TO THE EDITOR
I wish to commend Chen et al[1] for their comprehensive and impactful study, "Prognostic Value of Preoperative Systemic Immune-Inflammation Index/Albumin for Patients with Hepatocellular Carcinoma Undergoing Curative Resection" recently published in the World Journal of Gastroenterology. Their research represents a significant advancement in our understanding of prognostic indicators for hepatocellular carcinoma (HCC), specifically through elucidating the utility of the systemic immune-inflammation index/albumin (SII/ALB) ratio as a predictor of overall survival (OS) and recurrence-free survival (RFS) among patients undergoing hepatectomy.
The evidence presented by Chen et al[1] regarding the prognostic value of SII/ALB as an independent predictor of both survival and recurrence is of substantial clinical importance. The introduction of a cost-effective and easily quantifiable metric such as SII/ALB enhances clinicians' ability to stratify patients by risk, thereby enabling more individualized therapeutic approaches, particularly concerning adjuvant therapies and postoperative monitoring[2,3]. For instance, patients with a high SII/ALB ratio might be considered for more aggressive adjuvant treatment to mitigate recurrence risk, whereas those with a lower ratio could benefit from a less intensive follow-up regimen[4,5]. A study by Chen et al[1] demonstrated that SII is a valuable prognostic marker for colorectal cancer (CRC) patients, showing that higher SII levels correlate with worse overall and disease-free survival. Tian et al[6] demonstrated that elevated SII/ALB levels were significantly associated with reduced OS. The 2-year OS rates for the SII/ALB-low and SII/ALB-high groups were 70.3% and 48.5%, respectively. The development of a nomogram that integrates SII/ALB alongside other established prognostic factors, such as age, tumor size, alpha-fetoprotein (AFP) levels, and the presence of microvascular invasion, further underscores its clinical utility[7]. This tool holds potential as a mechanism for translating complex statistical risk data into actionable clinical insights, thereby enhancing precision medicine in HCC treatment. The integration of multiple clinical parameters into such predictive models is critical for refining patient-specific management strategies, ultimately improving patient outcomes.
Moreover, the simplicity of calculating the SII/ALB ratio, compared to more complex molecular or imaging biomarkers, makes it particularly advantageous in clinical practice. Its utility could extend beyond well-equipped medical centers, offering a viable tool for practitioners in community hospitals and resource-limited settings. By providing a metric that is both accessible and effective, SII/ALB may democratize the ability to predict prognosis for HCC patients, ensuring that high-quality care is not limited to high-income countries or sophisticated healthcare infrastructures. In resource-limited settings, the implementation of SII/ALB could be facilitated through existing healthcare networks that already conduct routine blood testing[8]. However, potential challenges such as the need for standardized protocols, training of healthcare workers, and ensuring consistent reagent supply must be addressed. Adaptations may also be required to integrate SII/ALB calculations into current workflows without adding excessive burden to healthcare providers, thus ensuring its broader applicability and sustainability. The broader implementation of such a prognostic tool could reduce disparities in cancer outcomes globally, contributing to more equitable cancer care.
Despite the utility of SII/ALB ratios in predicting disease outcomes, particularly in cancer and inflammatory diseases, their limitations cannot be ignored. For example, the SII/ALB ratios reflect the combined inflammatory and immune status of a specific patient but are not specific to a particular type of disease. Numerous factors, including infection, body mass index, nutritional status, chronic inflammation, and autoimmune conditions, can influence these indicators[9,10]. Consequently, the sole reliance on SII/ALB ratios may result in misclassification.
Nevertheless, additional multi-center validation of these findings is essential, particularly to assess the generalizability of the results across diverse patient populations. The current cohort predominantly comprises patients with hepatitis B virus-associated HCC, which may limit the applicability of the results to other etiologies, such as hepatitis C virus-related HCC or non-alcoholic fatty liver disease-associated HCC. Different etiologies may impact the prognostic power of SII/ALB due to distinct underlying inflammatory and metabolic profiles associated with each condition[11]. Expanding the study to encompass these varied etiological backgrounds would ensure that the SII/ALB ratio retains its prognostic robustness across different clinical contexts. Furthermore, prospective studies assessing dynamic changes in SII/ALB throughout the perioperative and postoperative periods could offer crucial insights into its value as a time-sensitive biomarker[12]. Such research could help determine whether temporal variations in SII/ALB are indicative of changes in patient prognosis, thus refining its role in monitoring and guiding treatment interventions throughout the disease course.
The concept of dynamic monitoring is particularly appealing, as it could transform SII/ALB from a static preoperative indicator into a longitudinal biomarker that guides therapy at multiple stages of treatment. For instance, in similar contexts such as CRC, dynamic monitoring of inflammatory biomarkers has successfully informed treatment modifications, leading to improved patient outcomes by enabling timely adjustments in adjuvant therapies[13]. For example, consistent monitoring of SII/ALB after hepatectomy could inform decisions about the timing and intensity of adjuvant therapies. Patients who exhibit increasing SII/ALB ratios during follow-up may benefit from early intervention or a shift in therapeutic strategy to preempt recurrence. This potential transformation of SII/ALB into a longitudinal indicator aligns well with the principles of personalized medicine, where patient management is continuously adapted based on evolving risk profiles.
The implications of the SII/ALB ratio extend beyond the context of curative resection, raising pertinent questions about its potential role across a broader range of treatment modalities[14]. It would be highly informative to evaluate whether SII/ALB can reliably predict clinical outcomes in patients receiving other forms of intervention, such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), or systemic therapies, including tyrosine kinase inhibitors (TKIs). For example, in a retrospective study including 295 patients who underwent TACE for HCC, patients with an SII/ALB/bilirubin score of 2 had the worst outcomes, with a median OS of 11 months (95%CI: 8.44–13.56 months); consequently, the SII/ALB/bilirubin score can be a simple indicator of the prognosis in individuals with HCC who are treated with TACE[15]. Similarly, in a retrospective study of 405 patients who underwent thermal ablation for HCC, the SII-ALBI grade was found to be an independent prognostic factor in multivariate Cox regression analysis. The cumulative 5-year OS rates were 81.7%, 63.2%, and 26.9% for patients with SII-ALBI grades 1, 2, and 3, respectively. Furthermore, SII-ALBI was predictive of OS, cancer-specific survival, and RFS in AFP-negative patients[16]. The SII/ALB grade can be used to predict the prognosis in patients with unresectable HCC who are treated with regorafenib[17] and the combination of baseline ALBI grade and the SII index serves as a simple yet robust parameter to predict the prognosis in unresectable HCC patients receiving regorafenib who were refractory to sorafenib treatment. This line of investigation could establish SII/ALB as a versatile prognostic tool applicable across different treatment paradigms for HCC, such as patients undergoing TACE, systemic therapies including TKIs, or RFA[18].
Identifying the specific modalities that may benefit most from incorporating SII/ALB could ultimately broaden its utility within the oncologic toolkit. For example, identifying patients with a high SII/ALB ratio could support decisions to combine local and systemic therapies more aggressively, thereby optimizing treatment efficacy and potentially improving survival outcomes in patients undergoing non-surgical interventions[19].
Further research should also explore how the SII/ALB ratio may influence patient selection for innovative therapies, such as immune checkpoint inhibitors or combination therapies involving novel molecular agents[20]. Preliminary evidence from other cancers has shown that inflammatory markers, similar to SII/ALB, have been effective in predicting response to immunotherapy, suggesting that SII/ALB could play a similar role in HCC treatment. Given the evolving landscape of HCC treatment, characterized by a rapid expansion of targeted and immune-based therapies, the identification of robust biomarkers is paramount[21]. The SII/ALB ratio, with its reflection of systemic inflammation and nutritional status, could provide a valuable adjunct to guide the incorporation of these new modalities into the clinical care of HCC patients. Additionally, the role of SII/ALB in determining eligibility for clinical trials of emerging therapeutics could help stratify participants, ensuring that high-risk patients receive optimal investigational interventions.
The SII/ALB ratio plays a significant role in predicting HCC prognosis, reflecting the influence of systemic inflammation and nutritional status on cancer outcomes. Chronic inflammation fosters a tumor-promoting microenvironment characterized by elevated cytokines, chemokines, and other inflammatory mediators that enhance tumor growth, survival, and metastasis[22]. For example, increased levels of C-reactive protein and various interleukins are associated with poor cancer prognosis[23]. Similarly, the neutrophil-to-lymphocyte ratio has emerged as a valuable biomarker of systemic inflammation in cancer, correlating with disease severity and treatment outcomes[24]. Moreover, nutritional status also plays a pivotal role in modulating immune function, particularly in cancer patients, who often experience immune suppression due to both the disease and its treatments. Nutritional interventions have proven effective in improving serum albumin levels and potentially reducing the SII/ALB ratio[25]. Adequate nutritional support is crucial in cancer care, not only to maintain physical strength and energy but also to optimize immune function, which can significantly enhance treatment tolerance and recovery[26]. Thus, understanding the interaction between systemic inflammation and cancer progression, combined with a comprehensive approach that incorporates nutritional assessment and tailored interventions, is essential for improving immune function and overall prognosis in cancer patients.
The systemic SII/ALB ratio has gained recognition as a significant biomarker in oncology and critical care. However, its application is accompanied by notable limitations. A key concern is the impact of sample size and selection bias. For instance, a study involving 185 patients receiving immunotherapy demonstrated the potential prognostic value of the SII/ALB ratio but was constrained by its retrospective design and small cohort size, raising questions about the reliability of its findings[2]. Additionally, the SII/ALB ratio is influenced by various factors, including age, sex, and comorbidities, which can complicate its interpretation[27]. Interpreting the SII/ALB ratio in clinical practice poses significant challenges. The complexity of the underlying biological mechanisms governing inflammation and nutritional status indicates that the SII/ALB ratio should not be considered in isolation[28]. To address these challenges, there is a critical need for standardized protocols and extensive validation studies to clarify the SII/ALB ratio's role in clinical decision-making and facilitate its integration into routine practice.
Furthermore, in addition to focusing on the predictive value of the SII/ALB ratio in HCC, the preoperative condition of the patient is important, furthermore, the intraoperative liver resection volume and postoperative management of the patient should also be considered, and other factors should be compared. Preoperative sarcopenia conditions and liver reserve function are also important factors to be considered. In future studies, we suggested including more comprehensive preoperative assessments, including quantitative evaluation of sarcopenia status (such as the measurement of skeletal muscle area via computed tomography scans) and hepatic reserve function (such as the use of ICG retention or the Child-Pugh score), to elucidate the impact of these factors on postoperative outcomes more comprehensively.
