제주 지역의 B형 간염 바이러스 유전자형

조지현,박도심,김태현,염주진,김학철,문주현,양재식 대한간학회 2004 Clinical and Molecular Hepatology(대한간학회지) Vol.10 No.1

목적: HBV 감염이 무증상의 자연 회복부터 간경변 혹은 간세포성 간암까지 다양하게 나타나는 요인들로 숙주의 요인과 바이러스의 요인으로 구분되어 제시되는데, 바이러스 요인으로는 감염된 바이러스이 유형이나 염기 변이들이 논의된다. HBV 유형을 구분하는 데는 혈청형과 유전자형이 이용되는데 근자에는 주로 유전자형이 이용된다. 이러한 HBV의 분포는 지역적으로 다르나 지역에 따라서 다른 유형들이 혼재되어 있다. 동남아시아는 B형이지만 극동아시아는 C형으로 알려져 있으며, 대만과 오키나와에서는 B와 C형이 혼재되어 나타난다. 이러한 결과로 미루어 보아 우리 나라의 남부지역에서는 B과 C형이 혼재되어 있을 가능성이 있다. 이에 본 연구는 제주 지역에서 HBV의 유전자형을 조사하고자 하였다. 대상과 방법: 원적지가 제주도이면사, HBsAg가 양성이었던 107명(평균 연령: 46.5세)을 대상으로 하였다. 이들의 혈청으로부터 HBsAg/antiHBe를 분석하고, DNA를 추출하여 7개의 유전자형에 따라 특이성을 갖는 시발체(genotype specific primer)들을 이용하여 PCR로 증폭한 후 이를 분석하였다. 주된 유전자형의 일부와 다른 유형에서 증폭에 이용되었던 시발체를 다르게 이용하여 hemi nested PCR로 증폭한 후 염기를 분석하여 계통발생학적 분석법을 이용하였다. 결과: 1. PCR에 의한 HBV DNA 양성은 107명 중 59명(55.1%)이 양성이었다. HBeAg/anti HBe의 발현 양태에 따라 음성/음성에서 2명(66.7%), 음성/양성에서 30명(41.1%), 양성/음성에서 24명(85.7%), 양성/양성에서는 3명(100%)에서 증폭되었다. 2. Multiplex PCR에서는 58명의 유전자형이 C형, 1명에서는 B형과 C형이 동반 출현하였다. 3. Genotype specific primer를 이용하여 각각 따로 PCR을 시행한 경우에 A형에 의하여 증폭된 예가 1예, B형에 의하여 증폭된 예가 1예, C형에 의하여 증폭된 예가 59예로 A형과 B형 모두가 C형에서 증폭된 예였다. 4. 한 쌍의 시발체에 의하여 증폭되었던 A형과 B형 및 C형의 일부에서 염기를 분석한 결과 모두 C 유전자형이었다. 결론: HBsAg이 양성인 제주 지역 주민의 HBV의 유전자형은 C형일 것으로 생각된다. Background/Aims: Hepatitis B virus (HBV) was classified into 8 genotypes by a sequence divergence in the entire genome designated from A o H. HBV genotypes have distinct geographic distributions. Recently, HBV genotypes have been partially found as influencing the clinical manifestation of chronic liver disease in hosts. In Korea, the distribution of HBV genotypes remains unclear. The aim of this study was to evaluate the prevalence of the HBV genotype on Jeju Island. Methods: Hepatitis B virus genotypes were evaluated among 107 hepatitis B carriers residing on Jeju Island. We used single PCR and multiplex-PCR assay with genotype-specific primer pairs for HBV genotypes A-F for the genotyping. Results: 1. Fifty nine samples (55%) were positive for HBV DNA. The positivity was different according to the pattern of HBeAg/anti-HBe expression, as -/-; 2/3 (66.7%), -/+; 30/73 (30%), +/-; 24/28 (85.7%) and +/+; 3/3 (100%). 2. In the single primer set of genotype-specific PCR, 59 samples (100%) were detected as genotype C and 2 (3%) were also detected as genotype A and B. 3. In multiplex-PCR, 58 samples (98%) were detected as genotype C and only one (2%) as a mixed pattern of genotype B and C. 4. When the PCR products were amplified with universal sense and genotype specific anti-sense from one genotype A, one B, and 2 C, all were included in genotype C. Conclusions: These results suggest that on Juju Island, almost all HBV genotypes are C.(Korean J Hepatol 2004;10:42-50)

Effects of Endoscopic Variceal Ligation in Lower Esophageal Motor Function: A Prospective Study

( Haak Cheoul Kim ),( Ju Hung Song ),( Hyeong Eon Kim ),( Suck Chei Choi ),( June Hyung Lyou ),( Tae Hyeon Kim ),( Bong Joo Shin ) 대한내과학회 1995 The Korean Journal of Internal Medicine Vol.10 No.2

Macroaspartasemia as a Cause of Isolated Elevation of Aspartate Aminotransferase - Its Biochemical and Physiological Characteristics -

( Haak Cheoul Kim ),( Je Hyung Kim ) 대한내과학회 1997 The Korean Journal of Internal Medicine Vol.12 No.2

HCV, Alcoholic : PO-14 ; The significance of megaloblastic change during treatment of hepatitis C patients

( Haak Cheoul Kim ),( Eun Young Cho ),( Young Bum Cho ),( Ji Won Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background and Aims: For Hepatitis C virus (HCV) infection, pegylated interferon and ribavirin treatment are used as standard treatments, but they can make various hematologic adverse events. If such an adverse event arises, does should be reduced dosage, which may drop the treatment response. Also it is often reported that anemia occurrence can be an indicator of the good treatment response. We confirmed that Mean corpuscular volume (MCV) increase was not unusual during the HCV standard treatment and tried to find out the meaning of MCV increase during the process of HCV treatment. Methods: The subjects of the study were 60 outpatients who visited Wonkwang University Hospital because of chronic C viral hepatitis and were treated with pegylated interferon and ribavirinfrom from 2005 to 2010 and whose SVR could be identified. The medical records of the subjects were analyzed. CBC, blood chemistry, HCV RNA (copies/mL), T4 free and TSH were reviewed at 0, 4, 12, 24, 48 and 72 week after the treatment, and aspartate aminotransferase to platelet ratio index(APRI) was calculated based on the blood test result. Additionally, abdomen ultrasound scan was performed to check if there is a cirrhotic change. Results: 1. The subjects were 31 males and 29 females by gender, and 19 Genotype 1, 40 Genotype 2 and 1 Genotype 3 by Genotype. 24 patients were treated with interferon α2a, and 36 with pegylated interferon α2b. Regarding ribavirin dose, 11 patients had less than 800mg, 37 patients had 800mg ~ <1000mg, and 12 patients had ≥1000mg. Ten patients showed significant drinking history (80 g/day). 2. When classifying the group with the baseline of MCV 95fL before the treatment (Group 1, MCV< 95 fL; Group 2, MCV ≥95 fL) 16 subjects showed over 95 fL MCV, and there was no significantly different factors between groups (all≥0.05). The only significantly different factor was average age such as 59.1±13.5 in Group 1 and 64.0±7.19 in Group 2, which showed borderline significance (p=0.076). 3. Regarding the increase of MCV during the treatment, it increased regardless of Genotype at 4, 12, and 24 weeks and decreased from 48 weeks. (Genotype 1: 90.92±3.62, 90.95±4.03, 94.52±6.74, 97.43±7.31, 93.68±5.36, 91.36±5.56 in week 0, week 4, week 12 (p=0.000), week 24 (p=0.024), week 48, week 72, retrospectively; Genotype 2: 92.26±5.87, 93.54±5.66, 97.13±6.55, 98.08±7.11, 92.72±4.82, 92.58±4.99 in week 0, week 4 (p=0.000), week 12 (p=0.000), week 24 (p=0.000), week 48, week 72, retrospectively) 4. There was statistically significant difference in Hemoglobin (week 0, 2, 4, 12, 24) and platelet count (week 0, 2, 12, 24, 48, 72) and albumin (week 0, 4, 12, 24, 48, 72) (all p≤0.05) when dividing group with the standard of MCV ≥100fL (Group 3, MCV< 100 fL; Group 4, MCV ≥100 fL), which showed significant correlation when it was divided by APRI >0.08. Group 4 had more patients who showed cirrhotic changes on the sonography comparing to Group 3 (3/29(21.4%) in Group 3, 11/31(78.6%) in Group 4, p=0.021). Conclusions: Although MCV increase during the treatment was not related with the treatment response, it seemed to be related with chronicity of hepatitis. Thus, such patients should be closely observed even after the termination of the treatment.

HCV, Alcoholic : PO-14 ; The significance of megaloblastic change during treatment of hepatitis C patients

( Haak Cheoul Kim ),( Eun Young Cho ),( Young Bum Cho ),( Ji Won Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background and Aims: For Hepatitis C virus (HCV) infection, pegylated interferon and ribavirin treatment are used as standard treatments, but they can make various hematologic adverse events. If such an adverse event arises, does should be reduced dosage, which may drop the treatment response. Also it is often reported that anemia occurrence can be an indicator of the good treatment response. We confirmed that Mean corpuscular volume (MCV) increase was not unusual during the HCV standard treatment and tried to find out the meaning of MCV increase during the process of HCV treatment. Methods: The subjects of the study were 60 outpatients who visited Wonkwang University Hospital because of chronic C viral hepatitis and were treated with pegylated interferon and ribavirinfrom from 2005 to 2010 and whose SVR could be identified. The medical records of the subjects were analyzed. CBC, blood chemistry, HCV RNA (copies/mL), T4 free and TSH were reviewed at 0, 4, 12, 24, 48 and 72 week after the treatment, and aspartate aminotransferase to platelet ratio index(APRI) was calculated based on the blood test result. Additionally, abdomen ultrasound scan was performed to check if there is a cirrhotic change. Results: 1. The subjects were 31 males and 29 females by gender, and 19 Genotype 1, 40 Genotype 2 and 1 Genotype 3 by Genotype. 24 patients were treated with interferon α2a, and 36 with pegylated interferon α2b. Regarding ribavirin dose, 11 patients had less than 800mg, 37 patients had 800mg ∼ <1000mg, and 12 patients had ≥1000mg. Ten patients showed significant drinking history (80 g/day). 2. When classifying the group with the baseline of MCV 95fL before the treatment (Group 1, MCV< 95 fL; Group 2, MCV ≥95 fL) 16 subjects showed over 95 fL MCV, and there was no significantly different factors between groups (all≥0.05). The only significantly different factor was average age such as 59.1±13.5 in Group 1 and 64.0±7.19 in Group 2, which showed borderline significance (p=0.076). 3. Regarding the increase of MCV during the treatment, it increased regardless of Genotype at 4, 12, and 24 weeks and decreased from 48 weeks. (Genotype 1: 90.92±3.62, 90.95±4.03, 94.52±6.74, 97.43±7.31, 93.68±5.36, 91.36±5.56 in week 0, week 4, week 12 (p=0.000), week 24 (p=0.024), week 48, week 72, retrospectively; Genotype 2: 92.26±5.87, 93.54±5.66, 97.13±6.55, 98.08±7.11, 92.72±4.82, 92.58±4.99 in week 0, week 4 (p=0.000), week 12 (p=0.000), week 24 (p=0.000), week 48, week 72, retrospectively) 4. There was statistically significant difference in Hemoglobin (week 0, 2, 4, 12, 24) and platelet count (week 0, 2, 12, 24, 48, 72) and albumin (week 0, 4, 12, 24, 48, 72) (all p≤0.05) when dividing group with the standard of MCV ≥100fL (Group 3, MCV< 100 fL; Group 4, MCV ≥100 fL), which showed significant correlation when it was divided by APRI >0.08. Group 4 had more patients who showed cirrhotic changes on the sonography comparing to Group 3 (3/29(21.4%) in Group 3, 11/31(78.6%) in Group 4, p=0.021). Conclusions: Although MCV increase during the treatment was not related with the treatment response, it seemed to be related with chronicity of hepatitis. Thus, such patients should be closely observed even after the termination of the treatment.

한국인 만성 B형 간염 바이러스 ( HBV ) 보유자에서 HBV 유전자형 - 일차 중합 효소 반응법에 의한 온전한 B 형 간염 바이러스 증폭 및 그의 염기 서열 -

김학철(Haak Cheoul Kim),서검석(Geom Suk Seo),김용성(Youg Sung Kim),송우건(Woo Gun Song),문형배(Hyung Bae Moon),조지현(Jie Heun Cho) 대한내과학회 2001 대한내과학회지 Vol.61 No.5

N/A Background : Hepatitis B virus (HBV) is major source of chronic liver disease in Korea. However this virus might have different nucleotide sequence according to races, different region, etc. Recently the novel method that allows sensitive amplification with dramatically decreased mis-incorporation has developed. We determined to get the major form of HBV nucleotide sequence from whole sequencing data of 26 Korean HBV carriers. Methods : HBV DNA were collected from 26 Korean chronic HBV carriers. We used the novel PCR with pfu for the amplification of HBV DNA, and specific primers were made with combination sequence bases of non-HBV part and HBV parts which were located head and tail in the virion. Then whole length of HBV were directly sequenced and analysed. Result : HBV DNA was consisted of 3215 bases in 20 cases of 26 Korean chronic HBV carriers. And the remainder had smaller or larger number due to deletion, insertion or both in pre-S2 and S gene. They were 99.03% homology of their nucleotide sequence and belong to genotype C. The variability of nucleotide sequence was significantly higher in the singly coding region (SCR) than doubly coding region (DCR), and also high in pre-S1 and pre-S2 gene among the DCR. Hot-spots were more frequently found in the SCR, pre-S1 and pre-S2 gene. Conclusion : In Korean chronic HBV carriers, HBV is consisted of 3215 nucleotides, and belongs to genotype C. And it might exist one genotype with the variability in Korea.(Korean J Med 61:479-488, 2001)

만성 B형간염의 질병 진행과 관련된 X-단백 발현조절 유전자의 염기변이 탐색(추계학술대회 초록집)

김학철 ( Haak Cheoul Kim ),조은영 ( Eun Young Cho ),소홍섭 ( Hong Seob So ),박찬희 ( Channy Park ) 대한간학회 2006 Clinical and Molecular Hepatology(대한간학회지) Vol.12 No.5(S)

Efficacy and Tolerability of Pegylated Interferon-α_2a plus Ribavirin versus Pegylated Interferon-α_2b plus Ribavirin in Treatment-Naive Chronic Hepatitis C Patients

Lee, Seok,Kim, In Hee,Kim, Seong Hun,Kim, Sang Wook,Lee, Seung Ok,Lee, Soo Teik,Kim, Dae Ghon,Lee, Chang Seop,Choi, Chang Soo,Cho, Eun Young,Kim, Haak Cheoul S. Karger AG 2010 Intervirology Vol.53 No.3

<P><I>Objectives:</I> The authors compared the efficacies and tolerabilities of pegylated interferon-α<SUB>2a</SUB> (PEG-IFN-α<SUB>2a</SUB>) + ribavirin and pegylated interferon-α<SUB>2b</SUB> (PEG-IFN-α<SUB>2b</SUB>) + ribavirin for the initial treatment of chronic hepatitis C. <I>Methods:</I> A total of 126 treatment-naive patients (29.4% genotype 1, 70.6% genotype non-1) were treated with PEG-IFN-α<SUB>2a</SUB> 180 μg/week (group A, n = 79) or PEG-IFN-α<SUB>2b</SUB> 1.5 μg/kg/week (group B, n = 47) with ribavirin (800 mg/day for genotype non-1 or 1,000-1,200 mg/day for genotype 1) for 24 (genotype non-1) or 48 weeks (genotype 1). <I>Results:</I> End-of-treatment virologic response, sustained virologic response, and biochemical response were not significantly different in groups A and B (84.8 vs. 89.4%, 70.9 vs. 72.3%, and 70.9 vs. 74.5%, respectively; p > 0.05). In patients with the HCV genotype 1 or non-1, treatment responses were not significantly different. Multivariate analysis showed that HCV genotype only was an independent factor that affected sustained virologic response (p = 0.048). The proportions of treatment discontinuations in groups A and B were similar (10.1 vs. 10.6%; p = 1.000). <I>Conclusions:</I> PEG-IFN-α<SUB>2a</SUB> or PEG-IFN-α<SUB>2b</SUB> + ribavirin combination therapies showed similar efficacies and tolerabilities as initial treatments for chronic hepatitis C.</P><P>Copyright © 2010 S. Karger AG, Basel</P>

Poster Exhibition : Clevudine has a more Potent Early Viral Response and Better Treatment Outcomes at 48 Weeks than Lamivudine in Patients with Chronic Hepatitis B (초)

In Hee Kim,Seok Lee,Kang Seok Koh,Sang Yeon Lee,Sang Woo Nam,Yoon Jae Lee,Seong Hun Kim,Sang Wook Kim,Seung Ok Lee,Soo Teik Lee,Dae Ghon Kim,Chang Soo Choi,Haak Cheoul Kim 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.4(S)

만성 B형 간염 바이러스를 보유한 젊은 남자에서 간손상, 혈청 HBV-DNA 및 간세포내 HBcAg의 발현 양상과의 관련성

김태현 ( Tae Hyeon Kim ),김용성 ( Yong Sung Kim ),염주진 ( Joo Jin Yeom ),조은영 ( Eun Young Cho ),김희식 ( Hee Sik Kim ),김학철 ( Haak Cheoul Kim ),박도심 ( Do Shim Park ),조지현 ( Ji Heun Cho ),윤기중 ( Gi Jung Yoon ),문형배 ( H 대한소화기학회 2004 대한소화기학회지 Vol.44 No.2

Background/Aims: Although the viral load is correlated with HBcAg, liver injury was not correlated to viral load in HBeAg positive patient. We aimed to study the inter-relationship of clinical parameters such as the level of HBV-DNA, the level of aminotra