{
  "abstract": "Objective The impact of nucleos(t)ide analogues (NAs) therapy on the long-term outcomes in chronic HBV infection individuals outside 2025 European Association for the Study of the Liver (EASL) strongly recommended treatment indications remains uncertain. We aimed to assess the association between NAs therapy and the risks of cirrhosis and hepatocellular carcinoma (HCC) in Chinese chronic HBV infection individuals outside these criteria.Design We analysed data from 30 784 chronic HBV infection individuals across 12 centres in China. We categorised individuals outside 2025 EASL strongly recommended treatment criteria into four groups: (1) hepatitis B e antigen (HBeAg)-positive, high replicative (age <30, HBV DNA ≥8 log₁₀IU/mL, normal alanine aminotransferase (ALT), no/mild fibrosis, no family history of liver cancer); (2) HBeAg-positive, impending phase transition (typically age ≥30, HBV DNA ≥6 log₁₀IU/mL, normal ALT, no advanced fibrosis); (3) HBeAg-negative, low replicative (HBV DNA <3.3 log₁₀IU/mL, normal ALT, no/mild fibrosis); (4) HBeAg-negative, high replicative, low-risk (HBV DNA 3.3–4.3 log₁₀IU/mL, normal ALT, no/mild fibrosis). The primary endpoints were the incidence of cirrhosis and HCC.Results Up to 5 years of follow-up (117 814 person-years), we documented 635 incident cirrhosis and 164 HCC cases. In multivariable analyses, NA therapy significantly reduced risks of cirrhosis (HR 0.18, 95% CI 0.11 to 0.32) and HCC (HR 0.03, 95% CI 0.01 to 0.21) in Group 1, and cirrhosis (HR 0.50, 95% CI 0.41 to 0.61) and HCC (HR 0.25, 95% CI 0.16 to 0.41) in Group 2. No significant associations were observed in Groups 3 and 4. Findings were consistent in propensity score matching analyses.Conclusion NAs therapy was associated with reduced risks of cirrhosis and HCC in HBeAg-positive individuals with high replicative or impending phase transition phenotypes, supporting the expansion of chronic HBV infection treatment criteria.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China",
        "Department of Hepatopancreatobiliary Surgery, Wanyuan People’s Hospital, Dazhou, Sichuan, China"
      ],
      "name": "Shichuan Tang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China",
        "Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Tingfeng Huang"
    },
    {
      "affiliations": [
        "The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China",
        "The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Ruijing Tang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Kongying Lin"
    },
    {
      "affiliations": [
        "Department of Hepatopancreatobiliary Surgery, Zizhong County People’s Hospital, Zizhong, China"
      ],
      "name": "Cong Luo"
    },
    {
      "affiliations": [
        "National Central Cancer Registry and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Beijing, China"
      ],
      "name": "Yubing Shen"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Wenjiang District People’s Hospital, Chengdu, China"
      ],
      "name": "Kailing Zhang"
    },
    {
      "affiliations": [
        "West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Yidan Tang"
    },
    {
      "affiliations": [
        "Department of Hepatopancreatobiliary Surgery, Heze Hospital Affiliated of Shandong First Medical University, Heze, China"
      ],
      "name": "Jie Kong"
    },
    {
      "affiliations": [
        "Department of Information Technology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China"
      ],
      "name": "Zhenwei Chen"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Jun Fu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China",
        "Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Qizhu Lin"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Luobin Guo"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China"
      ],
      "name": "Yeye Wu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China"
      ],
      "name": "Yuntong Li"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, China"
      ],
      "name": "Jianxi Zhang"
    },
    {
      "affiliations": [
        "Department of General Surgery, Guizhou Maotai Hospital, Zunyi, China"
      ],
      "name": "Zhenghong Sun"
    },
    {
      "affiliations": [
        "Biobank in Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China"
      ],
      "name": "Penghui You"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mindong Hospital of Fujian Medical University, Fuan, China"
      ],
      "name": "Daichang Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Ningde Hospital affiliated to Ningde Normal University, Ningde, China"
      ],
      "name": "Yanxin Chen"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Fuqing Hospital of Fujian Medical University, Fuqing, China"
      ],
      "name": "Xin Lin"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Longyan First Hospital, Longyan, China"
      ],
      "name": "Chengqian Zhong"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Zhangzhou Hospital of Fujian Medical University, Zhangzhou, China"
      ],
      "name": "Zhipeng Lin"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Hongzhi Liu"
    },
    {
      "affiliations": [
        "Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China"
      ],
      "name": "Zuxiong Huang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China"
      ],
      "name": "Weiping Zhou"
    },
    {
      "affiliations": [
        "Department of Liver Disease, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Peiling Dong"
    },
    {
      "affiliations": [
        "The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China",
        "The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Xiaolong Liu"
    },
    {
      "affiliations": [
        "National Central Cancer Registry and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Beijing, China"
      ],
      "name": "Hongmei Zeng"
    },
    {
      "affiliations": [
        "Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China",
        "Basic Medicine Research and Innovation Center of Ministry of Education, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Xiaolong Qi"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China",
        "The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Yongyi Zeng"
    }
  ],
  "title": "EASL 2025 indications revisited: phase-specific outcomes with and without nucleos(t)ide analogue therapy in chronic hepatitis B virus infection",
  "uid": "bea42cf3-30f4-5150-beb2-136eb49b6d02"
}