Young-Suk Lim

University of Ulsan, Urusan, Ulsan, South Korea

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Publications (81)354.19 Total impact

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    ABSTRACT: -There is conflict regarding the prevalence of coronary artery disease (CAD) in patients with liver cirrhosis (LC). This study aimed to investigate the prevalence of silent CAD compared with the general population, and to identify the relevant risk factors in LC patients.
    Circulation 08/2014; · 15.20 Impact Factor
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    ABSTRACT: To develop clinical predictive nomograms generating per-patient numerical probabilities of postoperative recurrence-free and overall survival at specific times.
    Annals of surgery. 06/2014;
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    ABSTRACT: There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients.
    Clinical and molecular hepatology. 06/2014; 20(2):177-84.
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    ABSTRACT: The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients. The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored. The interleukin-1-β-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues. The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.
    Clinical and molecular hepatology. 03/2014; 20(1):28-37.
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    ABSTRACT: The aim of this study was to re-evaluate the diagnostic performance of alpha-fetoprotein (AFP) as a surveillance test for hepatocellular carcinoma (HCC) in patients with hepatitis B virus-related chronic liver disease who were treated with entecavir (ETV). Between January 2007 and August 2012, we analyzed 373 treatment-naïve patients with HBV-related chronic hepatitis (n = 229) or cirrhosis (n = 144) who were candidates for surveillance test, and were treated with ETV (0.5 mg/day) for longer than 12 months. To minimize the effect of AFP elevation due to hepatitis activity, serum AFP levels were measured 12 months after the initiation of ETV treatment. HCC developed in 28 patients (7.5%) during a median follow-up period of 48.0 months (IQR = 40.5-57.3 months). The area under the receiver operating characteristic curve for AFP was 0.71 (95% CI = 0.59-0.84). The optimal AFP cutoff value was 13 ng/mL, leading to a sensitivity of 50.0%, specificity of 98.8%, positive predictive value of 77.8%, and negative predictive value of 96.1%. In multivariate Cox analysis, an older age, the presence of liver cirrhosis, and AFP levels of ≥ 20 ng/mL at 12 months after treatment were found to be significantly associated with an increased incidence of HCC. The role of serum AFP as a surveillance test should be re-evaluated in patients with HBV-related chronic liver diseases who were treated with antiviral therapy. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 02/2014; · 3.87 Impact Factor
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    ABSTRACT: & Aims: Little is known about whether the antiviral agent entecavir is more effective than a less potent drug, lamivudine, in reducing the risk of death and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We performed a retrospective analysis of data from 5374 consecutive adult patients with CHB, treated with entecavir (n=2000) or lamivudine (n=3374) at a tertiary referral hospital in Seoul, Korea from November 1, 1999 through December 31, 2011. Data were collected from patients for up to 6 years and analyzed by multivariable Cox proportional hazards model for the entire cohort and for propensity score matched cohorts. During the study period, 302 patients (5.6%) died, 169 (3.1%) received a liver transplant, and 525 (9.8%) developed HCC. Multivariable analyses showed that compared with lamivudine, entecavir therapy was associated with a significantly lower risk of death or transplantation (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.38-0.64), but a similar risk of HCC (HR, 1.08; 95% CI, 0.87-1.34). In the 1792 overall propensity-matched pairs, entecavir was again associated with a significantly lower risk of death or transplantation (HR, 0.49; 95% CI, 0.37-0.64) and a similar risk of HCC (HR, 1.01; 95% CI, 0.80-1.27). Entecavir also reduced risk of death or transplantation, compared with lamivudine, in 860 pairs of patients with cirrhosis (HR, 0.42; 95% CI, 0.31-0.57) but there were no differences in risk for HCC (HR, 1.00; 95% CI, 0.78-1.28). However, entecavir and lamivudine did not have significantly different effects on clinical outcome in 878 pairs of patients without cirrhosis. In a retrospective study of 5374 patients with chronic hepatitis B virus infection, entecavir therapy was associated with a significantly lower risk of death or transplantation than lamivudine. However, the drugs did not have different effects on HCC risk.
    Gastroenterology 02/2014; · 12.82 Impact Factor
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    ABSTRACT: Purpose To determine normal reference values of liver elasticity and measurement reliability by using real-time shear wave elastography (SWE) in patients with a range of ages and body mass index (BMI) measurements, with presence or absence of hepatic steatosis. Materials and Methods The institutional review board approved this study, and informed consent was waived because of the retrospective nature of the study. Two hundred thirty-eight patients who underwent SWE and ultrasonography-guided liver biopsies on the same day were identified retrospectively. The median kilopascal value of three consecutive measurements was used as a representative value for each subject. One hundred ninety-six patients who were potential donors for living-donor liver transplantation and had biopsy-proven normal (123 nonsteatotic and 73 steatotic) livers as the only histologic abnormality were included in the study. Reference ranges of normal hepatic elasticity were calculated by using lower and upper limits at the 2.5 and 97.5 percentiles. With the upper value of the reference range as a cutoff value, the sensitivity and specificity for the diagnosis of hepatic fibrosis were calculated. Measurement reliability was evaluated by using the intraclass correlation coefficient (ICC). To investigate the effects of potential confounding factors (age, hepatic steatosis, and BMI) on liver elasticity, the Pearson correlation test and the Student t test were performed. Results The reference range of normal hepatic elasticity was 2.6-6.2 kPa. With 6.2 kPa as a cutoff value, the sensitivity and specificity for the diagnosis of hepatic fibrosis were 91% (20 of 22 subjects) and 95.9% (188 of 196 subjects), respectively. The overall ICC for the elasticity measurements was 0.924. The potential confounding factors that we considered had negligible effects on the elasticity values. Conclusion Hepatic elasticity values measured with SWE in histologically proven normal livers ranged from 2.6 to 6.2 kPa, with high measurement reliability. The effect of the potential confounding factors on liver elasticity was negligible. © RSNA, 2014.
    Radiology 02/2014; · 6.34 Impact Factor
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    ABSTRACT: Objectives: The role of liver biopsy in selecting optimal donors is an area of continuing controversy in living donor liver transplantation (LDLT). Our aim was to assess the potential implications of pre- and intraoperative biopsies in evaluating donor liver fat content. Methods: Of 3,859 consecutive subjects who underwent predonation needle biopsy from the right lobe, 1,766 actually donated their livers in LDLT and underwent intraoperative wedge biopsies from paired right and left lobes. The preoperative workup protocol also included abdominal ultrasonography (USG) and computed tomography (CT). Intersample agreement on steatosis grades (<5%; 5-15%; 15-30%; and ≥30%) was calculated, and clinico-metabolic factors related to sampling variability were evaluated. Results: For the 3,859 potential donors, USG and CT had sensitivities and specificities of 84.9% and 57.3%, and 76.3% and 92.7%, respectively, for detecting ≥30% steatosis, and positive and negative predictive values of 29.6% and 48.0%, and 97.7% and 94.8%, respectively. Analyses of the 1,766 actual donors showed that with respect to total steatosis grade in intraoperative right and left biopsies versus preoperative biopsy, 36.7% and 36.0% pairs, respectively, differed from the weighted κ values of 0.44 and 0.40. Similar agreement levels existed for the macrovesicular and microvesicular steatosis subtypes. The per-subject agreement rate for total steatosis grade between the intraoperative right and left biopsies was of 83.6%. According to a multivariate analysis, the independent factors affecting the variability of the total steatosis results obtained from preoperative biopsy and intraoperative biopsies (major features) were higher systolic blood pressure, body mass index and alanine aminotransferase and lower high-density lipoprotein cholesterol. Conclusions: Imaging may be insufficiently sensitive for evaluating donor hepatic steatosis. Preoperative and selective intraoperative liver biopsies are mandatory for assessing donor steatosis in LDLT, unless preoperative imaging demonstrates no fat. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 01/2014; · 3.94 Impact Factor
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    ABSTRACT: Inflammatory pseudotumor (IPT) of the liver is a rare disease characterized by chronic infiltration of inflammatory cells. However, the clinical characteristics and outcomes of IPT remain uncertain. Clinical features, image findings, and outcomes of 55 patients with histologically proven IPT were evaluated. They consisted of 26 men and 19 women with median age of 65 years. Serum carcinoembryonal antigen and carbohydrate antigen 19-9 levels were normal in 42 patients (93.3%). Enhanced CT scans indicated poorly defined peripheral enhancement (82.5%) at the arterial phase and poorly defined hyperattenuating lesions with internal hypoattenuating areas at the equilibrium phase (77.0%). Gadolinium-enhancement MRI revealed poorly defined peripheral rim-like enhancement (77.8%). Ten patients underwent surgical resection and 35 were treated conservatively with or without antibiotics. No recurrence was noted after surgical resection during follow-up (1 to 48 months). In all patients who received conservative treatment, complete resolution or size reduction was noted during follow-up (1 to 192 months). CT and MRI provide clues to the diagnosis of IPT in patients with liver masses and normal tumor markers. However, due to the lack of pathognomonic findings, the clinician's suspicion and histological diagnosis are necessary to make an accurate diagnosis of IPT.
    Gut and Liver 01/2014; 8(1):58-63.
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    ABSTRACT: Background & Aims We assessed the clinical implications of the best response compared with the initial response during repeated transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods We evaluated 332 patients with intermediate-stage HCC and preserved liver function initially treated with repeated TACE. All had ⩾1 lesion measuring ⩾1 cm, and the response measured after each session was based on EASL and mRECIST criteria. We performed survival analyses according to response kinetics, and identified clinical factors associated with the need for repeated TACE to achieve the best response. Results An objective response, either a complete response (CR) or a partial response (PR), after the first TACE was seen in about 50% of patients by both EASL and mRECIST. In terms of the best response during serial TACE, 250 patients (75.3%) by EASL and 278 (83.7%) by mRECIST were overall responders. The sizes of the largest and second largest tumors were the only parameters positively correlated with the number of TACE session required to achieve the best response (p<0.05). Multivariate Cox analysis showed that achieving a CR or PR as the best response was the best predictor of survival following TACE with a hazard ratio of 0.45 by EASL and 0.24 by mRECIST, and more than 0.69 and 0.71, respectively for initial responders (p<0.05). Conclusions The best response observed during serial TACE, rather than the initial response, most strongly predicts the survival of patients with intermediate-stage HCC. The number of TACE sessions needed to achieve a best response is a function of tumor size.
    Journal of Hepatology 01/2014; · 9.86 Impact Factor
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    ABSTRACT: To evaluate usefulness of Barcelona Clinic Liver Cancer B subclassification (B1 to B4) proposed by Bolondi et al in subjects with hepatocellular carcinoma treated with transarterial chemoembolization according to the current Barcelona Clinic Liver Cancer policy. A total of 466 Barcelona Clinic Liver Cancer B patients initially treated with transarterial chemoembolization were included. The subclassification system was tested and modified on the basis of correlation with survival outcomes which were examined by Kaplan-Meier method and log-rank test. There were 101 (21.7%), 232 (49.8%), 35 (7.5%), and 98 (21.0%) patients in B1, B2, B3, and B4, respectively. There was a significant difference in median survival time between B1 and B2 (41.0 vs. 22.1 months, P<0.001), and B2 and B3 (22.1 vs. 14.1 months, P=0.004), but not between B3 and B4 (14.1 vs. 17.2 months, P=0.48). We therefore developed a modified subclassification, in which B3 subclass was merged with B4 as BIII, and BI and BII corresponded to B1 and B2. The median survival times differed between all three modified subclasses (41.0 vs. 22.1 vs. 17.0 months, P<0.001), and multivariate Cox analysis revealed that the modified Barcelona Clinic Liver Cancer B subclasses independently predicted overall survival (hazard ratios, 1.92 and 2.78 for BII and BIII vs. BI; P<0.001 for each). The modified subclassification which divides the Barcelona Clinic Liver Cancer B stage into 3 substages would be an effective tool for stratifying this heterogeneous population and facilitating per-subclass based treatment options.
    Journal of Gastroenterology and Hepatology 11/2013; · 3.33 Impact Factor
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    ABSTRACT: Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment. A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT. The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients' survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%). SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.
    PLoS ONE 11/2013; 8(11):e79854. · 3.73 Impact Factor
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    ABSTRACT: A primary non-response to oral drugs against hepatitis B virus (HBV) is a generally-accepted criterion for interrupting treatment. We investigated whether the concept of primary non-response suggested by current American (AASLD) and European (EASL) guidelines is appropriate for treatment with entecavir (ETV).The study included 1,254 treatment-naïve patients who had pretreatment HBV DNA levels of >2,000 IU/mL and received ETV 0.5mg/day for over 6 months. "Primary non-response" was defined as a <2 log drop in HBV DNA after 6 months of therapy by AASLD and as a <1 log drop after 3 months by EASL. The cumulative probability of virological response (VR; HBV DNA of <15 IU/mL) was compared in patients with and without primary non-response. Median time to achieve VR was significantly shorter in primary responders by AASLD than non-responders (12 vs. 24 months; P=0.004), but the cumulative probability of achieving a VR at 54 months was similar in the two groups (95.8% vs. 100%). Time to achieve a VR and cumulative probability of VR over time did not differ between primary responders and non-responders by EASL. On-treatment virological breakthrough occurred in 18 patients with a cumulative rate of 4.6% at 72 months. ETV resistance was detected in 13 of these 18 patients (72.2%), who were all classified as primary responder according to both guidelines. Conclusions: Long-term ETV therapy generally leads to a VR in treatment-naïve patients, although the time to achieve it is delayed in primary non-responders. The current recommendation to change therapy in primary non-responders needs to be modified to reflect drug differences in antiviral potency and resistance risk. (Hepatology 2013;).
    Hepatology 10/2013; · 12.00 Impact Factor
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    ABSTRACT: Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB). During a median follow-up period of 6 years (33 567 patient-years) of 5409 CHB patients who were initially treated with lamivudine or entecavir, a total of 110 achieved HBsAg seroclearance (0.33% annual seroclearance rate) and were included in this study. Baseline alanine aminotransferase (ALT) level >5 times of upper limit of normal was associated with higher probability of HBsAg seroclearance (HR 1.80, p<0.01), while HBeAg positivity (HR 0.46, p<0.01), high HBV DNA level (log10 IU/mL; HR 0.61, p<0.01), and cirrhosis (HR 0.48, p<0.01) were inversely associated with the probability of HBsAg seroclearance by multivariable analysis. During follow-up for 287 patient-years after HBsAg seroclearance, only two patients with baseline cirrhosis developed hepatocellular carcinoma (HCC) or died (0.7% annual risk), which was of a significantly lower rate compared with propensity score-matched patients without HBsAg seroclearance (HR 0.09, p<0.01). HBsAg reversion and/or HBV DNA reversion occurred in 18 patients, most of which were transient with extremely low serum levels of HBsAg (0.05-1.00 IU/mL) and HBV DNA (17-1818 IU/mL). None required retreatment. The cumulative probability of anti-HBs seroconversion (detection of anti-HBs) at 4 years was 67.4% by Kaplan-Meier analysis. Selection for lamivudine-resistance HBV mutants during treatment was not associated with composite reversion (p=0.66). HBsAg seroclearance achieved after NUC treatment was associated with favourable clinical outcomes and was durable in most cases during long-term follow-up.
    Gut 10/2013; · 10.73 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: In cases of small hepatocellular carcinoma (HCC) where established curative treatment cannot be applied, stereotactic body radiotherapy (SBRT) has been used as a non-invasive alternative treatment modality. However, short-course SBRT may not be safe if the tumor is located around a critical normal organ. Therefore, we applied hypofractionated radiotherapy for these tumors, and evaluated outcomes of this treatment. METHODS: Between December 2008 and August 2011, 26 patients (28 lesions) with HCC were treated with hypofractionated radiotherapy. Inclusion criteria were HCC not suitable for surgery or other local ablative therapy, a tumor size < 6 cm, adequate hepatic function, a HCC located within 2 cm of a critical organ, and no evidence of vascular invasion. A dose of 4-5 Gy per fraction was given, with a total dose of 40-50 Gy over two weeks. RESULTS: The overall response rate was 67.9%, with 7 complete responses (25.0%) and 12 partial responses (42.9%) at 3 months after radiotherapy. The overall survival rates at 1 and 2 years were 88.5% and 67.2%, respectively. The local control rate at 2 years was 87.6%. The Intrahepatic recurrence-free and distant failure-free survival rates at 2 years were 36.5% and 68.2%, respectively. Grade ≥ 3 hepatic toxicity was observed in 1 patient. CONCLUSIONS: Two-week schedule of hypofractionated radiotherapy for small HCC was feasible with good local control and safety. This fractionation schedule can be used as an alternative treatment option for HCC located close to a critical normal organ if short-course SBRT is not feasible.
    Journal of Gastroenterology and Hepatology 09/2013; · 3.33 Impact Factor
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    ABSTRACT: Background/Aims: To evaluate the clinical usefulness of endoscopic biliary drainage (EBD) in patients with hepatocellular carcinoma (HCC). Methods: A total of 111 jaundiced patients underwent attempted EBD for relief of HCC-related biliary stricture at our hospital over a 5-year period and all were included in the intention-to-treat (ITT) analysis. Results: After an endoscopic attempt at drainage, 46 (41.4%) of the 111 patients achieved a favorable response. Biliary cannulation failed in 5 patients. Child-Pugh class C, portal vein thrombosis and severe hyperbilirubinemia were negatively correlated with a favorable EBD response. In the ITT population, 40 (87.0%) of the favorable responders received further treatment for HCC, >2 (3.1%) of the unfavorable responders (p < 0.001). The median survival time for ITT patients with and without a favorable response to EBD was 8.7 and 1.3 months, respectively (p < 0.001). Cox's model showed that a favorable EBD response was an independent predictor of longer survival (hazard ratio 0.20, p < 0.001). Conclusions: For HCC patients with tumor-related biliary obstruction, predictors of effective endoscopic palliation of cholestasis were relatively mild hyperbilirubinemia and preserved liver function and intact portal vein flow. A favorable EBD response was associated with longer survival outcomes.
    Digestion 08/2013; 88(2):87-94. · 1.94 Impact Factor
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    ABSTRACT: Purpose:To compare the time to progression (TTP) and overall survival (OS) in patients with advanced-stage hepatocellular carcinoma (HCC) who are undergoing sorafenib treatment combined with transarterial chemoembolization (TACE) versus sorafenib monotherapy.Materials and Methods:The retrospective analysis of the data was approved by the institutional review board, and the requirement to obtain informed consent was waived. Of 355 patients with advanced-stage HCC (Barcelona Clinic Liver Cancer stage C) who were undergoing sorafenib therapy for at least 5 weeks between April 2007 and July 2011, 164 (46.2%) underwent repeat TACE (or chemolipiodolization if indicated) along with sorafenib therapy (combined group); the remaining 191 patients (53.8%) received sorafenib alone (monotherapy group). The median patient age was 53 years (range, 22-84 years). The median age was 53 years (range, 26-84 years) for men and 56 years (range, 22-75 years) for women. Propensity score-based methods were used to minimize bias when evaluating TTP on the basis of modified Response Evaluation Criteria in Solid Tumors and OS. Statistical analysis was performed with the Kaplan-Meier method by using the log-rank test and Cox regression models.Results:In the combined and monotherapy groups, respectively, 64.6% and 49.2% of patients had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. During follow-up (median duration, 5.5 months), the median TTP and OS in the combined group were longer than those in the monotherapy group (TTP: 2.5 months vs 2.1 months, respectively, P = .008; OS: 8.9 months vs 5.9 months, P = .009). At univariate and subsequent multivariate analyses, additional TACE was an independent predictor of favorable TTP and OS (adjusted hazard ratio: 0.74 and 0.57, respectively; P < .05 for both), consistent with the outcomes of inverse probability of treatment weighting. In the propensity score-matched cohort (96 pairs), the median TTP in the combined group was significantly longer than that in the monotherapy group (2.7 months vs 2.1 months, respectively; P = .011), but median OS was not (9.1 months vs 6.7 months, P = .21).Conclusion:In this retrospective study, TACE plus sorafenib was superior to sorafenib alone with respect to TTP in patients with advanced-stage HCC, although it may or may not improve OS.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130150/-/DC1.
    Radiology 07/2013; · 6.34 Impact Factor
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    ABSTRACT: One year trial with entecavir plus adefovir resulted in a higher rate of virological response (VR) compared with lamivudine plus adefovir in multiple drug-refractory chronic hepatitis B (CHB) patients. This extension study enrolled 89 of 90 patients who completed a 52-week randomized trial comparing treatment with entecavir plus adefovir (EA) to lamivudine plus adefovir (LA). At the baseline of the original study, all patients had lamivudine-resistant hepatitis B virus (HBV) and serum HBV DNA >2000 IU/mL despite prior lamivudine plus adefovir therapy. Forty-five patients initially randomized to entecavir plus adefovir (EA-EA) and the other 44 patients randomized to lamivudine plus adefovir (LA-EA) received entecavir plus adefovir for an additional 52 weeks. The proportion of patients with VR (serum HBV DNA <60 IU/mL) gradually increased in both groups, and was comparable at week 104 (42.2% in the EA-EA group and 34.1% in the LA-EA group, P=0.51). The mean reduction in serum HBV DNA from baseline was similar in the two groups (-2.8 log10 IU/mL and -2.8 log10 IU/mL, respectively, P=0.87). At week 104, the number of patients who retained the preexisting HBV mutants resistant to adefovir or entecavir has decreased from 8 to 2 in the EA-EA group and 15 to 6 in the LA-EA group (P=0.27). Both study groups had favorable safety profiles. In conclusion, up to 104 weeks of entecavir plus adefovir treatment was associated with a progressive VR, decrease of preexisting drug-resistant mutants, and no selection for additional resistance mutants of HBV in multiple drug-refractory CHB patients.
    Antimicrobial Agents and Chemotherapy 05/2013; · 4.57 Impact Factor
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    ABSTRACT: Identifying the impact of a patient's ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study. The clinical data of 272 treatment-naïve Korean CHC patients who were treated in a community-based clinical trial (Clinical Trial group; n=51) and in clinical practice (Cohort group; n=221), were analyzed and compared. All were treated with standard protocols of peginterferon alfa-2a plus ribavirin therapy. For patients with hepatitis C virus (HCV) genotype 1, the sustained virological response (SVR) rates in the Clinical Trial and Cohort groups were 81% (21/26) and 55% (58/106), respectively, by intention-to-treat (ITT) analysis (P=0.02), and 100% (13/13) and 80% (32/40), respectively, in treatment-adherent patients (P=0.18). For patients with HCV genotype 2, the SVR rates in these two groups were 96% (24/25) and 88% (101/115), respectively, by ITT analysis (P=0.31). Adherence and treatment duration were independent predictors of SVR for genotypes 1 and 2, respectively (P<0.01 for each). Korean patients with CHC achieved high SVR rates with peginterferon alfa-2a plus ribavirin in both the clinical trial and clinical practice settings. Measures to raise adherence to standard therapy in clinical practice may improve the SVR rates in these patients as effectively as adding protease inhibitors, thus obviating the need for the latter.
    Clinical and molecular hepatology. 03/2013; 19(1):60-69.
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    ABSTRACT: BACKGROUND AND AIM: The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). METHODS: A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. RESULTS: Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. CONCLUSIONS: Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.
    Digestive Diseases and Sciences 01/2013; · 2.26 Impact Factor

Publication Stats

965 Citations
354.19 Total Impact Points

Institutions

  • 2013–2014
    • University of Ulsan
      • Asan Medical Center
      Urusan, Ulsan, South Korea
    • Inje University Paik Hospital
      • Department of Internal Medicine
      Goyang, Gyeonggi, South Korea
  • 2004–2014
    • Asan Medical Center
      • Department of Gastroenterology
      Sŏul, Seoul, South Korea
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2002–2005
    • Seoul National University Hospital
      • Department of Internal Medicine
      Seoul, Seoul, South Korea