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만성 B형 간염 환자에서 경구용 항바이러스제 사용이 간 외 장기에 미치는 잠재적 발암성의 독성학적 평가에 대한 고찰

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Abstract
Background and Aims: Evidence on the carcinogenicity of oral nucleos(t)ide analogues (NAs) is still inconclusive lacking tenofovir disoproxil fumarate (TDF) data in patients with chronic hepatitis B (CHB). We aimed to provide confirmatory results for the relevant issue using a large set of CHB patients with data on all major NA drugs.

Methods: The study population consists of 10,331 patients with CHB receiving primary NA treatment longer than 6 months and 24,836 untreated controls followed at least during the period based on the International Council of Harmonization guidelines. Using an inverse-probability-of-treatment-weighted (IPTW) method, cumulative incidence of extrahepatic cancers was compared between treated and untreated patients and across the cyclopentane (entecavir), L-nucleoside (clevudine, lamivudine, and telvibudine), and acyclic phosphonate categories of NAs (adefovir, besifovir, and tenvofir). Analyses of individual cancers as sub-endpoints were additionally performed.

Results: During averages of 4.1 ± 3.1 years and 6.8 ± 5.5 years in the respective pairs, extrahepatic cancers occurred in 208 treated and 1,014 untreated patients. Cumulative incidence of overall extrahepatic malignancies did not differ between the two groups in the IPTW cohort (HR 1.002, 95% CI [0.859-1.169], p=0.977). Similar statistical trends were observed in analyses across the three NA chemical subsets and untreated set. Per-cancer analyses indicated that NA treatment was significantly associated with increased risks of colorectal/anal cancers and lymphoma (IPTW-adjusted HRs [95% CI], 1.538 [1.175-2.013]; and 1.784 [1.196-2.662]). Inversely, breast cancer and prostate cancer were less prevalent in the NA-treated group, compared to the counterpart (IPTW-adjusted HRs [95% CI], 0.669 [0.462-0.967]; and 0.521 [0.329-0.825]).

Conclusions: We found that long NA treatment had carcinogenic risks for colorectal/anal and lymphoid tissues in CHB patients, although it did not affect most of extrahepatic organs. Protective effects of NAs on breast and prostate cancers should be further confirmed.
Author(s)
임지혜
Issued Date
2021
Awarded Date
2021-02
Type
Dissertation
Keyword
carcinogenesishepatitis B virusnucleic acidsnucleotidesand nucleosidestoxicology
URI
https://oak.ulsan.ac.kr/handle/2021.oak/5812
http://ulsan.dcollection.net/common/orgView/200000364697
Alternative Author(s)
Jihye Lim
Affiliation
울산대학교
Department
일반대학원 의학과
Advisor
이한주
Degree
Doctor
Publisher
울산대학교 일반대학원 의학과
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medicine > 2. Theses (Ph.D)
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