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Open research questions in Liver physiology and pathology

54 unresolved questions extracted from the limitations and future-work sections of 210 Liver physiology and pathology papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Further validation of the diagnostic performance of the five key genes in a more strictly defined cohort of early-stage liver fibrosis. Investigation of the therapeutic potential of Yiguanjian for liver fibrosis.

    Core Active Ingredients and Therapeutic Targets of Yiguanjian for Liver Fibrosis: A Computational and Genetic Inference-based Study · 2026 · DOI

  • The active components and molecular targets of Yiguanjian for liver fibrosis are unclear. The causal relationship between feature genes and liver fibrosis is unclear.

    Core Active Ingredients and Therapeutic Targets of Yiguanjian for Liver Fibrosis: A Computational and Genetic Inference-based Study · 2026 · DOI

  • Steatotic liver disease is a heterogeneous group of chronic liver disorders with diverse pathophysiological drivers and variable clinical outcomes. Conventional histopathology lacks the resolution to capture spatial and mechanistic nuances of the disease. Patients are exposed to differing constellations of metabolic stress, alcohol-related toxicity, and inflammatory signaling.

    AI redefines fibrosis patterns in steatotic liver disease: Opportunities and challenges · 2026 · DOI

  • Diagnosing disease severity and predicting outcomes in DILI is challenging due to the lack of reliable biomarkers. The study faced challenges in investigating the cellular sources of IL-10 and CXCL-14 in DILI liver tissue.

    Hepatic expression of IL-8, IL-10, and CXCL-14 in drug-induced liver injury: correlation with histopathology and prognostic value · 2026 · DOI

  • Further studies are needed to investigate the cellular sources of IL-10 and CXCL-14 in DILI liver tissue. Studies could explore the potential of CXCL-14 as a biomarker for predicting unfavorable outcomes in DILI patients.

    Hepatic expression of IL-8, IL-10, and CXCL-14 in drug-induced liver injury: correlation with histopathology and prognostic value · 2026 · DOI

  • Liraglutide has shown antifibrotic effects in non-cirrhotic patients, but its impact in cirrhosis remains unknown.

    Microfluidic human liver slices reveal antifibrotic effects of liraglutide via HSC deactivation and ECM remodeling. · 2026 · DOI

  • Whole blood offers a non-invasive window into organ health, yet it remains unclear which organ pathologies leave a detectable trace in the blood transcriptome, and whether such traces are causal or reactive.

    Whole-blood transcriptomic traces of organ pathology and their causal triage · 2026 · DOI

  • Early evidence suggests it plays a key role during liver development, but its function remains unknown.

    From Development to Cancer : How One Protein Controls the Fate of Liver Cells · 2026 · DOI

  • Further study of the 'Chronological Decoupling' hypothesis and its implications for liver cirrhosis. Investigation of the potential therapeutic applications of 'Protocol Resynchronization' therapy. Exploration of the role of LOXL2 in ECM cross-linking and its potential as a therapeutic target.

    Liver cirrhosis and hepatocellular carcinoma: chronological decoupling of biochemical clearance and mechanical regeneration signals a systems biology hypothesis on programed deconstruction failure · 2026 · DOI

  • The traditional view of liver cirrhosis as the linear accumulation of extracellular matrix is insufficient to explain the stagnation of fibrosis reversal and the persistent risk of hepatocellular carcinoma. A new understanding of liver cirrhosis is needed to address these challenges.

    Liver cirrhosis and hepatocellular carcinoma: chronological decoupling of biochemical clearance and mechanical regeneration signals a systems biology hypothesis on programed deconstruction failure · 2026 · DOI

  • Current therapeutic options for advanced liver fibrosis are limited. There is an urgent need for the development of novel, targeted strategies to manage and reverse liver fibrosis.

    Gut-engineered Bacillus subtilis-mediated BAMBI delivery for the treatment of thioacetamide-induced liver fibrosis through mechanotransduction inhibition · 2026 · DOI

  • The lack of effective treatments for liver fibrosis. The limited understanding of the mechanisms by which the gut microbiome influences liver disease.

    Pharmabiotics, Phocaeicola dorei, ameliorates cholestatic liver fibrosis by alleviating macrophage efferocytosis of neutrophils · 2026 · DOI

  • Further investigation of MMCT's therapeutic potential in MASH treatment. Exploration of MMCT's applications in other inflammatory diseases. Evaluation of MMCT's long-term biosafety and efficacy in clinical settings.

    Engineered Ti₃C₂ MXene nanosystems for macrophage-targeted therapy of metabolic dysfunction-associated steatohepatitis · 2026 · DOI

  • The lack of effective therapeutic strategies for MASH. The need for novel therapeutic approaches to alleviate MASH.

    Engineered Ti₃C₂ MXene nanosystems for macrophage-targeted therapy of metabolic dysfunction-associated steatohepatitis · 2026 · DOI

  • Saikosaponin-d (SSd) has demonstrated antifibrotic effects, but its impact on the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway and epithelial-mesenchymal transition (EMT) during fibrosis remains poorly understood.

    Saikosaponin-d alleviates hepatic stellate cell activation and liver fibrosis by inhibiting the TGF-β1/Smads signaling pathway and blocking the EMT process · 2026 · DOI

  • The study only analyzed a limited number of datasets. The experimental design only included a CCl4-induced mouse model and human LX-2 hepatic stellate cells.

    Identification of mitochondria-related biomarkers in liver fibrosis via interpretable machine learning and WGCNA: transcriptomic analysis and In Vivo validation · 2026 · DOI

  • Further studies are needed to validate the findings and explore the therapeutic potential of ACOT9. The use of other machine learning algorithms and experimental designs to identify key genes associated with liver fibrosis. The study of other diseases related to mitochondria dysfunction.

    Identification of mitochondria-related biomarkers in liver fibrosis via interpretable machine learning and WGCNA: transcriptomic analysis and In Vivo validation · 2026 · DOI

  • The clinical relevance of the BRD4/PML-TIMP1 axis remains to be established. The broad biological functions of BRD4 and PML may limit the therapeutic potential of targeting this axis.

    Sinusoidal endothelial cells control liver inflammation and fibrosis · 2026 · DOI

  • heless, the clinical relevance of this signaling pathway remains to be established, particularly given the broad bio- logical functions of BRD4 and PML.

    Sinusoidal endothelial cells control liver inflammation and fibrosis · 2026 · DOI

  • Further studies are needed to validate the findings and develop clinical applications. The study's results could be used to develop new diagnostic tests for hepatic fibrosis. The potential of cell-free DNA methylation signatures as biomarkers for other diseases could be explored.

    Plasma PDGFRß and PSD4 methylation levels for non-invasive staging of liver fibrosis · 2026 · DOI

  • The lack of non-invasive diagnostic tests for hepatic fibrosis. The need for improved diagnosis and treatment of MASLD. The potential of cell-free DNA methylation signatures as biomarkers for liver fibrosis in MASLD.

    Plasma PDGFRß and PSD4 methylation levels for non-invasive staging of liver fibrosis · 2026 · DOI

  • Leveraging spatial tissue analytics to inform individualized, integrated management may represent one of the most impactful directions for research and clinical care.

    AI redefines fibrosis patterns in steatotic liver disease: Opportunities and challenges · 2026 · DOI

  • There is a need for new approaches to treating liver fibrosis. The use of melatonin-pretreated bone marrow mesenchymal stem cell-derived exosomes is a novel approach that addresses this gap. The study aims to assess the efficacy of this approach in mitigating liver fibrosis.

    Melatonin-treated bone marrow mesenchymal stem cell-derived exosomes reverse liver fibrosis induced by CCl4 in male wistar albino rats · 2026 · DOI

  • Integrating molecular, functional, and clinical parameters to translate findings into improved surgical strategies. Validating ribosomal biosynthesis markers in larger, tumor-bearing models and prospective human studies.

    Comment on “Exploration of ERK/Myc regulating ribosomal biosynthesis and promoting ALPPS-related liver regeneration” · 2026 · DOI

  • The need for biomarkers that reflect both regenerative kinetics and functional recovery. The requirement for validation of ribosomal biosynthesis markers in larger, tumor-bearing models and prospective human studies.

    Comment on “Exploration of ERK/Myc regulating ribosomal biosynthesis and promoting ALPPS-related liver regeneration” · 2026 · DOI

Most-cited papers in Liver physiology and pathology

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54 open questions have been extracted from the limitations and future-work passages of 210 Liver physiology and pathology papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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