• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.14 no.1
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• pp.59-66
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• 2011

Purpose: We previously reported that concurrent reactivation of latent Epstein-Barr virus (EBV) in children with hepatitis A virus (HAV) infection is common and EBV reactivation with HAV infection adversely affects the clinical features of hepatitis. However, the incidence of concurrent reactivation was not accurate because the detection of EBV reactivation was based on serologic methods. Therefore, we studied the effects of polymerase chain reaction (PCR)-proven EBV reactivation, thus a more precise concurrence, on acute HAV infection in children. Methods: PCR were conducted in 34 patients, who had enrolled previous study and diagnosed with acute HAV infection between January 2008 and June 2010. Their medical records were reviewed. Results: Among 34 patients with acute HAV infection, 12 patients (35.3%) had EBV reactivation which was proven using serologic and molecular biologic techniques. There were significant differences in the peak levels of AST and ALT between the reactivated and non-reactivated groups (p=0.001 and p<0.001, respectively). The duration of full recovery from hepatitis was more prolonged in the reactivated group (p<0.001). Clinical parameters, such as serum protein (p<0.001) and albumin concentrations (p<0.001), atypical lymphocyte count (p=0.001), prothrombin time-international normalized ratio (PT-INR, p<0.001), and splenomegaly (p<0.001), showed significant differences. The clinical features in the reactivated sub-group >10 years of age revealed more liver dysfunction compared to the non-reactivated sub-group. A comparison with a previous study was performed. Conclusion: PCR-proven reactivation of latent EBV in children with HAV infection is common and EBV reactivation with HAV infection adversely affects the clinical features of hepatitis, especially in older children.

• Korean Journal of Poultry Science
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• v.37 no.3
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• pp.255-263
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• 2010

Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) is an acute viral disease usually found in broilers aged from 3 to 5 weeks and causes up to 75% mortality. Among the 12 serotypes of fowl adenovirus group 1, serotype-4 (FAdV-4) was identified as a primary agent of IBH-HPS and was usually isolated in IBH-HPS cases in Korea since 2007. To prevent these IBH-HPS outbreaks in Korea, we developed the FAdV-4 inactivated vaccine using Korean isolate (ADL070244) and evaluated the efficacy of this vaccine. For the efficacy test, 2-week-old specific-pathogen-free (SPF) chickens intramuscularly inoculated with 1 or 2 dose of inactivated vaccine were used and challenged with FAdV-4 through either intramuscular or oral route at 2 weeks after vaccination. The vaccine induced good seroconversion which was confirmed by agar gel precipitation (AGP) test. In addition, the vaccine could decrease the FAdV-4 detection rate and histological lesion severity such as lymphocyte infiltration and necrosis in the liver comparing with those of non-vaccination group. Based on the current results, the developed FAdV-4 inactivated vaccine in this study was effective in the terms of reduction of virus detection rate and histological lesions severity. However, it was difficult to confirm the efficacy of the vaccine clearly because of no mortality and clinical signs in the non-vaccinated group after challenge. Therefore, we need further study to develop a standard challenged model system which could clearly evaluate the efficacy of the vaccines for FAdV-4.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.31-40
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• 2008

Background/Aims : Entecavir is a synthetic nucleoside analogue, cyclopentyl guanine nucleoside, which has a potent antiviral effect and the least viral breakthrough in hepatitis B virus (HBV) replication. Entecavir has been available in Korea since 2007 but there are few reports on its effects. The aim of this study was to evaluate the virological response (VR) and biochemical response (BR) to entecavir in HBV patients at 3, 6 and 9 months after treatment with entecavir. Materials and Methods : Thirty-three chronic hepatitis B patients who took entecavir for at least 9 months were enrolled. We investigated VR and BR by retrospectively reviewing medical records. Patients who satisfied the following criteria were chosen: 1) initial alanine aminotransferase (ALT) levels = 1.5upper limit of normal (ULN) and 2) initial HBV DNA levels = $5\;log_{10}\;copies/ml$. We measured ALT levels every 3 months until month 9. HBV DNA was measured every 2 or 3 months by polymerase chain reaction (PCR) method. Results : Most patients taking entecavir showed good BR (ALT < 40 IU/L). The BR rates were 61%, 73% and 67% at months 3, 6 and 9, respectively. VR (HBV DNA < $5\;log_{10}\;copies/ml$ or 2 log lower than initial HBV DNA) rates were 82%, 91% and 91% at months 3, 6 and 9, respectively. Undetectable HBV DNA (HBV DNA < 4 log10 copies/ml) rates were 49%, 73% and 85% at months 3, 6 and 9, respectively. Two patients presented with virological breakthrough without adverse effects until month 9. Conclusions : Entecavir showed good BR and VR from month 3 and these effects continued through the 9-month observation period. This suggests that entecavir is also a good choice for the first line treatment of chronic hepatitis B (CHB). Further studies are needed to determine the long-term efficacy and drug resistance of entecavir in Korean CHB patients.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.6 no.1
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• pp.32-38
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• 2003

Purpose: Hepatic allografts from donors with hepatitis B core antibody have been demonstrated to transmit hepatitis B virus (HBV) infection to recipients after liver transplantation (LT). The efficacy of hepatitis B immune globulin (HBIg) to prevent de novo hepatitis B was investigated by comparing active immunization in the early phase to HBIg monotherapy in the late phase of pediatric liver transplants at Samsung Medical Center. Methods: Among pediatric liver transplants, from May, 1996 to June, 2002, 15 recipients who were hepatitis B surface antigen (HBsAg) (-) received an allograft from a donor with hepatitis B core antibody (HBcAb) (+). Except two who died from unrelated causes, eleven of 13 recipients were HBsAb (+), and 2 were naive (HBsAb(-), HBcAb(-)). All patients were vaccinated for HBV before LT. In the early phase (January, 1997~November, 1997, 3 patients), HBsAb (+) recipients received booster vaccination after LT. In the late phase (December, 1997~, 10 patients), all recipients were given booster vaccination and received HBIg therapy in order to maintain HBsAb titer greater than 200 IU/L. Lamivudine was given in one case because of severe side effect of HBIg. We retrospectively analyzed the effect of the preventive therapy for de novo hepatitis B through medical records. Results: De novo hepatitis B developed in three of 13 recipients (23.1%). All of 3 patients who received active immunization in the early phase became HBsAg (+) at 7~19 months after transplantation. One of them was naive before LT and the other two were HBsAb (+). All of 10 recipients who were given HBIg in the late phase remained HBsAg (-) at 7~55 months' follow-up. Conclusion: Passive immunization with HBIg was effective for prevention of de novo hepatitis B in HBsAg (-) recipients of hepatic allografts from HBcAb (+) donors.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.14 no.1
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• pp.67-73
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• 2011

Purpose: Recently, the incidence of acute hepatitis A has increased nationwide and is related to a low rate of IgG anti-HAV production. To establish effective measures for preventing hepatitis A virus infection, an epidemiologic study on the seroprevalence of anti-HAV is needed. Thus, we investigated the seroprevalence of IgG anti-HAV in children living in Gwangju and Jeonnam. Methods: IgG anti-HAV levels were measured in a total of 1,435 patients who visited Chosun University Hospital between January 2009 and December 2009. Results: The overall seropositve rate was 40.8% (586/1,435). The seropositive rates were 41% among children under the age of 1 year, 49.9% for children 1~5 years old, 51.1% among individuals 5~10 years old, 12.9% for individuals 10~15 years old, and 8.2% for subjects over 15 years old. There was no significant difference between genders in any group. The seropositive rates in Gwangju and Jeonnam were 57.3% and 32.9% for children under the age of 1 year, 52.5% and 44.3% for children 1~5 years old, 60.2% and 33.9% among children 5~10 years old, 14.1% and 9.7% for children 10~15 years old, and 10.8% and 4.2% for individuals over 15 years old. Conclusion: The results demonstrated the low rates of IgG anti-HAV, particularly among subjects over 10 years old, which suggests the possibility of increasing clinical HAV infection rates among adults in the near future. We should actively prevent the spread of hepatitis A virus. Vaccination is the most effective means of preventing hepatitis A virus transmission among persons at risk for infection. Hepatitis A vaccination is recommended for children who have low IgG anti-HAV seropositive rates.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.13 no.1
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• pp.44-50
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• 2010

Purpose: To estimate the viral suppressive effect of entecavir monotherapy in Korean children and adolescents with lamivudine-resistant chronic hepatitis B (CHB). Methods: One milligram of entecavir was administered once daily to 6 patients (4 boys; mean age, 17.5 years; range, 15.10~24.6 years) with lamivudine-resistant CHB for a mean duration of therapy of 13.4 months (range, 1~21.1 months). The therapeutic results were compared with 11 patients who received adefovir (0.3 mg/kg/day [maximal dose 10 mg]) for at least 12 months (mean, 33.4 months; range, 12.4~58.3 months). The serum HBV DNA level and serologic markers were measured every 2 months. Results: The interval to a HBV DNA titer decrement (>1 $log_{10}$) was 1.2${\pm}$0.2 and 4.4${\pm}$5.2 months (p=0.185) for the entecavir and adefovir groups, respectively. The interval to a HBV DNA titer decrement (>2 $log_{10}$) was 2.4${\pm}$2.3 and 9.2${\pm}$7.3 months (p=0.025), for the entecavir and adefovir groups, respectively. Conclusion: The therapeutic efficacy of entecavir was favorable in children and adolescents, especially in shortening the interval to a >2 $log_{10}$ decrement in the HBV DNA titer. Long-term follow up is needed to determine the therapeutic efficacy of entecavir for lamivudine-resistant CHB in children and adolescents.

• The Korean Journal of Nuclear Medicine Technology
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• v.12 no.1
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• pp.78-81
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• 2008

Purpose: In this study, we evaluated unstable serum data of HBe antigen (HBeAg) or HBe antibody (HBeAb) in patients who experienced HBeAg seroconversion. This study have been performed to assist a medical technologist in the recognition of patients who were chronically infected with the hepatitis B virus (HBV). Materials and Methods: A total number of 3 patients were enrolled in this study. All patients experienced HBeAg seroconversion. Serum data of HBeAg and HBeAb were measured by radioimmunoassay. Results: The data of HBeAg or HBeAb showed an unstable change during seroconversion from HBeAg to HBeAb in chronic type B hepatitis (CBH). Conclusions: Serum data of HBeAg or HBeAb can change during HBe seroconversion. These data suggest that patients with HBe seroconversion can experience an unstable oscillation of HBeAg or HBeAb value from positive to negative. Unstable data can appear naturally due to the seroconversion process.

• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.605-608
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• 1992

This paper dealt with the clinical and pathological observations on the experimental rabbit viral hepatitis. Rabbits with 2-14 months of ages were intramuscularly inoculated with virus suspension. The results were summarized as follows. Ninety percents of experimental rabbits inoculated with virus died within 96 hours postinoculation. Common clinical signs were inappetence, increase in body temperature, depression, mild diarrhea and in three cases, bloody foam from nostrils was recognized. At necropsy, in most of the experimental cases, there were hyperemia or haemorrhages in many organs and pale liver. Intestinal catarrh and retention of turbid urine in urinary bladder were seen in some cases. Histopathologically, liver necrosis was found in all the cases died of this disease. However, there was a difference in the severity of hepatic necrosis. Haemorrhages were Iecognized in lungs, heart, liver, spleen, kidneys and thymus, in order. Liver necrosis was marked even in the cases with no haemorrhage. Perivascular cuffing in brain and catarrhal enteritis in small intestine were seen in many cases. From these results, consistent and primary lesion in this viral disease is hepatitis in susceptible rabbits. It was concluded that rabbit hepatitis virus might have the properties of hepatotropism and consequently induce peripheral necrosis in the liver leading to acute viremia with haemorrhages.

• Korean Journal of Clinical Pharmacy
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• v.22 no.2
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• pp.95-102
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• 2012

HIV 치료를 위한 강력한 항바이러스 약물요법이 널리 사용됨에 따라 HIV에 감염된 상태에서 신장질환 발생 위험성을 지닌 채 오랜 기간 생존하는 환자들이 증가하고 있다. 본 연구는 국립중앙의료원 감염병 센터를 내원한 만18세 이상의 HIV 감염 환자를 대상으로 HIV 감염 환자에게 신기능 장애를 유발하는 위험인자를 평가하고자 환자군 대조군 연구를 후향적으로 실시하였다. 2006년 1월부터 2011년 3월까지 5년 3개월 동안 신기능이 저하된 모든 HIV 감염 환자를 환자군으로 하며, 정상 신기능을 가진 HIV 감염 환자들 중 대조군을 무작위로 선정하여 환자군과 대조군을 1:2의 비율로 하였다. 환자군과 대조군을 비교해 만성신질환을 유발하는 위험인자를 평가하기 위한 분석변수로 성별, 연령, CD4+ 세포수, 혈중 바이러스 수, HAART 56일 이상 여부, 당뇨병과 C형 간염을 선정하였다. 또한 추가적으로 개별 antiretroviral 약물들 사용과 신기능이 얼마나 관련되어 있는지 알아보기 위해 각각의 약물과 eGFR의 상관관계를 분석하였다. 환자군은 CD4+ 세포수가 < $200{\times}10^6$ cells/l 인 군이 7.7배(OR: 7.7; 95% CI, 1.8-32.9) 단백뇨가 있는 환자의 경우 7.8배(OR: 7.8; 95% CI, 1.6-37.8) 더 유의하게 만성신질환 발생위험이 높았다. 개별 antiretroviral 약물들과 eGFR의 상관관계를 분석한 결과, lamivudine 이 eGFR 과 약한 음적 상관관계를 보이는 것으로 나타났으며(r = -.211, p < .05), 다른 약물들의 경우 통계적으로 유의한 값을 보이지 않았다. 이번 환자군-대조군 연구는 HIV 감염 환자들이 만성 신질환으로 발전하는데 여러 인자들의 역할에 대해 평가하고자 하였다. 여러 변수들을 평가해 본 결과, 만성 신질환 환자들의 경우 CD4+ 세포수가 < $200{\times}10^6$ cells/l 이거나 단백뇨를 동반한 경우가 통계적으로 유의하게 많았다.

• The Journal of Korean Society of Virology
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• v.27 no.2
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• pp.115-128
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• 1997

Three cDNA fragments located within NS5 region of HCV were synthesized by RT using viral RNA extracted from blood sample of Korean patient as a template. The cDNAs were amplified by PCR, cloned into the T-vector, and the nucleotide sequences were determined. Comparative analysis of the nucleotide and amino acid sequence of NS5 cDNAs showed that it is closely related with HCV type 1b. The cloned NS5 cDNA showed 91-94% homology at the nucleotide sequence level and 96-98% homology at the amino acid sequence level with several strains of the HCV type 1b. The NS5 cDNAs were subcloned into E. coli expression vectors to construct pRSETA5-1, pTHAN5-1, pRSETC5-2, pRSETBB1, pRESTCB1 and pRSETB-H3. Expression of the NS5 proteins was achieved by inducing the promoter with isopropyl-thio-${\beta}$-D-galactoside (IPTG) and confirmed by SDS-polyacrylamide gel electrophoresis. The NS5 proteins were immunoreactive against sera from Korean hepatitis C patients in Western blot analysis. Among the recombinant NS5 proteins, pRSETAS-1 plasmid derived protein, coded from aa2022 to aa2521 of HCV polyprotein, showed the strongest immunoreactivity against sera from Korean hepatitis C patients in immunoblot analysis. These results suggest that NS5 proteins would be useful as an antigen for detection of antibody against HCV in the blood samples.