核苷酸（t）ide类似物期间可检测到的HBV DNA对预测性肝细胞癌

StephenW

Detectable HBV DNA during nucleos(t)ide analogues stratifies predictive hepatocellular carcinoma risk score
Shun Kaneko  1 , Masayuki Kurosaki  1 , Kouji Joko  2 , Hiroyuki Marusawa  3 , Masahiko Kondo  4 , Yuji Kojima  5 , Yasushi Uchida  6 , Hiroyuki Kimura  7 , Keiji Tsuji  8 , Hitoshi Yagisawa  9 , Atsunori Kusakabe  10 , Haruhiko Kobashi  11 , Takehiro Akahane  12 , Nobuharu Tamaki  1 , Sakura Kirino  1 , Takehiko Abe  13 , Hideo Yoshida  14 , Tomomichi Matsushita  15 , Chitomi Hasebe  16 , Namiki Izumi  17
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
    2
    Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan.
    3
    Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
    4
    Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Shiga, Japan.
    5
    Department of Gastroenterology, Japanese Red Cross Ise Hospital, Mie, Japan.
    6
    Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Shimane, Japan.
    7
    Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
    8
    Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan.
    9
    Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan.
    10
    Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
    11
    Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan.
    12
    Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan.
    13
    Department of Gastroenterology, Japanese Red Cross Maebashi Hospital, Gunma, Japan.
    14
    Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan.
    15
    Department of Gastroenterology, Japanese Red Cross Gifu Hospital, Gifu, Japan.
    16
    Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan.
    17
    Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan. [email protected].

    PMID: 32747646 DOI: 10.1038/s41598-020-69522-w

Abstract

Nucleos(t)ide analogs (NA) suppress hepatitis B virus (HBV) replication and reduce the risk of hepatocellular carcinoma (HCC). However, NA cannot suppress carcinogenesis completely in patients with chronic hepatitis B. The aims of this study were to identify risk factors for HCC and develop a refined carcinogenesis prediction model. Patients receiving NA therapy (n = 1,183) were recruited retrospectively from the 16 hospitals. All patients had been receiving NA continuously for more than 1 year until the end of the follow-up. During a median follow-up of 4.9 (1.0-12.9) years, 52 (4.4%) patients developed HCC. A multivariate analysis revealed that male gender, older age, lower platelet counts at the baseline, and detectable HBV DNA during NA therapy were independent predictive factors of HCC development. The PAGE-B score was calculated by using these factors. 240 (20.3%), 661 (55.9%), and 282 (23.8%) patients were classified into low-, intermediate-, and high-risk groups, respectively. In the intermediate- and high-risk group, detectable HBV DNA was significantly associated with a higher risk of HCC development compared with continuously undetectable HBV DNA, respectively (HR 3.338; 95% CI 1.045-10.66/HR 3.191; 95% CI 1.543-6.597). PAGE-B-DNA, which is the combined PAGE-B and HBV DNA status, was valuable for a more refined stratification of PAGE-B.
Grant support

    JP19fk0210025h0003/the Ministry of Health, Labor and Welfare in Japan and Japan Agency for Medical Research and Development

StephenW

核苷酸（t）ide类似物期间可检测到的HBV DNA对预测性肝细胞癌风险评分进行分层
顺子金子1，黑崎昌行1，香次郎2，丸泽裕之3，近藤正彦4，小岛雄二5，内田靖6，木村裕之7，，次Tsu 8，八木仁志9，草坂淳10，小林晴彦11，竹Take弘11 12，玉木伸春1，樱花麒麟1，阿部武彦13，吉田秀夫14，松下智一15，长谷智美16，泉浪美17
隶属关系
隶属关系

    1个
    日本东京都武藏野市京南町1-26-1武藏野红十字医院消化内科和肝病科，日本180-8610。
    2
    日本爱媛县松山市红十字会医院肝胆胰疾病中心。
    3
    日本大阪红十字会大阪医院消化内科。
    4
    日本滋贺县日本红十字会大津医院消化内科。
    5
    日本三重市红十字会伊势医院消化内科。
    6
    日本岛根市日本红十字会松江医院消化内科。
    7
    日本京都红十字会京都第一医院消化内科。
    8
    日本广岛市红十字会医院消化科和原子弹幸存者医院。
    9
    日本秋田市日本红十字会秋田医院消化内科。
    10
    日本名古屋日本红十字会名古屋大日医院消化内科。
    11
    日本冈山日本红十字会冈山医院肝病科。
    12
    日本宫城市日本红十字会石卷医院消化内科。
    13
    日本群马市日本红十字会前桥医院消化内科。
    14
    日本东京红十字会医疗中心消化内科。
    15
    日本岐阜日本红十字会岐阜医院消化内科。
    16
    日本北海道日本红十字会旭川医院消化科。
    17
    日本东京都武藏野市京南町1-26-1武藏野红十字医院消化内科和肝病科，日本180-8610。 [email protected]。

    PMID：32747646 DOI：10.1038 / s41598-020-69522-w

抽象

核苷酸类似物（NA）抑制乙型肝炎病毒（HBV）复制并降低肝细胞癌（HCC）的风险。但是，NA不能完全抑制慢性乙型肝炎患者的癌变。本研究的目的是确定HCC的危险因素并建立完善的癌变预测模型。回顾性地从16家医院招募接受NA治疗的患者（n = 1,183）。所有患者一直接受NA超过1年，直到随访结束。在4.9（1.0-12.9）年的中位随访期间，有52（4.4％）位患者发生了HCC。多因素分析显示，男性，年龄较大，基线时血小板计数较低以及NA治疗期间可检测到的HBV DNA是HCC发生的独立预测因素。 PAGE-B得分是使用这些因素计算得出的。分别将240（20.3％），661（55.9％）和282（23.8％）患者分为低，中和高风险组。在中危和高危组中，与连续无法检测到的HBV DNA相比，可检测到的HBV DNA与更高的HCC发生风险显着相关（HR 3.338； 95％CI 1.045-10.66 / HR 3.191； 95％CI 1.543- 6.597）。 PAGE-B-DNA是PAGE-B和HBV DNA的组合状态，对于PAGE-B的更精细分层很有价值。
赠款支持

    JP19fk0210025h0003 /日本厚生劳动省和日本医学研究与发展局

StephenW

https://www.nature.com/articles/s41598-020-69522-w.pdf