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Open research questions in Liver Disease Diagnosis and Treatment

2,102 gap statements mined from Liver Disease Diagnosis and Treatment papers in our 7.9M-paper local library, which holds 8,386 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The need for further research on the relationship between MASLD and cardiovascular, renal, and metabolic dysfunction.

    Cardiovascular–Kidney–Metabolic Syndrome and Its Hepatic Dimension: A Narrative Review · 2026 · DOI

  • The incorporation of MASLD into the established CKM definition or staging system remains an evolving conceptual extension. The relationship between MASLD and cardiovascular, renal, and metabolic dysfunction is not fully understood.

    Cardiovascular–Kidney–Metabolic Syndrome and Its Hepatic Dimension: A Narrative Review · 2026 · DOI

  • The need for accurate assessment of hepatic fat accumulation in adults with overweight or obesity and metabolic dysfunction-associated steatotic liver disease. The lack of CT attenuation thresholds for grading hepatic steatosis in this population. The need for evaluation of the agreement between CT-predicted steatosis grades and US steatosis grading.

    CT Attenuation Thresholds for Grading Hepatic Steatosis in Adults with Overweight or Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease · 2026 · DOI

  • There is a need to evaluate the effects of aspirin and dapagliflozin on liver enzymes and FibroScan-derived parameters. The current study aims to fill this gap by comparing the effects of these two treatments on adults with MASLD.

    Anti-inflammatory versus metabolic therapy in MASLD: a randomized clinical trial of aspirin and dapagliflozin using fibroscan outcomes · 2026 · DOI

  • The complexity of obesity-associated liver injury and the lack of effective treatments. The need to identify the molecular targets of Magnolol in obesity-associated liver injury. The challenge of elucidating the molecular mechanisms underlying the hepatoprotective effects of Magnolol.

    Magnolol alleviates high-fat diet-induced steatosis, inflammation and fibrosis in obesity-associated liver injuries via MOGAT1-mediated lipid metabolism and NF-κB signaling · 2026 · DOI

  • Longitudinal studies are needed to establish the causal relationships between hepatic steatosis and glycemic control in T1D. Studies investigating the effects of hepatic steatosis on long-term clinical outcomes in T1D are needed. Research on the mechanisms underlying the association between hepatic steatosis and insulin resistance in T1D is needed.

    Hepatic steatosis is associated with postprandial dysglycemia in type 1 diabetes: insights from dual-modality liver assessment · 2026 · DOI

  • The specific mechanism of MASLD is not fully understood. The role of GSDMD in MASLD progression is not well characterized. The effects of O-GlcNAcylation on GSDMD-mediated mitochondrial dysfunction are not known.

    O-GlcNAcylation of GSDMD promotes mitochondrial dysfunction and hepatocyte injury in MASLD · 2026 · DOI

  • The limited understanding of the long-term clinical burden of liver disease in unselected type 2 diabetes populations. The lack of prospective cohort studies with long-term follow-up durations. The need to identify individuals at increased risk of hepatic and extrahepatic outcomes.

    Long-term hepatic and extrahepatic outcomes in type 2 diabetes: final results of the prospective DM-FibroScan Study · 2026 · DOI

  • The need to identify novel immunometabolic drivers of disease progression. The lack of understanding of the context-dependent dual roles of MDSCs in MAFLD. The need to develop rational therapeutic strategies that preserve beneficial immune regulation while targeting pathogenic MDSC activity.

    Myeloid-derived Suppressor Cells in Metabolic Dysfunction-associated Fatty Liver Disease · 2026 · DOI

  • Validation in models that progress to advanced steatohepatitis with fibrosis is needed to define MLN's therapeutic scope across the disease spectrum.

    Integrated chemical profiling and lipidomics reveal that Mailuoning oral liquid alleviates diet-induced MASLD via PPARα-mediated lipid homeostasis and COX-2 inhibition, with identification of potential active constituents · 2026 · DOI

  • Future studies employing dosetitration designs, pharmacokinetic-pharmacodynamic modeling, and systems pharmacology approaches will be necessary to fully elucidate the complex interplay among the multiple active constituents of MLN across different dose levels. Validation in models that progress to advanced steatohepatitis with fibrosis is needed to define MLN's therapeutic scope across the disease spectrum.

    Integrated chemical profiling and lipidomics reveal that Mailuoning oral liquid alleviates diet-induced MASLD via PPARα-mediated lipid homeostasis and COX-2 inhibition, with identification of potential active constituents · 2026 · DOI

  • The lack of effective therapies targeting the multifactorial pathogenesis of non-alcoholic steatohepatitis. The limited understanding of the subcellular mechanisms underlying non-alcoholic steatohepatitis. The need for novel therapeutic agents that can regulate lipid metabolism, oxidative stress, and inflammation in non-alcoholic steatohepatitis.

    Chondroitin Sulfate as a Lysosomal Enhancer Attenuates Lipid-Driven Inflammation via Lipophagy and Mitophagy · 2025 · DOI

  • The paper identifies the need for an appropriate classification of individual phenotypes. It highlights the complexity of the pathophysiological history of MASLD, making the selection of a single effective treatment a major challenge.

    Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options · 2024 · DOI

  • Further studies are needed to understand the role of genetic, epigenetic, and environmental factors in the pathogenesis of MASLD. Researchers are constantly looking for alternatives that could improve the outcomes of the approaches currently used for MASLD treatment.

    Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)? · 2024 · DOI

  • The lack of homogeneity between studies on the effects of resveratrol on MASLD. The low bioavailability of resveratrol. The population variability in clinical trials on the effects of resveratrol on MASLD.

    Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)? · 2024 · DOI

  • The long-term stability of the MHO phenotype is debated. Many MHO individuals eventually develop MetS and carry increased risk of cardiovascular disease and mortality over time. Accurate phenotyping of obese patients is thus critical for risk stratification and management.

    Metabolic profiling of healthy vs. syndrome-associated obesity and effects of six-month metformin therapy · 2026 · DOI

  • Few drugs have been employed in clinical MAFLD treatment, - Most of these drugs still need to be verified by multicenter randomized controlled studies, - The study used a specific mouse model…

    Ursolic acid ameliorates metabolic dysfunction-associated fatty liver disease by regulating the NOX4/ROS/NLRP3 pathway · 2026 · DOI

  • Multicenter randomized controlled studies are needed to verify the effectiveness of drugs for MAFLD treatment, - Further research on the interaction between NOX4 and NLRP3…

    Ursolic acid ameliorates metabolic dysfunction-associated fatty liver disease by regulating the NOX4/ROS/NLRP3 pathway · 2026 · DOI

  • Further large, high-quality randomized trials are needed to clarify the long-term benefits and optimal use of metformin across disease stages, - Research on the effect of metformin in later stages of liver disease…

    Metabolic profiling of healthy vs. syndrome-associated obesity and effects of six-month metformin therapy · 2026 · DOI

  • Further exploration of metabolic heterogeneity among normal-BMI individuals with HS, - Investigation of the association between HS and carotid plaque in different…

    BMI–hepatic steatosis phenotypes and prevalent carotid plaque: a cross-sectional health examination study · 2026 · DOI

  • The study is retrospective, - The sample size is limited to 286 patients, - The study only includes patients with early-onset type 2 diabetes…

    Association of longitudinal serum 25-hydroxyvitamin D trajectories with subsequent liver stiffness increase in patients with early-onset type 2 diabetes and metabolic dysfunction-associated steatotic liver disease · 2026 · DOI

  • Investigate the effects of vitamin D supplementation on liver stiffness in patients with type 2 diabetes and MASLD, - Examine the relationship between 25(OH)D trajectories and liver-related events in patients with type 2 diabetes and MASLD, - Study the impact of 25(OH)D trajectories on cardiovascular outcomes in patients with type 2 diabetes…

    Association of longitudinal serum 25-hydroxyvitamin D trajectories with subsequent liver stiffness increase in patients with early-onset type 2 diabetes and metabolic dysfunction-associated steatotic liver disease · 2026 · DOI

  • The study used anonymized data which could not be traced back to individual persons, - The study did not obtain informed consent from individual patients, - The study was limited to patients…

    Both Alcoholic and Non-Alcoholic Liver Cirrhosis Are Associated with an Increased Risk of HF—A Cohort Study Including 75,558 Patients · 2025 · DOI

  • Further studies are needed to investigate the mechanisms underlying the association between LC and HF, - Studies should explore the potential benefits of early intervention and treatment of LC to prevent HF, - Research should focus on the development of strategies to reduce the risk of HF in patients…

    Both Alcoholic and Non-Alcoholic Liver Cirrhosis Are Associated with an Increased Risk of HF—A Cohort Study Including 75,558 Patients · 2025 · DOI

  • The decrease in hepatic lipids was not statistically significant, - The study had a limited number of clinical trials, - The study did not provide a comprehensive analysis of the long-term effects…

    Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options · 2024 · DOI

Most-cited papers in Liver Disease Diagnosis and Treatment

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Open questions raised by papers listed on this page include: (1) The relationship between MASLD and cardiovascular, renal, and metabolic dysfunction is not fully understood (“Cardiovascular–Kidney–Metabolic Syndrome and Its Hepatic Dimension: A Narrative…”, 2026); (2) The lack of CT attenuation thresholds for grading hepatic steatosis in this population (“CT Attenuation Thresholds for Grading Hepatic Steatosis in Adults with…”, 2026); (3) There is a need to evaluate the effects of aspirin and dapagliflozin on liver enzymes and FibroScan-derived parameters (“Anti-inflammatory versus metabolic therapy in MASLD: a randomized clinical…”, 2026); (4) The complexity of obesity-associated liver injury and the lack of effective treatments (“Magnolol alleviates high-fat diet-induced steatosis, inflammation and fibrosis…”, 2026); (5) Longitudinal studies are needed to establish the causal relationships between hepatic steatosis and glycemic control in T1D (“Hepatic steatosis is associated with postprandial dysglycemia in type 1…”, 2026). 2,102 gap statements have been mined from Liver Disease Diagnosis and Treatment papers in our 7.9M-paper local library, which holds 8,386 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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