{
  "abstract": "Background\n\nPrimary biliary cholangitis (PBC) is a chronic autoimmune liver disease in which long-term clinical outcomes are difficult to assess within conventional trial durations. Alkaline phosphatase (ALP) and bilirubin are established biochemical endpoints in regulatory and clinical practice, and their relationship with long-term clinical outcomes has been demonstrated through a robust literature of analyses across different datasets. However, the magnitude and consistency of their association with long-term clinical outcomes have not been systematically quantified through meta-analysis.Objective\n\nThis systematic literature review and meta-analysis aimed to identify, evaluate, and summarize evidence on the correlation between surrogate biochemical endpoints and long-term clinical outcomes in patients with PBC.Methods\n\nA comprehensive search of key biomedical databases and reporting was conducted, in accordance with Cochrane, NICE and PRISMA guidelines. Meta-analysis was performed using Stata 19.5 SE software, with the DerSimonian and Laird (DL) random-effects model employed in the base-case, inverse-variance fixed-effect and DL + Hartung-Knapp-Sidik-Jonkman random effects model were used in sensitivity analyses. Other sensitivity analyses were performed based on study/follow-up duration, study quality, publication type, and removal of heterogeneous studies.Results\n\nOverall, 129 studies were included in the systematic literature review, among which 89 studies met criteria for meta-analysis. Failure to achieve ALP normalization was associated with significantly increased risks of composite clinical outcomes (HR; 95% CI: 1.46; 1.26-1.69), liver-related events (1.82; 1.41-2.34), and overall death and/or liver transplantation (1.52; 1.30-1.79). Similar findings were reported for other ALP response definitions. Nonresponse to composite criteria was also associated with significantly worse long-term outcomes. Sensitivity analyses yielded directionally consistent results.Discussion\n\nTo our knowledge, this research represents the first comprehensive meta-analytic evaluation integrating multiple surrogate biochemical endpoints with a broad spectrum of long-term clinical outcomes in PBC across a global study population. Associations were directionally consistent across ALP-, bilirubin-, and composite-based definitions and across all analyses.Conclusion\n\nThis meta-analysis provides robust evidence that ALP normalization, ALP-based response criteria, and composite biochemical response measures (comprising ALP and total bilirubin), were consistently associated with long-term clinical outcomes in PBC and may inform HTA, reimbursement, payer decision-making, and economic evaluation when mature long-term outcome data are unavailable.",
  "abstract_shown": true,
  "affiliations": [
    "Global Value and Access Gilead Sciences, Inc., Foster City, California, USA.",
    "HEOR Pharmacoevidence, Mohali, India."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dilip Makhija"
    },
    {
      "affs": [
        0
      ],
      "name": "Marvin Rock"
    },
    {
      "affs": [
        0
      ],
      "name": "Chong H Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryan Thaliffdeen"
    },
    {
      "affs": [
        1
      ],
      "name": "Pankaj Rai"
    },
    {
      "affs": [
        1
      ],
      "name": "Barinder Singh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/15rqph2z08xvf.bib",
  "cited_by": 0,
  "doi": "10.36469/001c.170737",
  "fulltext_url": "https://europepmc.org/articles/PMC13724029",
  "id": "15rqph2z08xvf",
  "issns": [
    "2326-697X",
    "2327-2236"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968947",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Nephrologic/Hepatologic Conditions"
    ],
    [
      "openalex",
      "2721|Liver Diseases and Immunity"
    ]
  ],
  "openalex": "W7224932625",
  "pdf_url": "https://europepmc.org/articles/PMC13724029?pdf=render",
  "pmcid": "PMC13724029",
  "pmid": "42968947",
  "published": "2026-10-30",
  "publisher": "Columbia Data Analytics, LLC",
  "ris": "https://research.draconitic.com/paper/15rqph2z08xvf.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42968947",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968947"
    },
    {
      "first_seen": "2026-11-04T12:22:33Z",
      "native_id": "PMC13724029",
      "source": "pmc",
      "url": "https://doi.org/10.36469/001c.170737"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver Diseases and Immunity",
      "subfield": "general"
    }
  ],
  "title": "Relationship of Biochemical Response as Surrogate Endpoints with Long-Term Outcomes in Primary Biliary Cholangitis: A Global Systematic Review and Meta-Analysis.",
  "title_text": "Relationship of Biochemical Response as Surrogate Endpoints with Long-Term Outcomes in Primary Biliary Cholangitis: A Global Systematic Review and Meta-Analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:44Z",
  "url": "https://research.draconitic.com/paper/15rqph2z08xvf",
  "venue": "Journal of health economics and outcomes research",
  "versions": []
}