• Journal of the Korea Institute of Military Science and Technology
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• v.27 no.1
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• pp.107-115
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• 2024

Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics. Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3- cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival. The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.63-73
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• 2012

Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children.

• YAKHAK HOEJI
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• v.49 no.2
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• pp.151-155
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• 2005

For decades, the demand for new antiviral strategies, especially in hepatitis, has increased markedly due to its devastating pathogenic outcome, In the present study, we examin ed the antiviral effect of the combination of amantadine and biphenyl dimethyl dicarboxylate (DDB) in HepG2 2.2.15, which is transfected with HBV DNA. The study demonstrated that the combination not the single treatment may have an anti-HBV effect through a synergism of antiviral, anti-inflammatory and cytoprotective activities in STAT1 ${\alpha}$, 6-16 gene, and pro-inflammatory components such as nitric oxide and IL-1${\beta}$ expression. In addition, hepatitis B surface and core gene expression were examined as a final end point for the anti-HBV activities, which was also significantly suppressed comparing to normal control (p<0.01).

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

• Korean Journal of Clinical Pharmacy
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• v.26 no.3
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• pp.220-229
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• 2016

Background: The treatment goal for patients with chronic hepatitis B infection is to prevent progression of the disease to cirrhosis and hepatocellular carcinoma. Current therapies include standard and pegylated interferon-alfa and nucleoside/nucleotide analogues: lamivudine, adefovir, entecavir, telbivudine, clevudine, and tenofovir. This study aims to analyze changes in the prescribing patterns of chronic hepatitis B (CHB) medications in South Korea between 2013 and 2014. Methods: A cross-sectional study was conducted using National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 and 2014. Patients with CHB were identified with Korean Standard Classification of Diseases code-6 (B18.0 and B18.1) and those who were maintaining active prescriptions with CHB medications covering the index date (December $1^{st}$, each year) were included. The utilization of antiviral therapy was investigated during 2013 and 2014. Results: A total of 4,204 and 4,552 patients in 2013 and 2014 respectively, were included in the analysis. The proportion of male patients was two of third and the patients 41-60 years old accounted for 60% of all analyzed patients. The most utilized drug was entecavir (55.1% in 2013 and 44.8% in 2014) and the second most utilized drug was tenofovir in both years (18.8% in 2013 and 29.0% in 2014). The percentage of combination therapy was 13.6% and 13.1% in 2013 and 2014, respectively. The proportion of tenofovir prescriptions was increased in 2014 compared with 2013. Conclusion: With the development of new drugs and the changes in clinical practice guidelines, the prescription pattern of the antiviral agents for patients with CHB has changed. The rate of utilization of tenofovir has increased.

• The Journal of Internal Korean Medicine
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• v.37 no.3
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• pp.529-538
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• 2016

Objectives: The purpose of this case study is to report the efficacy and safety of treatment with Korean medicine of a patient with HBeAg-positive chronic viral hepatitis B.Methods: The patient took Korean medicine (mainly Injinchunggan-tang-gamibang) from July 20th, 2010, to March 14th, 2016, without any antiviral or interferon therapy. Changes to laboratory records, abdomen ultrasonography, and clinical symptoms were reviewed.Results: The laboratory records showed that AST, ALT, and HBV DNA had decreased to normal ranges, and HBeAg showed seroconversion. Clinical symptoms also improved after taking Korean medicine.Conclusion: The results suggest that treatment with Korean medicine and without antiviral or interferon therapy could be effective for HBeAg-positive chronic hepatitis B.

• Molecules and Cells
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• v.40 no.6
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4291-4295
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• 2015

Background: Chemokines and their receptors influence carcinogenesis and cysteine-cysteine chemokine receptor 5 (CCR5) directs spread of cancer to other tissues. A 32 base pair deletion in the coding region of CCR5 that might alter the expression or function of the protein has been implicated in a variety of immune-mediated diseases. The action of antiviral drugs being proposed as adjuvant therapy in cancer is dependent on CCR5 wild type status. In the present study, distribution of CCR5${\Delta}32$ polymorphism was assessed in North Indian esophageal cancer patients to explore the potential of using chemokine receptors antagonists as adjuvant therapy. Materials and Methods: DNA samples of 175 sporadic esophageal cancer patients (69 males and 106 females) and 175 unrelated healthy control individuals (69 males and 106 females) were screened for the CCR5${\Delta}32$ polymorphism by direct polymerase chain reaction (PCR). Results: The frequencies of wild type homozygous (CCR5/CCR5), heterozygous (CCR5/${\Delta}32$) and homozygous mutant (${\Delta}32/{\Delta}32$) genotypes were 96.0 vs 97.72%, 4.0 vs 1.71% and 0 vs 0.57% in patients and controls respectively. There was no difference in the genotype and allele frequencies of CCR5${\Delta}32$ polymorphism in esophageal cancer patients and control group. Conclusions: The CCR5${\Delta}32$ polymorphism is not associated with esophageal cancer in North Indians. As the majority of patients express the wild type allele, there is potential of using antiviral drug therapy as adjuvant therapy.

• Toxicological Research
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• v.33 no.4
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• pp.343-350
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• 2017

Lamivudine belongs to the set of antiviral agents effective against hepatitis B virus infection. Given case reports on liver injuries after certain antiviral agent treatments, this study examined the effects of lamivudine on alanine aminotransferase (ALT) and total bilirubin (TB) using a medical system database. A total of 1,321 patients taking lamivudine alone or with others were evaluated using laboratory hits in an electronic medical system at Seoul National University Hospital from 2005 through 2011. The patients were grouped according to prior ALT results: G#1, ALT < 40 IU/L; G#2, 40 IU/L ${\leq}$ ALT < 120 IU/L; G#3, 120 IU/L ${\leq}$ ALT < 240 IU/L; and G#4, ALT ${\geq}$ 240 IU/L. In G#1 and G#2 patients, lamivudine or adefovir treatment decreased ALT and TB compared to prior values. In G#3 and G#4 patients with three times the upper limit of normal (ULN) ${\leq}$ ALT < 15 times the ULN, both ALT and TB were decreased after treatment with lamivudine alone, or adefovir following lamivudine therapy, indicating that lamivudine therapy ameliorated liver functions. However, in G#4 patients who experienced severely advanced hepatitis (ALT ${\geq}$ 15 times the ULN, or ${\geq}$ 600 IU/L), lamivudine augmented TBmax ($6.3{\rightarrow}13.3mg/dL$) despite a slight improvement in ALT ($839{\rightarrow}783IU/L$), indicative of exacerbation of bilirubinemia. Patients who used adefovir after lamivudine also showed a high incidence of hyperbilirubinemia when they experienced severely advanced hepatitis. Treatment with adefovir alone did not show the effect. In conclusion, lamivudine may increase the risk of hyperbilirubinemia in patients with severely advanced hepatitis, implying that caution should be exercised when using lamivudine therapy in certain patient populations.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.451-457
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• 2005

Experimental studies have demonstrated that the triple combination of amantadine (A)/ ursodeoxycholic acid (UDCA, U)/ biphenyl dimethyl dicarboxylate (DDB, D) might have a preferential antiviral effect compared with that observed in interferon-induced antiviral signal pathways, such as those of $STAT1\alpha$ and the 6-16 genes. To confirm the results, this study examined whether th signal transduction for the antiviral activity in HepG2 2.2.15 was induced dependently or independently of interferon. To accomplish this, the correlation between the $STAT1\alpha$ and 6-16 genes, and nitric oxide, for the mediation of the antiviral activity was assessed. The increase in nitric oxide in the UDCA groups suggests that the inhibition of viral gene replication was enhanced by the amantadine combinations (AU and AUD), and might be more effective if incubated for longer periods. It was found that $STAT1\alpha$ was activated by the amantadine combination, although to a lesser extent than that of $interferon-\alpha$, and the primary endpoints examined for the inhibition of gene expression (HBsAg and HBcAg) were remarkably well regulated. This suggests that the amantadine triple, or at least the double, combination had better clinical benefits than those of $IFN-\alpha$ and the nucleoside analogue single treatment. This demonstrates that the amantadine combination might be a substitute for the existing HBV therapy if the results of in vivo and in vitro studies concur.