{
  "abstract": "Introduction and Objectives: Up to one-third of treatment-naïve, HBeAg-negative chronic hepatitis B (CHB) patients with normal ALT do not meet the strict criteria for the inactive carrier (IC) phase, falling into a “Grey Zone” (GZIC). We aimed to delineate the longitudinal outcomes of GZIC patients compared with strictly defined IC patients. Patients and Methods: This retrospective cohort study included 386 HBeAg-negative, ALT-normal CHB patients (125 GZIC, 261 IC). Endpoints included phase transition to immune-active stages, antiviral initiation, and end-stage liver disease (cirrhosis or hepatocellular carcinoma (HCC)). Cumulative incidence was assessed using Kaplan–Meier analysis. Results: Over a median follow-up of 4.5 years, the GZIC cohort exhibited significantly higher cumulative incidence of phase transition (36.8% vs. 13.8%, p < 0.001), antiviral initiation (37.6% vs. 18.8%, p = 0.00014), and end-stage liver disease (4.8% vs. 1.5%, p = 0.049) compared with the IC cohort. All incident HCC cases occurred exclusively in the GZIC group. Multivariate analysis identified baseline GZIC status, male sex, and elevated AFP as independent risk factors. A lower ALT cutoff of 24.5 U/L was superior to 40 U/L in predicting phase transition (p < 0.01). Sex-stratified analyses confirmed that GZIC remained an independent risk factor for phase transition in both male and female patients (both p < 0.05). Conclusions: The GZIC phase is not a benign state. Compared with true inactive carriers, GZIC patients face a significantly elevated risk of progression and liver-related complications, supporting proactive surveillance and timely antiviral intervention.",
  "abstract_shown": true,
  "affiliations": [
    "The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Yuzhong District, Chongqing 400010, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yunling Xue"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengyuan Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Guorui Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiao Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingsong Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Zeng"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingli Peng"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoqing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Peng Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/88dr2bbpn4pq3.bib",
  "cited_by": 0,
  "doi": "10.3390/jcm15207832",
  "fulltext_url": null,
  "id": "88dr2bbpn4pq3",
  "issns": [
    "2077-0383"
  ],
  "landing_url": "https://www.mdpi.com/2077-0383/15/20/7832",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Hepatitis B Virus Studies"
    ]
  ],
  "openalex": "W7221532436",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/88dr2bbpn4pq3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "10.3390/jcm15207832",
      "source": "crossref",
      "url": "https://www.mdpi.com/2077-0383/15/20/7832"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Hepatitis B Virus Studies",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Natural History and Clinical Outcomes of HBeAg-Negative Chronic Hepatitis B Patients in the “Grey Zone”: A Longitudinal Cohort Study",
  "title_text": "Natural History and Clinical Outcomes of HBeAg-Negative Chronic Hepatitis B Patients in the “Grey Zone”: A Longitudinal Cohort Study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:00Z",
  "url": "https://research.draconitic.com/paper/88dr2bbpn4pq3",
  "venue": "Journal of Clinical Medicine",
  "versions": []
}