Jong Eun Yeon

Korea University, Sŏul, Seoul, South Korea

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Publications (162)717.98 Total impact

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    ABSTRACT: Entecavir (ETV) induces biochemical and histologic improvement of the liver in patients with chronic hepatitis B. This study aimed to confirm that 2 years of ETV treatment improves liver function and non-invasive fibrosis markers in patients with hepatitis B virus (HBV)-associated cirrhosis. A total 472 naïve patients with HBV-associated cirrhosis was treated with ETV for at least 2 years, between March 2007 and December 2012. Model for end-stage liver disease (MELD) and Child-Pugh (CP) score were used to evaluate the improvement of liver function. Aspartate transaminase to platelet ratio index (APRI), FIB-4 index, and fibrosis index (FI) were used to evaluate the improvement of fibrosis. The final 370 of 472 patients with HBV-associated cirrhosis were enrolled. Mean age was 51 ± 10 years and 240 patients (64.9%) were men. The distribution of CP class was 71.1% in A, 24.6% in B, and 4.3% in C. Mean MELD and CP score changed over the study period from 8.5 ± 4.6 to 6.2 ± 4.2 (P < 0.001) and from 6.2 ± 1.6 to 5.6 ± 0.9 (P < 0.001), respectively. APRI, FIB-4 index, and FI changed from 3.6 ± 4.5 to 1.5 ± 1.5 (P < 0.001), from 7.0 ± 6.2 to 3.9 ± 2.8 (P < 0.001), and from 3.3 ± 0.9 to 2.5 ± 1.1 (P < 0.001), respectively. After 2 years of treatment, entecavir improves liver function and non-invasive fibrosis markers in patients with HBV- associated cirrhosis. This article is protected by copyright. All rights reserved.
    Journal of Gastroenterology and Hepatology 06/2015; DOI:10.1111/jgh.13020 · 3.63 Impact Factor
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    The Korean Journal of Internal Medicine 05/2015; 30(3):398. DOI:10.3904/kjim.2015.30.3.398
  • Journal of Hepatology 04/2015; 62:S452-S453. DOI:10.1016/S0168-8278(15)30588-2 · 10.40 Impact Factor
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    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.
    Gastroenterology 03/2015; 148(7). DOI:10.1053/j.gastro.2015.02.055 · 13.93 Impact Factor
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    ABSTRACT: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), and colitis in interleukin (IL)-10(-/-) mice. To synchronize colitis, 8- to 10-wk-old IL-10(-/-) mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein (1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expressions were analyzed in IL-10(-/-) mice and in Colo 205 cells. Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon (IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines (IL-17A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for pSTAT3 and MMP-9 was significantly decreased in the butein-treated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells. Butein ameliorated colitis in IL-10(-/-) mice by regulating IL-6/STAT3 and MMP-9 activation.
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    ABSTRACT: Objectives: Interferon (IFN)-based therapy for chronic hepatitis C (CHC) is cost-effective and is associated with reduced risk of disease progression. We aimed to assess the incidence of cirrhosis and hepatocellular carcinoma (HCC) and to identify risk factors associated with disease progression. Methods: We retrospectively reviewed 280 CHC patients who were registered at our hospital between 2001 and 2010. Results: About 80% of patients received antiviral treatment. The 10-year cumulative incidence of cirrhosis was significantly lower among patients who received antiviral therapy than among those who did not (8.3 vs. 44.0%; p = 0.001). Among them, patients with sustained virological response (SVR) had a significantly lower incidence of cirrhosis than those without SVR (0.6 vs. 33.9%; p < 0.001). Cox proportional hazards regression showed that SVR was the significant independent factor for reducing the risk of cirrhosis (hazard ratio, HR = 0.03; p = 0.034). The 10-year cumulative incidence of HCC was higher among patients who did not receive antiviral therapy than among those who did (43.9 vs. 6.1%; p < 0.001). Multivariate analysis showed that underlying cirrhosis was the only independent risk factor associated with HCC development (HR = 7.70; p = 0.010). Conclusions: SVR secondary to IFN-based therapy could reduce cirrhosis development in CHC patients. Underlying cirrhosis was the strongest predictor of HCC development. © 2015 S. Karger AG, Basel.
    Intervirology 01/2015; 58(1):14-21. DOI:10.1159/000369206 · 1.77 Impact Factor
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    ABSTRACT: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and γ glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution. (Gut Liver, Published online December 5, 2014).
    Gut and liver 12/2014; 9(2). DOI:10.5009/gnl14047 · 1.49 Impact Factor
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    ABSTRACT: Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors' Summary.
    PLoS Medicine 12/2014; 11(12):e1001770. DOI:10.1371/journal.pmed.1001770 · 14.00 Impact Factor
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    ABSTRACT: Goals: The aim of this study was to evaluate the risk factors and clinical significance of terlipressin-induced hyponatremia. Background: Patients receiving terlipressin treatment frequently develop hyponatremia. However, its clinical significance and risk factors are not fully elucidated. Study: Records of patients treated with terlipressin for variceal bleeding were analyzed. Hyponatremia was defined as a decrease in serum sodium (Na) level of >5 mEq/L from the baseline level; severe hyponatremia as a decrease in serum Na level of >10 mEq/L from the baseline level; and rapid severe hyponatremia as a decrease in serum Na level of >10 mEq/L within 3 days of treatment. Results: The study involved 151 patients (mean age, 55.1+/-11.8 y) with male predominance (80.8%). Baseline serum Na and creatinine levels were 137.2+/-6.1 mEq/L and 0.9+/-0.4 mg/dL, respectively. Patients were treated with terlipressin for 4.5+/-1.9 days. Changes in serum Na levels from baseline were 0.4+/-4.1, -1.1+/-4.8, -4.0+/-7.0, -6.5+/-9.1, and -6.1+/-11.2 mEq/L, whereas the frequencies of hyponatremia and severe hyponatremia were 13.6%, 30.4%, 50.8%, 63.5%, and 66.9% and 0%, 8.8%, 23.3%, 33.0%, and 38.8% on days 1, 2, 3, 4, and 5 of treatment, respectively. Younger age, lower Child-Pugh score, higher serum Na level, and longer duration of terlipressin treatment were independent risk factors. Rapid severe hyponatremia developed in 29 patients (19.2%); lower body mass index was an additional risk factor in this group. Mortality was not associated with hyponatremia. Conclusions: Terlipressin-induced hyponatremia occurred frequently, especially in young patients with good liver function and higher Na level. Caution is required when administering terlipressin to patients with low body mass index. Copyright
    Journal of Clinical Gastroenterology 09/2014; DOI:10.1097/MCG.0000000000000217 · 3.19 Impact Factor
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    Jong Eun Yeon
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    ABSTRACT: Since the discovery of HBsAg in the early 1960s, presence of HBsAg in serum has only served to diagnose hepatitis B. Recent development in the quantitative measurement of serum HBsAg has enabled us to improve our understanding on the management of chronic hepatitis B. The surface antigen (sAg) level is at its highest in immune tolerance phase and decreases to the lowest level in immune control/inactive phase when HBeAg is cleared from the serum. Combination of serum sAg titer less than 1,000 IU/mL and serum HBV DNA less than 2,000 IU/mL can identify true inactive carrier from e antigen (eAg) negative hepatitis with diagnostic accuracy of 95%. During the natural course of chronic hepatitis B, changes or absolute level of sAg less than certain level can predict spontaneous sero-clearance of HBsAg. Although the decline of sAg is very slow in interferon (IFN)/pegylated interferon (PEG-IFN) or oral nucleos(-t)ide treated patients, interferon based therapy results in a greater decrease of sAg level and sAg loss. Lack of any decline in sAg titer during PEG-IFN therapy could identify the group of patients who do not response to IFN/PEG-IFN therapy. With the aid of serum HBV DNA, quantitative measurement of serum HBsAg level can be used to optimize the management of chronic hepatitis B in our daily practice. (Korean J Gastroenterol 2014;63:335-340).
    The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 06/2014; 63(6):335-40. DOI:10.4166/kjg.2014.63.6.335
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    ABSTRACT: Background & AimsEntecavir (ETV) is effective in the treatment of chronic hepatitis B virus (HBV) infections, even in patients with underlying cirrhosis. However, there is little information on the effect of telbivudine (TBV) in chronic hepatitis B patients with cirrhosis.This study compared the antiviral efficacy of TBV and ETV in HBV-related cirrhosis.Methods We consecutively enrolled 151 treatment-naïve patients with HBV-related cirrhosis who started antiviral therapy with TBV (n = 61) or ETV (n = 90).ResultsAfter 24 months of treatment, per-protocol analysis showed similar virological response rates (HBV DNA <20 IU/ml) in the TBV group (80.6%, 25/31) and in the ETV group (90.2%, 74/82) (P = 0.167). However, intention-to-treat analysis showed lower virological response rates in the TBV group (41.7%, 25/60) than in the ETV group (83.1%, 74/89) (P = 0.001). Mean reduction in HBV DNA levels was greater in the ETV group (−3.72 ± 1.94 vs. −4.87 ± 1.57 respectively, P = 0.001). Serologic and biochemical response rates at month 24 did not differ significantly between the groups. Child-Turcotte-Pugh score was significantly improved after 24 months compared to the pretreatment state without difference between the groups. During 24 months of therapy, 15 patients (27.3%) showed antiviral resistance to TBV while no resistance (0%) was reported in the ETV group (P = 0.001).Conclusions Compared to ETV, TBV therapy shows lower efficacy in viral suppression and higher risk of antiviral resistance despite comparable effect on improvement of hepatic function for the treatment of HBV-related cirrhosis.
    Liver international: official journal of the International Association for the Study of the Liver 06/2014; 35(3). DOI:10.1111/liv.12605 · 4.41 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S85-S86. DOI:10.1016/S0168-8278(14)60220-8 · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S150. DOI:10.1016/S0168-8278(14)60418-9 · 10.40 Impact Factor
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    ABSTRACT: α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC. We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis. The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors. The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.
    Gut and Liver 03/2014; 8(2):177-85. DOI:10.5009/gnl.2014.8.2.177 · 1.49 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea. Graphical Abstract
    Journal of Korean medical science 02/2014; 29(2):248-53. DOI:10.3346/jkms.2014.29.2.248 · 1.25 Impact Factor
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    ABSTRACT: Data regarding the management of adefovir (ADV) resistance are still limited. The aim of this study is to investigate treatment outcomes of rescue therapy in ADV-resistant chronic hepatitis B (CHB) patients. CHB patients who began rescue therapy due to documented genotypic resistance mutations to ADV between October 2006 and July 2012 were retrospectively reviewed. Sixty-three patients were included in this study. Most patients had history of lamivudine (LAM) resistance. Treatment response was evaluated at 3-month intervals up to 12 months. The cumulative rate of complete virologic response (CVR) in hepatitis B virus (HBV)-infected patients (HBV DNA<60 IU/mL) was 15.9%, 27.2%, 28.9%, and 31.7% after 3, 6, 9, and 12 months of rescue therapy. Thirty-five patients were treated with a combination of LAM plus ADV (LAM+ADV group) and 28 patients were treated with entecavir (ETV)-based therapy (ETV with or without ADV therapy, ETV±ADV group). The cumulative CVR rate was significantly higher in the ETV±ADV group than in the LAM+ADV group at month 12 (46.4% vs. 20.6%, respectively, P=0.040). Multivariate analysis showed that pretreatment serum HBV DNA levels at <6 log10 IU/mL (hazard ratio: 34.109, P=0.001) and type of rescue therapy (hazard ratio: 4.944, P=0.036) were associated with CVR. Lower baseline HBV DNA level and ETV±ADV therapy were the important predictive factors for CVR in ADV-resistant CHB patients. This study suggests the need of early switching to a rescue therapy such as ETV±ADV at the time of low-level viremia.
    Journal of clinical gastroenterology 01/2014; DOI:10.1097/MCG.0000000000000066 · 3.19 Impact Factor
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    ABSTRACT: We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies. Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored. Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log10 IU/mL to 2.0 log10 IU/mL and to 1.6 log10 IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed. TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients' adherence to medication is related to viral rebound.
    Gut and Liver 01/2014; 8(1):64-9. DOI:10.5009/gnl.2014.8.1.64 · 1.49 Impact Factor
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    ABSTRACT: In patients with liver cirrhosis, drugs acting on the central nervous system can lead to hepatic encephalopathy and the effects may be prolonged. Recently, misuse of propofol has been reported and the associated risk of death have become an issue. Propofol is commonly used during sedative endoscopy; therefore, its safety in high-risk groups must be further investigated. We performed a pilot study of the safety and efficacy of propofol during endoscopy in Korean patients with cirrhosis. Upper gastrointestinal endoscopy was performed under sedation with propofol along with careful monitoring in 20 patients with liver cirrhosis and 20 control subjects. The presence or development of hepatic encephalopathy was assessed using the number connection test and neurologic examination. Neither respiratory depression nor clinically significant hypotension were observed. Immediate postanesthetic recovery at 5 and 10 minutes after the procedure was delayed in the cirrhotic patients compared with the control group; however, at 30 minutes, the postanesthetic recovery was similar in both groups. Baseline psychomotor performance was more impaired in cirrhotic patients, but propofol was not associated with deteriorated psychomotor function even in cirrhotic patients with a minimal hepatic encephalopathy. Sedation with propofol was well tolerated in cirrhotic patients. No newly developed hepatic encephalopathy was observed.
    The Korean Journal of Internal Medicine 01/2014; 29(1):57-65. DOI:10.3904/kjim.2014.29.1.57
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    ABSTRACT: Although there are some differences in hepatitis B surface antigen (HBsAg) titers in infection with different hepatitis B virus (HBV) genotypes, the HBsAg titers for each HBV genotype have not been evaluated extensively. The aim of this study was to investigate HBsAg titers during the natural history of patients infected with HBV in Korea, where the HBV genotype C is endemic exclusively. Four hundred fifteen patients were enrolled retrospectively and classified according to definitions of the natural phases of HBV infection. In total, 73, 118, 147, and 77 patients were classified in the immune tolerance, immune clearance, low replicative, and HBeAg-negative hepatitis phases, respectively. HBsAg titers (4.35 ± 0.67, 3.74 ± 0.68, 2.39 ± 1.23, and 3.29 ± 0.64 log10 IU/ml) were significantly different in the immune tolerance, immune clearance, low replicative, and HBeAg-negative hepatitis phases, respectively (P < 0.001). The ratio of HBsAg to HBV DNA was highest in the low replicative phase (1.13 ± 0.71, all P < 0.001) and second highest in the HBeAg-negative hepatitis phase (0.58 ± 0.18, all P < 0.05). In multivariate analysis of all patients, the HBsAg titers did not correlate with alanine aminotransferase. However, the HBsAg titers correlated with age (P = 0.038), platelet count (P < 0.001) and HBV DNA (P < 0.001). In subgroup analysis, the HBsAg titers correlated with HBV DNA in all phases (P < 0.001), except for the HBeAg-negative hepatitis phase. HBsAg titers were significantly different across the four phases of the natural history of the infection and correlated significantly with HBV DNA titer in genotype C chronic hepatitis B patients. The HBsAg titer could be used as a biomarker to differentiate the natural history of HBV infection. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 01/2014; 86(1). DOI:10.1002/jmv.23767 · 2.22 Impact Factor
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    ABSTRACT: NS-398, a selective cyclooxygenase-2 inhibitor, and simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, both exert an anticancer effect on hepatocellular carcinoma cells, but the effect of co-administration of the 2 drugs remains unknown. We aimed to investigate the synergistic in vitro anticancer effect of co-administration of NS-398 and simvastatin and its mechanism. The Hep3B and Huh-7 cell lines were cultured. Cells were treated with simvastatin, NS-398, or a combination. 5-bromo-2'-deoxyuridine ELISA assay, flow cytometry, Western blot analyses, and immunofluorescence assay were performed. In both cell lines, co-administration of simvastatin and NS-398 resulted in a greater effect on proliferation and apoptosis. In Hep3B cells, co-administration of the 2 drugs resulted in a greater decrease in procaspase 3 and Bcl-2 and increase in cleaved caspase 9 than that noted with monotherapy. In Huh-7 cells, co-administration of the 2 drugs resulted in a greater decrease in procaspase 3 and cyclin D1 and increase in cleaved caspase 9. Expression of NF-κB and Akt were also decreased to a greater extent when the 2 drugs were co-administered in both cell lines. Immunofluorescence assay showed suppression of the nuclear localization of NF-κB by simvastatin or NS-398. The effect was greater by co-administration. The co-administration of NS-398 and simvastatin produced greater anti-proliferative and proapoptotic effects against Hep3B cells and Huh-7 cells. Inhibition of the NF-κB and Akt pathway and activation of caspase cascade, which are considered as the major mechanism of synergistic anti-cancer properties, were observed in both cell lines.
    Journal of Gastroenterology and Hepatology 12/2013; 29(6). DOI:10.1111/jgh.12503 · 3.63 Impact Factor

Publication Stats

1k Citations
717.98 Total Impact Points

Institutions

  • 1999–2015
    • Korea University
      • • Department of Internal Medicine
      • • Department of Gastroenterology
      Sŏul, Seoul, South Korea
  • 2012
    • Sun Yat-Sen University
      • Department of Infectious Diseases
      Shengcheng, Guangdong, China
  • 2006–2012
    • Yonsei University
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2011
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
    • University of Ioannina
      • School of Medicine
      Yannina, Epirus, Greece
  • 2006–2010
    • Konkuk University Medical Center
      • Department of Laboratory Medicine
      Changnyeong, South Gyeongsang, South Korea
  • 2007
    • Inje University Paik Hospital
      • Department of Internal Medicine
      Goyang, Gyeonggi, South Korea
  • 2006–2007
    • Konkuk University
      • Department of Internal medicine
      Sŏul, Seoul, South Korea
  • 2004–2006
    • Hallym University Medical Center
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
  • 2005
    • Kangwon National University Hospital
      Shunsen, Gangwon, South Korea
  • 2003
    • Rhode Island Hospital
      Providence, Rhode Island, United States