• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• Molecules and Cells
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• v.40 no.3
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• pp.202-210
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• 2017

The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor $(TNF)-{\alpha}$. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship. Chromatin immunoprecipitation was used to identify the combination of $NF-{\kappa}B$ and miR-503. We found that overexpression of NS5A inhibited $TNF-{\alpha}$-induced hepatocellular apoptosis via regulating miR-503 expression. The cell viability of the $TNF-{\alpha}$ induced Hep-mock cells was significantly less than the viability of the $TNF-{\alpha}$ induced Hep-NS5A cells, which demonstrates that NS5A inhibited $TNF-{\alpha}$-induced HepG2 cell apoptosis. Under $TNF-{\alpha}$ treatment, miR-503 expression was decreased and cell viability and B-cell lymphoma 2 (bcl-2) expression were increased in the Hep-NS5A cells. Moreover, the luciferase reporter gene experiment verified that bcl-2 was a direct target of miR-503, NS5A inhibited $TNF{\alpha}$-induced $NF-{\kappa}B$ activation and $NF-{\kappa}B$ regulated miR-503 transcription by combining with the miR-503 promoter. After the Hep-NS5A cells were transfected with miR-503 mimics, the data indicated that the mimics could reverse $TNF-{\alpha}$-induced cell apoptosis and blc-2 expression. Collectively, our findings suggest a possible molecular mechanism that may contribute to HCV treatment in which NS5A inhibits $NF-{\kappa}B$ activation to decrease miR-503 expression and increase bcl-2 expression, which leads to a decrease in hepatocellular apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5097-5099
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• 2012

Objective: To assess associations of Type II DM with hepatocellular carcinoma occurrence in Nepal. Materials and Methods: This case control study was carried out using data retrieved from the register maintained in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st January, 2012, and 31st August, 2012. The variables collected were age, gender, HbA1c. All biochemical parameters were analyzed in the Central Laboratory of our hospital by standard validated methods. One way ANOVA was used to examine the statistical significant difference between groups with the LSD post-hoc test for comparison of means of case groups. Odds ratios (OR) were calculated using simple logistic-regression analysis. Results: Etiological factors for HCC were HBV, HCV, alcohol and cryptogenic cirrhosis. The highest age group belonged to the etiological category of HCV with a mean of $71.9{\pm}3.6$ (CI 69.3, 74.5) years and the lowest age group to the etiological category of HBV with $61.7{\pm}5.3$(CI 57.9, 65.5) years. The main imperative basis of HCC in present study was HCV (39.5%) and second most significant cause of HCC was alcohol (26%). Glycated hemoglobin was found to be more in males with HCC (7.9%) as compared to females (7.3%). The percentage of Type II diabetes mellitus was greater in HCC patients when compared to controls. This difference was statistically significant with an odd ratio of 4.63 (p<0.001). Conclusion: Type II DM influences incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.

• Journal of Preventive Medicine and Public Health
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• v.37 no.3
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• pp.253-259
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• 2004

Objectives : To investigate the prevalence of hepatitis B and C virus infections and determine the associated risk factors among young adults in Busan, Korea, which is known to have a high incidence of liver cancer. Methods : The study population consisted of volunteer participants in a health survey during 2002, which included 1,350 students (515 males and 835 females) aged between 16 and 24 years, from three different schools in Busan. The participating students were asked to fill in a self-administered questionnaire which included lifestyle habits and risk factors of hepatitis. Sera obtained from the participants were studied for HBsAg, anti-HBs, and Anti-HCV by enzyme immunoassay (EIA) method and for liver function tests. Results : Among the study subjects (N=1,350), the seropositivities of HBsAg 7.9%(95% CI=7.8-8.0), 7.6%(95% CI=7.6-7.7) in male and 8.1%(95% CI=8.0-8.2) in female. And the seropositivity of Anti-HBs was 69.7%(95% CI=69.0-70.4), 70.5%(95% CI=69.8-71.2) in male and 69.2%(95% CI=68.5-69.9) in female. The seropositivity of Anti-HCV was 0.4%, 0.2% in male and 0.5% in female. The seropositivity for HBsAg in the subjects not having a hepatitis B vaccination history was twice(95% CI=1.0-4.4) that of those that did. Also, the seropositivity for HBsAg in subjects having experienced sexual intercourse was 1.7 times (95% CI=0.9-3.0) that of the subjects who had not. Conclusions : The present study confirmed the high prevalence of HBsAg seropositivity and sexual transmission of HBV among adolescents and young adults may occur. Further studies to evaluate the relationship between HBV vaccination and sexual transmission are required for the young population in Korea.

• Journal of Preventive Medicine and Public Health
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• v.54 no.4
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• pp.251-258
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• 2021

Hepatitis C infection is responsible for high morbidity and mortality rates globally as well as for significant indirect costs. The disease burden caused by the hepatitis C virus (HCV) is comparable to the one caused by human immunodeficiency virus or tuberculosis. Today, simple detection methods, highly effective and easy to administer therapies and efficient preventative measures are available to combat hepatitis C. Nevertheless, in most countries around the world, the World Health Organization target of eliminating this infectious disease and its consequences by 2030 are not being met. Significant gaps in care for hepatitis C sufferers still exist, the shortcomings ranging from education and treatment to aftercare. Hepatitis C infection was and still is not on the radar of most politicians and health authorities. National programmes and strategies to combat the disease exist or are being developed in many countries. However, for these to be implemented efficiently and successfully, clear political commitment, strong civil society actors, well-functioning public health structures and the relevant support from global donors are needed.

• Proceedings of the Microbiological Society of Korea Conference
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• 2005.05a
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• pp.228.3-228
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• 2005

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.735-742
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• 2013

Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.

• Journal of Preventive Medicine and Public Health
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• v.37 no.4
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• pp.337-344
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• 2004

Objectives : This study was performed to determine the incidence density and the prevalence of sero-positive hepatitis C from 1999 to 2002 among adults aged 20 and over residing in Seoul and the Gyeonggi province. Method : The data for period was obtained from 114,635 adults, residing in Seoul or the Gyeonggi province, who had undertaken comprehensive health screening tests from Jan 1999 to Dec 2002 in a University hospital in Seoul. Among them, subjects with sero-negative status against hepatitis C were selected (21,408 in 1999, 28,830 in 2000) and then followed up until Dec 2002 to determine the incidence of hepatitis C during this period. The serum was tested with the immunoradiometric assay (IRMA) which uses third generation HCV antibody. Age adjusted rates were estimated by direct standardization using a reference population of 2000 aged from 20 to 80 years. Results : The prevalence of anti-HCV from 1999 to 2002 was 2.1 per 1000 persons(95% CI $1.8{\sim}2.4$). Male showed 1.7 per 1000 persons (95% CI $1.4{\sim}2.1$), while female showed 2.7 per 1000 persons(95% CI $2.2{\sim}3.2$). Age?sex adjusted rate showed 2.8 per 1000 persons (95% CI $2.64{\sim}2.96$), which is lower than the results of some previous study. The prevalence showed a significantly increasing pattern with age both in males and females (p<0.05). The incidence density of anti-HCV among the population aged 20 and over was 1.1 per 104 person-years at risk (95% CI $0.6{\sim}2.4$); 1.2 (95% CI $0.6{\sim}2.7$) for males and 0.8 (95% CI $0.6{\sim}4.2$) for females. Age adjusted incidence density was 2.91 per 104 person-years at risk (95% CI $2.43{\sim}3.38$) for those aged 20 and over. It showed an increasing pattern with age (p<0.05), especially for those age over 50 years. Conclusion : The study subjects for this study were supposedly healthier than the general population so the prevalence and incidence for the general population are thought to be higher than the results of the present study.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7251-7256
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• 2013

Objectives: To estimate the proportion of liver cancer cases and deaths due to infection with hepatitis B virus (HBV), hepatitis C virus (HCV), aflatoxin exposure, alcohol drinking and smoking in China in 2005. Study design: Systemic assessment of the burden of five modifiable risk factors on the occurrence of liver cancer in China using the population attributable fraction. Methods: We estimated the population attributable fraction of liver cancer caused by five modifiable risk factors using the prevalence data around 1990 and data on relative risks from meta-analyses, and large-scale observational studies. Liver cancer mortality data were from the 3rd National Death Causes Survey, and data on liver cancer incidence were estimated from the mortality data from cancer registries in China and a mortality/incidence ratio calculated. Results: We estimated that HBV infection was responsible for 65.9% of liver cancer deaths in men and 58.4% in women, while HCV was responsible for 27.3% and 28.6% respectively. The fraction of liver cancer deaths attributable to aflatoxin was estimated to be 25.0% for both men and women. Alcohol drinking was responsible for 23.4% of liver cancer deaths in men and 2.2% in women. Smoking was responsible for 18.7% and 1.0%. Overall, 86% of liver cancer mortality and incidence (88% in men and 78% in women) was attributable to these five modifiable risk factors. Conclusions: HBV, HCV, aflatoxin, alcohol drinking and tobacco smoking were responsible for 86% of liver cancer mortality and incidence in China in 2005. Our findings provide useful data for developing guidelines for liver cancer prevention and control in China and other developing countries.

• Journal of Trauma and Injury
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• v.28 no.1
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• pp.9-14
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• 2015

Purpose: The aim of this study was to estimate the seropositive prevalence of blood-borne infection in neurotrauma patients who underwent emergent surgical intervention, especially patients with hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and human immunodefIciency virus (HIV). Methods: A retrospective review identified 559 patients with traumatic brain injury and spinal trauma who underwent emergent surgery between 2007 and 2014. We reviewed the medical records and extracted data, including age, sex, location of lesion, result of serologic tests, time interval of admission and surgery after presenting to emergency room. Serologic tests for HBV, HCV, syphilis and HIV were performed and analyzed to determine whether the seropositive results were confirmed by the surgeon before surgery. Results: The majority of the patients were male (74.6%), and the mean age was $55.4{\pm}20.2years$. Most patients underwent surgery due to traumatic brain injury (90.0%). Fifty-three patients (10.0%) showed a positive result on at least one serologic test. Seropositive rates according to pathogens were 0.5% for syphilis, 5.2% for HBV and 3.9% for HCV. No positive results were noted on the serologic tests for HIV. HBV in patients with spinal cord injury and age from 40 to 49 years were associated with high serologic positive rate, and that result was statistically significant. However, no statistically significant differences were found in the other variables. Serologic results could not confirmed before surgery in the majority of the cases (62.1%), and 10.4% of these patients showed seropositive results. Conclusion: The results of this study emphasize the importance of taking precautions and conducting rapid serologic testing in preventing the occupational transmission of blood-borne viruses to health-care workers.