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ABSTRACT: BACKGROUND: Metastatic tumor antigen 1 (MTA1) overexpression is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). It has been suggested that pegylated interferon (Peg-IFN) can prevent the occurrence of HCC in patients who have chronic viral hepatitis. In this study, the authors examined whether postoperative adjuvant Peg-IFN therapy can reduce the recurrence of MTA1-positive HCC after curative surgical resection. METHODS: In this case-control study, 93 patients with MTA1-positive HCC who underwent curative surgical resection were prospectively enrolled. The median patient age was 53 years (range, 27-78); there were 65 men and 28 women; the etiology was hepatitis B virus (HBV) in 77 patients, hepatitis C virus (HCV) in 6 patients, and non-HBV/non-HCV in 10 patients; 31 patients received Peg-IFN (Peg-INTRON(®) ) subcutaneously at a dose of 50 μg per week for 12 months (the Peg-IFN group); and the remaining 62 patients were followed only and did not receive any adjuvant therapies (control group). Patients were followed every 1 to 3 months for a median of 24 months. RESULTS: HCC recurred postoperatively in 26 of 93 patients (28%), and 9 patients (10%) died during follow-up. The overall cumulative recurrence rates were significantly lower in the Peg-IFN group than in the control group (7% and 14% vs 24% and 34% at 1 year and 2 years, respectively; P < .05). In addition, the 1-year and 2-year cumulative survival rates were higher in the Peg-IFN group compared with the control group (100% vs 93% and 100% vs 87%, respectively; P < .05). In multivariate analysis, the receipt of adjuvant Peg-IFN therapy, in addition to having a lower Cancer of the Liver Italian Program score and being a woman, was an independent, favorable factor for a lower risk of postoperative recurrence. CONCLUSIONS: The current data indicate that adjuvant Peg-IFN therapy may reduce the recurrence of HCC in patients who have MTA1-positive HCC after curative surgical resection. Cancer 2013. © 2013 American Cancer Society.
Cancer 04/2013; · 4.77 Impact Factor
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ABSTRACT: Overexpression of metastatic tumor antigen-1 (MTA-1) is suggested to be associated with frequent postoperative recurrence and poor survival of hepatocellular carcinoma (HCC) patients. In this study, we intended to determine clinical factors predisposing the overexpression of MTA-1 in patients with hepatitis B virus (HBV)-associated HCC and also examine whether MTA-1 overexpression affects the survival periods of these patients treated with curative surgical resection.
A total of 303 patients with HBV-associated HCC who underwent curative surgical resection were subjected. The expressions of MTA-1 in HCC and surrounding non-tumor liver tissues were evaluated using the immunohistochemical method. The clinical, radiological and histological characteristics of the patients were analyzed in relation to the expression of MTA-1 to find predisposing factors of MTA-1 overexpression.
MTA-1 was overexpressed in 104 HCC tissues (34.3 %) and none of the surrounding non-tumor tissues. Clinically, MTA-1 overexpression was significantly associated with younger age, female gender, higher serum alpha-fetoprotein level, and Child-Turcotte-Pugh class A. Also, portal vein thrombosis, microvascular invasion, capsular invasion and poorly histological differentiation were associated with overexpression of MTA-1. The cumulative survival rates were significantly lower in patients with MTA-1 overexpression compared with those in the MTA-1 negative group (P = 0.03). In addition to the overexpression of MTA-1, the presence of microvascular or capsular invasion was a significant factor determining the poor survival of the patients with HBV-associated HCC after curative resection.
MTA-1 is overexpressed in patients with HBV-associated HCC of invasive nature. MTA-1 overexpression is associated with shorter survival periods of patients with HBV-associated HCC after curative resection.
Digestive Diseases and Sciences 07/2012; 57(11):2917-23. · 2.12 Impact Factor
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Young-Joo Jin,
Ju Hyun Shim,
Young-Hwa Chung,
Jeong A Kim,
Jong Gi Choi, Won Hyung Park,
Danbi Lee,
Yoon Seon Lee,
Sung Eun Kim,
Sung Hoon Kim,
Soo Hyun Yang
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ABSTRACT: We intended to analyze the relationship between specific human leukocyte antigen (HLA)-DRB1 alleles and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients.
A database of 468 consecutive CHB patients who received lamivudine for more than 12 months between July 1996 and February 2011 was retrospectively analyzed. Sera and buffy coats samples were obtained between April 2008 and April 2010. Six-digit HLA-DRB1 genotyping was performed with sequence-based typing. Serum α fetoprotein levels and ultrasonography or computed tomography image studies were assessed every 3 to 6 months for surveillance of HCC.
At baseline, median age was 43 years (range, 16 to 71) [male: 359 (76.7%); HBeAg positivity: 385 (82.3%)]. Among the 27 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent (>10%). HCC was diagnosed in 36 (7.7%) patients during the median follow-up of 69 months. The frequency of the HLA-DRB1*140101 allele was 9.0% and significantly higher in patients of the HCC group than those of the non-HCC group (19.4 vs. 8.1%, P=0.014). The 2-year, 4-year, and 6-year cumulative rates of HCC development were markedly higher in patients with HLA-DRB1*140101 than those without HLA-DRB1*140101 (2.4, 8.2, and 25.1% vs. 1.9, 4.7, and 7.4%, respectively, P=0.011). No other HLA-DRB1 alleles were associated with HCC development. Baseline clinical characteristics did not differ between patients with and without HLA-DRB1*140101.
The HLA-DRB1*140101 allele may be potentially associated with increased risk of HCC development in CHB patients, irrespective of the replicative activity of hepatitis B virus and antiviral responsiveness.
Journal of clinical gastroenterology 05/2012; 46(5):420-6. · 2.21 Impact Factor
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Jong Gi Choi,
Young-Hwa Chung,
Jeong A Kim,
Young-Joo Jin, Won Hyung Park,
Danbi Lee,
Ju Hyun Shim,
Yoon Seon Lee,
Dong Dae Seo,
Myoung Kuk Jang,
Kang Mo Kim,
Young-Suk Lim,
Han Chu Lee,
Yung Sang Lee,
Eunsil Yu,
Young Joo Lee
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ABSTRACT: In this study the authors intended to investigate the relationship between intrahepatic hepatitis B virus (HBV)-DNA concentrations and posthepatectomy recurrence of HBV-associated hepatocellular carcinoma (HCC).
High HBV-DNA level is strongly associated with HCC development in chronic HBV infection and considered to be a risk factor of HCC recurrence.
A total of 109 patients with HBV-associated HCC who underwent curative surgical resection were followed up every 3 to 6 months for a median of 82 months. Intrahepatic total HBV-DNA titer was measured in HCC and surrounding liver tissues using a TaqMan probe-based real-time polymerase chain reaction method. HBV-DNA titers in HCC and surrounding liver were compared in accordance with patients' clinical, radiologic, and histopathological characteristics. The relationships between HBV-DNA titers in HCC or surrounding liver tissues and cumulative HCC recurrence rates were determined.
Of the 109 patients, 67 (62%) showed posthepatectomy recurrence of HCC. In all patients, total HBV-DNA titers were significantly higher in HCCs than in surrounding liver tissues (P=0.019). HCC recurred more frequently in patients with higher than those with lower HBV-DNA titers in surrounding liver tissues (P=0.009). In contrast, the HCC recurrence rates were similar in patients with higher and those with lower HBV-DNA titers in HCC specimens (P=0.301). Multivariate analysis showed that tumor size >5 cm (P=0.008), the presence of portal vein thrombus (P=0.001), and high HBV-DNA titer in surrounding liver tissues (P=0.002) were independent risk factors for posthepatectomy HCC recurrence in patients with HBV-associated HCC.
In patients with HBV-associated HCC, high HBV-DNA titer in surrounding liver rather than in the HCC itself is associated with posthepatectomy HCC recurrence after curative surgical resection.
Journal of clinical gastroenterology 11/2011; 46(5):413-9. · 2.21 Impact Factor
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Yoon-Seon Lee,
Young-Hwa Chung,
Jeong A Kim,
Young Joo Jin, Won Hyung Park,
Sung Eun Kim,
Danbi Lee,
Ju Hyun Shim,
Kang Mo Kim,
Young Suk Lim,
Han Chu Lee,
Yung Sang Lee,
Dong Jin Suh
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ABSTRACT: We intended to investigate the effects of pre-existing mutations at reverse transcriptase region of hepatitis B virus (HBV) on the occurrence of virological breakthrough (VB) to adefovir dipivoxil (ADV) in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB).
Ninety-seven patients with LAM-resistant CHB were treated with ADV at a dose of 10 mg daily, and were followed for a median period of 13 months. Just before the initiation of ADV therapy, the whole length of reverse transcriptase region of serum HBV-DNA was sequenced using direct sequencing.
All patients had genotype C HBV and mutations in the YMDD motif, specifically, YIDD (65%), YVDD (28%), or both (7%). The rtL180M and rtL80V/I mutations were identified in 68% and 69%, respectively. The cumulative probability of VB was 19% and 27% at 1 and 2 years, respectively. There was no difference in the occurrence of VB with regard to types of YMDD mutation or rtL80V/I. However, interestingly, patients carrying rtL180M experienced VB during ADV monotherapy more frequently than those not carrying rtL180M (2-year cumulative probability of VB: 37% vs 3% at 2 years, P < 0.01). On multivariate Cox proportional hazards analysis, rtL180M (hazard ratio [HR]: 8.62, 95% confidence interval: 1.08-69.09, P = 0.042) and decrease in HBV-DNA for 1 year of treatment (HR: 0.69, 95% CI: 0.51-0.95, P = 0.024) are independently associated with VB.
The rtL180M mutation of HBV, as well as a small decrease in HBV-DNA after 1 year of treatment might be closely associated with frequent occurrence of virological resistance to ADV in patients with LAM-resistant CHB.
Journal of Gastroenterology and Hepatology 07/2011; 27(2):300-5. · 2.87 Impact Factor
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ABSTRACT: Longstanding liver inflammation leads to hepatic regeneration and fibrosis, which subsequently progresses to cirrhosis in some patients with chronic hepatitis B virus (HBV) infection. It remains unclear, however, if the histological severity of chronic hepatitis B (CHB) may determine the development of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the effects of necroinflammation and fibrosis at presentation of CHB on the development of HCC.
Medical records and radiographs of 796 biopsy-confirmed CHB patients were reviewed retrospectively for a median period of 107 months (6-218) (median age 34 years (18-64), male:female 636:160). Eighty-five per cent (680/796) of patients were treated with antiviral agents such as interferon alpha and/or lamivudine. All the patients were followed at a regular interval of 3-6 months with routine laboratory tests. Abdominal imagings together with serum alpha-fetoprotein were checked every 6-12 months to detect new HCC. Necroinflammation and fibrosis were assessed semiquantitatively. Univariate and multivariate analyses were performed to identify significant risk factors for HCC.
HCC developed in 3.4% (27/796) of patients during follow-up. The overall cumulative occurrence rates of HCC were 0.5% and 3.5% at 5 and 10 years, respectively. In multivariate analysis, age over 40 years (p<0.001), advanced fibrosis (p=0.006) and severe lobular activity (p=0.038) at presentation were independent risk factors for the development of HCC.
Advanced fibrosis and severe lobular activity rather than porto-periportal activity on histology at presentation of CHB are independent predisposing risk factors for the development of HCC.
Journal of clinical pathology 07/2011; 64(7):599-604. · 2.43 Impact Factor
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ABSTRACT: The development of Information and Communication gives a lot of convenience in our lives, but on the other hand, the new cyber threat like viruses, computer intrusions and so on also increases. Especially, malicious codes such as viruses over the internet are distributed in large quantities. Several studies using reverse engineering or virtual machine have been carried out to analyze malicious codes, but studies on the analysis of the implications or the similarities between malicious codes have not been carried out in variety. Therefore, we suggest the analysis of similarity using N-Gram and Vector Space Model in this paper. The results shows that we can distinguish malicious codes from others using this method.
Information Science and Applications (ICISA), 2011 International Conference on; 05/2011
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ABSTRACT: Wireless network is one of the 2010s most important security issues. As smartphone(android) is popularize, the number of Wireless Internet users is really growing and wireless AP spring up everywhere. But most wireless AP have not being managed properly in terms of security, Wireless Internet users also dont recognize important of security. This situation causes grave security threats. This paper design and analyze a new cyber attack whose it circulates malware via QR code and activates Mobile AP to induce service charge. The new vulnerability we suggest forces to activate Mobile AP of smartphone based on Android and responds to all probe request are generated around, and brings induction of service charge and communication problems in its train.
Information Science and Applications (ICISA), 2011 International Conference on; 05/2011
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Young-Joo Jin,
Ju Hyun Shim,
Young-Hwa Chung,
Jeong A Kim,
Jong Gi Choi, Won Hyung Park,
Danbi Lee,
Sung Eun Kim,
Yoon Seon Lee,
Sung Hoon Kim,
Soo Hyun Yang
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ABSTRACT: We intended to evaluate the association between specific human leukocyte antigen (HLA)-DRB1 gene polymorphism and antiviral response to lamivudine (LAM) therapy in chronic hepatitis B (CHB) patients.
Six-digit HLA-DRB1 genotypes were determined using sequence-based typing in 334 CHB patients initially treated with LAM for at least 12 months. Antiviral response was evaluated every 3-6 months during LAM therapy.
Median age of the subjects was 43 years (range, 16-72). Median duration of LAM therapy was 69 months (range, 13-140). Median baseline serum hepatitis B virus (HBV DNA) level was 7.0 log(10) copies/ml (range, 5.5-9.1). At 12 months of LAM therapy, serum HBV DNA was undetectable by solution hybridization method in 308 (88%) patients. Among 25 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent alleles (>10%). HLA-DRB1*010101 was identified in 5.4% (18/334). The frequency of the HLA-DRB1*010101 allele was significantly lower in patients with virological response at 12 months of LAM therapy than in patients without it (4.2 vs. 19.2%, p = 0.025). The other HLA-DRB1 alleles were not associated with virological response. HBeAg loss/seroconversion and alanine aminotransferase normalization were not associated with HLA-DRB1 alleles.
The HLA-DRB1*010101 allele is closely associated with poor virological response to initial LAM therapy in CHB patients.
Digestion 01/2011; 84 Suppl 1:35-42. · 2.05 Impact Factor
