Young Myoung Moon

Yonsei University Hospital, Seoul, Seoul, South Korea

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Publications (63)318.15 Total impact

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    ABSTRACT: In the GLOBE trial, telbivudine demonstrated superior efficacy to lamivudine at 2 years in patients with chronic hepatitis B (CHB). Aims: To investigate the long-term efficacy and safety of telbivudine in the telbivudine-treated cohort from the GLOBE trial. Virological and biochemical responses were assessed in 213 HBeAg-positive and 186 HBeAg-negative CHB patients who continued telbivudine treatment for 3 years. Undetectable hepatitis B virus DNA and HBeAg seroconversions were achieved by 77 and 37% of HBeAg-positive patients respectively. Cumulative HBeAg seroconversion rate was 46%. HBeAg seroconversion was sustained at 52 weeks off therapy in 84% of the patients enrolled in the off-treatment follow-up arm of the study. Undetectable viraemia and normal alanine aminotransferase (ALT) levels at 3 years were achieved by 85 and 83% of HBeAg-negative patients respectively. Genotypic resistance rates for the study population who continued therapy during the third year were 11.3 in HBeAg-positive and 6.5% in HBeAg-negative patients. Patients with undetectable viraemia at treatment week 24 had optimal outcomes at 3 years. In the HBeAg-positive population, cumulative HBeAg seroconversion occurred in 58%. Resistance rates for HBeAg-positive and HBeAg-negative patients were 3.6 and 6.2% respectively. The telbivudine safety profile during prolonged therapy was similar to that in the GLOBE trial. Three years of telbivudine treatment yielded high rates of viral suppression and ALT normalization with a favourable safety profile. High rates of HBeAg seroconversion were achieved with prolonged telbivudine therapy and were sustained in the majority of patients over 52 weeks off therapy.
    Liver international: official journal of the International Association for the Study of the Liver 05/2011; 31(5):676-84. DOI:10.1111/j.1478-3231.2011.02490.x · 4.41 Impact Factor
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    ABSTRACT: Interferon beta (IFN-beta) has been shown to have antiviral activity, and thus could be useful in treating viral infections. Therefore, we compared the efficacy and safety of recombinant IFN-beta (IFN-beta-1a) plus oral ribavirin versus interferon alpha (IFN-alpha) plus ribavirin therapy for the treatment of chronic hepatitis C (HCV). Twenty treatment-naïve patients were randomized into two equal-sized treatment groups. Both IFN-beta-1a (44 microg) and IFN-alpha (3 MIU) were given subcutaneously three times a week, while ribavirin was given orally at 1,000-1,200 mg/day. Patients were treated for 24 weeks and followed for an additional 24 weeks. After 24 weeks of treatment, six (60%) and four patients (40%) in the IFN-beta-1a group and IFN-alpha groups, respectively, achieved viral clearance. The sustained virological response (SVR) at the end of the observation period was similar in both groups (40%). However, the baseline viral load was significantly higher (p=0.034) in the IFN-beta-1a group than in the IFN-alpha group, and there were more HCV genotype 1 patients in the IFN-beta-1a group (eight versus seven). The IFN-beta-1a group was associated with similar adverse events in terms of frequency and severity. The SVR rate and safety profile were similar for the combination of IFN-beta-1a and ribavirin and that of IFN-alpha and ribavirin.
    Gut and liver 03/2009; 3(1):20-5. DOI:10.5009/gnl.2009.3.1.20 · 1.49 Impact Factor
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    ABSTRACT: Monotherapy of lamivudine, interferon-alpha (IFN-alpha), and thymosin alpha-1 (Talpha1) is unlikely to be sufficient for the eradication of a chronic hepatitis B virus (HBV) infection. The aim of our study is to elucidate whether the combination of Talpha1 and lamivudine is superior to lamivudine monotherapy in hepatitis B e antigen (HBeAg) positive naïve patients with chronic hepatitis B. Sixty-seven patients were assigned to two different groups in a randomized manner. The combination group (n = 34) received Talpha1 (1.6 mg subcutaneously, twice a week) and lamivudine (100 mg orally, daily) for 24 weeks, followed by continuous lamivudine therapy. The monotherapy group (n = 33) received lamivudine monotherapy continuously. The incidence of HBeAg seroconversion at 24 weeks was 26.5% (9/34) in the combination group and 6.1% (2/33) in the monotherapy group (P = 0.024). However, there was no statistically significant difference between 26.5% (9/34) in the combination group and 12.1% (4/33) in the monotherapy group at 52 weeks (P = 0.138). The emergence of viral breakthrough gradually increased to 35.3% (12/34) in the combination group, and to 21.2% (7/33) in the monotherapy group at 52 weeks (P = 0.201). The combination treatment of Talpha1 and lamivudine did not have an obvious benefit of virological and biochemical response as compared to the lamivudine monotherapy during the combination period. In addition, after the cessation of Talpha1 treatment, the combination therapy did not prevent the occurrence of viral and biochemical breakthroughs.
    Journal of Gastroenterology and Hepatology 06/2008; 23(5):729-35. DOI:10.1111/j.1440-1746.2008.05387.x · 3.63 Impact Factor
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    ABSTRACT: The accurate staging of hepatocellular carcinoma (HCC) is important in establishing treatment strategies and prognosis. Among tumor factors, microvascular invasion, one of TNM staging components and prognostic factors, is underestimated preoperatively, due to inaccuracy of imaging modalities. We investigated preoperative predictors of microvascular invasion. We reviewed 190 consecutive HCC patients given curative resection from 1999 to 2006. All were treatment-naive and monitored every 3 months after resection. Tumor recurrence, survivals, and clinicopathological factors associated with microvascular invasion were analyzed. The 5-year disease-free survival (DFS) rate was 39.4%(median follow-up duration: 35 months). On resection pathology, 38.9% (74/190 patients) had microvascular invasion undetected preoperatively, using liver spiral computed tomography (CT) or angiography. Independent predictors of microvascular invasion were tumor size (P = 0.043), number (P = 0.011), and Edmondson grade (P = 0.001). Patients with Edmondson grade 1 and size <5 cm had no microvascular invasion, while those with grade > or =2 had higher incidences (7/18 patients, 38.8%) even in small tumor (<2 cm). When tumors recurred, presence of microvascular invasion independently increased incidences of multiple tumors, portal vein invasion, and diffuse-infiltrative patterns significantly. Preoperative predictors of microvascular invasion are tumor size, number, and Edmondson grade, which may be useful for making clinical decisions in both non-surgical and surgical candidates.
    Journal of Surgical Oncology 03/2008; 97(3):246-52. DOI:10.1002/jso.20953 · 2.84 Impact Factor
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    ABSTRACT: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence. We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100,000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA (<100,000 copies/ml), while 68 (viraemia group) had consistently positive DNA (>100 000copies/ml). Serum DNA level, biochemical tests, alpha-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery. There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P=0.043). In multivariate analysis, sustained viraemia (P=0.041) increased recurrence independently. Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.
    Liver international: official journal of the International Association for the Study of the Liver 03/2008; 28(3):393-401. DOI:10.1111/j.1478-3231.2007.01625.x · 4.41 Impact Factor
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    ABSTRACT: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine. Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265 [ClinicalTrials.gov].).
    New England Journal of Medicine 01/2008; 357(25):2576-88. DOI:10.1056/NEJMoa066422 · 54.42 Impact Factor
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    ABSTRACT: The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus (HBV) suppression. To compare the antiviral efficacy of telbivudine and adefovir dipivoxil, and the effects of switching from adefovir to telbivudine, in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B. Randomized, controlled, open-label trial. 16 outpatient clinics. 135 treatment-naive, HBeAg-positive adults with chronic hepatitis B. Patients were randomly assigned in a 1:1:1 ratio to 52 weeks of telbivudine (group A) or adefovir (group B), or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks (group C). One hundred thirty-one patients completed 52 weeks of treatment. The primary efficacy comparison was serum HBV DNA reduction at week 24, with a secondary comparison at week 52. At week 24, mean HBV DNA reduction was greater in group A than in pooled groups B and C (-6.30 vs. -4.97 log10 copies/mL; difference, -1.33 log10 copies/mL [95% CI, -1.99 to -0.66 log(10) copies/mL]; P < 0.001), and more patients in group A were polymerase chain reaction-negative (39% vs. 12%; odds ratio, 4.46 [CI, 1.86 to 10.72]; P = 0.001). At week 52, the mean residual HBV DNA level was lower in group A and group C than in group B (3.01 log10 copies/mL [group A] and 3.02 log10 copies/mL [group C] vs. 4.00 log10 copies/mL [group B]; difference, -0.99 log10 copies/mL [CI, -1.67 to -0.32 log10 copies/mL] and -0.98 log10 copies/mL [CI, -1.64 to -0.32 log10 copies/mL]; P = 0.004). Adverse events were similar across groups; the most common were upper respiratory symptoms, headache, back pain, and diarrhea. The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy. Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment. After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir.
    Annals of internal medicine 01/2008; 147(11):745-54. · 16.10 Impact Factor
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    ABSTRACT: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.
    The Korean Journal of Hepatology 01/2008; 13(4):503-12. DOI:10.3350/kjhep.2007.13.4.503
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    ABSTRACT: Hepatocellular carcinoma (HCC) with an extension to the inferior vena cava (IVC) or right atrium is uncommon, and its prognosis remains unclear due to the few case reports. In order to elucidate the natural history and treatment outcome, this study investigated advanced HCC patients with an IVC invasion or atrial tumor thrombus. Between November 1987 and June 2004, a total of 41 patients were diagnosed as having HCC with IVC or right atrial involvement using the new imaging techniques including a two-dimensional echocardiography. Those patients were stratified into the untreated 'control group' (n=17) and 'treated group' (n=24). The clinical features, treatment outcome and prognosis including patient survival were analyzed. The mean age of the total patients was 55 years (male:female, 33:8). The most common cause of HCC was a hepatitis B virus infection (85.4%), followed by a hepatitis C virus infection (7.4%). According to the Child-Pugh classification, 24 patients were Child-Pugh class A (58.5%), 15 were Child-Pugh class B (36.6%), and 2 were Child-Pugh class C (4.9%). Lung metastases were identified in 10 patients (24.5%). The treatment modalities of the treated group included 11 systemic chemotherapy regimens (5-FU and cisplatin), 10 transarterial chemotherapy regimens, 2 chemoradiation procedures and 1 hepatic resection. The overall survival was 3.0 months (range, 1-29 months). The 6 month survival rate was 23.5% (4/17) in the control group and 29.2% (7/24) in the treated group. The 12 months survival rate was 0% (0/17) and 25.0% (6/24), respectively. Independent prognostic factor affecting the survival was whether or not any treatment had been carried out. Although the prognosis of advanced HCC with IVC invasion or a right atrial tumor thrombi is poor, treatment might improve the survival rate.
    The Korean Journal of Hepatology 10/2007; 13(3):387-95. DOI:10.3350/kjhep.2007.13.3.387
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    ABSTRACT: Few noninvasive models of chronic hepatitis B (CHB) to predict liver cirrhosis have been studied. The aim of the current study is to investigate the diagnostic accuracy of two simple novel models of spleen-platelet ratio index (SPRI) and age-spleen-platelet ratio index (ASPRI) in patients with CHB. A total of 346 consecutive treatment-naïve patients with CHB were retrospectively studied. The aspartate to alanine aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), SPRI, and ASPRI were compared with liver histology. AAR, APRI, SPRI, API, and ASPRI correlated significantly to fibrosis stage (all P<0.001). The diagnostic accuracy of ASPRI was the highest among five tests for prediction of cirrhosis (area under receiver operating characteristic curve, AUROC=0.893). Using a cutoff score of ASPRI>12, the presence of cirrhosis could be correctly identified with a high accuracy (96.3% positive predictive value) in 35 (10.1%) of 346 patients. Similarly, using a cutoff of <5, the presence of cirrhosis could be totally excluded with 100% of negative predictive value in 120 (34.7%) of 346 patients. ASPRI was accurate in predicting cirrhosis and screening with ASPRI has the potential to reduce the number of liver biopsies in CHB patients.
    Liver international: official journal of the International Association for the Study of the Liver 09/2007; 27(7):969-76. DOI:10.1111/j.1478-3231.2007.01519.x · 4.41 Impact Factor
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    ABSTRACT: Hepatic arterial infusion chemotherapy (HAIC) has often been selected as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the efficacy and safety of repetitive HAIC with high-dose 5-fluorouracil (5-FU) and cisplatin given for 3 days in patients with advanced HCC. Between January 2001 and December 2004, a total of 41 patients with unresectable advanced HCC were enrolled. The patients underwent HAIC via the implantable port system with 5-FU (at a dose of 500 mg/m(2) on Days 1-3) and cisplatin (at a dose of 60 mg/m(2) on Day 2) every 4 weeks. Tumor response was assessed at the end of every 3 cycles. The median age of the patients was 53 years and 34 patients (82.9%) had evidence of portal vein thrombosis. In total, 230 cycles of HAIC were administered to the 41 patients, with a median of 6 cycles given (range, 1-14 cycles). Nine patients (22.0%) achieved a partial response and 14 patients (34.1%) had stable disease. The median time to disease progression and overall survival were 7.0 months and 12.0 months, respectively. The overall survival was found to be significantly longer in the successful disease control group (patients with a complete response, partial response, and stable disease) than in the disease progression group (median of 14.0 months vs 6.0 months; P < .001). Adverse reactions were tolerable and successfully managed with conservative treatment. HAIC with high-dose 5-FU and cisplatin given for 3 days achieved effective and safe results in patients with advanced HCC. Therefore, repetitive short-course HAIC with high-dose 5-FU and cisplatin may be useful as an alternative therapeutic option for patients with advanced HCC.
    Cancer 07/2007; 110(1):129-37. DOI:10.1002/cncr.22759 · 4.90 Impact Factor
  • Journal of Hepatology 04/2007; 46. DOI:10.1016/S0168-8278(07)61722-X · 10.40 Impact Factor
  • Journal of Hepatology 04/2007; 46. DOI:10.1016/S0168-8278(07)62106-0 · 10.40 Impact Factor
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    ABSTRACT: Spontaneous bacterial peritonitis (SBP) is a prototypical infectious disease of cirrhotic patients. It has been suggested that cirrhotic patients' response to infection is less effective because of differences in the inflammatory and immune reactions. This study aimed to investigate the expression of the inflammatory cytokines monocyte chemotactic protein-1 (MCP-1) and interleukin-10 (IL-10) in cirrhotic patients with SBP. The MCP1 and IL-10 levels in the sera and ascitic fluids of cirrhotic patients with (n = 40) or without SBP (n=17) were serially analyzed by ELISA. In the non-SBP group, the mean MCP-1 levels in sera and ascites were 53.0 +/- 45.8 pg/mL and 197.5 +/- 109.5 pg/mL, respectively, and the IL-10 levels were 10.9 +/- 9.5 pg/mL and 77.6 +/- 79.7 pg/mL, respectively. In the SBP group, the mean MCP-1 levels in serum and ascites before treatment were 164.7 +/- 126.4 pg/mL and 365.3 +/- 583.0 pg/mL, respectively, and the IL-10 levels were 31.4 +/- 44.1 pg/mL and 188.1 +/- 189.5 pg/mL, respectively. The sera MCP-1 and ascites IL-10 levels differed significantly between the two groups. In the SBP group, sera and ascitic MCP-1 and IL-10 levels fell during treatment. The low MCP-1 and IL-10 levels on the seventh day of treatment were found to have a statistically significant relationship to patient survival. MCP-1 and IL-10 levels in sera and ascites may be related to the clinical course of SBP.
    Journal of Interferon & Cytokine Research 04/2007; 27(3):227-30. DOI:10.1089/jir.2006.0055 · 3.90 Impact Factor
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    ABSTRACT: This study evaluated the long-term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage. A total of 188 patients with chronic hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re-evaluated based on histological grade and stage. During follow-up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto-periportal activity. The development of cirrhosis correlated well with the grade of porto-periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared-up without normalization than in patients whose ALT levels flared-up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow-up were independent prognostic factors for chronic hepatitis B. The results demonstrate that histological grade and stage, and biochemical profile during follow-up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long-term outcome of chronic hepatitis B patients.
    Journal of Gastroenterology and Hepatology 04/2007; 22(3):383-8. DOI:10.1111/j.1440-1746.2007.04857.x · 3.63 Impact Factor
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    ABSTRACT: Combination therapy with interferon alpha (IFN-alpha) and ribavirin for 24 or 48 weeks according to HCV genotype has improved the overall sustained virological response (SVR) rates to approximately 40%. The aim of this study was to investigate the long-term efficacy of combination therapy with IFN-alpha and ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients with chronic hepatitis C who received this combination therapy between 1995 and 2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6 million units three times weekly in combination with 900-1200 mg/day of ribavirin for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a median of 41 months (range, 12-105 months) after completion of therapy. In all of the SVR patients (57 patients), SVR was conserved during the follow-up period. None of the patients progressed to decompensated liver disease or hepatocellular carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to decompensated liver disease or HCC. In conclusion, combination therapy with IFN-alpha and ribavirin shows good long-term efficacy in patients with chronic hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV) infection.
    Yonsei Medical Journal 01/2007; 47(6):793-8. DOI:10.3349/ymj.2006.47.6.793 · 1.26 Impact Factor
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    ABSTRACT: Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. The aim of current study was to investigate the association of clearance of hepatitis B virus (HBV) with promoter polymorphisms within the CC chemokine receptor 5 (CCR5) and its major ligand, regulated upon activation, normal T cells expressed and secreted (RANTES) genes. Five chemokine system polymorphisms (CCR5 Delta32, CCR5 promoter 59029G/A, 59353C/T, RANTES -403G/A, and -28C/G) were studied in a total of 698 subjects. The carriage of each genetic variant was compared among "spontaneously recovered" group (n = 243), "chronic carrier" group (n = 349), and "unexposed" group (n = 106). CCR5 59029G promoter variant was associated with clearance of HBV infection in an acute phase (OR = 1.71, P = 0.006, dominant model; OR = 2.17, P < 0.001, recessive model) and amelioration of hepatic inflammation (P = 0.003) with the control of HBV replication (P = 0.04) in chronic carriers. Interestingly, CCR5 59029 was linked completely to CCR5 59353, and CCR5 Delta32 homozygosity or heterozygosity was not found in any Korean patient. No association was seen with RANTES polymorphisms at position -403 and -28. The CCR5 59029G/CCR5 59353T polymorphism may play a role in the clearance of HBV infection.
    Journal of Medical Virology 12/2006; 78(12):1564-71. DOI:10.1002/jmv.20739 · 2.22 Impact Factor
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    ABSTRACT: Gram-positive bacterial products such as peptidoglycan (PGN) and lipoteichoic acid (LTA) are potent stimulators of innate inflammatory responses. We previously reported that lipopolysaccharide (LPS), a major biologically active agent of gram-negative bacteria, induces a proinflammatory response via the Toll-like receptor (TLR) 4 in hepatic stellate cells (HSCs). Here we investigated the mechanism of proinflammatory action by PGN and LTA in activated human HSCs. Following treatment with either TNF-alpha or IL-1beta, expression of TLR2 and CD14 was determined by real-time PCR and Western blotting. NF-kappaB activation was assessed by NF-kappaB-driven luciferase assay and electrophoretic mobility shift assay. Interleukin-8 (IL-8) from culture supernatant was measured by ELISA. Activated human HSCs express TLR2 and CD14, which are receptors for PGN and LTA signaling. TNF-alpha and IL-1beta significantly upregulated the expression of TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-kappaB activation and stimulated production of IL-8 in HSCs. Pretreatment with TNF-alpha or IL-1beta augmented NF-kappaB activation and IL-8 production in response to PGN or LTA. Both PGN- and LTA-induced NF-kappaB activation and IL-8 secretion were completely inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF-alpha or IL-1beta primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system.
    Laboratory Investigation 08/2006; 86(7):676-86. DOI:10.1038/labinvest.3700422 · 3.83 Impact Factor
  • Gastroentérologie Clinique et Biologique 08/2006; 30(8):1075-1075. DOI:10.1016/S0399-8320(06)73462-5 · 1.14 Impact Factor
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    ABSTRACT: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4 x 10(5)) genomes/mL, Digene Diagnostics, Silver Spring, USA). The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant.
    The Korean Journal of Hepatology 07/2006; 12(2):163-72.

Publication Stats

2k Citations
318.15 Total Impact Points

Institutions

  • 1995–2009
    • Yonsei University Hospital
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
  • 2008
    • Kwandong University
      Gangneung, Gangwon, South Korea
  • 2000–2008
    • Yonsei University
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2002–2005
    • National Health Insurance Corporation Ilsan Hospital
      Sŏul, Seoul, South Korea