• 한국임상약학회지
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• 제27권3호
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• pp.150-160
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• 2017

Background: Recently, a fixed combination of grazoprevir and elbasvir (GE) has been introduced to the arsenal of chemotherapeutics to fight against this virus. The study aimed to provide information on the efficacy and safety of GE for the treatment of HCV infection by performing a meta-analysis of literature data. Methods: PubMed and EMBASE database searches were conducted. Among the literature retrieved, pivotal Phase III clinical studies were analyzed. Statistical analysis of the data was performed by RevMan. Results: Four pivotal Phase III clinical studies compared the efficacy and safety of GE. When HCV patients were treated with GE for 12 weeks, the sustained virologic response, defined as the viral RNA level below the lower limit of quantification at 12 weeks after the cessation of therapy (SVR12), was 94.7%. The clinical advantage of GE involves its use by patients with cirrhosis and/or renal failure without dose adjustment. If the genotype (GT) of the causative virus was GT1a with NS5A polymorphism or GT4 with resistance to peginterferon/ribavirin, treatment with GE plus ribavirin for 16 weeks resulted in a better outcome compared to treatment with GE alone for 12 weeks. Adverse events reported during the four clinical studies were 71.09% in the GE arms and it was 76.61% in the non-GE arms, with the most frequent events being mild central nervous system symptoms. Conclusion: GE was generally safe and effective for the treatment of HCV infection. However, since HCV mutates very rapidly and becomes resistant to antiviral agents, long-term monitoring should be mandatory.

• Gut and Liver
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• 제12권6호
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• pp.694-703
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• 2018

Background/Aims: Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. Methods: All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR12) after treatment, and adverse reactions were compared between the groups. Results: A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. Conclusions: In a real-world setting, DAA regimens have lower SVR12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.

• The Korean journal of internal medicine
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• 제39권4호
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• pp.577-589
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• 2024

Background/Aims: Four high-genetic barrier nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB), namely entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and besifovir dipivoxil maleate (BSV), have been established. The aim of this study is to investigate the efficacy of four high-genetic barrier NAs using a network meta-analysis of randomized trials and propensity score-matched cohorts. Methods: Systematic search was performed using PubMed, Cochrane library, and EMBASE and included randomized controlled trials and cohort studies that used propensity score matching. Studies on treatment-naïve CHB patients treated with ETV, TDF, TAF, or BSV were included. Outcomes included alanine aminotransferase normalization and hepatitis B e antigen seroclearance at week 48 and undetectable hepatitis B virus DNA at weeks 48 and 96. Network meta-analysis was performed to synthesize the results. Results: In total, 15,000 patients from 16 studies were included. In terms of 48- and 96-week virologic response (VR), TDF outperformed ETV with statistical significance (48 weeks: odds ratio [OR], 1.38; p < 0.001; 96 weeks: OR, 1.57; p = 0.004). ETV was ranked first for 48-week biochemical response (BR) and outperformed TDF (OR, 0.76; p = 0.028). In the sensitivity analyses, 48-week VR from randomized-controlled trials were compiled, and the same trend toward the superiority of TDF over ETV was found (OR, 1.51; p = 0.030). Conclusions: Four high-genetic barrier NAs were compared, and TDF was more likely to achieve a VR after 48 weeks, while ETV provided a superior BR after 48 weeks.

• 대한간학회지
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• 제24권4호
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• pp.351-357
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• 2018

The advent of novel, direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) infection has revolutionized its treatment by producing a sustained virologic response of more than 95% with few side effects and no comorbidities in the general population. Until recently, ideal DAA regimens have not been available to patients with severe renal impairment and end-stage renal disease because there are limited data on the pharmacokinetics, safety, and efficacy of treatment in this unique population. In a hemodialysis context, identifying patients in need of treatment and preventing HCV transmission may also be a matter of concern. Recently published studies suggest that a combination of paritaprevir/ritonavir/ombitasvir and dasabuvir, elbasvir/grazoprevir, or glecaprevir/pibrentasvir successfully treats HCV infection in chronic kidney disease stage 4 or 5 patients with or without hemodialysis.

• Journal of Microbiology and Biotechnology
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• 제28권1호
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• pp.165-174
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• 2018

Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma. However, a direct link between KSHV infection and glioblastoma is currently not known. In this study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV to establish an in vitro cell model for KSHV-infected glioblastoma cells and glioma stem-like cells in order to identify virologic outcomes that overlap with markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs were successfully established. Additionally, using these cell models, we found that KSHV infection modulates the proliferation of glioma stem-like cells.

• 대한미생물학회지
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• 제20권1호
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• pp.115-125
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• 1985

Hemorrhagic fever with renal syndrome (HFRS) is a debilitating disease of humans caused by Hantaan virus (HV), the prototype member of a newly proposed genus of Bunyaviridae. Studies of HV pathogenesis have been limited by the absence of a well defined model for a virus-induced disease state. In an attempt to devise a model for HV pathogenesis in laboratory rodents, newborn outbred suckling ICR mice were shown to be uniformly susceptible to lethal infection with non- mouse adapted HV by intracerebral (IC), intraperitoneal (IP), intramuscular (IM), and subcutaneous (SC) inoculation routes. Clinical coures, mean time to death, and fatal outcome were age-dependent. With an inoculum of 10 $LD_{50}$, mortality was 100% in mice infected within 72h of birth, but declined to 50% by 7 days. By 2-2.5 weeks, animals developed complete resistance to clinical disease. Virus was consistently detected in serum by day 6 post-infection in IC- and IP- inoculated animals, and reached peak levels of $10^5\;PFU/ml$ by day 8 Mice infected IM and SC showed delays in onset of viremia, but achieved similar titers. Immunofluorescent antibody appeared by 17-18 days, and neutralizing antibody by 15 days, in all experimental groups. Two of 8 inbred mouse strains were identified as resistant to clinical disease : SJL/J and A/J. Manipulation of this model will allow investigation of natural rodent pathogenesis with HV, as well as offer insight into disease mechanisms and therapy of HFRS.

• 대한세포병리학회지
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• 제7권2호
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• pp.192-196
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• 1996

The principal significance of the urothelial changes caused by polyomavirus activation is in an erroneous diagnosis of urothelial cancer; however, the clue to their benign nature is the smooth structureless nuclear configuration and the relative paucity of affected cells. Though virologic studies and electron microscopy are usually needed to firmly establish the diagnosis, cytology is the most readily available and rapid means of establishing a presumptive diagnosis of human polyomavirus infection. A urine specimen of a 24-year-old man with hemorrhagic cystitis beginning two months after bone marrow transplantation for acute myeloblastic leukemia(M2) was submitted for cytologic evaluation. Cytologic findings revealed a few inclusion-bearing epithelial cells intermingled with erythrocytes, neutrophils, lymphocytes, and macrophages. Most of the inclusion-bearing fells had large, round to ovoid nuclei almost completely filled with homogeneous dark, basophilic inclusion. The chromatin was clumped along the periphery and the cytoplasm was mostly degenerated. The other cells exhibited irregular inclusions attached to the nuclear membrane surrounded by an indistinct halo. These findings were consistent with polyomavirus infection.

• Pediatric Infection and Vaccine
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• 제25권2호
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• pp.72-81
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• 2018

목적: 만성 B형 간염으로 치료가 필요하였던 소아청소년 중 lamivudine을 투여하면서 전향적으로 관찰한 자료를 검토하여 약제에 대한 치료 효과를 파악하고자 하였다. 방법: 2003년 6월 1일부터 2015년 10월 30일까지 가톨릭대학교 성빈센트병원 소아청소년과를 방문하여 만성 B형 간염의 첫 치료로 lamivudine (3 mg/kg, 최대 100 mg)을 3개월 이상 투여한 55명을 대상으로 하였다. 약제 투여 후 1개월, 3개월째, 이후는 매 3개월마다 B형 간염 바이러스(hepatitis B virus [HBV]) 표지자, HBV-DNA, 간기능을 추적하였다. 치료 중단은 alanine aminotransferase (ALT) 정상, HBeAg 음성 및 anti-HBe 양성 결과가 처음 발견된 시기로부터 12개월 후로 정하였다. 결과: 연구군은 남자가 31명(56.4%), 여자가 24명(43.6%)이었고, 약제의 첫 투여 연령은 평균 8.1세, 투여기간은 평균 23.4개월이었다. ALT 정상화는 98.2% (54/55), HBeAg 양성에서 anti-HBe 양성으로의 혈청 전환은 70.6% (36/51), HBsAg 소실은 10.9% (6/55)에서 이루어졌는데 모두 7세 미만 연령이었다. 약제 투여 6개월 시 HBV-DNA <2,000 IU/mL 바이러스 반응은 78.7% (37/47)이었고, 약제 중단 12개월 후에도 바이러스 반응이 유지되는 경우는 87.2% (34/39)이었다. Lamivudine 약제 내성이 발현된 경우는 16.4% (9/55)이었다. 결론: 만성 B형 간염을 가진 국내 소아청소년에 대한 lamivudine의 치료 효과는 유사한 외국 연구 결과에 비해 더 우수하였다. 새로 권고되고 있는 다른 항바이러스제 치료에 대한 국내에서의 지속적인 연구도 필요할 것으로 판단된다.

• 대한수의학회지
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• 제30권2호
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• pp.177-186
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• 1990

To investigate the etiology, pathogenicity and virological properties of NYJ-1-87 strain of Aujeszky's disease virus (ADV) that was isolated from the diseased piglet in Korea, the virus at $10^{6.0}TCID_{50}/0.1ml$ was inoculated intranasally and subcutaneously into 30 to 35 days-old piglets. Results obtained through the experiments were summarized as follows. 1. Ten of the infected piglets were clinically observed for 15 days. On the 2nd day post-inoculation(pi), the signs of pyrexia, anorexia and convulsion were noted. On the 4th to 7th days pi, nervous signs of incoordination and intermittent spasm were shown in the most of piglets, and one out of 5 piglets infected intranasally was died with severe nervous signs at the 7th day pi. The signs became relieved on the 8th day pi and all of remainder were completely recovered on the 13th to 14th days pi. 2. In hematological study, prominent decrease in the number of total leukocyte and lymphocyte was shown in the ADV-infected piglets on the 6th day pi. On the 8th day pi, the cell numbers were slightly increased and returned to normal level on the 10th day pi. 3. Viral excretion of the ADV-inoculated piglets was examined by swabbing of nasal and oral cavities, and rectal feces. During the periods of the 3rd to 11th days pi, the virus was excreted intermittently from nasal and oral cavities, and rectal feces. The nasal excretions were shown the highest virus concentration of $10^{5.2}TCID_{50}/0.1ml$ at the 5th day pi. 4. Recovery of the inoculated virus from various organs of the piglets that were died or experimentally slaughtered was attempted, and the virus was isolated from the tissues of brain and tonsil by the cultured cell-inoculation method. The highest recovery rate was noted in the tonsil. By indirect immunofluorescence antibody assay using ADV-monoclonal antibody, the viral antigens were detected in tissues of spleen and liver as well as brain and tonsil on the 7th to 9th days pi. The virus was not isolated from blood and the tissues of lung and kidney throughout the experiments. 5. Titers of virus neutralizing antibody in the piglets experimentally infected with ADV became increased after the 6th to 9th days pi in both of intranasal and subcutaneous inoculation showing the highest titers of 64 to 128 on the 29th day pi. When the antibody levels were measured by radial immunodiffusion enzyme assay, the reactive diameter was enlarged to be positive after the 4th to 6th days pi in both of intranasal and subcutaneous inoculation showing the largest diameter of 13 to 14mm on the 29th day pi.