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Open research questions in Liver Diseases and Immunity

90 unresolved questions extracted from the limitations and future-work sections of 237 Liver Diseases and Immunity papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Investigating the therapeutic potential of ixekizumab in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, - Exploring the role of IL-17 in autoimmune hepatitis, - Studying the effects of blocking IL-17 cytokines or their receptors on AIH, - Investigating the potential of future therapies targeting IL-17

    Interleukin-17 in Health and Disease: Special Focus on Its Role in Autoimmune Hepatitis · 2026 · DOI

  • Investigating the underlying biological mechanisms of the genetic causal relationships between PBC and IBD, - Examining the potential therapeutic implications of the findings, - Replicating the study in different populations to confirm the results

    Primary biliary cirrhosis and inflammatory bowel disease: a two-sample bidirectional Mendelian randomization study · 2026 · DOI

  • The genetic causal relationship between PBC and IBD is unknown. Prior studies have reported an association between PBC and IBD, but the underlying genetic mechanisms are unclear. This study aims to address this gap by investigating the genetic causal relationship between PBC and IBD.

    Primary biliary cirrhosis and inflammatory bowel disease: a two-sample bidirectional Mendelian randomization study · 2026 · DOI

  • The complexity of biliary atresia etiology, involving multiple factors and cell populations. The need to consider the role of the biliary epithelium in local inflammatory amplification. The potential for domination by very abundant cell populations in cell-cell communication analysis.

    Integrated single-cell and bulk-tissue transcriptomic analysis reveals an epithelial-stromal inflammatory microenvironment in biliary atresia · 2026 · DOI

  • further study on the role of biliary epithelium in the inflammatory microenvironment, - investigation of the underlying mechanisms of biliary atresia, - analysis of cell-cell communication in other disease contexts

    Integrated single-cell and bulk-tissue transcriptomic analysis reveals an epithelial-stromal inflammatory microenvironment in biliary atresia · 2026 · DOI

  • This article presents two patients who were diagnosed with genuine autoimmune liver disease (autoimmune hepatitis and primary biliary cholangitis overlap syndrome) during anti-tuberculosis therapy, which is a rarely reported occurrence.

    AIH-PBC Overlap Syndrome Unmasked by Tuberculosis Treatment: Report of Two Cases and Literature Review · 2025 · DOI

  • Background Previous studies have suggested that the gut microbiota (GM) is closely associated with the development of autoimmune cholestatic liver disease (ACLD), but limitations, such as the presence of confounding factors, have resulted in a causal relationship between the gut microbiota and autoimmune cholestatic liver disease that remains uncertain.

    Association between gut microbiota and autoimmune cholestatic liver disease, a Mendelian randomization study · 2024 · DOI

  • The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated.

    Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome · 2024 · DOI

  • There is a need for non-invasive biomarkers for the diagnosis and prognosis of PBC. Current diagnostic methods have limitations, such as invasiveness and sampling error.

    Serum matrix metalloproteinase-7 as a diagnostic and prognostic biomarker in primary biliary cholangitis · 2026 · DOI

  • While MMP-7 has emerged as a promising biomarker for fibrosis in hepatocyte-centric diseases like NAFLD, its role in PBC—a disease centered on biliary injury—remains poorly defined (22, 23).

    Serum matrix metalloproteinase-7 as a diagnostic and prognostic biomarker in primary biliary cholangitis · 2026 · DOI

  • Liver diseases often develop gradually and may remain asymptomatic for a long time. Many patients are diagnosed at advanced stages, when structural and functional liver damage is already pronounced. The immune system plays a direct role in hepatocellular injury in autoimmune and immune-mediated liver diseases.

    THE IMPORTANCE OF IMMUNODIAGNOSTICS IN THE DIAGNOSIS OF LIVER DISEASES IN MODERN MEDICINE · 2026 · DOI

  • The current criterion of biochemical response to UDCA is an ALP level of ≤1.67 × ULN after 12 months of treatment, but this may not be sufficient to identify patients at risk of poor outcomes. There is a need to establish ALP normalization as a core treatment target and identify early intervention windows for treatment.

    A Dual Time Window-driven Strategy to Optimize Primary Biliary Cholangitis Treatment via Alkaline Phosphatase Normalization · 2026 · DOI

  • The complexity of PSC-UC increases due to the coexistence of the two diseases. There is a lack of effective drug treatment regimens for PSC in clinical practice. The diagnosis and treatment of PSC-UC are challenging due to the rarity of the condition.

    Primary sclerosing cholangitis complicated with ulcerative colitis and double gene mutations of UGT1A1 and SLC25A13: a case report · 2026 · DOI

  • There is a lack of effective drug treatment regimens for PSC in clinical practice. The pathogenesis of PSC-UC is not fully understood, and the role of genetic susceptibility is unclear.

    Primary sclerosing cholangitis complicated with ulcerative colitis and double gene mutations of UGT1A1 and SLC25A13: a case report · 2026 · DOI

  • Renal involvement in PBC is a rare finding and is not well understood. dRTA is an uncommon but clinically relevant manifestation of PBC that requires early recognition and treatment.

    A rare renal manifestation of primary biliary cholangitis: case report and brief review · 2026 · DOI

  • Inflammatory and fibrogenic stimuli, such as transforming growth factor-{beta} (TGF{beta}) and lipopolysaccharide (LPS) signaling, drive these processes, but their underlying transcriptional mechanisms in cholangiocytes remain incompletely defined.

    Cholangiocyte RUNX1 Orchestrates Fibrogenic and Inflammatory Signaling to Drive Biliary Fibrosis · 2026 · DOI

  • The study is limited by the heterogeneity of the included meta-analyses. The study did not evaluate the long-term efficacy and safety of combination therapy. The study did not assess the cost-effectiveness of combination therapy.

    Comparative efficacy and safety of ursodeoxycholic acid, fibrates, and combination therapy in primary biliary cholangitis: an umbrella meta-analysis of meta-analyses · 2026 · DOI

  • Future studies should evaluate the long-term efficacy and safety of combination therapy in PBC. Future studies should assess the cost-effectiveness of combination therapy in PBC. Future studies should explore the potential benefits and risks of combination therapy in individual patients.

    Comparative efficacy and safety of ursodeoxycholic acid, fibrates, and combination therapy in primary biliary cholangitis: an umbrella meta-analysis of meta-analyses · 2026 · DOI

  • The underlying mechanisms and triggers of AIH have not yet been clarified. The pathogenesis of AIH is not yet fully understood.

    Hepatitis A virus-induced autoimmune hepatitis: A case-based review · 2026 · DOI

  • There is a need to understand the role of IL-17 in AIH. The current understanding of IL-17's involvement in the inflammatory response is incomplete. There is a gap in the development of effective therapies targeting IL-17.

    Interleukin-17 in Health and Disease: Special Focus on Its Role in Autoimmune Hepatitis · 2026 · DOI

  • The pathogenesis of PBC remains incompletely understood. The study aims to address the gap in knowledge regarding the genetic mechanisms of PBC.

    Genetic mechanisms of primary biliary cholangitis and its association with immune cells using mendelian randomization and biological annotation · 2026 · DOI

  • The complexity of immune-mediated liver damage. The need to understand the contributions of T-cell activity and autoantibody production to immune-mediated liver damage. The requirement for therapeutic strategies for autoimmune liver diseases.

    Process Flow Outlining the Mechanisms of Immune-Mediated Liver Damage: Comprehensive Analysis of T-Cell Activity and Autoantibody Contributions in Hepatocellular Injury · 2026 · DOI

  • The mechanisms underlying immune-mediated liver damage are not fully understood. The contributions of T-cell activity and autoantibody production to immune-mediated liver damage require further elucidation.

    Process Flow Outlining the Mechanisms of Immune-Mediated Liver Damage: Comprehensive Analysis of T-Cell Activity and Autoantibody Contributions in Hepatocellular Injury · 2026 · DOI

  • The study is limited by its retrospective design. The number of patients who developed severe AC is small (n = 18). Multivariate analysis using logistic regression was deemed inappropriate due to the limited number of events.

    Clinical Predictors of Worsening in Non-severe Acute Cholangitis · 2026 · DOI

  • There is a lack of specific biomarkers for DILI. Cholestatic DILI associated with leflunomide is relatively rare.

    Cholestatic Drug-Induced Liver Injury In A Rheumatoid Arthritis Patient Receiving Leflunomide: A Clinical Case Report · 2026 · DOI

Most-cited papers in Liver Diseases and Immunity

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90 open questions have been extracted from the limitations and future-work passages of 237 Liver Diseases and Immunity 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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