한빛사
>
한빛사논문
한빛사논문
- 조회143
Lancet Gastroenterol. Hepatol., Jan 31 2025, S2468-1253(24)00431-X | https://doi.org/10.1016/S2468-1253(24)00431-X
Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial
Prof Young-Suk Lim MD a *, Prof Ming-Lung Yu MD c *, Jonggi Choi MD a *, Chi-Yi Chen MD d *, Won-Mook Choi MD a, Wonseok Kang MD e, Gi-Ae Kim MD f, Prof Hyung Joon Kim MD g, Prof Yun Bin Lee MD h, Prof Jeong-Hoon Lee MD h, Prof Neung Hwa Park MD b, Prof So Young Kwon MD i, Prof Soo Young Park MD j, Prof Ji Hoon Kim MD k, Gwang Hyeon Choi MD l, Prof Eun Sun Jang MD l, Prof Chien-Hung Chen MD m, Prof Yao-Chun Hsu MD n, Ming-Jong Bair MD o, Prof Pin-Nan Cheng MD p, Hung-Da Tung MD q, Prof Te-Sheng Chang MD r, Ching-Chu Lo MD s, Prof Kuo-chih Tseng MD t, Sheng-Shun Yang MD u, Prof Cheng-Yuan Peng MD v, Seungbong Han PhD w
aDepartment of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
bUlsan University Hospital, University of Ulsan College of Medicine, Seoul, South Korea
cKaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
dDitmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
eSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
fKyung Hee University Hospital, Kyung Hee University, Seoul, South Korea
gChung-Ang University Hospital, Chung-Ang University, Seoul, South Korea
hSeoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
iKonkuk University Medical Center, Konkuk University, Seoul, South Korea
jKyungpook National University Hospital, Kyungpook National University, Daegu, South Korea
kKorea University Guro Hospital, Korea University, Seoul, South Korea
lSeoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
mKaohsiung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Kaohsiung, Taiwan
nE-Da Hospital, Kaohsiung, Taiwan
oTaitung Mackay Memorial Hospital, New Taipei, Taiwan
pNational Cheng Kung University Hospital, Tainan, Taiwan
qChi Mei Hospital, Liouying, Taiwan
rChang Gung Memorial Hospital, Chia-Yi, Taiwan
sSt Martin De Porres Hospital, Chia-Yi, Taiwan
tDalin Tzu Chi Hospital, Chia-Yi, Taiwan
uTaichung Veterans General Hospital, Taichung, Taiwan
vChina Medical University Hospital, Taichung, Taiwan
wDepartment of Biostatistics, Korea University, Seoul, South Korea
*Contributed equally as first authors
Correspondence to: Professor Young-Suk Lim
aDepartment of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
bUlsan University Hospital, University of Ulsan College of Medicine, Seoul, South Korea
cKaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
dDitmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
eSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
fKyung Hee University Hospital, Kyung Hee University, Seoul, South Korea
gChung-Ang University Hospital, Chung-Ang University, Seoul, South Korea
hSeoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
iKonkuk University Medical Center, Konkuk University, Seoul, South Korea
jKyungpook National University Hospital, Kyungpook National University, Daegu, South Korea
kKorea University Guro Hospital, Korea University, Seoul, South Korea
lSeoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
mKaohsiung Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, Kaohsiung, Taiwan
nE-Da Hospital, Kaohsiung, Taiwan
oTaitung Mackay Memorial Hospital, New Taipei, Taiwan
pNational Cheng Kung University Hospital, Tainan, Taiwan
qChi Mei Hospital, Liouying, Taiwan
rChang Gung Memorial Hospital, Chia-Yi, Taiwan
sSt Martin De Porres Hospital, Chia-Yi, Taiwan
tDalin Tzu Chi Hospital, Chia-Yi, Taiwan
uTaichung Veterans General Hospital, Taichung, Taiwan
vChina Medical University Hospital, Taichung, Taiwan
wDepartment of Biostatistics, Korea University, Seoul, South Korea
*Contributed equally as first authors
Correspondence to: Professor Young-Suk Lim
Abstract
Background: Current guidelines for chronic hepatitis B recommend antiviral therapy for individuals with non-cirrhotic chronic hepatitis B only if they have significant liver fibrosis or elevated alanine aminotransferase (ALT) concentrations. We aimed to assess the efficacy of early antiviral treatment in preventing serious liver-related adverse events in individuals with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated ALT concentrations.
Methods: ATTENTION is an ongoing randomised controlled trial being conducted at 22 centres in South Korea and Taiwan. Adults aged 40-80 years with non-cirrhotic chronic hepatitis B and serum hepatitis B virus (HBV) DNA concentrations between 4 log10 IU/mL and 8 log10 IU/mL, and ALT concentrations lower than 70 U/L for males and 50 U/L for females were recruited and randomly assigned (1:1) to receive either oral tenofovir alafenamide (25 mg daily) or no antiviral treatment (observation). The primary endpoint was a composite of hepatocellular carcinoma, hepatic decompensation (eg, development of portal hypertensive complications including ascites, gastro-oesophageal varices, or Child-Pugh score of ≥7), liver transplantation, or death from any cause, analysed in the intention-to-treat population. The safety population comprised all randomly assigned participants who received at least one dose of the study treatment. This interim analysis was prespecified at 4 years after enrolment of the first participant. This study is registered with ClinicalTrials.gov, NCT03753074.
Findings: Between Feb 8, 2019 and Oct 17, 2023 (the cutoff date for the first interim analysis), 798 individuals were screened and 734 were randomly assigned (369 to tenofovir alafenamide and 365 to observation). At a median follow-up of 17·7 months (IQR 8·3-24·4), the primary endpoint occurred in 11 participants: two in the tenofovir alafenamide group (both hepatocellular carcinoma) and nine in the observation group (seven hepatocellular carcinoma, one hepatic decompensation, and one death), corresponding to an incidence rate of 0·33 per 100 person-years in the tenofovir alafenamide group and 1·57 per 100 person-years in the observation group (hazard ratio 0·21 [97·5% CI 0·04-1·20]; p=0·027). The difference between the two groups did not surpass the prespecified boundaries required to stop the trial early. Serious adverse events, excluding primary endpoints, were reported in 23 (6%) participants in the tenofovir alafenamide group and 24 (7%) in the observation group.
Interpretation: The results of this interim analysis suggest that early treatment with tenofovir alafenamide reduces the risk of liver-related serious adverse events compared with observation in adults with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated ALT concentrations. Although these findings await confirmation in planned future analyses, they suggest that existing guidelines could be expanded to allow early antiviral therapy in patients with a moderate or high HBV viral load, irrespective of ALT concentrations.
Methods: ATTENTION is an ongoing randomised controlled trial being conducted at 22 centres in South Korea and Taiwan. Adults aged 40-80 years with non-cirrhotic chronic hepatitis B and serum hepatitis B virus (HBV) DNA concentrations between 4 log10 IU/mL and 8 log10 IU/mL, and ALT concentrations lower than 70 U/L for males and 50 U/L for females were recruited and randomly assigned (1:1) to receive either oral tenofovir alafenamide (25 mg daily) or no antiviral treatment (observation). The primary endpoint was a composite of hepatocellular carcinoma, hepatic decompensation (eg, development of portal hypertensive complications including ascites, gastro-oesophageal varices, or Child-Pugh score of ≥7), liver transplantation, or death from any cause, analysed in the intention-to-treat population. The safety population comprised all randomly assigned participants who received at least one dose of the study treatment. This interim analysis was prespecified at 4 years after enrolment of the first participant. This study is registered with ClinicalTrials.gov, NCT03753074.
Findings: Between Feb 8, 2019 and Oct 17, 2023 (the cutoff date for the first interim analysis), 798 individuals were screened and 734 were randomly assigned (369 to tenofovir alafenamide and 365 to observation). At a median follow-up of 17·7 months (IQR 8·3-24·4), the primary endpoint occurred in 11 participants: two in the tenofovir alafenamide group (both hepatocellular carcinoma) and nine in the observation group (seven hepatocellular carcinoma, one hepatic decompensation, and one death), corresponding to an incidence rate of 0·33 per 100 person-years in the tenofovir alafenamide group and 1·57 per 100 person-years in the observation group (hazard ratio 0·21 [97·5% CI 0·04-1·20]; p=0·027). The difference between the two groups did not surpass the prespecified boundaries required to stop the trial early. Serious adverse events, excluding primary endpoints, were reported in 23 (6%) participants in the tenofovir alafenamide group and 24 (7%) in the observation group.
Interpretation: The results of this interim analysis suggest that early treatment with tenofovir alafenamide reduces the risk of liver-related serious adverse events compared with observation in adults with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated ALT concentrations. Although these findings await confirmation in planned future analyses, they suggest that existing guidelines could be expanded to allow early antiviral therapy in patients with a moderate or high HBV viral load, irrespective of ALT concentrations.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-02-07)
- 국내(교신)+국외 연구진
- 의약학 > 응용의학
관련 보도자료
만성 B형간염, 조기 치료해야 간암 발생 및 사망 위험 줄어
만성 B형간염은 간암 원인의 70%를 차지하므로 적절한 시기에 치료를 시작하는 게 중요한데, 현재 B형간염 치료지침은 간수치가 크게 상승했거나 간경화로 진행된 환자에 한해 항바이러스 치료를 개시하도록 되어있다. 그런데 최근 국내 연구진이 기존 치료기준인 간수치 혹은 간경화 여부와는 상관없이 혈액 내 간염 바이러스 수치에 따라 항바이러스 치료를 일찍 시작해야 만성 B형간염이 간암이나 사망으로 이어지는 위험을 크게 줄일 수 있다는 연구결과를 발표했다.
- Bio통신원
- 2025. 03. 04
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
