Young-Suk Lim

Asan Medical Center, Sŏul, Seoul, South Korea

Are you Young-Suk Lim?

Claim your profile

Publications (108)551.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background & aims: Current diagnostic imaging criteria for hepatocellular carcinoma (HCC) are dedicated to imaging with nonspecific extracellular contrast agents. This study aimed to evaluate diagnostic criteria for HCC ⩽3 cm on magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent through an inception cohort study. Methods: Of 291 patients with chronic liver disease and new nodules of 1-3 cm in diameter at surveillance ultrasonography, 295 solid nodules (194 HCCs, 98 benign nodules, and three other malignancies) in 198 patients with a confirmed final diagnosis or ⩾24 months follow-up were evaluated on gadoxetic acid-enhanced MRI. Through univariate and multivariate logistic regression analyses, various diagnostic criteria were developed by combining significant MRI findings for diagnosing HCC. The diagnostic performance of each criterion was compared with that of the European Association for the Study of the Liver (EASL) criteria. Results: Four MRI findings (arterial-phase hyperintensity, transitional-phase hypointensity, hepatobiliary-phase hypointensity, and rim enhancement) were independently significant for diagnosis of HCC ⩽3 cm. For whole nodules, EASL criteria showed the best performance for diagnosing HCC (sensitivity, 83.5%; specificity, 81.2%). For nodules ⩽2 cm in diameter, a new criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) showed a significantly higher sensitivity than that of the EASL criteria (83.0% versus 74.5%, p=0.008), without a significantly different specificity (76.7% versus 81.1%, p=0.125). Conclusions: EASL criteria exhibit the best diagnostic performance for HCC ⩽3 cm on hepatocyte-specific contrast-enhanced MRI. A newly identified criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) may increase the diagnostic sensitivity of small (⩽2 cm) HCC.
    No preview · Article · Jan 2016 · Journal of Hepatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To validate and reappraise the Assessment for Retreatment with Transarterial chemoembolization (ART) score comprising three parameters (>25 % increase in aspartate aminotransferase [AST], increase in Child-Pugh score and tumour response), determined prior to subsequent transarterial chemoembolization (TACE). Methods: Enrolled patients were diagnosed with unresectable non-metastatic hepatocellular carcinoma and underwent multiple TACEs between June 2006 and December 2007 (N = 153). Subgroupings were classified according to the established cut-off (≤1.5 vs. ≥2.5). Survival analysis using the Kaplan-Meier curve was performed. Results: The original ART score dichotomized patients according to their overall survival (P = 0.004). We found several patients who actually survived longer than others were assigned to a poor prognostic group due to the AST component. Parameter estimates for AST obtained from our analysis were much lower than the original version (0.5 vs. 2.1). We adjusted the component according to the value of our parameter estimates, and patients with >25 % AST increase received 1.0 point. After this modification, patients assigned to the favourable prognostic group were more likely to have a better survival outcome (median 23.9 vs. 12.2 months, P < 0.001). Conclusions: In hepatitis B virus-endemic regions, the ART score is valid and can better predict post-TACE survival after the AST component is modified. Key points: • The ART score was validated in a HBV-endemic region. • The modified ART score improved prognostic performance by reappraising the AST component. • The modified ART score helps physicians make decisions for further TACE.
    No preview · Article · Jan 2016 · European Radiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: This study aimed to assess the prognostic impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term survival outcomes in patients undergoing resection of small solitary hepatocellular carcinoma (HCC). Methods: Enrolled patients had undergone macroscopic curative resection of solitary 2-5 cm HCC with (n = 105) or without (n = 830; control group) preoperative TACE. Results: TACE group was divided into subgroups A (n = 68, 1-2 TACEs within 12 months), B (n = 23, ≥3 TACEs within 12 months), and C (n = 14, TACE prior to 12 months). The number of TACE sessions was 1.8 ± 1.6. In TACE A-C subgroups, pathological response of tumor necrosis >50 % at median post-TACE period after final TACE was observed in 41 (60.3 %) at 1.9 months, 10 (43.5 %) at 2.1 months, and 2 (14.3 %) at 18.9 months, respectively. The 5-year tumor recurrence and patient survival rates were 62.8 and 70.4 % in TACE group and 51.4 and 83.4 % in control group, respectively (p ≤ 0.003). Median periods of postoperative tumor recurrence in TACE A-C subgroups and control group were 35, 13, 14, and 55 months, respectively (p < 0.001); and postoperative survival periods at 75 % survival rate were 51, 38, 51, and 98 months, respectively (p = 0.003). TACE-induced extensive tumor necrosis did not improve postoperative prognosis in TACE A subgroup (p ≥ 0.053). Postoperative prognosis after preoperative sequential TACE and portal vein embolization was comparable to that of the control group (p ≥ 0.052). Conclusions: Preoperative TACE for small solitary HCCs may adversely affect post-resection prognosis, irrespective of pathological responses. Preoperative TACE should be avoided for patients with resectable small HCCs.
    No preview · Article · Dec 2015 · World Journal of Surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To develop a prognostic nomogram based on specific patient and tumor factors capable of estimating individual survival outcomes after radiofrequency (RF) ablation as a primary therapy for hepatocellular carcinoma (HCC). Materials and methods: This retrospective study included 893 patients who were initially treated with curative RF ablation for HCC; patients were temporally divided into derivation (n = 607) and validation (n = 286) cohorts. A multivariate Cox proportional hazards model for overall survival was developed and validated. The discriminatory accuracy of the model was compared with the preexisting Cancer of the Liver Italian Program (CLIP) system and the Tokyo score previously proposed for percutaneous therapy for HCC by analyzing receiver operating characteristic (ROC) curves. Results: A nomogram was generated for 3-year survival, incorporating largest tumor diameter and number of tumors, serum albumin and creatinine, platelet count, prothrombin time, and serum α-fetoprotein on a logarithmic scale. It had good calibration and discrimination abilities with a C-index of 0.74. The validation results also showed that the nomogram performed well in terms of goodness-of-fit and discrimination (C-index, 0.72). Analysis of ROC curves in the validation cohort indicated that the model had better predictive power than CLIP and Tokyo scores (C-indexes, 0.54 and 0.66, respectively). Conclusions: This prognostic tool quantifying per-patient expected survival after RF ablation can be used in daily clinical decision making with regard to patients with HCC deemed suitable for radical ablation and is probably more reliable than existing guidelines.
    No preview · Article · Nov 2015 · Journal of vascular and interventional radiology: JVIR
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and aim: To investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE). Methods: A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias. Results: The median follow-up period was 11.1 months (range, 3.1-82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001). Conclusions: AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.
    Full-text · Article · Aug 2015 · PLoS ONE

  • No preview · Article · Jul 2015 · Circulation
  • [Show abstract] [Hide abstract]
    ABSTRACT: To construct prognostic nomograms capable of estimating individual probabilities of tumor progression and overall survival (OS) at specific time points during serial transarterial chemoembolization for hepatocellular carcinoma (HCC). The study included 1,181 consecutive patients with nonmetastatic HCC undergoing repeated transarterial chemoembolization at a single tertiary referral center. Patients were assigned to 2 cohorts according to the first transarterial chemoembolization date: derivation (2004-2006; n = 854) and validation (2007; n = 327) sets. Multivariate Cox proportional hazards models were developed based on covariates derived before transarterial chemoembolization and assessed for their association with 5-year OS and 3-year progression-free survival (PFS). The accuracy of the models was internally and externally validated. The 5-year OS of the derivation set was 25.4%, and 3-year PFS was 20.8%. Nomograms for OS and PFS were built into the derivation set incorporating the following factors: log [tumor volume] calculated as 4/3 × 3.14 × (maximum radius of tumor in cm(3)); tumor number; tumor type (nodular or infiltrative); Child-Pugh class (A or B); (model for end-stage liver disease score/10)(-2); log [α-fetoprotein]; and portal vein invasion. The models had good discrimination and calibration abilities with C-indexes of 0.80 (5-y survival) and 0.77 (3-y progression). The results of external validation confirmed that these models performed well in terms of discrimination and goodness-of-fit (C-indexes 0.77 for 5-y survival and 0.73 for 3-y progression). Nomograms quantifying the survival and progression outcomes in patients treated with transarterial chemoembolization are useful clinical aids in providing personalized care. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Journal of vascular and interventional radiology: JVIR
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and study aims: New methods for the endoscopic selective ablation of locally advanced pancreaticobiliary malignancies as a minimally invasive approach are needed. Our aim was to examine the feasibility and safety of endoscopic ultrasonography (EUS)-guided photodynamic therapy (PDT) for local tumor control in patients with locally advanced pancreaticobiliary malignancies. Patients and methods: A chlorin e6 derivative and a flexible laser-light catheter were used to perform EUS-guided PDT in four patients with locally advanced pancreaticobiliary malignancies. Results: EUS-guided PDT was technically feasible in all four patients with locally advanced pancreaticobiliary malignancies (two in the caudate lobe of the liver, one in the far distal bile duct, and one in the tail of the pancreas). No treatment-related complications occurred. The median volume of necrosis produced by PDT was 4.0 cm(3) (range 0.7 - 11.3). Disease remained stable in all four patients during a median follow-up of 5 months (range 3 - 7). Conclusion: These preliminary data suggest that EUS-guided PDT with a second-generation photosensitizer and a flexible laser probe is feasible and safe. © Georg Thieme Verlag KG Stuttgart · New York.
    No preview · Article · Jun 2015 · Endoscopy
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify factors associated with non-alcoholic fatty liver disease (NAFLD) in healthy Asian subjects. A propensity score-matched case-control study was designed. To investigate the effects of demographic and clinical factors on the presence of NAFLD, a baseline-category logit model was used. Potential living liver donors with no hepatic steatosis (<5%: n=1,353, group 1) were considered the baseline category, and subjects with mild (5-33%: n=724, group 2) and moderate/severe (>33%: n=116, group 3) hepatic steatosis were defined as cases. Age and gender were matched between cases and controls, which resulted in 83 matched subjects in each of the three groups. The area of abdominal (visceral and subcutaneous) fat was directly measured in all subjects by unenhanced computed tomography. Serum aspartate aminotransferase, alanine aminotransferase (ALT), gamma-glutamyltranspeptidase, total cholesterol and triglyceride levels, waist circumference, and visceral fat amount were directly correlated with the grade of hepatic steatosis, and high-density lipoprotein cholesterol levels were inversely correlated with it (all P values <0.05) In a multivariate model, visceral fat amount was significantly correlated with both mild (group 2) and moderate to severe (group 3) NAFLD, with respective odds ratios (ORs) of 1.03 relative to group 1 (Ps<0.05). Body mass index (BMI), ALT, and subcutaneous fat were significant predictors of only moderate to severe NAFLD (ORs of 0.54, 1.20, and 1.02, respectively, for group 3 vs. group 1; Ps<0.05). Our results indicate that visceral adiposity makes non-obese subjects more susceptible to NAFLD, compared with subcutaneous fat and BMI. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Journal of Gastroenterology and Hepatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to generate and validate a novel risk prediction model for patients with hepatocellular carcinoma (HCC) undergoing trans-arterial chemoembolization (TACE). Patients receiving TACE as the first-line therapy between 2006 and 2009 were selected from the databases of two major tertiary hospitals in Korea. The study population was randomly assigned into training (n=340) and validation (n=145) sets. From a multivariate Cox-regression model for overall survival (OS), tumor Size, tumor Number, baseline Alpha-fetoprotein level, Child-Pugh class, and Objective radiological Response after the first TACE session were selected and then scored to generate a 10-point risk prediction model (named as "SNACOR" model) in the training set. Thereafter, the prognostic performance was assessed in the validation set. In the training set, the time-dependent areas under receiver-operating characteristic curves (AUROCs) for OS at 1-, 3-, and 6-years were 0.783, 0.754, and 0.742, respectively. According to the score of the SNACOR model, patients were stratified into three groups; Low- (score 0-2), Intermediate- (score 3-6), and High-risk group (score 7-10), respectively. The Low-risk group had the longest median OS (49.8 months), followed by Intermediate- (30.7 months) and High-risk group (12.4 months) (log-rank, p<0.001). Compared to the Low-risk group, the Intermediate-risk (hazard ratio [HR] 2.13, p<0.001) and High-risk group (HR 6.17, p<0.001) retained significant risks of death. Similar results were obtained in the validation set. A simple-to-use SNACOR model for patients with HCC treated with TACE might be helpful in appropriate prognostification and guidance for decision of further treatment strategies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Liver international: official journal of the International Association for the Study of the Liver
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: No adjuvant therapy has been shown to extend survival of patients with hepatocellular carcinoma (HCC) receiving curative treatment. We investigated whether injections of activated cytokine-induced killer (CIK) cells (CD3+/CD56+ and CD3+/CD56- T cells and CD3-/CD56+ natural killer cells) prolongs recurrence-free survival of patients following curative therapy for HCC. We performed a multi-center, randomized, open-label, phase 3 trial of the efficacy and safety of adjuvant immunotherapy with activated CIK cells (created by incubation of patients' peripheral blood mononuclear cells with interleukin-2 and an antibody against CD3). The study included 230 patients with HCC treated by surgical resection, radiofrequency ablation, or percutaneous ethanol injection at university-affiliated hospitals in Korea. Patients were randomly assigned to receive immunotherapy (injection of 6.4 ×10⁹ autologous CIK cells, 16 times during 60 weeks) or no adjuvant therapy (controls). The primary endpoint was recurrence-free survival; secondary endpoints included overall survival, cancer-specific survival, and safety. The median time of recurrence-free survival was 44.0 months in the immunotherapy group and 30.0 months in the control group (hazard ratio [HR] with immunotherapy, 0.63; 95% confidence interval [CI], 0.43-0.94; P=.010 by one-sided log-rank test). HRs were also lower in the immunotherapy than control group for all-cause death (0.21; 95% CI, 0.06-0.75; P=.008) and cancer-related death (0.19; 95% CI, 0.04-0.87; P=.02). A significantly higher proportion of patients in the immunotherapy group than the control group had an adverse event (62% vs 41%, P=.002), but the proportion of patients with serious adverse events did not differ significantly between groups (7.8% vs 3.5%, P=.15). In patients who underwent curative treatment for HCC, adjuvant immunotherapy with activated CIK cells increased recurrence-free and overall survival. ClinicalTrials.gov number: NCT00699816. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · Gastroenterology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.
    Preview · Article · Mar 2015 · Clinical and molecular hepatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) has a high rate of intrahepatic recurrence after curative treatment, possibly because metastases are not always identified before treatment. Magnetic resonance (MR) imaging with a liver-specific contrast agent, gadoxetic acid, can detect small HCCs with high levels of sensitivity. We investigated whether MR imaging with gadoxetic acid increases overall and recurrence-free survival of patients initially assessed by computed tomography (CT). We performed a retrospective study of data from 700 patients diagnosed with a single-nodular HCC by dynamic 4-phase CT in Seoul, Korea from January 2009 through December 2010. Of these patients, 323 underwent additional evaluation with gadoxetic acid-enhanced MR imaging (CT+MR group). The 377 patients who did not undergo MR imaging analysis are referred to as the CT group. The CT and CT+MR groups were comparable in most baseline characteristics (Child-Pugh class A, 93.1% vs 94.7%; median size of the primary HCCs, 2.8 cm vs 2.6 cm). Seventy-four additional HCC nodules were detected in 53 (16.4%) of the patients who underwent MR evaluation following CT (CT+MR group). These detections increased Barcelona Clinic Liver Cancer stages for 43 patients (13.3%) and modified their treatment plans. Upon multivariable analyses, the CT+MR group had a significantly lower rate of HCC recurrence (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.54-0.96) and lower overall mortality (HR, 0.65; 95% CI, 0.44-0.96) than the CT group. In an analysis of 285 pairs of patients matched on the basis of propensity score, the CT+MR group had significantly lower overall mortality (HR, 0.66; 95% CI, 0.44-0.99). Among patients who underwent dynamic CT analysis of a single-nodular HCC, additional evaluation by MR imaging with gadoxetic acid led to detection of additional HCC nodules in 16% of patients, reduced risk of disease recurrence, and lowered overall mortality. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Feb 2015 · Gastroenterology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: GS-9620 is an oral agonist of toll-like receptor 7, a pattern-recognition receptor whose activation results in innate and adaptive immune stimulation. We evaluated the safety, pharmacokinetics, and pharmacodynamics of GS-9620 in patients with chronic hepatitis B. In two double-blind, phase 1b trials of identical design, 49 treatment-naïve and 51 virologically suppressed patients were randomized 5:1 to receive GS-9620 (at doses of 0.3 mg, 1 mg, 2 mg, 4 mg) or placebo as a single dose or as two doses 7 days apart. Pharmacodynamic assessment included evaluation of peripheral mRNA expression of interferon-stimulated gene 15 (ISG15), serum interferon gamma-induced protein 10 and serum interferon (IFN)-alpha. Overall, 74% of patients were male and 75% were HBeAg negative at Baseline. No subject discontinued treatment due to adverse events. Fifty-eight percent experienced ⩾1 adverse event, all of which were mild to moderate in severity. Overall, the most common adverse event was headache. No clinically significant changes in HBsAg or HBV DNA levels were observed. Overall, a transient dose-dependent induction of peripheral ISG15 gene expression was observed peaking within 48 hours of dosing followed by return to baseline levels within 7 days. Higher GS-9620 dose, HBeAg positive status, and low HBsAg level at baseline were independently associated with greater probability of ISG15 response. Most patients (88%) did not show detectable levels of serum IFN-alpha at any time point. Oral GS-9620 was safe, well tolerated, and associated with induction of peripheral ISG15 production in the absence of significant systemic IFN-alpha levels or related symptoms. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Feb 2015 · Journal of Hepatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare efficacy of transarterial chemoembolization with and without radiation therapy (RT) versus sorafenib for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). This single-center retrospective study involved 557 patients with HCC with PVTT who initially received chemoembolization (1997-2002; n = 295), chemoembolization and RT (2003-2008; n = 196), or sorafenib (2009-2012; n = 66) according to eligibility criteria among an initial population of 617. The three groups were divided into three pairs (chemoembolization vs chemoembolization/RT, chemoembolization vs sorafenib, and chemoembolization/RT vs sorafenib), and time to progression (TTP) and overall survival (OS) were compared by propensity-score analyses. The chemoembolization/RT group had longer median TTP and OS than the chemoembolization-alone and sorafenib groups (P < .001). Multivariate Cox analysis revealed that chemoembolization/RT treatment was an independent predictor of favorable TTP and OS. In the matched cohort, median TTP and OS were significantly longer in the chemoembolization/RT group than the chemoembolization-alone group (102 pairs; TTP, 8.7 mo vs 3.6 mo [P < .001]; OS, 11.4 mo vs 7.4 mo [P = .023]) or the sorafenib group (30 pairs; TTP, 5.1 mo vs 1.6 mo [P < .001]; OS, 8.2 mo vs 3.2 mo [P < .001]), in agreement with the inverse probability of treatment weighted (IPTW) outcomes. In matching analyses, the chemoembolization-alone group had longer median TTP and OS than the sorafenib group (46 pairs; TTP, 3.4 mo vs 1.8 mo [P < .001]; OS, 5.9 mo vs 4.4 mo [P = .003]). There was no significant difference in terms of OS with the IPTW approach (P = .108), but there was one in terms of TTP (P < .001). Within the limitation of a retrospective study, the present data indicate that transarterial chemoembolization combined with RT could be considered as an alternative to the standard sorafenib in the treatment of patients with advanced-stage HCC with PVTT. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · Journal of vascular and interventional radiology: JVIR
  • [Show abstract] [Hide abstract]
    ABSTRACT: Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV. In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks. Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs 73%; p=0.81). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.65 vs -3.77 log10 IU/mL; p=0.69). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups. TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. ClinicalTrials.gov ID NCT01639092. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · Jan 2015 · Gut
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the optimal radiologic method for measuring hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) in order to assess suitability for liver transplantation (LT). Two-hundred-and-seventy-one HCC patients undergoing TACE prior to LT were classified according to both the Milan and up-to-seven criteria after TACE using the enhancement or size method on computed tomography images. The cumulative incidence function curves with competing risks regression was used in post-LT time-to-recurrence analysis. The predictive accuracy for recurrence was compared using area under the time-dependent receiver operating characteristic curves (AUC) estimation. Of the 271 patients, 246 (90.8%) and 164 (60.5%) fell within Milan and 252 (93.0%) and 210 (77.5%) fell within up-to-seven, when assessed by enhancement and size methods, respectively. Competing risks regression analyses adjusting for covariates indicated that meeting the criteria by enhancement and by size methods was independently related to post-LT time-to-recurrence in the Milan or up-to-seven model. Higher AUC values were observed with the size method only in the up-to-seven model (p<0.05). Mean differences in the sum of tumor diameter and number of tumors between pathologic and radiologic findings were significantly less by the enhancement method (p<0.05). Cumulative incidence curves showed similar recurrence results between patients with and without prior TACE within the criteria based on either method, except for the within up-to-seven by the enhancement method (p=0.017). The enhancement method is a reliable tool for assessing the control or downstaging of HCC within Milan after TACE, although the size method may be preferable when applying the up-to-seven criterion. Copyright © 2014. Published by Elsevier B.V.
    No preview · Article · Dec 2014 · Journal of Hepatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Little is known about whether surveillance for hepatocellular carcinoma (HCC) is worthwhile in chronic hepatitis B virus (HBV)-infected patients who have achieved HBsAg seroclearance. A retrospective analysis of 829 patients (mean age, 52.3 years; 575 male; 98 with cirrhosis) achieving HBsAg seroclearance was performed at a tertiary hospital in Korea between 1997 and 2012. We evaluated incidence rates of HCC, and validated CU-HCC score based on data at the time of HBsAg seroclearance. Results: During a follow-up of 3,464 patients-years, 19 patients developed HCC (annual rate: 0.55%). Liver cirrhosis (hazard ratio [HR], 10.80; 95% confidence interval [CI], 4.25-27.43), male gender (HR, 8.96; 95% CI, 1.17-68.80), and age ⩾ 50 years at the time of HBsAg seroclearance (HR, 12.14; 95% CI, 1.61-91.68) were independently associated with HCC. The estimated annual incidence of HCC was 2.85% and 0.29% in patients with and without cirrhosis, respectively. Among the non-cirrhotic patients, the annual rate of HCC was higher in the male patients than in the females (0.40% vs. 0%, respectively), and all the HCCs developed after age 50. The time-dependent area under the receiver operating characteristic curves for the CU-HCC score for 5 year and 10 year HCC prediction were 0.85 and 0.74, respectively. HCC surveillance should be considered for cirrhotic patients and non-cirrhotic male patients over age 50, even after HBsAg seroclearance, especially those infected with HBV genotype C. HBsAg seroclearance at age ⩾ 50 years was also an independent predictor for HCC. Copyright © 2014. Published by Elsevier B.V.
    No preview · Article · Nov 2014 · Journal of Hepatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate clinicobiochemical factors predicting severe hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. Tertiary institution. 859 treatment-naïve Korean patients with HCV who underwent liver biopsy. Severe fibrosis was defined as fibrosis stage ≥3 based on the METAVIR system. Clinicobiochemical factors predicting severe hepatic fibrosis. The median serum alanine aminotransferase (ALT) level was 68 IU/L and body mass index (BMI) was 24.2 kg/m(2). Severe fibrosis was observed in 326 (39.7%) of the 859 patients. The frequencies of severe fibrosis were 0%, 37.8%, 41.9% and 42% in patients with serum ALT concentrations (IU/L) of ≤20, 20-30, 30-40 and >40 (p<0.01), respectively, and 10.7%, 19.8%, 30.5%, 39.2% and 55.6% in patients <30, 30-40, 40-50, 50-60 and ≥60 years old, respectively (p<0.01). Categorised age in years (50-60 (OR 4.26, p=0.03) and ≥60 (OR 7.53, p<0.01) compared with <30), categorised ALT level in IU/L (20-30 (OR 16.76, p<0.01), 30-40 (OR 20.02, p<0.01) and >40 (OR 21.49, p<0.01) compared with ≤20) and BMI >27.5 kg/m(2) (OR 1.65, p=0.03) were independently related to severe fibrosis in patients with chronic HCV. The severe fibrosis rate was 60.6% in patients aged ≥50 years with ALT >20 IU/L and BMI >27.5 kg/m(2). More advanced age (≥50 years), obesity and serum ALT>20 IU/L are associated with severe fibrosis in patients with chronic HCV. Anti-HCV therapy may be considered for these patients without histological confirmation, regardless of HCV genotype. A wait-and-see policy may be justified for patients with serum ALT ≤20 IU/L. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Preview · Article · Nov 2014 · BMJ Open

  • No preview · Article · Sep 2014

Publication Stats

2k Citations
551.11 Total Impact Points

Institutions

  • 2005-2016
    • Asan Medical Center
      • Department of Gastroenterology
      Sŏul, Seoul, South Korea
  • 2005-2015
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2004-2015
    • University of Ulsan
      • • Asan Medical Center
      • • Department of Internal Medicine
      • • College of Medicine
      Ulsan, Ulsan, South Korea
  • 2012
    • Yonsei University Hospital
      Sŏul, Seoul, South Korea
  • 2002-2005
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea