• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2857-2860
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• 2016

Background: Chronic hepatitis B (CHB) infection is one of the important causes of hepatocellular carcinoma (HCC) in Thailand, involved in the pathogenesis and leading to a development of HCC with or without cirrhotic changes of the liver. This study was aimed to investigate the predictive factors for HCC among CHB patients in a tertiary care center in Thailand. Materials and Methods: We conducted a retrospective study of CHB patients with or without HCC during the period of January 2009 and December 2014 at Thammasat University Hospital, Pathumthani, Thailand. Data on clinical characteristics, biochemical tests and radiologic findings were collected from review of medical records. Results: A total of 266 patients were diagnosed with CHB in Thammasat university hospital during the study period. However, clinical information of only 164/266 CHB patients (98 males, 66 females with mean age of 49.4 years) could be completely retrieved in this study. The prevalence of HCC in CHB infection in this study was 38/164 (23.2%). CHB patients with HCC had a mean age older than those without HCC (59.5 vs 47 years, P-value = 0.01). Furthermore, history of upper GI bleeding, tattooing, blood transfusion, and chronic alcoholism were significantly more common in CHB patients with HCC than patients without HCC (13.2% vs 3.2% P-value 0.03, OR = 4.6, 95%CI = 1.2-18.1, 20% vs 3.9%, P-value = 0.01, OR= 6.1, 95% CI= 1.6-23.6, 20% vs 6.3%, P-value = 0.03, OR = 3.8, 95%CI =1.1-12.7, 62.2% vs 30.3%, P-value <0.0001, OR = 3.7, 95%CI= 1.7-8.1 respectively). Interestingly, more CHB patients with HCC had evidence of cirrhosis than those without HCC (78.9% vs 20.4%, P-value <0.0001, OR = 14.6, 95%CI = 5.8-36.7). In CHB patients with HCC, surgical therapy provided longer survival than radiofrequency ablation (RFA) (72 vs 46.5 months, P-value= 0.04). The mean survival time after HCC diagnosis was 17.2 months. Conclusions: HCC remains a major problem among patients with CHB infection in Thailand. Possible risk factors are male gender, history of upper GI bleeding, chronic alcoholism, tattooing, blood transfusion and evidence of cirrhosis. For early stage HCC patients, surgical treatment provided longer survival time than RFA. Most HCC patients presented with advanced disease and had a grave prognosis. Appropriate screening of CHB patients at risk for HCC might be an appropriate approach for early detection and improvement of long-term outcomes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7213-7218
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• 2014

Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• 핵의학기술
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• 제23권1호
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• pp.35-39
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• 2019

[목적] B형 간염바이러스(hepatitis B virus, HBV)감염은 전세계적으로 중요한 공중 보건 문제이며 만성간염, 간 경변, 간암의 주요 원인으로 알려져 있으며, 이러한 질환의 진단 및 치료에 B형 간염바이러스의 혈청학적 검사는 필수적이다. 항 바이러스 치료중인 B형 간염 환자를 대상으로 면역방사계수 측정법(IRMA; Immunoradiometric assay)과 화학발광 미세입자 면역분석법(CMIA; Chemiluminescent Micropartical Immunoassay)을 이용하여 HBe-Ag 검사를 시행하였고, 실시간 중합효소 연쇄반응(RT-PCR; Realtime-Polymerase Chain Reaction)법을 이용하여 혈청 내 HBV DNA 검출율 을 비교 분석 하였다. [대상 및 방법] 항 바이러스 치료가 시행중인 B형 간염 환자 270명을 대상으로 HBeAg 혈청 검사와 HBV DNA 정량 검사를 실시하였다. HBeAg 혈청 검사는 검출 원리가 다른 두 가지 혈청학적 검사법(IRMA, CMIA)을 적용 하였고, 혈청 내 HBV DNA는 Abbott m2000 System을 사용하여 실시간 중합효소 연쇄반응(RT-PCR; Realtime-Polymerase Chain Reaction)법으로 정량 측정 하였다. [결과] HBeAg 검출율은 면역방사계수법(IRMA)의 경우 24.1% (65/205), 화학발광 미세입자 면역 분석법(CMIA)에서는 82.2% (222/48)의 결과를 보였다. 혈청학적 검사방법(IRMA, CMIA)에 따른 HBeAg 검사결과의 일치율은 33% (89/270)이다. 실시간 중합효소 연쇄반응(RT-PCR)을 이용한 혈청 내 HBV DNA의 검출율은 29.3% (79/191)를 보였고, 혈청 내 HBV-DNA 농도는 $16IU/mL{\times}1.0{\times}10^9IU/mL$ 이며 검출한계는 <15IU/mL 이다. 면역방사계수법(IRMA)으로 HBeAg 검출결과가 양성일때 55.4%, 그리고 음성일때 20.9%의 HBV DNA 검출율과 $1.1{\times}10^8IU/mL$, $5.7{\times}10^5IU/mL$의 혈청내 HBV DNA농도를 나타냈다. 이에 반해 화학발광 미세입자 면역 분석법(CMIA)의 경우 HBeAg 검출결과가 양성일때 HBV DNA 검출율은 28.4%, 음성일때 33.3%의 결과를 나타냈으며 혈청 내 HBV DNA농도는 $6.0{\times}10^7IU/mL$, $2.4{\times}10^5IU/mL$ 이었다. 면역방사계수법과 화학발광 미세입자 면역 분석법에서 동일하게 HBeAg 검출 결과가 양성인 경우 HBV DNA 검출율은 62.3%의 결과를 보였으며, 혈청 내 HBV DNA 농도는 $1.1{\times}10^8IU/mL$ 이다. [결론] 혈청학적 검사법에 따른 HeAg 검출율은 많은 차이를 보였다. 이러한 차이는 검사kit에 사용된 Ab의 특성과 epitope, HBV의 genotype등 여러 가지 원인으로 생각된다. 혈청학적 검사 결과로 분류 된 그룹별 HBV DNA의 검출율과 농도를 비교한 결과, Group II(IRMA 양성, CMIA 양성, N=53)에서 높은 검출율과 농도를 확인할 수 있었다.

• Molecules and Cells
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• 제40권6호
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• pp.418-425
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• 2017

Interferon-${\gamma}$-inducible protein 10 (IP-10), also known as chemokine C-X-C motif ligand (CXCL) 10, is closely associated with antiviral immunity and the progression of chronic hepatitis B (CHB). However, the value of baseline serological and histological IP-10 expression levels in predicting the efficacy of the antiviral response to nucleoside/nucleotide analogues (NAs) is still unknown. In our research, intrahepatic and peripheral IP-10 expression levels were systemically examined before and after treatment with entecavir (ETV). Baseline serological and histological IP-10 expression levels were significantly increased in patients with CHB, particularly in patients with higher degrees of liver inflammation and liver fibrosis. Moreover, higher baseline intrahepatic IP-10 levels indicated better prognoses in patients with CHB after entecavir therapy. The baseline IP-10 level was also positively associated with several clinical parameters, including baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg), and with the decrease in HBsAg levels after treatment. In addition, monocyte-derived IP-10 was expressed at higher levels in patients with CHB than in patients with liver cirrhosis (LC) and healthy controls (HC). According to the results of our in vitro experiments, IP-10 directly promoted hepatocyte apoptosis. Based on these findings, baseline serological and histological IP-10 levels might predict CHB severity and the decrease in HBsAg levels after entecavir therapy.

• Radiation Oncology Journal
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• 제29권1호
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• pp.53-62
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• 2011

방사선간염은 대개 황달을 동반하지 않은 알칼리인산 분해효소(alkaline phophatase)의 상승을 특징으로 보인다. 하지만, 방사선간염 환자의 일부에서는 아미노전달효소(transaminase)의 상승을 특징적인 소견으로 보이고, 이러한 소견은 특히 간암 환자의 70~90%가 B형 간염 바이러스 보균자인 아시아 지역에서 흔하게 관찰된다. 또한 B형 간염 바이러스 보균자인 간암 환자를 방사선으로 치료했을 때 방사선간염이 더 흔하게 발생한다. 이런 사실들은 B형 간염 바이러스 보균자에서 방사선간염의 발생 기전이 비보균자에서의 그것과 다를 수 있다는 것을 시사하고, B형 간염 바이러스 보균자에서 발생하는 방사선간염의 발생기전은 B형 간염 바이러스의 재활성화와 연관이 있을 것으로 추측된다. 하지만, 현재 간암의 방사선치료 후 B형 간염 바이러스의 재활성화에 대한 연구는 미미한 수준이다. 이에 저자들은 간암 환자의 토모테라피 후 발생한 B형 간염 바이러스 재활성화 3예를 보고하고자 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4131-4136
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• 2016

Background: The population in northeast Thailand continues to present with hepatobiliary abnormalities, particularly periductal fibrosis (PDF) which is the result of chronic infection with liver fluke (Opisthorchis viverini; OV) and may lead to the development of cholangiocarcinoma (CCA). Although the prevalence of OV infection has been decreased due to a liver fluke control program over decades, the prevalence of PDF remains high. This study aimed to investigate demographic factors associated with PDF risk based on ultrasonography (US) screening. Materials and Methods: This cross-sectional study is part of the Cholangiocarcinoma Screening and Care Program (CASCAP), a prospective cohort study. Multiple logistic regression was used for data analysis. Results: In 55,246 subjects, the overall prevalence of PDF was 33.0% (95%CI: 32.6 - 33.4). Males (33.9 %) were at higher risk for developing PDF than females (32.2 %) (ORcrude = 0.93; 95%CI: 0.89 - 0.96; p-value < 0.001). Factors associated with an increased PDF risk, in addition to OV infection, included old age (${\geq}70$ years) (ORadj = 1.28, 95% CI: 1.14 - 1.44, p < 0.001) and hepatitis B infection (ORadj = 1.31, 95% CI: 1.11 - 1.55, p = 0.001). In contrast, number of praziquantel treatments (> 2 times) (ORadj = 0.54, 95% CI: 0.47 - 0.63, p < 0.001) and diabetes mellitus (ORadj = 0.57, 95% CI: 0.49 - 0.65, p < 0.001) were significantly associated with a decreased PDF risk. Conclusions: Future US screening should closely examine older people and hepatitis B subjects for the purpose of PDF surveillance among high risk groups for CCA. However, the results of inverse associations require further investigation in order to confirm our findings.

• Bulletin of the Korean Chemical Society
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• 제28권10호
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• pp.1756-1762
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• 2007

Envelope proteins of virus contain a segment of hydrophobic amino acids, called as fusion peptide, which triggers membrane fusion by insertion into membrane and perturbation of lipid bilayer structure. Potential fusion peptide sequences have been identified in the middle of L or M proteins or at the N-terminus of S protein in the envelope of human hepatitis B virus (HBV). Two 16-mer peptides representing the N-terminal fusion peptide of the S protein and the internal fusion peptide in L protein were synthesized, and their membrane disrupting activities were characterized. The internal fusion peptide in L protein showed higher activity of liposome leakage and hemolysis of human red blood cells than the N-terminal fusion peptide of S protein. Also, the membrane disrupting activity of the extracellular domain of L protein significantly increased when the internal fusion peptide region was exposed to N-terminus by the treatment of V8 protease. These results indicate that the internal fusion peptide region of L protein could activate membrane fusion when it is exposed by proteolysis.

• Pediatric Infection and Vaccine
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• 제15권1호
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• pp.1-4
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• 2008

Immunizations are among the most cost-effective and widely used public health interventions. This is a report a revision of recommendation of immunization for children by Korean Pediatric Society. Immunization. Vaccines were divided into 4 groups. 1) Vaccines that are recommended to all infants and children (BCG, hepatitis B vaccine, DTaP, Td, Polio vaccine, Japanese encephalitis vaccine, MMR, varicella vaccine, influenza vaccine [6-23 months of age], H. influenzae type b vaccine), 2) those that can be administered to all infants and children, but decision of administration is made by parents (pneumococcal conjugate vaccine, hepatitis A vaccine, influenza vaccine [healthy children ${\geq}24$ months of age], rotavirus vaccine, human papilloma virus vaccine), 3) those that should be given to high risk group (pneumococcal polysaccharide vaccine [high risk patients ${\geq}24$ months of age], influenza vaccine [high risk patients ${\geq}24$ months of age], typhoid vaccine), and 4) those administered for control of outbreaks or prevention of emerging infectious diseases. Immunization schedule recommended by Korean Pediatric Society in 2008 is presented.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권5호
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• pp.362-365
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• 2000

A rapid immunochromatographic assay kit using whole blood to screen hepatitis B surface antigen was developed and evaluated by using sera from 240 patients. The reference diagnosis was based on the results obtained with GENEDIA Anti-HBs Rapid kit which is very similar to the above kit except for the use of serum. The test demonstrated a good correlation with the reference immunochromatographic assay kit, that is, the sensitivity and the specificity of the kit was 100%, respectively. The rapid test kit using whole blood should be more convenient and useful for the diagnosis of hepatitis B virus because the kit does not need machines and time to prepare serum. In addition, this kit is safe from inadvertent infection during sample treatment because the blood is sterilized with hydrogen peroxide, eliminates the procedure required to prepare serum and reduces the possibility of exposure to infectious agents.