patients (15.2%). In a multivariate analysis, advanced fibrosis stage (F3-4) was the only factor that was negatively correlated with one-stage discordance (p=0.042). Moreover, advanced fibrosis stage was negatively (p=0.016) correlated and body mass index (BMI) was positively (p=0.006) correlated with two-stage discordance. CONCLUSIONS: Advanced fibrosis stage (F3-4) was a predictor of nondiscordance between LB and ARFI elastography; BMI also influenced the accuracy of ARFI elastography.
Body Mass Index
;
Elasticity Imaging Techniques/*methods
;
Female
;
Hepatitis B, Chronic/*complications
;
Humans
;
Liver/diagnostic imaging/pathology
;
Liver Cirrhosis/*diagnostic imaging/etiology
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Predictive Value of Tests
;
Prospective Studies
;
ROC Curve
;
Republic of Korea
9.The Impact of Functional Constipation on the Quality of Life in the Elderly over 60 Years.
Hyeok Kyu KWON ; Hyun Jin DO ; Hye Jung KIM ; Seung Won OH ; Youl Lee LYM ; Jae Kyung CHOI ; Hee Kyung JOH ; Hyuk Jung KWEON ; Dong Yung CHO
Korean Journal of Family Medicine 2010;31(1):35-43
BACKGROUND: Constipation is one of the most common digestive complaints. Although, there are increased interest on the socioeconomic effect of constipation and studies associated with quality of life on constipation, there is no study about the influence of constipation onto quality of life (QOL) in Korea. We studied the impact of functional constipation on QOL. METHODS: Between March to June 2008, person to person survey with 844 elderly aged over 60 years was performed at two senior care centers, a public health center, and secondary hospital in Seoul metrocity and Chung-ju city. The diagnosis of functional constipation was based on the Rome III criteria and QOL was measured by the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36). RESULTS: The average age was 73.6 years and the prevalence rate of constipation was 20.3%. The average SF-36 score was 63.5 in total population, 57.9 in constipation group, and 64.9 in normal group. CONCLUSION: These results suggest that the constipation lowers QOL in adults aged over 60 years old. Further study will be necessary to explore if QOL changes according to the severity of constipation and its treatment and to assess QOL using a disease-specific measurement tool that can be used for Korean environment.
Adult
;
Aged
;
Constipation
;
Health Surveys
;
Humans
;
Korea
;
Prevalence
;
Public Health
;
Quality of Life
;
Rome
10.The Impact of Functional Constipation on the Quality of Life in the Elderly over 60 Years.
Hyeok Kyu KWON ; Hyun Jin DO ; Hye Jung KIM ; Seung Won OH ; Youl Lee LYM ; Jae Kyung CHOI ; Hee Kyung JOH ; Hyuk Jung KWEON ; Dong Yung CHO
Korean Journal of Family Medicine 2010;31(1):35-43
BACKGROUND: Constipation is one of the most common digestive complaints. Although, there are increased interest on the socioeconomic effect of constipation and studies associated with quality of life on constipation, there is no study about the influence of constipation onto quality of life (QOL) in Korea. We studied the impact of functional constipation on QOL. METHODS: Between March to June 2008, person to person survey with 844 elderly aged over 60 years was performed at two senior care centers, a public health center, and secondary hospital in Seoul metrocity and Chung-ju city. The diagnosis of functional constipation was based on the Rome III criteria and QOL was measured by the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36). RESULTS: The average age was 73.6 years and the prevalence rate of constipation was 20.3%. The average SF-36 score was 63.5 in total population, 57.9 in constipation group, and 64.9 in normal group. CONCLUSION: These results suggest that the constipation lowers QOL in adults aged over 60 years old. Further study will be necessary to explore if QOL changes according to the severity of constipation and its treatment and to assess QOL using a disease-specific measurement tool that can be used for Korean environment.
Adult
;
Aged
;
Constipation
;
Health Surveys
;
Humans
;
Korea
;
Prevalence
;
Public Health
;
Quality of Life
;
Rome

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