• Annals of Laboratory Medicine
• /
• v.38 no.6
• /
• pp.578-584
• /
• 2018

Background: Accurate, rapid, and cost-effective screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be useful in laboratories that cannot afford automated chemiluminescent immunoassays (CLIAs). We evaluated the diagnostic performance of a novel rapid automated fluorescent lateral flow immunoassay (LFIA). Methods: A fluorescent LFIA using a small bench-top fluorescence reader, Automated Fluorescent Immunoassay System (AFIAS; Boditech Med Inc., Chuncheon, Korea), was developed for qualitative detection of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HCV (anti-HCV) within 20 minutes. We compared the diagnostic performance of AFIAS with that of automated CLIAs-Elecsys (Roche Diagnostics GmbH, Penzberg, Germany) and ARCHITECT (Abbott Laboratories, Abbott Park, IL, USA)-using 20 seroconversion panels and 3,500 clinical serum samples. Results: Evaluation with the seroconversion panels demonstrated that AFIAS had adequate sensitivity for HBsAg and anti-HCV detection. From the clinical samples, AFIAS sensitivity and specificity were 99.8% and 99.3% for the HBsAg test, 100.0% and 100.0% for the anti-HBs test, and 98.8% and 99.1% for the anti-HCV test, respectively. Its agreement rates with the Elecsys HBsAg, anti-HBs, and anti-HCV detection assays were 99.4%, 100.0%, and 99.0%, respectively. AFIAS detected all samples with HBsAg genotypes A-F and H and anti-HCV genotypes 1, 1a, 1b, 2a, 2b, 4, and 6. Cross-reactivity with other infections was not observed. Conclusions: The AFIAS HBsAg, anti-HBs, and anti-HCV tests demonstrated diagnostic performance equivalent to current automated CLIAs. AFIAS could be used for a large-scale HBV or HCV screening in low-resource laboratories or low-to middle-income areas.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.7
• /
• pp.3381-3384
• /
• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• Molecules and Cells
• /
• v.45 no.10
• /
• pp.702-717
• /
• 2022

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulates beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediates protein interplay between NS5A and IKKε, thereby contributing to NS5A mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

• BMB Reports
• /
• v.38 no.2
• /
• pp.151-160
• /
• 2005

By a cDNA array representing 2308 signal transduction related genes, we studied the expression profiles of HeLa cells stably transfected by Hepatitis C virus nonstructural protein 4B (HCV-NS4B). The alterations of the expression of four genes were confirmed by real-time quantitative RT-PCR; and the aldo-keto reductase family 1, member C1 (AKR1C1) enzyme activity was detected in HCV-NS4B transiently transfected HeLa cells and Huh-7, a human hepatoma cell line. Of the 2,308 genes we examined, 34 were up-regulated and 56 were down-regulated. These 90 genes involved oncogenes, tumor suppressors, cell receptors, complements, adhesions, transcription and translation, cytoskeletion and cellular stress. The expression profiling suggested that multiple regulatory pathways were affected by HCV-NS4B directly or indirectly. And since these genes are related to carcinogenesis, host defense system and cell homeostatic mechanism, we can conclude that HCV-NS4B could play some important roles in the pathogenesis mechanism of HCV.

• BMB Reports
• /
• v.41 no.2
• /
• pp.158-163
• /
• 2008

Hepatitis B virus X protein (HBx) is essential for hepatitis B virus infection and exerts a pleiotropic effect on various cellular machineries. HBx has been also demonstrated as an indirect transcriptional transactivator of various different viral and cellular promoters. In addition, HBx is involved in the development of various liver diseases including hepatocellular carcinoma. However the mechanism of HBx in hepatocellular carcinogenesis remains largely unknown. In this study, to identify possible new cellular proteins interacting with HBx, we carried out yeast two-hybrid assay. We obtained several possible cellular partners including VBP1, a binding factor for VHL tumor suppressor protein. The direct physical interaction between HBx and VBP1 in vitro and in vivo was confirmed by immunoprecipitation assay. In addition, we found that VBP1 facilitates HBx-induced $NF{\kappa}B$ activation and cell proliferation. These results implicate the important role of HBx in the development of hepatocellular carcinoma through its interaction with VBP1.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2865-2869
• /
• 2013

Hepatitis B virus (HBV) infection can become chronic and if left untreated can progress to hepatocellular carcinoma (HCC).Thailand is endemic for HBV and HCC is one of the top five cancers, causing deaths among Thai HBV-infected males. A single nucleotide polymorphism (SNP) at the KIF1B gene locus, rs17401966, has been shown to be strongly associated with the development of HBV-related HCC. However, there are no Thai data on genotypic distribution and allele frequencies of rs17401966. Thai HBV patients seropositive for HBsAg (n=398) were therefore divided into two groups: a case group (chronic HBV with HCC; n=202) and a control group (HBV carriers without HCC; n=196). rs17401966 was amplified by polymerase chain reaction (PCR) and analyzed by direct nucleotide sequencing. The genotypic distribution of rs174019660 for homozygous major genotype (AA), heterozygous minor genotype (AG) and homozygous minor genotype (GG) in the case group was 49.5% (n=100), 40.1% (n=81) and 10.4% (n=21), respectively, and in controls was 49.5% (n=97), 42.3% (n=83) and 8.2% (n=16). Binary logistic regression showed that rs17401966 was not statistically associated with the risk of HCC development in Thai chronic HBV patients (p-value=0.998, OR=1.00 and 95% CI=0.68-1.48). In conclusion, the KIF1B gene SNP (rs174019660) investigated in this study showed no significant association with HBV-related HCC in Thai patients infected with HBV, indicating that there must be other mechanisms or pathways involved in the development of HCC.

• Journal of Microbiology
• /
• v.43 no.6
• /
• pp.529-536
• /
• 2005

Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing $\alpha-mannosidase-like$ protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.

• Journal of Nutrition and Health
• /
• v.6 no.2
• /
• pp.17-24
• /
• 1973

The function of the liver is so complicated and important that various Hepatic diseases are occured due to functional retardation of liver. Above all, the incidence of Hepatitis and liver cirrhosis among Koreans has shown an increasing tendency recently. 113 cases of Hepatitis and 125 cases of liver cirrhosis which had been admitted, more than 10 days, to KOREA Hospital between November, 1968 and July,1972, were studied through clinic charts. (A) Hepatitis 1) of the 113 cases; 54 cases (47.7%) were Infectious hepatitis; 40 cases (35.4%) were chronic hepatitis 2) of the 113 cases ; 80 cases (70.8%) were male and 33 cases (29.2%) were female; the sex ratio was 2.4 : 1 The ages of the onset of the disease was as follows; 34 cases (30.1%) were among $30{\sim}40$. 3) Patients had abdominal pain (77.9%) anorexia (66.4 %) and general weakness(82.3%) as symptom and jaundice (94.7%) hepatomegaly (76.1%) as sign 4) 57 cases of all had complication 26 cases (45.6%) were parasite, 12 cases (21.1%) were diabeties mellitus. 5) 99 casea (87.6%) of all were improved and recovered. (B) Liver Cirrhosis 1) Etiologic factors are hepatitis (56cases) and alcoholics (28 cases). 2) of the 125 cases, 84 cases (67.2%) were male and 41 cases (32.8%) were female; the sex ratio was 2 : 1 The age of the onset of the disease was as follows; 47 cases (37.6%) were among 41-50. 3) Patients had symptoms: indigestion (64.8%), Abdominal pain (60%), general wenkness (35.2%) and signs; Hepatomegaly (61.6%) Ascites (59.2%), Jaundice(56.8%). 4) 107 cases of all had complications; Hepatic coma was 20 cases (18.7 %), Ascites was 16 cases (15.0%). 5) 69 cases (55.2%) were improved. (c) Treatment of Hepatitis and cirrhosis. 1) Absolutely (bed) rest. 2) A well-balanced diet adequate in calorie value, showed be given (High Carbohydrate, High Protein, High vitamin diet) if the patient's appetite is good and easily digested. 3) Drugs; (1) Vitamins (2) Digestants (3) Tranquize

• Journal of Microbiology and Biotechnology
• /
• v.20 no.3
• /
• pp.510-512
• /
• 2010

A series of thiobarbituric acid derivatives were constructed and evaluated for inhibitory activity on hepatitis C virus NS5B polymerase. In biochemical assays using purified viral polymerase and RNA template, the $IC_{50}$ value was improved to 0.41 ${\mu}M$ from the original compound's 1.7 ${\mu}M$ value. In HCV sub genomic replicon assay, the $EC_{50}$ value was improved to 3.7 ${\mu}M$ from the original compound's 12.3 ${\mu}M$ value. $CC_{50}$ was higher than 77 ${\mu}M$ for all compounds tested, suggesting that they are useful candidates for anti-HCV therapy.

• Korean Journal of Clinical Pharmacy
• /
• v.22 no.1
• /
• pp.81-86
• /
• 2012

This study was aimed to examine the prescribing patterns of antivirals in outpatients with chronic hepatitis B (CHB), using National Health Insurance adjudicated claims data (total 1,426,065 claims) dated March 19, 2008 submitted from nationwide healthcare providers to Health Insurance Review and Assessment Service. From the data, there were 2,965 claims with CHB diagnosis (ICD-10 code B18.0 and B18.1), and 44.2% (1,311 claims) of the CHB related claims included antivirals such as lamivudine, clevudine, adefovir and entecavir. Lamivudine, adefovir, clevudine and entecavir shared 54.9%, 19.9%, 13.2% and 11.9%, respectively, among antiviral prescriptions. Adefovir and entecavir 1mg presumed as the 2nd line therapy for HBV resistant cases were shared 23.3% of overall antiviral prescriptions. There were statistically significant difference in prescription patterns according to age and institution type: Lamivudine usage was higher in younger (< 20 years old) and older age group (> 70 years old) than the others (p = 0.016), and adefovir and entecavir, which were relatively newer antivirals, had higher prescription rates in higher level of institutions such as tertiary hospitals than the others (p < 0.001). This study would be of help to make an appropriate drug therapy plan for patients with CHB.