Rescue monotherapy in lamivudine-resistant hepatitis B e antigen-positive chronic hepatitis B: adefovir versus entecavir.

Lee, Jung Min,Kim, Hyung Joon,Park, Jun Yong,Lee, Chun Kyon,Kim, Do Young,Kim, Ja Kyung,Lee, Hyun Woong,Paik, Yong Han,Lee, Kwan Sik,Han, Kwang-Hyub,Chon, Chae Yoon,Hong, Sun Pyo,Nguyen, Tin,Ahn, Sang International Medical Press 2009 ANTIVIRAL THERAPY Vol.14 No.5

<P>BACKGROUND: The efficacy of adefovir dipivoxil (ADV) or entecavir (ETV) rescue monotherapy has not been directly compared in hepatitis B e antigen (HBeAg)-positive patients with lamivudine (3TC)-resistant chronic hepatitis B (CHB). We compared the efficacy of ADV and ETV rescue monotherapy in HBeAg-positive patients with confirmed genotypic 3TC resistance. METHODS: A total of 160 HBeAg-positive patients with confirmed 3TC resistance underwent switch therapy (91 ADV and 59 ETV). Parameters assessed included alanine aminotransferase (ALT) normalization, HBeAg seroconversion, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower detection limit <300 copies/ml), virological breakthrough and initial virological response (IVR) at 3 (IVR-3) and 6 (IVR-6) months. RESULTS: Following 52 weeks of treatment in the ADV and ETV groups, serum HBV DNA became undetectable in 25 (27.5%) and 21 (35.6%; P=0.292) patients, ALT normalization occurred in 67/78 (85.9%) and 43/47 (91.5%; P=0.351), HBeAg seroconversion in 4 (4.4%) and 1 (1.7%; P=1.000), IVR-3 in 19 (20.9%) and 18 (30.5%), IVR-6 in 40 (44.0%) and 25 (42.4%) and virological breakthrough in 2 (2.2%) and 1 (1.7%; P=1.000) patients, respectively. CONCLUSIONS: ADV and ETV revealed comparable efficacy after 52 weeks of treatment in HBeAg-positive patients with 3TC resistance. Undetectable HBV DNA in serum following 52 weeks of treatment was predictable with IVR-3 and IVR-6 in both groups.</P>

Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg‐positive chronic hepatitis B

Lee, Hyun Woong,Lee, Heon Ju,Hwang, Jae Seok,Sohn, Joo Hyun,Jang, Jae Young,Han, Ki Jun,Park, Jun Yong,Kim, Do Young,Ahn, Sang Hoon,Paik, Yong Han,Lee, Chun Kyon,Lee, Kwan Sik,Chon, Chae Yoon,Han, Kwa Wiley Subscription Services, Inc., A Wiley Company 2010 Hepatology Vol.51 No.2

<P><B>Abstract</B></P><P>The reported durability of virologic response after successful lamivudine monotherapy is variable, and the question remains as to whether virologic responses can be maintained over an extended follow‐up period. The aim of this study was to investigate posttreatment durability, the optimal duration of additional treatment after HBeAg clearance or seroconversion, and determinants for sustained virologic response (SVR) following lamivudine monotherapy in patients with HBeAg‐positive chronic hepatitis B (CHB). From January 1999 to August 2004, 178 Korean patients with HBeAg‐positive CHB were treated with lamivudine and achieved complete responses, defined as a loss of serum HBeAg and hepatitis B virus DNA, and alanine aminotransferase normalization. The mean duration of lamivudine monotherapy was 26 months (range, 12‐77). SVR was maintained in 138 patients (77.5%). Host and viral factors were compared between 138 patients with SVR and 40 patients whose response was not sustained. The cumulative relapse rates increased from 15.9% at 1 year to 30.2% at 5 years, with a mean time to relapse after cessation of lamivudine of 12 months (range, 7‐42). Most relapses occurred within 2 years after discontinuation of lamivudine (33/40, 82.5%). On multivariate analysis, age ≤40 years and additional treatment for more than 12 months after HBeAg clearance or seroconversion were independent factors for SVR. <I>Conclusion:</I> The lamivudine‐induced virologic response was durable in patients under 40 years old and those receiving lamivudine for more than 12 months after HBeAg clearance or seroconversion. Age and additional treatment were major predictive factors for SVR. (H<SMALL>EPATOLOGY</SMALL> 2010.)</P>

Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B (초)

( Hyun Woong Lee ),( Heon Ju Lee ),( Jae Seok Hwang ),( Joo Hyun Sohn ),( Jae Young Jang ),( Ki Jun Han ),( Jun Yong Park ),( Do Young Kim ),( Sang Hoon Ahn ),( Yong Han Paik ),( Chun Kyon Lee ),( Kwa 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3(S)

An External Validation of FibroScan-AST Score (FAST) for Non-Invasive Identification of Patients at Risk of Progressive Non-Alcoholic Steatohepatitis

( Jae Seung Lee ),( Hye Won Lee ),( Jun Yong Park ),( Do Young Kim ),( Sang Hoon Ahn ),( Soo Young Park ),( Jae Young Jang ),( Young Eun Chon ),( Chun Kyon Lee ),( Seung Up Kim ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

포스터전시 : 라미부딘 내성인 HBeAg 양성 만성 B형간염 환자에서의 아데포비어와 엔테카비어의 단독치료에 대한 비교 연구

Jung Min Lee,Hyung Joon Kim,Jun Yong Park,Chun Kyon Lee,Do Young Kim,Ja Kyung Kim,Hyun Woong Lee,Yong Han Paik,Kwan Sik Lee,Kwang Hyub Han,Chae Yoon Chon,Sun Pyo Hong,Tin Nguyen 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.3(S)

HCV, Acute, LT : HCV Genotype 1 Koreans with Favourable IL28B Genotypes can Benefit from the Dose Reduction of Peginterferon ALFA-2A: A Prospective Randomized Multicenter Study

( Jung Hyun Kwon ),( Si Hyun Bae ),( Youn Jae Lee ),( Jin Woo Lee ),( Young Seok Kim ),( Jae Seok Hwang ),( Won Young Tak ),( Jeong Won Jang ),( Byung Seok Lee ),( June Sung Lee ),( Chun Kyon Lee ),( 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Racial and genetic factors play a role in the virologic response to peginterferon and ribavirin in chronic hepatitis C. This study investigated the effect of peginter- feron dose reduction on the virologic response and anal- ysed single nucleotide polymorphisms (SNPs) of several genes in Koreans with HCV genotype 1. Methods: A total of 178 na?ve patients with HCV genotype 1 were prospectively enrolled in a multicentre-study. All week for 48 weeks (full-dose group, n=92), or 180-mg pe- ginterferon alfa 2a per week during the first 12 weeks fol- lowed by 135-mg per week for the next 36 weeks (dose-re- duction group, n=86). SNPs related to the IL28B (rs12979860, rs8099917), ITPA (rs1127354), C20orf194 (rs6051702) and SLC29A1 (rs760370) were genotyped. Results: The frequencies of major allele homozygote (rs12979860 CC and rs8099917 TT) of IL28B were over 80% in this study population. The rates of sustained virologic response (SVRs) in patients with IL28B major allele homo- zygote were significantly higher than those with IL28B het- erozygote and minor allele homozygote. However, for the ITPA, C20orf194 and SLC29A1 genes, SVRs were not differ- ent as genotypes. The virologic response at weeks 4, 12, 48, and 72 was not different between full-dose group and dose-reduction group. In those patients with favourable IL28B major allele homozygote genotypes, there was no different in the SVR rate between the full-dose and dose-reduction groups. However, among the unfavourable IL28B hetero- zygote and minor allele homozygote genotypes, patients in dose-reduction group were less likely to achieve SVR compared to those in full-dose group. Conclusions: Out data suggest that in Korean HCV geno- type 1 patients, the major alleles of IL28B gene are preva- lent and the patients with favourable IL28B genotypes can benefit from the dose reduction of peginterferon alfa-2a.

소화관 내시경 검사에 의한 감염

이천균,박인서 한국의학사 1997 診斷과治療 Vol.17 No.4

급성 악화를 보인 만성 B형 간염의 치료에 있어서 Lamivudine 즉시 투여의 적절성

이천균,서정훈,조용석,원선영,박인서 대한간학회 2004 Clinical and Molecular Hepatology(대한간학회지) Vol.10 No.1

목적: 만성 B형 간염의 급성 악화시 즉시 라미부딘 치료를 하는 것이 합리적인지에 대해 이해가 부족한 바, 이들의 자연경과를 알아보고 라미부딘 투여군의 비교를 통해서 라미부딘 치료의 적절한 시점을 알아보고자 하였다. 대상과 방법: 2000년 3월부터 2003년 5월까지 본원에 내원한 만성 B형 간염 환자 중 혈중 HBV DNA 또는 HBeAg 양성, ALT>400 IU/L인 35명을 대상으로 혈청 HBV DNA, HBeAg, anti-HBe, ALT를 포함한 간기능 검사를 1-3개월 간격으로 측정하였으며 ALT가 재상승한 경우, 100 IU/L 이상시 라미부딘 100 ㎎을 매일 경구 투여하고, 무작위로 선출된 환자에게 내원 당시 즉시 라미부딘을 투여하고 상기의 방법으로 검사를 시행하여 라미부딘의 효과를 비교하였다. 결과: 내원 당시 혈청 ALT가 400 IU/L 이상의 소견을 보인 27명의 환자를 대상으로 항바이러스제를 투여하지 않고 경과 관찰을 시행하였으며 이중 5명의 환자에게서 평균 19개월 추적관찰중 정상 ALT, HBeAg의 음성, HBV DNA의 음성상태가 유지되었고(제1a군) 3명의 환자에서 ALT가 약간 상승하거나 정상이었지만 HBeAg의 자연 음전은 유도되지 않았다(제1b군). 반면, 19명의 환자에서는 평균 5개월 만에 ALT의 재상승 소견을 보여 라미부딘 치료를 시작하였다(제2군). 제1a군과 제2군 사이에서 혈청 HBV DNA의 중앙값은 각각 6.5 pg/mL과 518.1 pg/mL로 제1a군에서 현저히 낮았으며 HBV DNA가 20 pg/mL 이하였던 환자 7명 중 5명(71.4%)에서 자연음전이 유도되었다. 경과 관찰 중 재상승한 환자 19명 중 16명의 환자와 급성 악화로 내원 즉시 라미부딘을 투여한 환자 8명(제3군)을 비교한 결과, 제2군에서는 3군에 비해 치료시 혈청 ALT는 낮고 HBV DNA는 높았으며 첫 내원시보다 오히려 혈중 HBV DNA가 높은 상태에서 라미부딘 치료가 시작되었다. 양군 간의 라미부딘 치료 효과는 2군에서 56.3% (9/16)로 3군의 62.5% (5/8)와 차이가 없었다. 결론: 급성 악화를 동반한 만성 B형 간염 환자의 경우 내원 당시 혈중 HBV DNA가 현저히 낮은 경우는 HBeAg의 자연음전을 기대할 수 있으나, 대부분의 경우 라미부딘의 즉시 치료를 통한 HBeAg의 음전을 시도하는 것이 바람직하다고 생각된다. Background/Aims: It has been unclear whether immediate antiviral therapy or observation under the expectation of spontaneous inactivation of hepatitis B virus (HBV), is more appropriate for the treatment of chronic hepatitis B (CHB) with acute exacerbation. We intended to analyze the short-term natural course of CHB with acute exacerbation and evaluate the efficacy of lamivudine. Methods: We analyzed 35 CHB patients with acute exacerbation (positive HBV DNA or HBeAg and ALT>400 IU/L) between March 2000 and May 2003. We regularly checked serum HBV DNA, HBeAg and liver unction tests including ALT every 1 to 3 months. If ALT was above 100 IU/L during the follow-up period, patients were treated with 100 ㎎ lamivudine orally once a day. We compared the efficacy of lamivudine use between this group and the group provided with immediate lamivudine trial at their first visit. Results: 27 CHB patients with acute exacerbation were observed without immediate lamivudine trial. In 5 of these patients normal ALT, negative HBeAg and HBV DNA were maintained during 19 months (group la). Slightly elevated or normal ALT was maintained without HBeAg seroconversion in 3 patients (group 1b). However, serum ALT flared up above 100 IU/L in 19 patients within 5 months. So, lamivudine was tried on these patients (group 2). The serum HBV DNA was extremely low, being 6.5 pg/mL in group la compared to 518.1 pg/mL in group 2. Spontaneous inactivation of HBV was observed in 71.4% (5/7) of patients with HBV DNA less than 20 pg/mL at the first visit. ALT was lower and HBV DNA was higher in group 2 than the 8 patients who received immediate lamivudine trial at the first visit (group 3). The response rate of lamivudine was similar between group 2, 56.3% (9/16) and group 3, 62.5% (5/8). Conclusions: Spontaneous inactivation of HBV was expected in CHB with acute exacerbation and extremely low level of HBV DNA (less than 20 pg/mL) in a short term follow-up period. Immediate lamivudine therapy might be more appropriate in most CHB patients with acute exacerbation.(Korean J Hepatol 2004;10:22-30)

내시경적 유두괄약근절개술의 조기합병증 및 위험인자에 관한 연구

이천균,송시영,이루다,정재복,강진경,김원호,문영명,박인서 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.30 No.6

만성 B 형 간염에서 HLA A2/core 18-27 tetramer 복합체를 이용한 B형 간염바이러스 특이 CD8+ 림프구의 분석

이천균,서정훈,조용석,한광협,정재복,전재윤,문영명 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.2

목적 : HBV의 조절 및 간세포 손상에 있어 HBV 특이 세포독성 T 림프구가 중요한 역할을 하는 것으로 보고되고 있다. 이에 본 연구에서는 tetramer 분석방법을 통하여 만성 B형 간염의 혈액과 간에서 HBV 특이 세포독성 T 림프구를 측정할 수 있는지를 알아보고 이를 기초로 HBV 특이 세포 독성 T 림프구의 간내침윤 유무를 규명하고 HBV 특이 세포독성 T 림프구와 바이러스 증식여부, 간세포 손상 정도를 비교하고자 하였다. 대상과 방법 : 33명의 HLA-A2 양성 및 8명의 HLA-A2 음성, 만성 B형 간염 환자의 혈액으로부터 단핵구를 분리하여 anti-CD8 항체와 tetrameric HLA-A2/core 18-27 복합체를 이용하여 혈중 core 18-27 특이 CD8+ 림프구를 측정하였으며 이중 11명의 HLA-A2 양성 및 8명의 HLA-A2 음성 환자에서 간내 core 18-27 특이 CD8+ 림프구를 측정하였다. 환자의 혈중 HBV-DNA와 ALT치를 측정하여 이들과 core 18-27 특이 CD8+ 림프구의 빈도를 비교하였다. 결과 : 33명의 HLA-A2 양성 환자중 14명의 혈중에서 50,000개의 CD8+ 세포중 9-101개의 tetramer 특이 세포가 관찰되었으며 간내 단핵구의 분석이 가능하였던 11명의 HLA-A2 양성 환자중 8명의 환자에서 50,000개의 CD8+ 세포중 121-2100개의 core 18-27 특이 CD8+ 세포가 관찰되었고 8명의 환자 모두에서 간내 tetramer 특이 세포의 빈도가 혈중에 비해 17.4-150배 이상 높았다. 혈중 HBV-DNA가 0.5 pg/mL 이하, 혈중 ALT가 40 IU/L 이하였던 18명의 환자중 10명의 혈액에서 tertramer특이 세포가 증가되어 있었으나 혈중 HBV-DNA가 800 pg/mL 이상, 혈중 ALT가 70 IU/L 이상이었던 15명의 환자에서는 4명에서만 tertramer특이 세포의 증가가 관찰되었다. 간내 T c18-27 특이 세포의 빈도는 혈중 HBV-DNA나 혈중 ALT의 상승 정도와는 상관 관계가 없었다. 그러나 간내 T c18-27 특이 세포의 빈도가 높은 3명의 환자는 모두 혈중 HBV-DNA가 낮았으며 혈중 ALT는 정상이었다. 결론 : 본 연구에서는 혈중과 간내 HBV 특이 세포독성 T 림프구를 직접 측정함으로써 만성간염에서도 상당량의 HBV 특이 세포독성 T 림프구가 존재함을 알 수 있었으며, 바이러스가 조절되고 간세포 손상이 뚜렷치 않은 환자에서 활발한 HBV 특이 세포독성 T 림프구의 작용을 관찰함으로써 바이러스의 조절과 간세포 손상은 서로 다른 기전에 의해 이루어지는 것으로 추정된다. Backgrounds/Aims: Hepatitis B virus(HBV) specific cytotoxic T lymphocyte (CTL) response is believed to play a major role in virus control and liver damage in chronic hepatitis B(CHB). We performed this study to evaluate whether HBV specific CTL could be visualized directly by tetrameric HLA-A2/core 18-27 complex(Tc18-27) in the peripheral blood and liver of patients with CHB. On the basis of our results we clarified patients intrahepatic compartmentalization and correlation with HBV specific CTL and viral replication or liver damage. Methods: We stained peripheral blood mononuclear cells of 33 HLA-A2 + and 8 HLA-A2 patients with CHB with cychrome conjugated anti-CD8 mAb and phycoerythrin conjugated T c18-27. Among these we analysed intrahepatic lymphocyte of 11 HLA-A2 + patients. We compared the frequency of T c18-27 specific CD8+ cells with serum HBV-DNA levels or alanine aminotransferase(ALT) levels. Results: The frequency of circulating T c18-27 specific CD8+ cell was higher(9-101 cells per 50,000 CD8+ cells) than background level in 14 among 33 patients. The frequency of intrahepatic T c18-27 specific CD8+ cells was 12-2100 cells per 50,000 CD8+ cells in 8 out of 11 patients whose liver was obtained This was 17.4-150 times higher than circulating T c18-27 specific CD8+ cells. The frequency of circulating T c18-27 specific CD8+ cells was increased in 10 out of 18 patients with serum HBV DNA level <0.5 pg/mL and ALT < 40 IU/L. It was increased in just 4 out of 15 patients with HBV DNA level > 800 pg/mL and ALT >70 IU/L. The frequency of intrahepatic T c18-27 CTL tended to be lower in high levels of serum HBV DNA and was not correlated with liver inflammation. Conclusion: This study provess that if HBV-specific CTLs are barely detectable in the peripheral blood of CHB, much more HBV-specific CTLs are in the liver and most HBV-specific CTLs are infiltrated in the liver. Also, in the presence of an effective HBV specific CD8 response the inhibition of viral replication can be independent of liver damage.(Korean J Hepatol 002;8:139-148)