• Title/Summary/Keyword: Anti-hepatitis B virus

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Chronic HBV Infection in Children: The histopathologic classification and its correlation with clinical findings (소아의 만성 B형 간염: 새로운 병리조직학적 분류와 임상 소견의 상관 분석)

  • Lee, Seon-Young;Ko, Jae-Sung;Kim, Chong-Jai;Jang, Ja-June;Seo, Jeong-Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.1 no.1
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    • pp.56-78
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    • 1998
  • Objective: Chronic hepatitis B infection (CHB) occurs in 6% to 10% of population in Korea. In ethinic communities where prevalence of chronic infection is high such as Korea, transmission of hepatitis B infection is either vertical (ie, by perinatal infection) or by close family contact (usually from mothers or siblings) during the first 5 years of life. The development of chronic hepatitis B infection is increasingly more common the earlier a person is exposed to the virus, particularly in fetal and neonatal life. And it progress to cirrhosis and hepatocellular carcinoma, especially in severe liver damage and perinatal infection. Histopathology of CHB is important when evaluating the final outcomes. A numerical scoring system which is a semiquantitatively assessed objective reproducible classification of chronic viral hepatitis, is a valuable tool for statistical analysis when predicting the outcome and evaluating antiviral and other therapies. In this study, a numerical scoring system (Ludwig system) was applied and compared with the conventional histological classification of De Groute. And the comparative analysis of cinical findings, family history, serology, and liver function test by histopathological findings in chronic hepatitis B of children was done. Methods: Ninety nine patients [mean age=9 years (range=17 months to 16 years)] with clinical, biochemical, serological and histological patterns of chronic HBV infection included in this study. Five of these children had hepatocelluar carcinoma. They were 83 male and 16 female children. They all underwent liver biopsies and histologic evaluation was performed by one pathologist. The biopsy specimens were classified, according to the standard criteria of De Groute as follows: normal, chronic lobular hepatitis (CLH), chronic persistent hepatitis (CPH), mild to severe chronic active hepatitis (CAH), or active cirrhosis, inactive cirrhosis, hepatocellular carcinoma (HCC). And the biopsy specimens were also assessed and scored semiquantitatively by the numerical scoring Ludwig system. Serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (IgG, IgM), and HDV were measured by radioimunoassays. Results: Male predominated in a proportion of 5.2:1 for all patients. Of 99 patients, 2 cases had normal, 2 cases had CLH, 22 cases had CPH, 40 cases had mild CAH, 19 cases had moderate CAH, 1 case had severe CAH, 7 cases had active cirrhosis, 1 case had inactive cirrhosis, and 5 cases had HCC. The mean age, sex distribution, symptoms, signs, and family history did not differ statistically among the different histologic groups. The numerical scoring system was correlated well with the conventional histological classification. The histological activity evaluated by both the conventional classification and the scoring system was more severe as the levels of serum aminotransferases were higher. In contrast, the levels of serum aminotransferases were not useful for predicting the degree of histologic activity because of its wide range overlapping. When the histological activity was more severe and especially the cirrhosis more progressing, the prothrombin time was more prolonged. The histological severity was inversely related with the duration of seroconversion of HBeAg. Conclusions: The histological activity could not be accurately predicted by clinical and biochemical findings, but by the proper histological classification of the numerical scoring system for the biopsy specimen. The numerical scoring system was correlated well with the conventional histological classification, and it seems to be a valuable tool for the statistical analysis when predicting the outcome and evaluating effects of antiviral and other therapies in chronic hepatitis B in children.

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Prevalence of Aflatoxin Induced p53 Mutation at Codon 249 (R249s) in Hepatocellular Carcinoma Patients with and without Hepatitis B Surface Antigen (HBsAg)

  • Chittmittrapap, Salyavit;Chieochansin, Thaweesak;Chaiteerakij, Roongruedee;Treeprasertsuk, Sombat;Klaikaew, Naruemon;Tangkijvanich, Pisit;Komolmit, Piyawat;Poovorawan, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7675-7679
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    • 2013
  • Background: A missense mutation in exon 7 (R249S) of the p53 tumor suppressor gene is characteristic of aflatoxin B1 (AFB1) exposure. AFB1 is believed to have a synergistic effect on hepatitis virus B (HBV) carcinogenesis. However, results of studies comparing R249S prevalence among patients are conflicting. The aim of this study was to determine the prevalence of the R249S mutation in hepatocellular carcinoma (HCC) patients with or without positive HBsAg. Materials and Methods: Paraffin embedded liver tissues were obtained from 124 HCC patients who underwent liver resection and liver biopsy in King Chulalongkorn Memorial Hospital. Restriction fragment length polymorphism (RFLP) was utilized to detect the R249S mutation. Positive results were confirmed by direct sequencing. Results: Sixty four (52%) patients were positive for HBsAg and 18 (15%) were anti-HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were confirmed to be R249S positive by Sanger sequencing (AGG to AGT). Out of these 10, six were HBsAg positive, and out of the remaining 4, two were anti-HCV positive. The R249S prevalence among HCC patients with positive HBsAg was 9.4% compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation were younger ($55{\pm}10$ vs $60{\pm}13$ year-old) and tended to have a more advanced Edmonson-Steiner grade of HCC, although differences did not reach statistical significance. Conclusions: Our study shows moderate prevalence of aflatoxin B1-related p53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status was not associated with R249S prevalence.

The Effects of Maternal HBs antigenemia on the Neonatal Health (산모(産母)의 B형 간염(肝炎) Virus 보유(保有)가 신생아(新生兒) 건강(健康)에 미치는 영향(影響))

  • Park, Jung-Han;Yoon, Sung-Do;Kim, Chang-Youn;Lee, Sung-Kwan
    • Journal of Preventive Medicine and Public Health
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    • v.17 no.1
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    • pp.47-55
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    • 1984
  • To study the risk factors associated with maternal HBsAg carrier and the effects of maternal HBs antigenemia on the neonatal health, sera of 729 pergnant women admitted to the Keimyung University Hospital for delivery during the period of February 1-May 30. 1982 were tested for HBsAg by RPHA method and for anti-HBs by PHA method. Among them 43 women (5.9%) had HBsAg and 246 women (33.7%) had anti-HBs giving an infection rate of 39.6%. The interview data for 43 HBsAg positive mothers and randomly selected 210 HBsAg negative mothers showed a statistically significant association between acupuncture history and HBsAg positive rate (p<0.005) which suggest that acupuncture might have contributed significantly to the propagation of viral hepatitis in Korea. The living standard of HBsAg positive mothers was generally lower than that of HBsAg negative mothers which supports the hypothesis that environmental factors are associated with viral hepatitis B infection. None of the 43 neonates born to HBsAg positive mothers had HBsAg in their cord blood. Three months after birth, 35 out of 43 infants were retested and only one infant became HBsAg positive. At six months of age, 32 out of 35 infants were retested and none of them were HBsAg positive except the same infant who was positive at three months. Among 20 control infants of HBsAg negative mothers, all of them were HBsAg negative at three and six months follow-up. These findings are not consistent with the supposition that perinatal infection is a main route of viral hepatitis B transmission in south-east Asia including Korea. HBsAg positive mothers had significantly higher rate of premature delivery (27.9%) than HBsAg negative mothers (11.7%) (p<0.05). Also, the low birthweight incidence rate was higher among HBsAg positive mothers (23.3%) than negative mothers (14.1%) but this was not statistically significant (P=0.16). The premature rupture of membrane was more frequent among HBsAg positive mothers (25.5%) than negative mothers (11.1%) (p<0.05). There were no significant differences in the stillbirth rate and incidence of congenital anomalies between HBsAg positive and negative groups. It was not clarified in this study due to small sample size whether higher incidence of premature delivery and premature rupture of membranes among HBsAg positive mothers was due to HBs antigenemia per so or their lower living standard than HBsAg negative mothers.

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Induction of Demyelination of Neuronal cells by Sindbis Virus (Sindbis Virus에 의한 뉴런세포의 탈수초의 유도)

  • Sa, Young-Hee;Kim, Hyun Joo;Kweon, Tae Dong;Kim, Ji-Young;Lee, Bae Hwan;Hong, Seong-Karp
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2018.05a
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    • pp.584-587
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    • 2018
  • Many viruses including mouse hepatitis virus, corona, measles, and sidbis viruses are known as causative virus of inducing demyelination which means destruction of myelination in nervous system of mice. The purpose of this study is to investigate processing of myelination by co-culture of Schwann cells and neuronal cells and demyelination induced by infection of sindbis virusin rat. Schwann cells and neuronal cells from dorsal root ganglion (DRG) in embryos (E16) of rat were cultured in vitro respectively. The purified neuronal cells with anti-mitotic agents and purified Schwann cells were co-cultured. After that, infection of sindbis virus into this myelinated co-culture system was performed. Myelination and demyelination process were observed using antibody of myelin basic protein meaning presence of myelination.We identified myelination and demyelination processing using antibody of peripheral myelin protein 22 (PMP 22) meaning presence of myelinated neuron. This study was supported by the Basic Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015R1C1A1A01053484 and 2017R1A2B3005753).

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RNAi and miRNA in Viral Infections and Cancers

  • Mollaie, Hamid Reza;Monavari, Seyed Hamid Reza;Arabzadeh, Seyed Ali Mohammad;Shamsi-Shahrabadi, Mahmoud;Fazlalipour, Mehdi;Afshar, Reza Malekpour
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7045-7056
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    • 2013
  • Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

Donor Specific Antibody Negative Antibody-Mediated Rejection after ABO Incompatible Liver Transplantation

  • Lee, Boram;Ahn, Soomin;Kim, Haeryoung;Han, Ho-Seong;Yoon, Yoo-Seok;Cho, Jai Young;Choi, Young Rok
    • Korean Journal of Transplantation
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    • v.32 no.4
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    • pp.108-112
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    • 2018
  • Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation. According to the 2016 Banff Working Group on Liver Allograft Criteria for the diagnosis of acute AMR, a positive serum donor specific antibody (DSA) is needed. On the other hand, the clinical significance of the histological findings of AMR in the absence of DSA is unclear. This paper describes a 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. Pre-operative DSA and cross-matching were negative. After transplantation, despite the improvement of the liver function, acute AMR was observed in the protocol biopsy on postoperative day 7; the cluster of differentiation 19+ (CD19+) count was 0% and anti-ABO antibody titers were 1:2. This paper presents the allograft injury like AMR in the absence of DSA after ABOi living donor liver transplantation with low titers of anti-ABO antibody and depleted serum CD19+ B cells.

An OTHBVS Cell Line Expresses the Human HBV Middle S Protein

  • Park, Sung-Gyoo;Guhung Jung
    • Journal of Microbiology
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    • v.37 no.2
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    • pp.86-89
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    • 1999
  • An OTHBVS cell line from HepG2 was established. This cell line stably expresses the human hepatitis B virus (HBV) middle S protein that includes the preS2 region which is important for HBV particle entry into the hepatocyte. To establish this cell line, the middle S open reading frame (ORF), with a promoter located in the 5' region and enhancer located in the 3' region, was cloned downstream from the metallothionine (MT) promoter of the OT1529 vector. In this vector, expression of the middle S protein was constructed to be regulated by its own promoter and enhancer. Expression of the large S protein which contains the preS1 region in addition to the middle S protein was designed to be regulated by the MT promoter. When extracts of OTHBVS cells were examined with an S protein detection kit (RPHA, Korea Green Cross Co.), an S protein was detected. Total mRNA of OTHBVS cell examined by northern blot analysis with an S ORF probe revealed small/middle S transcripts (2.1 kb). When the MT promoter was induced by Zn, large S transcripts (2.4 kb) were detected. The GP36 and GP33 middle S proteins were presumably detected, but large S proteins were not detected by immunostain analysis using anti-preS2 antibody.

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Comparision of Hepatitis B Virus Markers in the Serum and the Cerebrospinal Fluid (혈청과 뇌척수액에서 B형 간염 바이러스 표식자 존재의 비교)

  • Suh, Sang-Dug;Kim, Seong-Min;Lee, Jun;Park, Gun-Ju;Do, Hyun-Cheal;Byun, Yeung-Ju
    • Journal of Yeungnam Medical Science
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    • v.12 no.2
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    • pp.282-291
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    • 1995
  • We investigated HBV markers in serum and cerebrospinal fluid of 50 subjects with neurologic disorders or other disorders, who visited Dept. of neurology, college of medicine, Yeungnam University, from April-1 to August-31 1994 and were performed cerebrospinal fluid analysis to investigate the detection rate of HBV markers in cerebrospinal fluid and the possibility of neurologic disorders associated with HBV infection. The results were as follows. The positivity of HBsAg and HBV prevalence rate in serum were 6(12.0%) and 37(74.0%). The number of patient with HBsAg, only anti-HBV and no markers were 6(12.0%), 31(62.0%) and 13(26.0%), respectively. The positivity of HBsAg and HBV prevalence rate in cerebrospinal fluid were 3(6%) and 18(36.0%). The number of patient with HBsAg, only anti-HBV and no markers were 6(100.0%), 12(38.7%) and 0(0.0%) respectively. The number of patient with virus associated diseases(VAD) and non virus associated diseases(NVAD) were 26(52%) and 24(48%). The HBV prevalence rate in serum of VAD and NVAD groups were 88.5% and 58.3% (p<0.05). The HBV prevalence rate in CSF of VAD and NVAD groups were 53.8% and 16.7%(P<0.05). The HBV prevalence rate in serum and CSF of VAD and NVAD groups were 60.9% and 28.6%. Aa a conclusion, the HBV markers in the CSF were partially detected at the presence of the HBV markers in serum. The prevalance rate of HBV in the CSF was increased at the HBsAg positive in the serum and the serum and the CSF was significantly increased at the VAD group than the NVAD group.

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Effect of ${\alpha}$-Interferon Treatment on Serum ALT Levels in Patients with Chronic Hepatitis C (만성 C형 간염에 대한 ${\alpha}$-interferon 치료 후 ALT치의 변화)

  • Lee, Heon-Ju
    • Journal of Yeungnam Medical Science
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    • v.10 no.1
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    • pp.190-196
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    • 1993
  • The prognosis of chronic hepatitis C is very variable. In some, the disease is progressive and cirrhosis can develop from chronic hepatitis C. Hepatitis C virus(HCV) may act as a trigger towards hepatocellular carcinoma in patients with cirrhosis. Interferon has been used for the treatment of chronic hepatitis C in abroad, 16 patients with chronic C liver disease were treated with ${\alpha}$-interferon (alfa-2b; "Intron A" Schering Corp. Kenilworth. NJ). All patients were given ${\alpha}$-interferon in subcutaneous doses of 3 million units three times weekly for 1 to 9 months. During therapy, CBC and ALT levels were checked weakly to monthly. After therapy, patients were followed for 1 to 8 months. Among 16 patients treated with ${\alpha}$-interferon, progressive decrease of ALT levels was observed in 14(87.5%). In 11 patients(68.8%), ALT levels fell into the normal range during therapy, and in 9 of 11, within one month after therapy, 6 months after the completion of therapy in 4 of 9 patients(44.4%) whose ALT levels were in the normal range, ${\alpha}$-interferon seems to have effect in controlling disease activity in patients with chronic hepatitis C. But the changes in the usage of ${\alpha}$-interferon, dose and duration, long term follow up and more convenient and simple tests for HCV detection are recommended for the better effect and the exact evaluation on the effect of ${\alpha}$-interferon therapy in patients with chronic hepatitis C.

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The Effect of Herbs on Inhibition of HBeAg Production in HepG2.2.15 Cell line (수종의 한약재가 HepG 2.2.15 Cell의 HBeAg발현 억제에 미치는 효과(效果))

  • Woo, Hong-Jung;Lee, Jang-Hoon;Kim, Young-Chul
    • The Journal of Internal Korean Medicine
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    • v.20 no.1
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    • pp.122-132
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    • 1999
  • Purpose : Hepatitis B virus DNA transfected cell line(HepG2.2.15) was cultured to evaluate the effect of herbs on the expression of HBeAg and the replication of HBV. HepG2.2.15 produces HBV particles as well as viral proteins into cell culture media. Methods : Extracts of herbs were adminitered to the cells on the proper concentration. Culture media was collected 48 hours after the herbal administration and HBeAg level in the media was examined by ELISA method. To confirm that the anti-viral effect was not due to direct cytotocixity of the extracts, normal cell proliferation was shown by cell counting. And as of the interference in protein synthesis of HepG2.2.15 by herb-extracts, we used the result of study that we performed before by ${\alpha}FP$ assay using EIA method. Results& Conclusion : Herb medicines like 地楡(Sanguisorbae Radix) and 覆盆子(Rubi Frusctus) showed significant inhibitory effect on HBeAg expression at p<0.01 and 五味子(Acanthopanacis Cortex) at p<0.05. Whereas, though some herbs such as ?草根(Rubiae Radix), 山査(Crataegii Fructus), 白芍藥(Paeoniae Radix Alba), and 大黃(Rhei Radix et Rhizoma) showed the tendecy to suppress HBeAg. most of them were not significant statistically. From the above, we could conclude that those herb medicines can be applied to patients effectively and further studies on effective fraction of some herbs are thought to be needed.

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