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We aimed to provide definitive results on this issue using a large set of CHB patients and data on all major NA drugs. The study population consisted of 10,331 patients with CHB receiving primary NA treatment for more than 6\u00a0months, and 24,836 untreated controls followed for at least as long as the treated patients. Using the inverse\u2010probability\u2010of\u2010treatment\u2010weighted (IPTW) method, the cumulative incidence of extrahepatic cancers was compared in the treated and untreated patients and across the cyclopentane, L\u2010nucleoside and acyclic phosphonate categories of NAs. Analyses of individual cancers as sub\u2010endpoints were also performed. The cumulative incidence of overall extrahepatic malignancies did not differ between the two groups in the IPTW cohort (hazard ratio [HR] 1.002; 95% confidence interval [CI] [0.859\u20131.169]). Similar statistical trends were observed in analyses across the three NA chemical subsets and controls. Per\u2010cancer analyses indicated that NA treatment was significantly associated with increased risks of colorectal\/anal cancers (HRs [95% CI], 1.538 [1.175\u20132.013]) and lymphoma (1.784 [1.196\u20132.662]). Conversely, breast cancer (HRs [95% CI], 0.669 [0.462\u20130.967]) and prostate cancer (0.521 [0.329\u20130.825]) were less prevalent in the NA\u2010treated group. In conclusion, prolonged NA treatment presents carcinogenic risks for colorectal\/anal and lymphoid tissues in CHB patients, although it does not affect most extrahepatic organs. The protective effect of NAs on breast and prostate cancers should be confirmed.<\/jats:p>","DOI":"10.1111\/jvh.13721","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T05:34:27Z","timestamp":1655703267000},"page":"756-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extrahepatic carcinogenicity of oral nucleos(t)ide analogues in chronic hepatitis B carriers: A 35,000\u2010Korean outcome study"],"prefix":"10.1111","volume":"29","author":[{"given":"Jihye","family":"Lim","sequence":"first","affiliation":[{"name":"Gastroenterology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung\u2010Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics University of Ulsan College of Medicine, Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0110-0965","authenticated-orcid":false,"given":"Jihyun","family":"An","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hanyang University College of Medicine  Guri Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gi\u2010Won","family":"Song","sequence":"additional","affiliation":[{"name":"Hepatobiliary Surgery and Liver Transplantation, Surgery, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"},{"name":"Asan Liver Center, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang Mo","family":"Kim","sequence":"additional","affiliation":[{"name":"Gastroenterology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"},{"name":"Asan Liver Center, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7631-4124","authenticated-orcid":false,"given":"Han Chu","family":"Lee","sequence":"additional","affiliation":[{"name":"Gastroenterology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"},{"name":"Asan Liver Center, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7336-1371","authenticated-orcid":false,"given":"Ju Hyun","family":"Shim","sequence":"additional","affiliation":[{"name":"Gastroenterology, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"},{"name":"Asan Liver Center, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2019.1002"},{"key":"e_1_2_10_3_1","unstructured":"World Health Organization.Hepatitis B. 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