{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:32:55Z","timestamp":1781764375024,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Patients with a chronic hepatitis B virus (HBV) infection who are treated with nucleos(t)ide analogues (NAs) are still at risk for hepatocellular carcinoma (HCC), and it has been clinically questioned whether patients with a high risk of HCC can be identified efficiently. We aimed to clarify the risk factors associated with the development of HCC during NA therapies. A total of 611 chronically HBV-infected patients without a history of HCC, who were treated with NAs for more than 6 months (median 72 months), from 2000 to 2021, were included from 16 hospitals in the Tohoku district in Japan. Incidences of HCC occurrence were analyzed with clinical factors, including on-treatment responses. Alanine aminotransferase (ALT) normalization, based on the criteria of three guidelines, was analyzed with other parameters, including the age\u2013male\u2013ALBI\u2013platelets (aMAP) risk score. During the observation period, 48 patients developed HCC, and the cumulative HCC incidence was 10.6% at 10 years. Non-achievement of ALT normalization at 1 year of therapy was mostly associated with HCC development when ALT \u2264 30 U\/L was used as the cut-off (cumulative incidence, 19.9% vs. 5.3% at 10 years, p &lt; 0.001). The effectiveness of the aMAP risk score at the start of treatment was validated in this cohort. A combination of an aMAP risk score \u2265 50 and non-achievement of ALT normalization could stratify the risk of HCC significantly, and notably, there was no HCC development in 103 patients without these 2 factors. In conclusion, non-achievement of ALT normalization (\u226430 U\/L) at 1 year might be useful in predicting HCC during NA therapies and, in combination with the aMAP risk score, could stratify the risk more precisely.<\/jats:p>","DOI":"10.3390\/jcm11092354","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T08:14:06Z","timestamp":1650701646000},"page":"2354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Non-Achievement of Alanine Aminotransferase Normalization Associated with the Risk of Hepatocellular Carcinoma during Nucleos(t)ide Analogue Therapies: A Multicenter Retrospective Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1171-7835","authenticated-orcid":false,"given":"Jun","family":"Inoue","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Tohoku Rosai Hospital, Sendai 981-8563, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-2120","authenticated-orcid":false,"given":"Takehiro","family":"Akahane","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki 986-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, South Miyagi Medical Center, Ogawara 989-1253, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Iwata","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Iwaki City Medical Center, Iwaki 973-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Kisara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japan Community Health Care Organization Sendai South Hospital, Sendai 981-1103, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Sato","sequence":"additional","affiliation":[{"name":"LC Clinic, Sendai 980-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Nagasaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sendai City Hospital, Sendai 982-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahito","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Omagari Kousei Medical Center, Daisen 014-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Yamagata City Hospital Saiseikan, Yamagata 990-8533, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruyuki","family":"Umetsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kesennuma City Hospital, Kesennuma 988-0181, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitoshi","family":"Sano","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mio","family":"Tsuruoka","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masazumi","family":"Onuki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Niitsuma","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-7282","authenticated-orcid":false,"given":"Atsushi","family":"Masamune","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"THERME Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, March 12). 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