Open research questions in Hepatocellular Carcinoma Treatment and Prognosis

What the literature leaves open

• hepatocellular on carcinoma. Hepatol Int. [12] Zandieh G, Yazdaninia I, Afyouni S, et al. Spectrum of Imaging Findings and Complications After Hepatic Transarterial Chemoembolization for Liver Tumors. J Comput Assist Tomogr. 2024;48(5):701-712. doi:10.1097/RCT.0000000000001610 ARTICLE IN PRESSACCEPTED MANUSCRIPTARTICLE IN PRESS [13] Piscaglia F, Tovoli F, Pini P, Salvatore V. A new horizon in the prevention of the postembolization syndrome after transcatheter arterial chemoembolization for hepatocellular carcinoma. Hepatology. 2018;67(2):467-469. doi:10.1002/hep.29517 [14] Mason MC, Massarweh NN, Salami A, Sultenfuss MA, Anaya DA. Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma. HPB (Oxford). 2015;17(12):1137-1144. doi:10.1111/hpb.12487 [15] Zhao J, Zou Z, Zheng Q, Liu C. Clinical predictors for liver function impairment and post-embolization syndrome following transcatheter arterial chemoembolization in primary hepatic carcinoma patients: a retrospective study. Am J Cancer Res. 2025;15(5):2259-2274. Published 2025 May 15. doi:10.62347/PJVG6340 [16] Bai J, Huang M, Zhou J, Song B, Hua J, Ding R. Development of a predictive nomogram for postembolization syndrome after transcatheter arterial chemoembolization of hepatocellular carcinoma. Sci doi:10.1038/s41598-024-53711-y Rep. 2024;14(1):3303.

  Analysis of risk factors for post-transarterial chemoembolization syndrome in patients with liver cancer: a systematic review protocol · 2026 · DOI

• Although current research focuses on the risk factors for embolization syndrome after TACE in liver cancer patients, the studies are scattered and the results are contradictory.

  Analysis of risk factors for post-transarterial chemoembolization syndrome in patients with liver cancer: a systematic review protocol · 2026 · DOI

• These findings, together with consistent evidence from the broader literature, support the biological relevance of epigenetic regulators in HCC and warrant further investigation in larger prospective studies to clarify the roles of EZH2 and INI-1 as prognostic biomarkers and potential therapeutic targets.

  Immunohistochemical Expression of EZH2 and INI-1 in Hepatocellular Carcinoma: Prognostic Significance in a Retrospective Cohort Study · 2026 · DOI

• level intensified during surgery and in the early postoperative period, and may be appropriately reduced once blood glucose levels stabilize (16, 21, 23). 16.During the perioperative period, ensure safe handover procedures between the operating room, anesthesia recovery room, and patient ward. Maintain complete documentation of blood glucose monitoring results, medication administration, and relevant medical orders (21). 17. Develop personalized blood glucose monitoring protocols. Blood glucose monitoring is performed upon patient admission, on the morning of surgery, during surgery, and upon return to the ward postoperatively. For patients with abnormal blood glucose levels, monitoring is conducted every 30–60 minutes during surgery and every 1–2 hours postoperatively. In cases of abnormal blood glucose fluctuations, monitoring frequency should be increased as necessary based on blood glucose levels, or CGM should be employed. This should be combined with blood gas analysis to ensure effective management of blood glucose, electrolytes, and acid-base balance (18, 21, 22, 26) 18. Intraoperative blood glucose targets should be maintained between 6.0–10.0 mmol/ L, with routine point-of-care testing (POCT) monitoring every 2 hours (17, 21, 24). 19. Minimize blood glucose fluctuations in patients with perioperative stress hyperglycemia (SH) during nutritional support therapy, maintaining blood glucose levels between 8.0–10.0 mmol/L (22). 20. The target blood glucose level within 3 days postoperatively should be <12.0 mmol/ L (21). 21.Definition of hypoglycemia: CBG <4 mmol/L; For individuals with lower hypoglycemia risk managed by diet and medication: Recommended target range is 4–12 mmol/L; For most patients using hypoglycemic agents/insulin: Intervention should be considered at CBG <6.0 mmol/L to prevent hypoglycemia (16, 17). 22. Hypoglycemia is a significant perioperative risk. When hypoglycemia is suspected during the perioperative period, point-of-care testing (POCT) should be performed immediately and reported to the physician. For patients with confirmed hypoglycemia, monitoring intervals should be shortened based on clinical condition until blood glucose is corrected (21, 24). 23. Intervention should be considered when blood glucose exceeds 10 mmol/L. Discontinue VRIII and treat hypoglycemia when glucose falls below 6 mmol/L, then restart within 20 minutes. If glucose remains above 12 mmol/L for three consecutive readings with insufficient decline, increase the infusion rate. Reduce the VRIII rate if hypoglycemia risk factors are present (16, 17). 24. When hypoglycemia is confirmed by a conscious individual, immediately administer 15 g of carbohydrates. Perform a point-of-care test (POCT) after 15 minutes. If blood glucose remains uncorrected, repeat the above measures. If blood glucose has been corrected to 3.9 mmol/L or above but the next meal is more than 1 hour away, continue providing starchy or protein-containing foods (21). 25.If the patient experiences discomfort or persistent hyperglycemia (>13 mmol/L on two or more consecutive occasions), measure capillary blood ketones. For patients regularly using SGLT2 inhibitors, daily blood ketone monitoring is recommended during hospitalization (17). 26.When blood glucose exceeds 13.9 mmol/L or symptoms such as nausea and vomiting occur, immediately notify the physician for intervention and perform POCT testing once every 30 minutes (21). 27.For patients with primary liver cancer and diabetes undergoing surgery, implementing glycemic index (GI)-based dietary guidance in addition to conventional dietary advice improves glucose metabolism control during the 1–3 months postsurgery (29). 28. Diabetes education for patients and their families is provided throughout the perioperative period (23).

  Evidence summary on perioperative blood glucose management in liver cancer patients · 2026 · DOI

• level team-based perioperative glycemic management 1. Supported by a team of diabetes specialists, it helps standardize blood glucose monitoring and intervention (21). preoperative assessment management medication and nutritional management 2. Establish a multidisciplinary blood glucose management team led by hepatobiliary surgery, incorporating endocrinology, anesthesiology, nutrition, rehabilitation, and nursing teams, and provide specialized training for medical staff across relevant departments (21, 23, 26). 3. Utilizing an information-based blood glucose management system enables real-time monitoring, sharing, and automated alerts for perioperative blood glucose data (26). 4. Upon admission, liver cancer patients should undergo point-of-care testing (POCT), fasting blood glucose, and HbA1c assessments to evaluate baseline glycemic control and antidiabetic medication use. A comprehensive evaluation should include liver disease status, Child-Pugh classification, severity of hepatitis or cirrhosis, AFP levels, and endorgan damage (21). 5. Preoperative HbA1c testing is recommended to assess glycemic control over the past 3 months, supplemented by venous fasting blood glucose (FBG) and capillary blood glucose (CBG) to evaluate perioperative glucose levels. HbA1c ≥bA mmol/mol (6.5%) indicates diabetes, while HbA1c ≥bA mmol/mol (9.0%) suggests poor glycemic control. Elective surgery should be postponed to allow for glycemic optimization. Preoperative HbA1c should be optimized to <69 mmol/mol (8.5%) whenever possible. Values >69 mmol/mol (8.5%) warrant specialist consultation (16, 17) (21, 23, 24) 6. All diabetic patients should have a clear, written perioperative blood glucose management plan established prior to surgery, including fasting arrangements, adjustments to hypoglycemic medications, blood glucose monitoring frequency, and protocols for managing abnormal blood glucose levels (16). 7.Patients with perioperative hyperglycemia should receive the same level of perioperative blood glucose monitoring and management as those with known diabetes (16). 8. Adjust hypoglycemic therapy during the perioperative period based on drug type. All non-insulin hypoglycemic agents should be discontinued on the day of surgery. Among these, SGLT2 inhibitors should be stopped at least 2 days prior to surgery and on the day of surgery to reduce the risk of normal glycemic ketoacidosis. Continue basal insulin therapy perioperatively; avoid complete discontinuation of insulin. If patients are at risk for nocturnal or recent hypoglycemia, reduce basal insulin dosage by approximately 20% (16). 9. Variable Rate Intravenous Insulin Infusion (VRIII) is prioritized for: skipping >1 meal, T1DM without basal insulin, HbA1c >6.9% (8.5%), most emergency cases, and persistent perioperative hyperglycemia. The recommended fluid for the VRIII bypass is 5% glucose + 0.45% saline + KCl; alternating 5% glucose and 0.9% saline based on blood glucose levels is not recommended (17). 10. Intravenous administration of 2500 U/kg of ulinastatin prior to anesthesia induction and at the start of surgery in patients undergoing partial hepatectomy effectively prevents intraoperative insulin resistance (27). 11.For elderly patients undergoing liver resection, the intraoperative use of dexmedetomidine may help stabilize the stress response and thereby provide some assistance in controlling post-operative blood glucose levels (28). 12.The stress hyperglycemia ratio (SHR) can serve as an indicator for monitoring blood glucose levels in perioperative patients during nutritional support therapy (22). 13.For patients with perioperative hyperglycemia undergoing nutritional support, continuous insulin infusion via an intravenous infusion pump is an ideal strategy (19, 22). 14. For patients undergoing planned liver resection, minimize fasting duration by implementing a 6-hour preoperative fasting period and a 2-hour fluid restriction. Providing moderate carbohydrate beverages the night before surgery and 2 to 4 hours prior to anesthesia induction improves postoperative glucose control and significantly reduces perioperative insulin resistance compared to traditional overnight fasting (16– 20, 22, 25) blood glucose monitoring and targets 15.Appropriate blood glucose monitoring methods should be selected for different perioperative phases, with point-of-care testing (POCT) being the preferred choice, particularly for hemodynamically stable patients.

  Evidence summary on perioperative blood glucose management in liver cancer patients · 2026 · DOI

• (2) For the problem of the high imbalance in the number of foreground and background pixels or voxels in an image, it should be further investigated the rational use of the hybrid loss function to better distinguish the foreground from the background. (3) In order to extract more effective features to improve segmentation performance and reduce redundant operations to improve computational efficiency, improved methods of network structure, such as path connectivity and convolution operations, should be further investigated.

  Retraction Notice: Liver tumor segmentation method based on U-Net architecture: a review · 2026 · DOI

• This case adds to the limited literature describing HART in patients with CHB and emphasizes that, despite advances in liver imaging, histopathological evaluation remains the gold standard for diagnosis.

  Hepatic Adrenal Rest Tumour (HART) Preoperatively Diagnosed as Hepatocellular Carcinoma in a Patient With Chronic Hepatitis B: Radiological Similarities in Lesions · 2026 · DOI

• Addition- ally, future studies should explore its potential synergistic effects with other therapeutic approaches, which may contribute to more effective strategies for HCC management. The present findings also warrant further investigation into the underlying mecha- nisms of action of SEx-NP, particularly across different stages of liver disease.

  Therapeutic and preventive potential of novel sulfur nanoparticles via immunomodulation in hepatocellular carcinoma · 2026 · DOI

• Locoregional therapies, including hepatic artery infusion pump (HAIP) delivery of floxuridine, have not been thoroughly evaluated for treatment of ACC liver metastasis, likely due to its rare incidence and highly aggressive nature.

  Study protocol: targeted delivery of interleukin-12 in combination with hepatic artery infusion pump therapy for patients with adrenocortical carcinoma liver metastases · 2026 · DOI

• We included only patients covered by OHIP, excluding refugees, Indigenous patients, and military personnel with federal coverage. Although these groups represent a small proportion of the Ontario population, their exclusion may lead to underrepresentation of certain populations. The organization of Ontario’s health care system into 14 regional LHINs was replaced by a single agency (Ontario Health) in 2019. This administrative change had a limited impact on delivery of patient care, and LHINs remain a useful geographic framework for examining regional treatment patterns and population-level variation in access.39 Furthermore, patients with HCC may travel or temporarily relocate to access specialized care, Can J Surg/J can chir 2026;69(3) E313 RESEARCH such that LHIN of residence may not reflect the site of diagnosis or treatment. Therefore, geographic variations in treatment and survival should be interpreted as reflecting population-level data rather than centre-level perform ance. We identified patients with HCC using a previously validated case definition with high performance. This definition captures patients with HCC using diagnostic and procedural codes, with certain combinations incorporating a diagnosis of cirrhosis to improve performance.18 Although this approach may modestly underestimate the absolute incidence of HCC arising in noncirrhotic livers, the same criteria were applied uniformly across all regions, limiting its effect on relative geographic comparisons. This work was intentionally framed as a descriptive study to characterize regional variation in treatment and survival across Ontario. Treatment of HCC depends on patient and disease factors such as size, vascular involvement, and tumour burden, which are not captured in administrative databases. Without adjustment for these clinical determinants, it is not possible to attribute observed differences solely to regional access - ibility. Rather, our intention was to highlight the presence and magnitude of variation within Ontario, which is likely multifactorial and warrants further investigation with more granular clinical data. Finally, given challenges in reliable case identification, we did not report variation in nonsurgical treatments in granular detail and grouped such treatments broadly as “other.” This was a purposeful methodological decision, as preliminary analysis revealed regional variations in coding practices for locoregional therapies and the absence of validated administrative codes. Future work evaluating regional patterns of nonsurgical treatments will require validation of these modalities to ensure accurate comparisons across regions.

  Trends in the incidence and surgical treatment of hepatocellular carcinoma in Ontario · 2026 · DOI

• Traditional MIS scores are poorly studied in RLS, and conventional statistics often oversimplify the multifactorial and interrelated nature of these complications.

  Validation of the three-level hepatectomy complexity classification and its AI application in robotic liver surgery · 2026 · DOI

• ctDNA is emerging as a prognostic and potentially predictive biomarker in CRLM. Multiple studies have demonstrated that ctDNA positivity following curative resection is associated with early recurrence and inferior survival, while ctDNA negativity identifies patients with more indolent disease biology [33,34]. Prospective trials [35,36] are now exploring the role of ctD- NA-guided adjuvant therapy. In practical terms, ctDNA offers a route beyond broad clinicopathologic surrogates toward molecular residual disease stratification. This would involve enriching postoperative systemic therapy for patients with persistent ctDNA positivity while identifying lower-risk patients in whom treatment could potentially be de-escalated or withheld. Therefore, ctDNA may help define which patients are most likely to benefit from perioperative chemotherapy. Integrating ctDNA with clinicopathologic and molecular risk factors may further refine individualized treatment sequencing in the future.

  Resect first in resectable colorectal liver metastases: recalibrating the default · 2026 · DOI

• The choice of liver-based normalization for choline PET/CT remains a matter of debate, as no standardized threshold for lesion segmentation in HCC has been estab- lished.

  Limited Added Prognostic Value of Choline PET/CT in Treatment-Naïve Hepatocellular Carcinoma · 2026 · DOI

• The protein toxicity induced by ned- dylation inhibition is irreversible; although cells activate survival signals (upregulation of β-catenin/PD-L1) in the early stages, this compensatory response is insufficient to offset the ongoing stress damage, ultimately triggering the mitochondrial apoptosis pathway.

  Identifying Neddylation-modified features to assess prognosis and immune efficacy in hepatocellular carcinoma · 2026 · DOI

• However, the relative impact of lesion location and tumor size on postoperative outcomes following trans-arterial embolization (TAE) combined with laparoscopic microwave ablation (LMWA) remains incompletely defined.

  Laparoscopic microwave ablation for hepatic hemangiomas with different locations: A comparative study · 2026 · DOI

• Results: PET–CBCT-HA fusion improved detection and delineation of viable tumor components that were occult or insufficiently defined on CBCT-HA alone, particularly in post-chemotherapy or previously treated lesions.

  Enhancing Catheter-Assisted C-Arm CT-Guided Ablation with PET/CT Fusion: A Pictorial Overview of Multimodal Synergy for Improving Local Tumor Control in Liver Metastasis · 2026 · DOI

• However, the comparative efficacy and safety of different ICI-based regimens—and their consistency across etiologic subgroups [HBV, HCV, and non-HBV/non-HCV (NBNC)]—remain uncertain.

  First-line immunotherapy for advanced hepatocellular carcinoma: a network meta-analysis of randomized trials with overall and HBV/HCV-stratified efficacy and safety · 2026 · DOI

• A supplementary controlled benchmark on the public LiTS dataset, limited to a single pre-fixed validation fold because only 131 public cases have released annotations for local evaluation, provided directionally consistent contextual evidence under an identical pipeline.

  Efficient transformer integration in nnU-Net for liver tumor segmentation: an external validation study · 2026 · DOI

• For AFP–negative patients, imaging evaluation remains the primary method for monitoring effi- cacy, whereas the value of other potential markers such as des–gamma–carboxy prothrombin (DCP), Golgi protein 73 (GP73), or circulating tumor deoxyribonucleic acid (DNA) warrants further exploration [29].

  Predictive Value of Dynamic Changes in Serum AFP for Survival in Hepatocellular Carcinoma Patients Treated With TACE Combined With Immunotherapy · 2026 · DOI

• Significant advancements in aHCC treatment have estab- lished ICI-based combinations as the cornerstone of front- line systemic therapy, relegating TKIs to later treatment lines. The increased efficacy of first-line therapy has led to a broader adoption of subsequent treatments. However, while first-line strategies are well-established, the optimal approach for later-line therapy remains uncertain. The sec- ond-line agents with phase III trial evidence—regorafenib, cabozantinib, and ramucirumab—were evaluated in an era when sorafenib was the dominant first-line therapy. Con- sequently, their trial outcomes may not fully apply to the current treatment landscape, where ICIs or, in some cases, lenvatinib are preferred as initial therapy. Additionally, reg- istrational trials often enrolled patients with clinical profiles that do not fully reflect the broader, more diverse population encountered in real-world practice. While retrospective and small prospective studies sug- gest that MTAs remain effective and safe in ICI pre- treated patients, with some evidence indicating a potential 1 3Current Oncology Reports (2026) 28:57 57 Page 26 of 33 Fig. 4 Proposed framework to guide the selection of second-line thera- pies across diverse clinical scenarios in advanced HCC. The predictors and decision-making factors presented include both validated vari- ables (underlined) and predominantly putative factors (italics) derived from exploratory analyses and/or retrospective studies, which are not yet sufficiently validated for routine clinical practice advantage for lenvatinib, there is no clear guidance on the optimal therapy in the post-IO setting. A key question is whether second-line treatment should prioritize tradition- ally second-line MTAs (regorafenib, cabozantinib, or ramu- cirumab) or repurpose historically first-line TKIs (sorafenib or lenvatinib) to preserve the former agents for third-line use. Another critical consideration is identifying patients who may benefit from continuing ICI therapy beyond pro- gression and evaluating the efficacy of ICI rechallenge strategies. These may include dual immunotherapy combi- nations, or ICI-based regimens paired with alternative anti- angiogenic agents or TKIs. Additionally, the therapeutic landscape for treatment- refractory aHCC is expected to expand further, introducing even more complexity to clinical decision-making. Some of the currently investigated approaches include FGFR4 and FGFR4/3 inhibitors (such as fisogatinib, irpagratinib, and TYRA-430) [210, 211], therapies targeting proteins over- expressed in HCC such as glypican-3, including chimeric antigen receptor (CAR) T-cell strategies [212], and Wnt inhibitors (e.g., ETN101, WNTinib), which may be par- ticularly beneficial in immune-excluded β-catenin-mutated HCC [213, 214]. As the number of effective first-line therapies contin- ues to grow, the need for prospective randomized trials in pretreated patients becomes increasingly urgent. Such trials, incorporating biomarker-driven approaches, are essential for defining evidence-based treatment sequencing strategies in the evolving therapeutic landscape of aHCC. Author Contributions Conceptualization, P.T.W., L.K.; methodology P.T.W., L.K.; data curation P.T.W.; writing—original draft P.T.W., L.K.; writing—review and editing all; visualization P.C.; supervision L.K., J.J.; project administration L.K.; funding acquisition L.K. All au- thors have read and agreed to the published version of the manuscript. Data Availability No datasets were generated or analysed during the current study.

  Advancing Systemic Treatment beyond First Line for Advanced Hepatocellular Carcinoma · 2026 · DOI

• The main limitations of this study include: (1) Single- center, small-sample design (n = 107; S3-4 subgroup n = 52). This limits generalizability and statistical power; the non-significant interaction between TBRmax and fibrosis stage is likely attributable to the latter. The cohort was predominantly Asian, HBV-related HCC, with few cholangiocarcinoma cases. Thus, model performance in other etiologies (e.g., metabolic dysfunction-associated steatotic liver disease [MASLD], HCV), cancer types, ethnicities, or centers using different protocols remains unknown. (2) Retrospective design, with inherent selec- tion and information biases. (3) Lack of separate valida- tion cohort. Bootstrap resampling (optimism-corrected AUC = 0.780) suggests robustness but does not substi- tute for true internal or external validation. Separately, PT outperformed INR in our model, which may limit comparability with INR-based studies. (4) Exclusion of moderate-to-severe steatosis. This is a major limita- tion for generalizability to Western populations where MASLD is prevalent. Steatosis was excluded to avoid confounding with FAPI uptake, yet steatosis and fibro- sis often coexist in practice. Therefore, our findings may not apply to patients with significant steatosis. (5) lim- ited staging granularity (S0-2 combined) and surrogate markers (portal vein diameter for portal hypertension; no systematic FLR measurement). FLR was measured only for major hepatectomy. Notably, this limitation also high- lights why FLR measurement is complementary to FAPI: FAPI may quantify functional quality when FLR quan- tity is adequate but advanced fibrosis impairs function. (6) No elastography comparison. This study does not compare FAPI PET/CT with elastography-based fibro- sis staging. (7) Predominance of grade A PHLF (25/30, 83.3%). While grade A PHLF provides early warning of borderline functional reserve, the ability of TBRmax to predict clinically significant (grade B/C) PHLF could not be reliably assessed due to the limited number of such events. Larger studies with sufficient grade B/C events are needed. To address these limitations, we plan multicenter, larger- scale, prospective studies to: (1) perform internal/external validation; (2) include diverse etiologies, steatosis grades, tumor types, and ethnicities; (3) analyze S0-4 subgroups to validate the observed numerical differences; (4) system- atically collect FLR for quantity-quality assessment; and (5) perform head-to-head comparisons with elastography, ⁹⁹ᵐTc-mebrofenin SPECT, and ICG clearance.

  Preoperative ⁶⁸Ga-FAPI-04 PET/CT-derived liver fibrosis quantification independently predicts post-hepatectomy liver failure: a histologically validated study · 2026 · DOI

• The combination of CLCVP and IOUS can partially compensate for the inability to perform the Pringle maneuver, but this approach remains limited to long-term carefully selected patients, and outcomes warrant further study.

  Recurrent hepatocellular carcinoma treated by laparoscopic non-anatomical liver resection via the retroperitoneal approach: a case report · 2026 · DOI

• This study has several notable strengths. First, it represents the largest comparative analysis of robotic versus laparo- scopic living donor hepatectomy to date, including over 15,000 donors across seven contemporary studies published between 2022 and 2025. Second, we evaluated both donor and recipient outcomes, providing a comprehensive assess- ment of the impact of surgical modality across the entire Journal of Robotic Surgery (2026) 20:500 1 3 500 Page 16 of 19 transplantation process, addressing an important gap in prior reviews that primarily focused on donor outcomes. However, several limitations must be acknowledged. First, all included studies were observational; no random- ized controlled trials directly comparing R-LDH and L-LDH are currently available. An additional consideration is the inclusion of studies reporting different graft types, includ- ing right, left, and left lateral hepatectomies. These proce- dures vary in technical complexity and risk profile and may contribute to clinical heterogeneity across studies. Because several large comparative studies reported outcomes across multiple graft types, these studies were included to reflect contemporary clinical practice in living donor hepatectomy. Nevertheless, future investigations with graft-specific strati- fication may help clarify whether procedural complexity modifies the relative benefits of robotic assistance. Second, substantial heterogeneity was observed in oper- ative time, blood loss, and length of hospital stay, likely reflecting variations in center volume, surgeon experience, and perioperative protocols. Sensitivity analysis showed that excluding the large LDLT registry study reversed the pooled estimate for donor major morbidity, suggest- ing a higher risk with the robotic approach. This finding should be interpreted cautiously, as the registry represents the largest donor cohort and reflects outcomes from mul- tiple high-volume centers. In addition, Doi plot analysis demonstrated major asymmetry (LFK index > ± 2) across several outcomes, indicating potential small-study effects whereby smaller studies may preferentially report favorable robotic outcomes. Together, these factors suggest that some observed advantages of robotic donor hepatectomy should be interpreted cautiously and warrant confirmation in larger prospective or registry-based studies. Third, the majority of included studies originated from high-volume centers in East Asia with extensive experience in both LDLT and minimally invasive surgery, potentially limiting generalizability to lower-volume centers or other regions. Fourth, we did not extract or pool economic out- comes, and cost reporting in donor hepatectomy remains sparse and heterogeneous; therefore, no conclusions regarding cost-effectiveness can be drawn. Fifth, defini- tions and reporting of biliary complications were not fully standardized across studies—often representing composite endpoints—contributing to heterogeneity, particularly in donor analyses. Even in propensity score–matched studies, residual confounding related to case selection, anatomical complexity, and institutional pathways may persist. Finally, long-term donor-reported outcomes, including quality of life, psychological impact, and late complications, remain underreported.

  From laparoscopy to robotics in living donor hepatectomy: a systematic review and meta-analysis of comparative outcomes · 2026 · DOI

• The need for homegrown economic evidence to guide China's reimbursement policies and clinical guidelines for advanced HCC is emphasized, as extrapolating findings from foreign analyses requires caution.

  The cost effectiveness of toripalimab plus bevacizumab versus sorafenib for the first-line treatment of advanced hepatocellular carcinoma in China · 2026 · DOI

• The extrapolation of survival curves introduces uncertainty, which may affect the precision of the results, and no universally accepted method currently exists to fully address this challenge.

  The cost effectiveness of toripalimab plus bevacizumab versus sorafenib for the first-line treatment of advanced hepatocellular carcinoma in China · 2026 · DOI

Most-cited papers in Hepatocellular Carcinoma Treatment and Prognosis

• Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma · New England Journal of Medicine · 2020 · 6,521 citations
• Precision treatment in advanced hepatocellular carcinoma · Cancer Cell · 2024 · 395 citations
• Risk Factors for the Rising Rates of Primary Liver Cancer in the United States · Archives of Internal Medicine · 2000 · 310 citations
• Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma · Annals of Oncology · 2024 · 295 citations
• Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update · Journal of Clinical Oncology · 2024 · 256 citations
• Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial · The Lancet · 2024 · 168 citations
• ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma · Acta Pharmacologica Sinica · 2020 · 144 citations
• EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. · Journal of Clinical Oncology · 2024 · 138 citations
• Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): First results from CheckMate 9DW. · Journal of Clinical Oncology · 2024 · 132 citations
• Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial · Nature Medicine · 2024 · 117 citations

Most recent work

• Hepatic radiofrequency ablation induces widespread cellular activation throughout the liver · European Radiology Experimental · 2026
• Vector Physics Applied: A Strategic Approach to Optimized Retraction in Robotic Liver Surgery · Annals of Surgical Oncology · 2026
• The Efficacy and Safety of Atezolizumab Plus Bevacizumab after Durvalumab Plus Tremelimumab for the Treatment of Hepatocellular Carcinoma · Internal Medicine · 2026
• Establishing the Minimum Future Liver Remnant Volume for Safe Hepatectomy · Journal of the American College of Surgeons · 2026
• Laparoscopic Anterior-Approach Right Posterior Sectionectomy for Huge Hepatocellular Carcinoma: Technique and Short-Term Outcomes · Annals of Surgical Oncology · 2026
• The Use of Non‐Contrast Abbreviated <scp>MRI</scp> for the Detection of Recurrent Hepatocellular Carcinoma in Postoperativ Surveillance · Journal of Magnetic Resonance Imaging · 2026
• Limitations of adult post-hepatectomy liver failure criteria in pediatric liver tumor surgery: A single-center retrospective study · Journal of Pediatric Surgery · 2026
• Evaluating Accuracy of LI-RADS Nonradiation Treatment Response Algorithm v2024 and Ancillary Features at Hepatobiliary MRI versus CT · Radiology · 2026
• In Regard to Yeung et al · International Journal of Radiation Oncology*Biology*Physics · 2026
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