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Open research questions in Hepatocellular Carcinoma Treatment and Prognosis

1,331 gap statements mined from Hepatocellular Carcinoma Treatment and Prognosis papers in our 7.9M-paper local library, which holds 5,350 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 lack of a standardized benchmark for evaluating HCC segmentation models. The need for a comprehensive evaluation of HCC segmentation models across different phases and datasets.

    Hepatocellular Carcinoma Segmentation on MRI: Five-Fold ATLAS Benchmarking, Phase-Wise External Stress Testing, and Multiphasic OpenSwissHCC Ablation · 2026 · DOI

  • The optimal assessment time point and AFP decline threshold for lenvatinib response remain unstandardized. There is a need to evaluate the association between AFP change and imaging response in patients with HCC treated with lenvatinib. The study aims to address this gap by determining the predictive value of on-treatment AFP change for lenvatinib response.

    Predictive Value of On-Treatment Alpha-Fetoprotein Change for Lenvatinib Response in Patients with Hepatocellular Carcinoma: A Real-World Retrospective Study in Vietnam · 2026 · DOI

  • The risk of biliary complications, including bile leaks, is a potential challenge of mesohepatectomy. The need to preserve the future liver remnant while achieving oncological clearance is a key challenge of this technique.

    Parenchyma-Preserving Mesohepatectomy for Centrally Located Hepatic Tumors: A Single-Institution Experience · 2026 · DOI

  • Traditional management of centrally located hepatic tumors may result in an inadequate future liver remnant. Parenchyma-preserving mesohepatectomy may provide a viable alternative, but its feasibility and outcomes are not well established. There is a need for further research on the use of this technique in achieving oncological clearance while preserving the future liver remnant.

    Parenchyma-Preserving Mesohepatectomy for Centrally Located Hepatic Tumors: A Single-Institution Experience · 2026 · DOI

  • The literature has no consensus on the size at which a hemangioma is considered giant. There is a need for a safe and effective alternative treatment option to surgery.

    Management and Clinical Outcomes of Liver Hemangiomas: A Retrospective Comparative Study of Transcatheter Arterial Embolization and Surgery · 2026 · DOI

  • The study notes that the evidence remains retrospective and mostly Asian, with wide variation between studies. The study highlights the challenge of heterogeneity in outcomes across studies, which limits the interpretability of the results. The study also notes the challenge of publication bias, which is assessed using funnel plots and Egger's linear regression test.

    Post-transplant oncologic outcomes after locoregional downstaging before living donor liver transplantation for hepatocellular carcinoma beyond Milan criteria: a systematic review and meta-analysis of selected cohorts · 2026 · DOI

  • Lack of biomarkers for predicting treatment efficacy in uHCC receiving T-B-S therapy. Need for a noninvasive and easily assessable clinical model to predict prognosis. Limited understanding of the prognostic factors for overall survival in uHCC receiving T-B-S therapy.

    ABT score based clinical model predicts prognosis in unresectable hepatocellular carcinoma treated with TACE combined with bevacizumab and sintilimab therapy · 2026 · DOI

  • The urgent need for novel combination strategies to improve treatment outcomes for unresectable hepatocellular carcinoma. The limited understanding of the efficacy and safety of combining transarterial chemoembolization with systemic agents for advanced-stage disease.

    Efficacy and safety of sintilimab plus bevacizumab with or without transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score-matched retrospective cohort study · 2026 · DOI

  • Limited data on the costs of percutaneous segmentectomy. Difficulty in comparing costs across different treatments and studies.

    Cost Analysis of Percutaneous Segmentectomy Versus Chemoembolisation and Radioembolisation in Hepatocellular Carcinoma: A Retrospective Multicentre Cohort Study · 2026 · DOI

  • Limited cost comparisons between percutaneous segmentectomy and other treatments. Need for a comprehensive cost analysis of these treatments. Uncertainty about the effectiveness of these treatments in terms of life-years.

    Cost Analysis of Percutaneous Segmentectomy Versus Chemoembolisation and Radioembolisation in Hepatocellular Carcinoma: A Retrospective Multicentre Cohort Study · 2026 · DOI

  • The inclusion of numerous HLA allotypes in the analysis was exploratory in nature and, combined with a sample size limited to our institutional experience, the conclusions should be considered hypothesis-generating rather than definitive.

    HLA-C*04 and hepatocellular carcinoma post-surgical survival in Hawaii · 2026 · DOI

  • Future work should confirm whether HLA allotypes correlate with survival outside of early stage, predominantly Asian and Pacific Islander populations. Future studies may benefit from selecting RFS or HCC-specific survival as an endpoint to isolate the HLA-specific contribution.

    HLA-C*04 and hepatocellular carcinoma post-surgical survival in Hawaii · 2026 · DOI

  • Financial constraints limited the patient's access to standard treatment. The patient experienced grade 2 hand-foot skin reaction with regorafenib. The patient had a large tumor with IVC tumor thrombus, posing a severe therapeutic challenge.

    Dramatic and sustained regression of an inferior vena cava tumor thrombus in a patient with unresectable giant hepatocellular carcinoma following sequential systemic therapy: a case report and literature review · 2026 · DOI

  • The precise timing of liver fibrosis progression remains unclear because it was determined at the second liver biopsy, introducing interval censoring. The study might miss medical interventions that affect prognostic risk in the retrospective clinical database, such as detailed information about anti-HBV therapies.

    Serum secretome signatures for risk of hepatocellular carcinoma and fibrosis progression in chronic liver diseases in the U.S. · 2026 · DOI

  • The lack of validated biomarkers for predicting disease progression is a major gap. The majority of proposed biomarkers and clinical scores have not been satisfactorily validated for clinical translation. There is a need for improved prediction accuracy according to patient characteristics.

    Serum secretome signatures for risk of hepatocellular carcinoma and fibrosis progression in chronic liver diseases in the U.S. · 2026 · DOI

  • The Milan criteria exclude many patients who could achieve favorable outcomes with liver transplantation. There is a need to identify prognostic factors associated with long-term survival in patients with hepatocellular carcinoma beyond the Milan criteria. The effectiveness of locoregional therapy in downstaging tumors is not well established.

    Prognostic Stratification after Successful Downstaging of Hepatocellular Carcinoma beyond the Milan Criteria: Potential Implications for Liver Transplant Candidate Selection · 2026 · DOI

  • The study faces challenges in terms of the limited granularity of treatment data in the SEER database. The study is restricted by the lack of detailed information on the specific types or intent of surgeries performed. The study faces challenges in terms of the potential influence of external factors, such as the COVID-19 pandemic, on the results.

    Ten-Year Trends in Hepatocellular Carcinoma Mortality: Examining the Interaction Between Fibrosis Score and Patient Age · 2025 · DOI

  • Lack of predictive biomarkers for ICIs. Limited understanding of drug resistance mechanisms in HCC. Need for tailored interventions for individual patients.

    Hepatocellular Carcinoma Immunotherapy: Predictors of Response, Issues, and Challenges · 2024 · DOI

  • Investigation of diagnostic performance of CT and MRI features for tumour thrombus, - Study of the relative frequency of synchronous and metachronous dissemination, - Research on the biological and small-lesion limitations of functional…

    The Thoracic Footprint of Hepatocellular Carcinoma: A Mechanism-Based Imaging Narrative Review · 2026 · DOI

  • Prospective intention-to-treat studies are needed, - Studies with comparison groups are necessary, - Research on the benefit of downstaging itself…

    Post-transplant oncologic outcomes after locoregional downstaging before living donor liver transplantation for hepatocellular carcinoma beyond Milan criteria: a systematic review and meta-analysis of selected cohorts · 2026 · DOI

  • The study was retrospective, - The sample size was limited to 156 patients, - The follow-up time interval was short…

    ABT score based clinical model predicts prognosis in unresectable hepatocellular carcinoma treated with TACE combined with bevacizumab and sintilimab therapy · 2026 · DOI

  • Further in vivo studies are needed to determine whether RA can serve as a DDP-sensitizing agent - Clinical studies are needed to determine whether the effects of RA and DDP on HCC cells translate into clinical benefit - Studies on the molecular mechanisms of RA and DDP in HCC cells…

    Rosmarinic acid combined with cisplatin induces proliferation inhibition of hepatocellular carcinoma · 2026 · DOI

  • Ongoing research is focused on refining molecular classifications and advancing precision medicine strategies to improve outcomes - Research is needed to identify predictive biomarkers and personalize therapy - Studies are required to optimize treatment and improve early…

    Hepatocellular Carcinoma: A Comprehensive Review · 2025 · DOI

  • The SEER database does not provide detailed information on the specific types or intent of surgeries performed, - Chemotherapy data in SEER lack granularity regarding treatment type and regimen, - The study was limited to data from the SEER program, which encompasses approximately 28% of the national…

    Ten-Year Trends in Hepatocellular Carcinoma Mortality: Examining the Interaction Between Fibrosis Score and Patient Age · 2025 · DOI

  • Identification of reliable predictive biomarkers - Overcoming ICI resistance - Efficient management…

    Hepatocellular Carcinoma Immunotherapy: Predictors of Response, Issues, and Challenges · 2024 · DOI

Most-cited papers in Hepatocellular Carcinoma Treatment and Prognosis

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Open questions raised by papers listed on this page include: (1) The lack of a standardized benchmark for evaluating HCC segmentation models (“Hepatocellular Carcinoma Segmentation on MRI: Five-Fold ATLAS Benchmarking,…”, 2026); (2) There is a need to evaluate the association between AFP change and imaging response in patients with HCC treated with lenvatinib (“Predictive Value of On-Treatment Alpha-Fetoprotein Change for Lenvatinib…”, 2026); (3) Parenchyma-preserving mesohepatectomy may provide a viable alternative, but its feasibility and outcomes are not well established (“Parenchyma-Preserving Mesohepatectomy for Centrally Located Hepatic Tumors: A…”, 2026); (4) There is a need for a safe and effective alternative treatment option to surgery (“Management and Clinical Outcomes of Liver Hemangiomas: A Retrospective…”, 2026); (5) Lack of biomarkers for predicting treatment efficacy in uHCC receiving T-B-S therapy (“ABT score based clinical model predicts prognosis in unresectable…”, 2026). 1,331 gap statements have been mined from Hepatocellular Carcinoma Treatment and Prognosis papers in our 7.9M-paper local library, which holds 5,350 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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