1.Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B
Mi Young JEON ; Beom Kyung KIM ; Jae Seung LEE ; Hye Won LEE ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Seung Up KIM
Clinical and Molecular Hepatology 2021;27(2):295-304
Background/Aims:
The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT.
Methods:
Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of <1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch.
Results:
The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices <1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P<0.001).
Conclusions
The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.
2.Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B
Mi Young JEON ; Beom Kyung KIM ; Jae Seung LEE ; Hye Won LEE ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Seung Up KIM
Clinical and Molecular Hepatology 2021;27(2):295-304
Background/Aims:
The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT.
Methods:
Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of <1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch.
Results:
The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices <1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P<0.001).
Conclusions
The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.
3.Proposal of a New Risk Score for Patients Treated with Transarterial Chemoembolization due to Recurrent Hepatocellular Carcinoma after Curative Resection: A Multicenter Study
Mi Young JEON ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Jeong-Hoon LEE ; Su Jong YU ; Yoon Jun KIM ; Jung-Hwan YOON ; Eun Ju CHO ; Seung Up KIM
Gut and Liver 2020;14(4):477-485
Background/Aims:
Prognostic models are lacking for patients with recurrent hepatocellular carcinoma (HCC) following surgical resection. This study devised and validated a new hepatoma arterial-embolization prognostic (HAP) score optimized for use in patients undergoing treatment with transarterial chemoembolization (TACE) for recurrence subsequent to surgical resection of HCC.
Methods:
Training cohort (n=424) and validation cohort (n=350) patients with recurrent HCC after resection treated with TACE between 2003 and 2016 were enrolled. Cox regression and area under the receiver operating characteristic curve (AUC) analyses were used to identify risk factors for survival and to calculate the predictive performance of risk scores, respectively.
Results:
The median age of the study population was 59.2 years. α-Fetoprotein >400 ng/mL (hazard ratio [HR]=1.815), serum albumin ≤3.5 g/dL (HR=1.966), tumor number ≥2 (HR=1.425), tumor size >5 cm at resection or recurrence (HR=1.356), segmental portal vein invasion at resection or recurrence (HR=2.032), and time from resection to recurrence ≤1 years (HR=1.849) independently predicted survival (all p<0.05). The postoperative HAP (pHAP) model based on the rounded HRs of these variables showed an AUC of 0.723 for predicting survival at 3 years, which was significantly higher than AUCs of other HAP-based models, including HAP, modified HAP, and modified HAP-II scores (0.578-0.621) (all p<0.05). The accuracy of pHAP was maintained in the entire cohort (n=774; AUC=0.776 at 3 years).
Conclusions
A new pHAP score optimized for patients treated with TACE due to recurrent HCC after resection showed acceptable accuracy and was externally validated. Further studies of means by which to select treatment options other than TACE for high-risk patients according to pHAP scores are warranted.
4.Sarcopenia Is Independently Associated with the Degree of Liver Fibrosis in Patients with Type 2 Diabetes Mellitus
Min Je SUNG ; Tae Seop LIM ; Mi Young JEON ; Hye Won LEE ; Beom Kyung KIM ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Jun Yong PARK ; Seung Up KIM
Gut and Liver 2020;14(5):626-635
Background/Aims:
Sarcopenia is associated with liver fi-brosis in patients with nonalcoholic fatty liver disease and chronic hepatitis B. We investigated the association between sarcopenia and hepatic fibrotic burden in patients with type 2 diabetes mellitus (T2DM).
Methods:
Patients with T2DM who had received a comprehensive medical health checkup were recruited. Muscle mass was assessed using com-puted tomography. Fibrotic burden was assessed using the fibrosis-4 index (FIB-4). The study population was divided by quartile stratification of the lumbar skeletal muscle index (LSMI).
Results:
Among 309 patients with T2DM, 75 (24.3%) had sarcopenia. These patients were significantly older and had higher FIB-4, whereas they had significantly lower body mass index (BMI) and LSMI than patients without sarcopenia (all p<0.05). The LSMI showed a significant negative cor-relation with the FIB-4 when analyzed in terms of quartile stratification (p=0.003). Multivariate analysis showed that female sex and higher BMI were independently associated with a reduced risk of sarcopenia (odds ratio [OR], 0.388;95% confidence interval [CI], 0.199 to 0.755 and OR, 0.704;95% CI, 0.618 to 0.801; all p<0.05), whereas a higher FIB-4 was independently associated with an increased risk of sarcopenia (OR, 1.817; 95% CI, 1.180 to 2.797; p=0.007).Among patients with a BMI <25 kg/m 2 (n=165), those with sarcopenia (n=54, 32.7%) had a significantly higher FIB-4 than those without (n=111, 67.3%; 1.66 vs 1.38, p=0.004).
Conclusions
Sarcopenia is independently associated with fibrotic burden in patients with T2DM. Further studies should investigate whether the improvement of sarcopenia can ameliorate liver fibrosis in patients with T2DM.
5.Health-Related Quality of Life, Perceived Social Support, and Depression in Disease-Free Survivors Who Underwent Curative Surgery Only for Prostate, Kidney and Bladder Cancer: Comparison among Survivors and with the General Population.
Dong Wook SHIN ; Hyun Sik PARK ; Sang Hyub LEE ; Seung Hyun JEON ; Seok CHO ; Seok Ho KANG ; Seung Chol PARK ; Jong Hyock PARK ; Jinsung PARK
Cancer Research and Treatment 2019;51(1):289-299
PURPOSE: The purpose of this study was to compare health-related quality of life (HRQoL) of disease-free prostate (PC), kidney (KC), and bladder cancer (BC) survivors with that of the general population. MATERIALS AND METHODS: Our study included 331 urological cancer (UC) survivors (114 PC, 108 KC, and 109 BC) aged ≥ 50 years disease-free for at least 1 year after surgery. The control group included 1,177 subjects without a history of cancer. The HRQoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30, the Duke-UNC Functional Social Support Questionnaire, and the Patient Health Questionnaire-9. RESULTS: There was no significant difference between the groups in terms of any of the functioning sub-scales and symptoms, except significantly lower social functioning observed in BC survivors than that observed in KC survivors. Although the three groups of UC survivors showed essentially similar functioning sub-scales and symptoms when compared to the general population, PC and BC survivors showed significantly lower social functioning and a lower appetite than that observed in controls. KC survivors showed lower physical functioning, as well as higher pain and dyspnea. Although all three groups of UC survivors reported higher financial difficulties, they also reported higher perceived social support than that reported by the non-cancer control group. No statistically significant difference was observed in terms of depressive symptoms between each group of UC survivors and the general population. CONCLUSION: Disease-free survivors of the three major types of UCs showed generally similar HRQoL compared to the general population, as well as compared to each other.
Appetite
;
Depression*
;
Dyspnea
;
Humans
;
Kidney Neoplasms
;
Kidney*
;
Prostate*
;
Prostatic Neoplasms
;
Quality of Life*
;
Survivors*
;
Urinary Bladder Neoplasms*
;
Urinary Bladder*
;
Urologic Neoplasms
6.Health-Related Quality of Life Changes in Prostate Cancer Patients after Radical Prostatectomy: A Longitudinal Cohort Study
Dong Wook SHIN ; Sang Hyub LEE ; Tae Hwan KIM ; Seok Joong YUN ; Jong Kil NAM ; Seung Hyun JEON ; Seung Chol PARK ; Seung Il JUNG ; Jong Hyock PARK ; Jinsung PARK
Cancer Research and Treatment 2019;51(2):556-567
PURPOSE: Health-related quality of life (HRQOL) information related to radical prostatectomy (RP) is valuable for prostate cancer (PC) patients needing to make treatment decisions. We aimed to investigate HRQOL change in PC patients who underwent three types of RP (open, laparoscopic, or robotic) and compared their HRQOL with that of general population. MATERIALS AND METHODS: Patients were prospectively recruited between October 2014 and December 2015. European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) and PC-specific module (PR25) were administered before surgery (baseline) and at postoperative 3 and 12 months. At each time point, HRQOL was compared, and a difference of 10 out of 0-100 scale was considered clinically significant. RESULTS: Among 258 screened patients, 209 (41 open, 63 laparoscopic, and 105 robotic surgeries) were included. Compared to baseline, physical, emotional, and cognitive functioning improved at 12 months. Role functioning worsened at 3 months, but recovered to baseline at 12 months. Pain, insomnia, diarrhea, and financial difficulties also significantly improved at 12 months. Most PR25 scales excluding bowel symptoms deteriorated at 3 months. Urinary symptoms and incontinence aid recovered at 12 months, whereas sexual activity and sexual function remained poor at 12 months. Clinically meaningful differences in HRQOL were not observed according to RP modalities. Compared to the general population, physical and role functioning were significantly lower at 3 months, but recovered by 12 months. Social functioning did not recover. CONCLUSION: Most HRQOL domains showed recovery within 12 months after RP, excluding sexual functioning and social functioning. Our findings may guide patients considering surgical treatment for PC.
Cohort Studies
;
Diarrhea
;
Humans
;
Prospective Studies
;
Prostate
;
Prostatectomy
;
Prostatic Neoplasms
;
Quality of Life
;
Sexual Behavior
;
Sleep Initiation and Maintenance Disorders
;
Weights and Measures
7.Conditional Survival Estimates Improve Over Time for Patients with Hepatocellular Carcinoma: An Analysis for Nationwide Korea Cancer Registry Database
Jae Seung LEE ; In Rae CHO ; Hye Won LEE ; Mi Young JEON ; Tae Seop LIM ; Oidov BAATARKHUU ; Do Young KIM ; Kwang Hyub HAN ; Jun Yong PARK
Cancer Research and Treatment 2019;51(4):1347-1356
PURPOSE: Conditional survival estimates (CSE) can provide additional useful prognostic information on the period of survival after diagnosis, which helps in counseling patients with cancer on their individual prognoses. This study aimed to analyze conditional survival (CS) for hepatocellular carcinoma (HCC) using a Korean national registry. MATERIALS AND METHODS: Patients with HCC, registered in the Korean cancer registry database, were retrospectively reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method. The 1-year CS at X year or month after diagnosis were calculated as CS₁=OS((X+1))/OS((X)). CS calculations were performed in each Barcelona Clinic Liver Cancer stage, after which patients at stage 0, A, and B underwent subgroup analysis using initial treatment methods. RESULTS: A total of 4,063 patients diagnosed with HCC from January 2008 to December 2010, and 2,721 who were diagnosed from January 2011 to December 2012, were separately reviewed. In 2008-2010, the 1-year CS of 1, 2, 3, 4, and 5-year survivors was 82.9%, 85.1%, 88.3%, 88.0%, and 88.6%, respectively. Patients demonstrated an increase in CSE over time in subgroup analysis, especially in the advanced stages. In 2011-2012, the 1-year CS of 6, 12, 18, 24, 30, and 36 months was 81.5%, 83.8%, 85.3%, 85.5%, 86.5%, and 88.8%, respectively. The subgroup analysis showed the same tendency towards increased CSE in the advanced stages. CONCLUSION: Overall, the CS improved with each additional year after diagnosis in both groups. CSE may therefore provide a more accurate prognosis and hopeful message to patients who are surviving with or after treatment.
Carcinoma, Hepatocellular
;
Counseling
;
Diagnosis
;
Hope
;
Humans
;
Korea
;
Liver Neoplasms
;
Methods
;
Prognosis
;
Republic of Korea
;
Retrospective Studies
;
Survivors
8.Influence of hepatic steatosis on the outcomes of patients with chronic hepatitis B treated with entecavir and tenofovir
David Sooik KIM ; Mi Young JEON ; Hye Won LEE ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang Hyub HAN ; Seung Up KIM
Clinical and Molecular Hepatology 2019;25(3):283-293
BACKGROUND/AIMS: The influence of hepatic steatosis (HS) on chronic hepatitis B (CHB) is unclear. We evaluated the influence of the degree of HS, assessed using the controlled attenuation parameter (CAP) of transient elastography (TE), on treatment outcomes in CHB patients initiated on antiviral therapy. METHODS: A total of 334 patients who were initiated on entecavir or tenofovir between 2007 and 2016 with available TE results were recruited. RESULTS: Of the total study population, 146 (43.7%) patients had HS (CAP > 238 dB/m). Three-hundred-three patients (90.7%) achieved complete virological response (CVR) (hepatitis B virus DNA<12 IU/L), and 25 patients (7.5%) developed hepatocellular carcinoma (HCC). Among hepatitis B e antigen (HBeAg)-positive patients (n=172, 51.5%), 37 (21.5%) experienced HBeAg loss. On univariate analysis, CAP value was not associated with the probability of HCC development (P=0.380). However, lower CAP value was independently associated with higher probability of HBeAg loss among HBeAg-positive patients (hazard ratio [HR]=0.991, P=0.026) and with CVR achievement in the entire study population (HR=0.996, P=0.004). The cumulative incidence of HBeAg loss among HBeAg-positive patients was significantly higher in patients without HS than in those with HS (log-rank, P=0.022). CONCLUSIONS: CAP values were not correlated with HCC development in patients initiated on entecavir and tenofovir. However, CAP values were negatively correlated with the probability of HBeAg loss among HBeAg-positive patients and with CVR achievement.
Carcinoma, Hepatocellular
;
Elasticity Imaging Techniques
;
Fatty Liver
;
Hepatitis B
;
Hepatitis B e Antigens
;
Hepatitis B, Chronic
;
Hepatitis, Chronic
;
Herpesvirus 1, Cercopithecine
;
Humans
;
Incidence
;
Tenofovir
9.The Effect of Psychological Factors on Postoperative Pain in Gastric Tumor Patients after Endoscopic Submucosal Dissection
Joon Hyub LEE ; Han Ho JEON ; San LEE ; Hyeok LEE ; Seung Taek OH ; Jhin Goo CHANG ; Woo Young IM ; Jaesub PARK ; Won Jung CHOI
Korean Journal of Psychosomatic Medicine 2018;26(1):68-75
OBJECTIVES: Since pain in cancer patients is an important factor that greatly affects the quality of life and prognosis, many attempts have been actively made to reduce the pain. Despite continuous effort on reducing pain after Endoscopic submucosal dissection (ESD), research has not been done on psychological factors as much as on biological factors affecting pain. The objective of this study is to investigate the psychological factors affecting postoperative pain in gastric tumor patients who underwent gastric ESD. METHODS: 91 gastric tumor patients who visited National Health Service Ilsan Hospital in Korean between May 2015 and June 2016, and received ESD were evaluated. Baseline characteristics including sociodemographic factors, anxiety, depression, and resilience were evaluated before the procedure. Multivariate logistic regression was done to analyze factors affecting postoperative pain. RESULTS: The group with high postoperative pain showed lower alcohol consumption and higher depressive symptom scores than the group with low postoperative pain. Also, the group with high postoperative pain showed lower total resilience score with lower subtotal scores in self-control and positive item. Multivariate logistic regression analysis of the postoperative pain showed that patients with lower score in self-control of resilience [odd ratio (OR), 0.911 ; 95% CI, 0.854–0.971, p=0.004) reported more pain after ESD. CONCLUSIONS: This study showed that patients with lower self-control ability of resilience felt more pain after ESD. Among the psychological factors evaluated in this study, resilience of an individual seems to have effect on pain.
Alcohol Drinking
;
Anxiety
;
Biological Factors
;
Depression
;
Humans
;
Logistic Models
;
National Health Programs
;
Pain, Postoperative
;
Prognosis
;
Psychology
;
Quality of Life
;
Self-Control
10.Survival Estimates after Stopping Sorafenib in Patients with Hepatocellular Carcinoma: NEXT Score Development and Validation.
Hye Won LEE ; Hyun Soo KIM ; Seung Up KIM ; Do Young KIM ; Beom Kyung KIM ; Jun Yong PARK ; Sang Hoon AHN ; Mi Young JEON ; Ja Yoon HEO ; Soo Young PARK ; Yu Rim LEE ; Sun Kyung JANG ; Su Hyun LEE ; Se Young JANG ; Won Young TAK ; Kwang Hyub HAN
Gut and Liver 2017;11(5):693-701
BACKGROUND/AIMS: Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model. METHODS: Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed. RESULTS: In the training cohort, four factors were independent negative predictors of survival (p<0.05). Based on the β regression coefficient of each factor, we established the NEXT score (Survival after Stopping Nexavar Treatment), allocating 1 point each for an Eastern Cooperative Oncology Group score ≥2, Child-Pugh class B or C, serum sodium ≤135 mEq/L, and α-fetoprotein >400 ng/mL. Area under the receiver operating characteristic curve values to predict 1-, 3-, and 6-month survival rates were 0.805, 0.809, and 0.774, respectively, in the training cohort and 0.783, 0.728, and 0.673, respectively, in the validation cohort (n=137). When the training and validation cohorts were stratified into three risk groups (NEXT score 0 [low-risk] vs 1 to 2 [intermediate-risk] vs 3 to 4 [high-risk]), survival differed significantly between the groups (p<0.05, log-rank test). CONCLUSIONS: In patients with HCC, survival after stopping sorafenib is poor. However, risk estimates based on a new “NEXT score” may help predict survival and prognosis even in patients who discontinue sorafenib treatment.
Carcinoma, Hepatocellular*
;
Cohort Studies
;
Humans
;
Prognosis
;
ROC Curve
;
Sodium
;
Survival Rate

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