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Open research questions in Liver Disease and Transplantation

172 unresolved questions extracted from the limitations and future-work sections of 522 Liver Disease and Transplantation papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • the study was conducted at a single institution, - the cohort was limited to patients with cirrhosis, - approximately half of the patients classified as low risk nevertheless had HREV

    A non-invasive nomogram for high-risk esophageal varices in cirrhosis without transient elastography: development and internal validation · 2026 · DOI

  • further validation of the HREV-nomogram in larger and more diverse populations, - exploration of the nomogram's performance in different clinical settings

    A non-invasive nomogram for high-risk esophageal varices in cirrhosis without transient elastography: development and internal validation · 2026 · DOI

  • Future research should focus on integrated classification systems and prospective comparative studies to establish standardized, individualized management algorithms.

    Pathophysiological management of gastric varices: From hemodynamics to targeted therapies · 2026 · DOI

  • In clinical datasets, missingness patterns may also carry predictive information, but their value for cirrhosis identification remains insufficiently investigated.

    Missingness-aware machine learning using routine laboratory data for distinguishing hepatitis from cirrhosis · 2026 · DOI

  • Currently, standardized diagnostic and therapeutic protocols are lacking for managing congenital portosystemic shunts accompanied by multifocal HB.

    Multidisciplinary management of congenital portosystemic shunt complicated by multifocal hepatoblastoma: a case report · 2026 · DOI

  • However, limited data exist on the pathogen distribution and severity of liver injury in children with CAP-associated liver injury.

    Pathogen distribution and liver injury severity in children with community-acquired pneumonia complicated by liver injury in Suzhou, China · 2025 · DOI

  • The prognosis of isolated cases is generally favorable; however, the exact incidence remains unknown.

    Perinatal outcomes in cases of umbilical-portal-systemic venous shunts: experience of a tertiary center · 2025 · DOI

  • However, its potential role in predicting all-cause mortality in patients with liver failure remains unexplored.

    Association between lactate-to-albumin ratio and mortality in hepatic failure: a retrospective cohort study · 2025 · DOI

  • FINDINGS: From the focus group interviews, three themes were identified: medical culture, gaps in knowledge, and bias against those with self-induced causes of ESLD.

    A qualitative study of end‐stage liver disease and liver transplant referral practices among primary care providers in nonurban America · 2024 · DOI

  • Despite its common occurrence, the etiology and pathogenesis of liver cirrhosis remain incompletely understood, posing a significant health threat.

    Liver cirrhosis: current status and treatment options using western or traditional Chinese medicine · 2024 · DOI

  • In future, the efficacy and safety of tenecteplase should be explored in acute extensive PVST cases.

    Case Report: First attempt by off-label use of tenecteplase to treat acute extensive portal venous system thrombosis · 2024 · DOI

  • In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear.

    Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study · 2024 · DOI

  • Most existing studies rely on cross-sectional or static observational designs, which limit the exploration of the temporal sequence and potential causal relationships among symptoms. There is a need for prospective longitudinal studies to investigate the trajectories of symptom burden in patients with liver cirrhosis.

    Trajectories of symptom burden and associated factors in patients with liver cirrhosis: a prospective study · 2026 · DOI

  • The incidence of HE after TIPS is as high as 54.5%, affecting quality of life and survival. There is a need for a predictive model to forecast OHE within 1 year post-TIPS.

    A new direction in personalized medicine: multimodal joint prediction of hepatic encephalopathy risk post-TIPS · 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

  • High short-term mortality rate associated with acute-on-chronic liver failure. Complexity of the clinical syndrome. Limited understanding of the risk factors for common complications.

    Risk factors for pneumonia, hepatic encephalopathy, and acute kidney injury in patients with hepatitis B virus–related acute-on-chronic liver failure · 2026 · DOI

  • Limited data regarding the risk factors for pneumonia, hepatic encephalopathy, and acute kidney injury in patients with hepatitis B virus-related acute-on-chronic liver failure.

    Risk factors for pneumonia, hepatic encephalopathy, and acute kidney injury in patients with hepatitis B virus–related acute-on-chronic liver failure · 2026 · DOI

  • The lack of a universally accepted definition for ACLF. The need for a harmonized definition to facilitate comparability across studies.

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

  • There is a need for effective treatment options for Budd-Chiari syndrome complicated with IVC/SVC stenosis.

    Simultaneous IVC/SVC Endovascular Sharp Recanalization in A Patient with Budd-Chiari Syndrome, Systemic Lupus Erythematosus and Antiphospholipid Syndrome, A Case Report · 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

  • Identifying and treating precipitating factors. Managing other decompensating cirrhosis-related complications. Delaying further liver disease progression.

    Reducing the Risk of Overt Hepatic Encephalopathy Recurrence: A Narrative Review · 2026 · DOI

  • Investigational agents, such as nitazoxanide, fecal microbiota transplantation, and the use of artificial intelligence, app-based technology, and wearable devices, should be further studied. More research is needed on the use of lactulose and other pharmacotherapies in the management of HE.

    Reducing the Risk of Overt Hepatic Encephalopathy Recurrence: A Narrative Review · 2026 · DOI

  • The role of midodrine in patients with high MELD ACLF remains unknown. There is a need for studies to evaluate the effect of midodrine on outcomes in these patients.

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

  • Future research can use the model to investigate the effects of different treatments on liver blood flow. Future research can aim to validate the model using experimental data.

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

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172 open questions have been extracted from the limitations and future-work passages of 522 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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