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Open research questions in Liver Disease and Transplantation

36 unresolved questions extracted from the limitations and future-work sections of 407 Liver Disease and Transplantation papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • ABSTRACT Background and Aims It remains unclear whether different factors influence 30‐ and 90‐day readmission rates.

    Comparison of Factors Associated With 30‐Day and 90‐Day Readmission Among a Global Cohort of Patients Hospitalised With Cirrhosis · 2026 · DOI

  • Thrombocytopenia (TCP) is prevalent in these patients; however, the prognostic significance of severe TCP, defined as a platelet count < 50 × 109/L, on TIPS outcomes remains unclear.

    Association of severe thrombocytopenia with prognosis following transjugular intrahepatic portosystemic shunt in cirrhotic patients with portal hypertension · 2026 · DOI

  • Future studies should aim to address these gaps with adequately powered, multicenter RCTs. Standardized reporting of outcomes, including bleeding, mortality, adverse events, and quality of life, will be critical for more precise comparisons. Subgroup analyses stratified by cirrhosis etiology, baseline HVPG, and degree of decompensation could help identify which patients benefit most from carvedilol vs EVL. Moreover, as carvedilol may influence other complications of portal hypertension, future trials should extend beyond bleeding to include ascites, encephalopathy, and survival endpoints[27,51,52]. ⌃ Additionally, cost-effectiveness analyses and patient-reported outcome measures should be incorporated, as these factors are increasingly important in clinical decision-making. With growing evidence favoring carvedilol, guideline committees may consider recommending it as the default strategy for primary prophylaxis, reserving EVL for patient’s intolerant to NSBBs or with contraindications. Ultimately, the goal should be to develop an individualized, patient-centered approach that maximizes efficacy,  minimizes harm, and optimizes resource use in diverse healthcare settings. CONCLUSION This meta-analysis suggests that carvedilol and other NSBBs are associated with a lower risk of first variceal hemorrhage compared with EVL for primary prophylaxis in patients with cirrhosis. Despite no significant difference in bleeding-related mortality was observed, the reduction in first bleeding represents a clinically relevant benefit. Given the limited number of studies and heterogeneity in study design, these findings should be cautiously interpreted. Differences in safety profiles characterized by systemic adverse effects related to NSBBs and procedure-related complications associated with endoscopic ligation, highlight the importance of individualized treatment decisions. Future large-scale randomized trials should confirm these findings and explore the broader disease-modifying potential of carvedilol beyond bleeding prevention.

    Carvedilol and nonselective-beta-blockers <i>vs</i> endoscopic ligation for prophylaxis of esophageal variceal hemorrhage in cirrhosis: Systematic review and meta-analysis · 2026 · DOI

  • Background: Non-operative management (NOM) has become the standard of care for haemodynamically stable patients with liver trauma, yet robust data from low- and middle-income countries (LMICs) remain scarce, particularly in settings with a high burden of penetrating trauma.

    Outcomes of non-operative management of liver trauma in a low- and middle-income country: A single-centre experience from South Africa · 2026 · DOI

  • As an easily obtainable clinical metric, CG-CrCl may serve as a readily available risk marker, warranting further investigation as a potential component of risk assessment.

    Nonlinear association between cockcroft-gault creatinine clearance and all-cause mortality in critically ill cerebrovascular disease patients: a retrospective cohort study · 2026 · DOI

  • The role of albumin in these settings remains under discussion and is not fully established across all treatment scenarios. Therefore, further research into the health economics of albumin therapy across different settings may serve to 60 Hepatology ● July 2026 ● Copyright © 2026 EMJ ● CC BY-NC 4.

    Albumin Therapy for Advanced Liver Disease: New Data from the EASL Congress 2026 · 2026 · DOI

  • This study has several limitations. First, its retrospective design and reliance on EHR-based administrative coding introduce the possibility of residual confounding and misclassification. Although propensity score matching balanced measured covariates, unmeasured factors—such as cirrhosis severity (e.g., Model for End-Stage Liver Disease [MELD] or Child-Pugh scores), medication adherence, and alcohol consumption patterns—could not be assessed. Second, due to platform limitations, we could not ascertain cause-specific mortality or indications for hospitalization, nor could we determine the timing of SGLT2i discontinuation. Finally, generalizability may be limited to the healthcare systems represented in TriNetX.

    Empagliflozin versus dapagliflozin in patients with liver cirrhosis: A comparative real-world study on hepatic decompensation · 2026 · DOI

  • Notably, she also developed TRALI (defined by new-onset, non- cardiogenic pulmonary edema and acute hypoxemia developing during or within six hours of a blood and fresh frozen plasma transfusion and ACS (diagnosed by intra- abdominal hypertension of more than 20 mmHg and recent two organ dysfunction) - complications that have not been widely reported in association with AFLP.

    Acute Fatty Liver of Pregnancy: An Obstetric Emergency · 2026 · DOI

  • Long-standing hemodynamic alterations associated with IVC abnormalities may contribute to intrahepatic vascular remodeling and the development of portal hypertension, although a direct causal relationship remains uncertain.

    Absent inferior vena cava combined with idiopathic noncirrhotic portal hypertension resulting esophagogastric variceal bleeding: A case report · 2026 · DOI

  • Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) offer non-invasive alternatives, but their utility in tracking transjugular intrahepatic portosystemic shunt (TIPS)-induced hemodynamic changes remains unclear.

    Spleen stiffness accurately tracks early and sustained portal pressure changes after transjugular intrahepatic portosystemic shunt · 2026 · DOI

  • We assessed the strengths and limitations of this study and proposed future research directions to refine the research model and deepen our understanding of PBLSs characteristics in acute exacerbations of ACLF.

    Letter to the Editor: Characteristics of peripheral blood lymphocyte subpopulations in acute-on-chronic liver failure: A call for further exploration · 2026 · DOI

  • Multicenter prospective studies with larger, etiology-strat- ified cohorts across diverse geographic and ethnic popu- lations are needed to validate these findings and establish reliable, population-specific diagnostic thresholds. Lon- gitudinal cohort studies tracking children without varices at baseline would clarify the true predictive value of these markers for variceal development and bleeding risk over time. Integration of emerging technologies such as tran- sient elastography and shear-wave elastography, when available, may further improve risk stratification. Collabo- rative registries across MENA-region pediatric hepatology centers could address the current evidence gap and provide adequately powered data for developing and validating region-specific clinical prediction rules.

    Noninvasive indices associated with esophageal varices in children with portal hypertension: a single-center exploratory diagnostic accuracy study · 2026 · DOI

  • umin dosing in ACLF as of now, the dose chosen in our study was arbitrary and not protocolized, which is a major limitation. Lastly, the included patients were outpatients with ACLF type A (APASL) and lower MELD scores, and the results may not be generalizable to high MELD ACLF type B (EASL-CLIF and NAC- SELD) patients, who are typically in the inpatient cohort.

    Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites—A randomized trial (MIDAS trial) · 2026 · DOI

  • While emergency percutaneous transhepatic coil embolization of bleeding peristomal varices serves as a safe and effective life-saving option - particularly when a TIPS is contraindicated - the long-term threat of recurrence remains a significant limitation of local interventions.

    Ileal Conduit Peristomal Varices Treated via Percutaneous Transhepatic Embolization: A Case Report · 2026 · DOI

  • All included studies were retrospective observational cohorts, precluding causal inference. Residual confounding by cirrhosis severity persists despite propensity score adjustment, as SGLT2i may have been preferentially prescribed to less advanced patients. The small number of studies per outcome (two to three) limited statistical power and precluded publication bias assessment. Substantial heterogeneity for mortality and decompensation was driven by aetiological diversity - alcohol-related in Saffo 2021, viral hepatitis- predominant in the Taiwanese cohorts, and MASLD in Abu-Hammour 2025. Cirrhosis severity by Child-Pugh or MELD was inconsistently reported, preventing disease-stage subgroup analyses.

    Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes Mellitus and Liver Cirrhosis: A Systematic Review and Meta-Analysis · 2026 · DOI

  • Prospective randomised trials comparing SGLT2i with DPP4i in established cirrhosis, stratified by Child- Pugh class and aetiology, are a research priority. Standardised, graded definitions for HE are essential given the discordance between the contributing studies. Trials should include variceal events, ascites-free survival, 2026 Shetty et al. Cureus 18(5): e109532. DOI 10.7759/cureus.109532 8 of 10 and HCC as pre-specified long-term outcomes. Individual patient data meta-analysis would enable subgroup analyses by cirrhosis severity and specific SGLT2i agent that the current study-level analysis could not perform.

    Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes Mellitus and Liver Cirrhosis: A Systematic Review and Meta-Analysis · 2026 · DOI

  • This article discusses the case of a 71-year-old patient with known splenomegaly, which had not been fully investigated and lacked a hematological explanation.

    Portosinusoidal vascular disease with portal hypertension – a case report · 2024 · DOI

  • Currently, there is insufficient scientific data on renal function in patients with comorbid course of liver cirrhosis (LC) and atrial fibrillation (AF), as well as the effect of anticoagulant treatment on kidney function in these patients.

    Assessment and comparative analysis of renal function parameters in patients with liver cirrhosis and atrial fibrillation · 2023 · DOI

  • The excerpt is incomplete and cuts off mid-sentence regarding the Child-Turcotte-Pugh (CTP) score discussion, leaving the full context and conclusions about this prognostic factor unclear.

    THE CORRELATION BETWEEN SONOGRAPHIC PORTAL AND SPLENIC VEIN DIAMETERS WITH CLINICOPATHOLOGICAL LIVER STATUS IN CIRRHOTIC PATIENTS. · 2016 · DOI

  • Importantly, no data exist (to the best of our knowledge) for determining whether a log-normal dis- tribution is an appropriate choice for modeling sinusoidal alterations due to cirrhosis and what values of csin and σ (Table 3) are most accurate for the healthy and cirrhotic liver.

    Lumped parameter modeling of changes in liver hemodynamics due to cirrhosis · 2026 · DOI

  • The precise pathophysiology remains incompletely understood, but proposed mechanisms include peripheral nerve hyperexcitability from oxidative stress, altered amino acid and energy metabolism, and deficiencies in taurine, carnitine, and branched-chain amino acids.

    Muscle cramps in liver cirrhosis: Pathophysiology, burden, and emerging therapeutic approaches · 2026 · DOI

  • 12 Similarly, “gastrointestinal failure” was loosely defined and has not been validated in ACLF.

    Consensus versus Outcome-based Definitions of Acute-on-chronic Liver Failure: Implications for Risk Stratification and Case Identification · 2026 · DOI

  • Sarcopenia, a common muscle-wasting syndrome in cirrhosis, is tied to portal hypertension, but its role in TIPS efficacy remains unclear.

    Sarcopenia as a novel biomarker for predicting TIPS outcomes in cirrhotic patients with refractory ascites: Mechanisms linking muscle loss, metabolic dysregulation, and portal hemodynamics · 2025 · DOI

  • The impact of comorbidities caused by the cardiovascular system, in particular diffuse lesions of internal organs are not fully investigated under this condition.

    The dynamics of cytolytic syndrome parameters in the period of late manifestations of cranioskeletal trauma in case of concomitant chronic hepatitits and the effectiveness of armadine correction · 2021 · DOI

  • Future work directions regarding potential clinical applications of portal and splenic vein diameter measurements for cirrhosis staging or prognosis are not explicitly stated in this excerpt.

    THE CORRELATION BETWEEN SONOGRAPHIC PORTAL AND SPLENIC VEIN DIAMETERS WITH CLINICOPATHOLOGICAL LIVER STATUS IN CIRRHOTIC PATIENTS. · 2016 · DOI

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36 open questions have been extracted from the limitations and future-work passages of 407 Liver Disease and Transplantation 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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