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The predictive value of PIV, PLR, LMR, NPR, and NLR for the prognosis of transarterial chemoembolization in patients with hepatocellular carcinoma combined with liver cirrhosis

BMC Gastroenterology volume 25, Article number: 315 (2025) Cite this article

Abstract

Background

Transarterial chemoembolization (TACE) is a primary treatment for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. Prognostic markers that reliably predict outcomes in these patients post-TACE remain insufficiently defined. Systemic inflammatory markers such as the Pan-Immunological Value (PIV), Platelet-Lymphocyte Ratio (PLR), Lymphocyte-Monocyte Ratio (LMR), Neutrophil-Platelet Ratio (NPR), and Neutrophil-Lymphocyte Ratio (NLR) offer potential prognostic insights for various disease. This study aims to evaluate this markers to ascertain their predictive value in determining prognosis post-TACE.

Methods

This retrospective study involved 216 patients with HCC and cirrhosis treated with TACE at a single hospital from May 2017 to May 2023. Patients were stratified into good (n = 92) and poor prognosis groups (n = 124) based on one-year post-operative outcomes using the Response Evaluation Criteria in Solid Tumors (RECIST). We evaluated preoperative inflammatory markers, biochemical and imaging data, and utilized univariate and multivariate logistic regression analyses to determine predictive factors for prognosis.

Results

Patients in the poor prognosis group exhibited significantly higher PIV, PLR, NLR, and NPR, and lower LMR (P < 0.05). Multivariate analysis identified PIV and NPR as the strongest independent predictors of poor prognosis (OR: 1.021, P < 0.001 and OR: 2.909, P < 0.001, respectively). ROC analysis demonstrated that PIV had the greatest predictive accuracy (AUC = 0.803).

Conclusion

PIV, PLR, LMR, NPR, and NLR serve as significant prognostic markers for patients with HCC undergoing TACE in the context of liver cirrhosis.

Peer Review reports

Introduction

Hepatocellular carcinoma (HCC) was one of the most prevalent malignancies worldwide and the leading cause of cancer-related mortality [1, 2]. Often developing in the context of chronic liver disease and cirrhosis, HCC presents unique challenges due to its complex interplay with underlying hepatic dysfunction [3]. Current treatment modalities including surgical resection, liver transplantation, and locoregional therapies like transarterial chemoembolization (TACE) were used based on disease stage, hepatic reserve, and overall patient health [4]. Among these, TACE stands out as the mainstay treatment for intermediate-stage HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging system [5]. TACE works by selectively delivering chemotherapy agents and embolic particles to the tumor vasculature, leading to ischemic necrosis and direct cytotoxic effects [6].

Despite the widespread use of TACE, predicting clinical outcomes post-treatment remains a significant challenge. Considerable heterogeneity exists in patient responses, attributable to variations in tumor biology, liver function, and the degree of systemic inflammation. In this regard, systemic inflammatory markers have emerged as promising tools for risk stratification and prognostication in various cancers, including HCC [7].

The systemic inflammatory response, reflected through a variety of hematological parameters, correlates with worse clinical outcomes. Of late, composite indices derived from routine blood counts, such as the Pan-Immunological Value (PIV), Platelet-Lymphocyte Ratio (PLR), Lymphocyte-Monocyte Ratio (LMR), Neutrophil-Platelet Ratio (NPR), and Neutrophil-Lymphocyte Ratio (NLR), have been recognized for their predictive capabilities in numerous malignancies [8]. Each of these markers captures a unique aspect of the inflammatory milieu: PIV combines neutrophil, monocyte, and platelet counts relative to lymphocytes, emphasizing the net pro-tumorigenic potential of the immune response [9, 10]; PLR highlights the interaction between platelet-driven thrombo-inflammatory processes and lymphocyte-mediated immunity [11, 12]; LMR offers insights into monocyte-driven tumor-associated macrophage activity versus lymphocyte counteraction [13, 14]; NPR and NLR gauge the dual role of neutrophils in promoting oncogenic processes and modulating adaptive immune responses [15].

Given the pivotal role of inflammation in cancer progression, evaluating these markers could provide insights into the tumor-host dynamics specific to HCC and its often-present cirrhotic environment. Moreover, the addition of these inflammatory markers may augment traditional prognostic indicators such as tumor stage and liver function scores, potentially improving individualized treatment strategies.

Existing literature has demonstrated the value of these inflammatory markers in various cancers [16], but their specific utility in the context of HCC patients undergoing TACE requires further elucidation. With the evolving landscape of HCC management, there was a pressing need to incorporate these markers into clinical practice to enhance prognostic accuracy and treatment decision-making. The intersection of tumor biology, hepatic impairment, and systemic inflammation in these patients necessitates an integrative approach for effective management.

This study aims to bridge this gap by evaluating the prognostic value of PIV, PLR, LMR, NPR, and NLR in predicting outcomes in a cohort of HCC patients with underlying cirrhosis undergoing TACE.

Materials and methods

Study design

This retrospective case-control study included 216 patients diagnosed with liver cancer and cirrhosis who underwent TACE at our hospital between May 2017 and May 2023. Patient demographic data were systematically collected, encompassing general information, inflammatory markers, biochemical indicators, imaging data, and perioperative parameters. Information regarding previous HCC treatments (including surgical resection, percutaneous ablation, or prior TACE) was also recorded to account for potential effects on laboratory parameters and liver function. The study received approval from the hospital’s ethics review board and ethics committee, adhering to the guidelines outlined in the Declaration of Helsinki. The ethical approval number for this study was 2023-SXY-528.

Inclusion and exclusion criteria, and grouping standards

Inclusion criteria were as follows: (1) Patients had to meet the diagnostic criteria for primary liver cancer combined with liver cirrhosis as outlined in clinical guidelines, with confirmation by pathological examination [17]; (2) All participants needed indications for interventional embolization and were required to undergo TACE treatment; (3) Patients’ liver function had to be classified as Child-Pugh grade A or B; (4) Patients were classified according to the Barcelona Clinic Liver Cancer (BCLC) staging system, with the majority falling into stages B and C, as these stages are the standard indications for TACE according to current guidelines.

Exclusion criteria included: (1) Patients with known acute or chronic inflammatory diseases preoperatively, or any evidence of clinical infections, such as high fever; (2) Patients taking medications like aspirin or clopidogrel that could affect peripheral blood cell indices prior to the operation; (3) Individuals with hematologic disorders or immunological diseases; (4) Those who underwent only palliative surgery or had distant metastases; (5) Patients with incomplete clinical and pathological data, or those lost to follow-up; (6) Patients who succumbed to intraoperative complications or severe postoperative complications; (7) Patients who had received systemic therapy within one month before TACE, which might affect inflammatory markers.

Prognosis evaluation and grouping method

The prognoses of patients were recorded within one year post-operation, with the effectiveness of observational indicators evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) [18]. Patients exhibiting Progressive Disease (PD) or who had deceased were categorized into the poor prognosis group (n = 124). Conversely, those demonstrating Complete Response (CR), Partial Response (PR), or Stable Disease (SD) were placed in the good prognosis group (n = 92).

Main methods of TACE

In accordance with the “Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)“ [17], TACE was administered to patients. Following standard preoperative preparation, the femoral artery was punctured and cannulated using the Seldinger technique. Angiography was conducted on the common hepatic artery and the superior mesenteric artery to evaluate tumor staining and portal vein filling. Subsequently, superselective catheterization was performed on the tumor-feeding vessels whenever technically feasible. When superselective catheterization was not possible due to anatomical variations or technical difficulties, selective catheterization of the hepatic arterial branch supplying the tumor segment was performed.The extent of selectivity achieved was recorded as either selective (lobar/segmental branch) or superselective (subsegmental branch directly feeding the tumor). Following catheterization, slow injection of an emulsion containing 20–40 mg of epirubicin, 0.5–1.0 g of 5-fluorouracil, and 5–25 ml of liquid lipiodol into the target vessel was performed for embolization. The quantity of lipiodol used was determined by the size of the tumor, and absorbable gelatin sponge particles were employed to embolize the tumor-feeding arteries.

For patients with multiple nodules, we treated a maximum of 3–4 nodules per TACE session, prioritizing the largest nodules or those with the most aggressive imaging features. The technical success rate of the procedure was defined as successful catheterization and delivery of the chemoembolization mixture to the target lesions.

Data collection

  1. (1)

    Patient Demographic and Clinical Data: This includes age, Body Mass Index (BMI), gender, employment status, marital status, residence, smoking history, drinking history, presence of hypertension and diabetes, the number of TACE treatments received, BCLC stage, T stage, Child-Pugh classification, previous HCC treatments (including surgical resection, percutaneous ablation, or prior TACE), and the presence of poor prognosis factors.

  2. (2)

    Preoperative Inflammatory Markers: These include the PIV, PLR, LMR, NLR, and NPR. For blood testing, a 5 ml sample of venous blood was collected from fasting patients before 8 a.m. Neutrophils, lymphocytes, platelets, and monocytes were measured using the DxH800 blood analyzer (Beckman Coulter, Inc., Brea, CA, USA). The inflammatory markers were calculated with the following formulas: PIV = (Neutrophil Count × Monocyte Count × Platelet Count) / Lymphocyte Count; PLR = Platelet / Lymphocyte; LMR = Lymphocyte / Monocyte; NPR = Neutrophil / Platelet; NLR = Neutrophil / Lymphocyte.

  3. (3)

    Preoperative Biochemical Markers: These include Alanine Transaminase (ALT), Aspartate Transaminase (AST), Gamma-Glutamyl Transferase (GGT), and Alpha-Fetoprotein (AFP). Blood samples for these markers were collected after an overnight fast before 8 a.m. The serum was separated by centrifugation at 3000 rpm for 10 min and stored at -80 °C until analysis. ALT, AST, and GGT levels were assessed using an automated biochemical analyzer (Hitachi 7600, Hitachi High-Technologies Corporation, Tokyo, Japan) with reagent kits from Roche Diagnostics (Basel, Switzerland). AFP levels were measured using chemiluminescent immunoassay (CLIA) on a Roche Cobas e601 immunoanalyzer (Roche Diagnostics, Basel, Switzerland) with corresponding Roche reagents.

  4. (4)

    Preoperative Imaging Data: This includes tumor characteristics such as number, maximum diameter, and degree of differentiation, as well as invasion indicators like lymph node metastasis, arteriovenous fistula, and portal vein tumor thrombosis. Imaging data were primarily obtained from abdominal MRI, with CT and ultrasound utilized if MRI was unavailable.Assessment of portal hypertension was conducted using abdominal ultrasound to evaluate spleen size, presence of ascites, and portal vein diameter. Upper gastrointestinal endoscopy was performed to assess for esophageal and gastric varices. When available, liver stiffness measurement by transient elastography was also used to evaluate the degree of portal hypertension.

  5. (5)

    Perioperative Parameters: These encompass the duration of the surgery, the type of iodized oil deposition, and the postoperative hospital stay length. Iodized oil deposition types were categorized as I, II, III, or IV based on the extent of tumor staining and arterial occlusion [19].

Follow-up method

This study primarily conducted follow-ups through outpatient visits, scheduled for every three months. Patients who did not return for their scheduled visits were followed up by contacting their family members by phone at predetermined intervals. The follow-up period extends until May 2024. Survival time was measured from the date of surgery until the patient was lost to follow-up, had passed away, or the last follow-up date. The follow-up information included details on postoperative recurrence, tumor metastasis, and overall survival status. For deceased patients, the cause and time of death were meticulously recorded.

Statistical analysis

Data analysis was performed using SPSS version 29.0 statistical software (SPSS Inc., Chicago, IL, USA). Categorical data were presented as [n (%)]. The chi-square test was applied when the sample size was ≥ 40 and the theoretical frequency (T) was ≥ 5, with the test statistic denoted as χ². If the sample size was ≥ 40 but the theoretical frequency ranged from 1 to 5, the chi-square test was adjusted using a correction formula. For sample sizes < 40 or theoretical frequencies T < 1, Fisher’s exact probability method was used for statistical analysis. Continuous variables were evaluated for normal distribution using the Shapiro-Wilk test. Univariate and multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for each parameter considered as a continuous variable. Spearman’s rank correlation coefficient was employed to assess correlations between variables. For normally distributed continuous data, results were presented as (mean ± standard deviation), and comparisons were made using a t-test. A p-value of < 0.05 was considered statistically significant.

Results

Baseline characteristics

Comparison of baseline characteristics between patients with good versus poor prognosis showed no statistically significant differences in mean age (57.32 ± 10.21 vs. 59.93 ± 10.42 years, P = 0.067), body mass index (22.55 ± 3.24 vs. 22.68 ± 3.12 kg/m², P = 0.766), gender distribution, employment status, marital status, residence, smoking, drinking history, hypertension, and diabetes (P > 0.05) (Table 1). Significant differences were observed in BCLC stage, T stage, and Child-Pugh classification. The poor prognosis group had a higher proportion of patients with BCLC stage C (44.35% vs. 21.74%, P < 0.001) compared to the good prognosis group which had more patients in BCLC stage B (78.26% vs. 55.65%, P < 0.001). Patients with a poor prognosis exhibited higher T stages (T3 and T4: 56.46% vs. 27.18%, P < 0.001) compared to those with a good prognosis who displayed a greater proportion in T1 and T2 stages (72.82% vs. 43.73%, P < 0.001). Additionally, the distribution of Child-Pugh classification differed significantly between groups, with the poor prognosis group having a higher percentage of patients in Class B (35.48% vs. 21.74%, P = 0.029).Regarding previous treatments, the poor prognosis group had a higher proportion of patients who had undergone prior surgical resection (27.42% vs. 15.22%, P = 0.034) and percutaneous ablation (24.19% vs. 13.04%, P = 0.040) compared to the good prognosis group. Additionally, signs of portal hypertension were more commonly observed in the poor prognosis group (65.32% vs. 47.83%, P = 0.011).The number of TACE treatments showed a trend towards significance (P = 0.098), with a larger portion of patients undergoing multiple treatments (≥ 3 times) in the poor prognosis group (37.10% vs. 32.61%). Overall, these findings highlight the relevance of BCLC stage, T stage, Child-Pugh classification, previous treatments, and portal hypertension in predicting prognosis post-TACE.

Table 1 Comparative analysis of baseline characteristics between patients with good and poor prognosis
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Baseline inflammatory

The PIV was notably higher in the poor prognosis group compared to the good prognosis group (382.13 ± 66.27 vs. 303.11 ± 63.62, P < 0.001) (Table 2). Similarly, patients with poor prognosis exhibited elevated levels of platelet-to-lymphocyte ratio (PLR) (119.88 ± 24.47 vs. 109.76 ± 23.34, P = 0.006), neutrophil-to-lymphocyte ratio (NLR) (2.89 ± 1.21 vs. 2.31 ± 1.12, P = 0.002), and neutrophil-to-platelet ratio (NPR) (2.27 ± 0.71 vs. 1.91 ± 0.63, P = 0.004) when compared to their good prognosis counterparts. Conversely, the lymphocyte-to-monocyte ratio (LMR) was significantly lower in the poor prognosis group (1.81 ± 0.79 vs. 2.26 ± 0.86, P = 0.001). These significant disparities in inflammatory marker levels suggest their potential predictive value in determining patient outcomes post-TACE.

Table 2 Comparative analysis of baseline inflammatory marker differences between the two groups of patients
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Biochemical markers

The poor prognosis group demonstrated higher levels of ALT and AST than the good prognosis group (ALT: 52.89 ± 6.38 U/L vs. 50.72 ± 7.96 U/L, P = 0.033; AST: 73.69 ± 10.58 U/L vs. 70.92 ± 9.35 U/L, P = 0.048) (Table 3). Additionally, elevated GGT levels were more prevalent in the poor prognosis group, with 88.71% exhibiting GGT > 50 U/L compared to 72.83% in the good prognosis group (P = 0.003). A significant difference was also noted in AFP levels, where 54.84% of the poor prognosis group had AFP levels > 400 µg/L, compared to 28.26% in the good prognosis group (P < 0.001). These findings indicate that higher levels of ALT, AST, GGT, and AFP were associated with a poorer prognosis after TACE treatment.

Table 3 Comparison of biochemical markers between good and poor prognosis groups
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Preoperative imaging data

Tumor number was a distinguishing factor, with the poor prognosis group showing a higher incidence of multiple tumors (21.77% vs. 9.78%, P = 0.019) (Table 4). Additionally, patients in the poor prognosis group had larger tumors, with 54.84% having a maximum diameter of ≥ 5 cm compared to 38.04% in the good prognosis group (P = 0.015). The degree of tumor differentiation also varied significantly, as the poor prognosis group had a higher percentage of poorly differentiated tumors (37.00% vs. 23.40%, P = 0.011). Lymph node metastasis was more common in the poor prognosis group, with 37.10% affected compared to 22.83% in the good prognosis group (P = 0.025). Arteriovenous fistula occurrence was substantially higher in the poor prognosis group (21.03% vs. 5.43%, P = 0.001). Notably, portal vein tumor thrombosis was significantly more prevalent in patients with poor prognosis (67.74% vs. 41.3%, P < 0.001). Tumor location showed no significant difference between the groups (P = 0.908). These findings underscore the importance of tumor burden and vascular invasion as predictive factors in patient prognosis post-TACE.

Table 4 Comparison of preoperative imaging data between the two groups of patients
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Clinical and pathological data

The lipiodol sedimentation score was significantly associated with prognosis, as a higher percentage of patients in the poor prognosis group were classified as Score II (54.03% vs. 30.43%), while the good prognosis group had a larger proportion in Scores III and IV (42.39% vs. 13.71%, P < 0.001) (Table 5). No significant differences were observed with respect to the duration of surgery (P = 0.935) and length of hospital stay (P = 0.846), as these parameters showed similar distributions between the two groups. These findings highlight the relevance of lipiodol sedimentation patterns in predicting patient outcomes post-TACE.

Table 5 Differences analysis of clinical and pathological data between the two groups of patients
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Correlation analysis

The correlation analysis identified several variables significantly associated with poor prognosis in patients undergoing TACE for HCC with liver cirrhosis (Table 6). Notably, portal vein tumor thrombosis (rho = 0.523, P < 0.001) and PIV (rho = 0.520, P < 0.001) demonstrated the strongest correlations with poor prognosis. Other significant variables included T stage (rho = 0.320, P < 0.001), NPR (rho = 0.273, P < 0.001), AFP levels > 400 µg/L (rho = 0.265, P < 0.001), PLR (rho = 0.212, P = 0.002), GGT > 50 U/L (rho = 0.204, P = 0.003), tumor differentiation degree (rho = 0.199, P = 0.003), and lipiodol sedimentation score (rho = 0.222, P = 0.001). Negative correlation was observed with LMR (rho = -0.239, P < 0.001). Other variables, such as ALT (P = 0.021), tumor number (P = 0.019), tumor maximum diameter (P = 0.014), lymph node metastasis (P = 0.025), and Child-Pugh classification B (P = 0.029), were also positively associated with poor prognosis but to a lesser extent. AST levels did not show a statistically significant correlation (P = 0.089). These findings underscore the multifactorial nature of prognosis determination, highlighting variables that may serve as predictive markers for assessing patient outcomes post-TACE.

Table 6 Correlations analysis between various variables and poor prognosis
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Univariate logistic regression analysis

The univariate logistic regression analysis identified several inflammatory markers as significant predictors of prognosis in patients with liver cancer and cirrhosis undergoing TACE (Table 7). The PIV emerged as a robust risk factor, with each unit increase associated with an odds ratio (OR) of 1.019 (95% CI, 1.014–1.025; P < 0.001). Similarly, the platelet-to-lymphocyte ratio (PLR) showed a significant association, with an OR of 1.018 (95% CI, 1.006–1.030; P = 0.003). The neutrophil-to-lymphocyte ratio (NLR) and the NPR were also significant, with ORs of 1.537 (95% CI, 1.212–1.974; P < 0.001) and 2.231 (95% CI, 1.471–3.475; P < 0.001), respectively. Conversely, the lymphocyte-to-monocyte ratio (LMR) was inversely associated with poor prognosis, presenting an OR of 0.515 (95% CI, 0.359–0.724; P < 0.001). These findings suggest that higher levels of PIV, PLR, NLR, and NPR were associated with increased risk of poor prognosis, while higher LMR levels were protective, providing valuable predictive insights for clinical decision-making.

Table 7 Univariate logistic regression analysis of inflammatory markers influencing prognosis in patients with liver Cancer and cirrhosis
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Multivariate logistic regression analysis

The multivariate logistic regression analysis demonstrated that multiple inflammatory markers significantly predicted prognosis in patients undergoing TACE for HCC with liver cirrhosis (Table 8). The PIV was a strong predictor, with an odds ratio (OR) of 1.021 (95% CI, 1.014–1.028; P < 0.001), indicating that higher PIV levels were associated with poorer prognosis. Similarly, the platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) were significant predictors, with ORs of 1.027 (95% CI, 1.011–1.044; P = 0.001) and 1.697 (95% CI, 1.238–2.327; P = 0.001), respectively. The NPR exhibited the highest association with future prognosis, with an OR of 2.909 (95% CI, 1.656–5.112; P < 0.001). Conversely, a negative coefficient for the lymphocyte-to-monocyte ratio (LMR) was observed, indicating a protective effect, with an OR of 0.630 (95% CI, 0.401–0.991; P = 0.046). These results highlight these inflammatory markers as independent risk factors for evaluating prognosis in this patient population.

Table 8 Multivariate logistic regression analysis of inflammatory markers predicting prognosis in patients with liver Cancer and cirrhosis
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Predictive performance of PIV, PLR, LMR, NLR, NPR for poor prognosis

This study evaluated the predictive value of PIV, PLR, LMR, NPR, and NLR for the prognosis of patients with HCC and liver cirrhosis undergoing TACE. The areas under the curve (AUC) for these markers were 0.803, 0.624, 0.639, 0.637, and 0.659, respectively (Fig. 1). The decision curve analysis (DCA) and confusion matrix analysis were presented in Figs. 2 and 3. These results indicate that PIV has a highly reliable predictive value for the prognosis of these patients.

Fig. 1
figure 1

ROC analysis between PIV (A), PLR (B), LMR (C), NLR (D), NPR (E) and Poor Prognosis

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Fig. 2
figure 2

DCA curve between PIV (A), PLR (B), LMR (C), NLR (D), NPR (E) and Poor Prognosis

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Fig. 3
figure 3

Confusion matrix analysis between PIV (A), PLR (B), LMR (C), NLR (D), NPR (E) and Poor Prognosis

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Discussion

The present study investigates the predictive utility of five preoperative inflammatory markers—PIV, PLR, LMR, NPR, and NLR—for assessing prognosis in patients with HCC combined with liver cirrhosis undergoing TACE.

This study underscores the substantial prognostic relevance of PIV, which stood out as a significant predictor of poor prognosis. The elevated PIV in patients with unfavorable outcomes hints at an intertwining relationship between intensified systemic inflammation and impaired immune surveillance against tumors. The formula for PIV incorporates neutrophils, monocytes, and platelets in relation to lymphocytes. Each element reflects distinct yet overlapping processes: neutrophils and monocytes indicate the body’s response to tumor-associated inflammation [20, 21], while platelets may facilitate metastasis [22, 23]; conversely, lymphocytes were pivotal in immune-mediated tumor suppression [24, 25]. This inverse relationship with lymphocytes highlights the potential immunosuppressive environment in advanced disease stages, aligning with existing literature where lymphopenia correlates with worse outcomes in various malignancies [26].

The predictive power of classic systemic inflammatory indexes like PLR and NLR in this study reinforces their acknowledged roles in oncological prognostication [27]. The elevated PLR observed in the poor prognosis group might reflect an orchestrated tumor-host interaction, wherein thrombocytes promote angiogenesis and tumor cell protection, while a relative reduction in lymphocytes illustrates compromised antitumor immunity. Similarly, the increased NLR in patients with adverse outcomes underscores the dual role of neutrophils in promoting tumor progression and suppressing adaptive immune responses, coupled with a reduced lymphocyte-mediated antitumor response. These ratios serve as surrogate markers of systemic immune dysfunction and reinforce the need for early intervention to restore immune competence in managing such patients.

The heightened NPR observed aligns with observations of thrombocytosis serving as a marker of tumor burden, which when coupled with rising neutrophil counts, amplifies inflammatory cascades that might aid tumor progression. This finding suggests that the NPR could reflect a balance tipped towards promotion of a protumorigenic milieu, with neutrophils and platelets synergistically aggravating local and systemic conditions favorable for cancer cell proliferation and dissemination.

On the contrary, a decreased LMR within the poor prognosis cohort might signify skewed balance towards monocyte-mediated inflammatory responses at the expense of lymphocytic activity. Monocytes can contribute to a tumor-enabling environment through their differentiation into tumor-associated macrophages, which were instrumental in remodeling tumor stroma, facilitating invasion, and promoting immunosuppression [28, 29]. Therefore, a low LMR signifies potential exacerbation of such mechanisms, reflecting a breakdown in the immunological equilibrium poised against tumor development.

Analyzing biochemical markers, alongside inflammatory indexes, brings forth the significance of evaluating liver function and metabolic indicators of hepatocellular injury, such as elevated ALT, AST, and GGT, which were also associated with poor prognosis [30]. These markers not only highlight liver dysfunction but might interact with tumor biology to exacerbate inflammation or promote fibrogenesis, fueling tumor progression. Elevated AFP further indicates significant tumor burden and aggressive disease biology, compounding the prognostic implications when interpreted alongside inflammatory indices.

Moreover, the imaging findings emphasize that greater tumor burden and advanced vascular invasion detected in the poor prognosis group might potentiate inflammatory responses captured in blood test markers. This underlies a possible mechanistic interplay between tumor characteristics, systemic inflammation, and liver function impairment inherent in cirrhotic settings, driving poor outcomes post-TACE. The higher prevalence of multiple, larger, and poorly differentiated tumors, coupled with vascular invasions such as portal vein thrombosis, may further exacerbate the pro-inflammatory state, reflecting in blood indices.

Our study highlights the importance of portal hypertension assessment in patients undergoing TACE. The higher prevalence of portal hypertension signs in the poor prognosis group suggests that this condition may contribute to systemic inflammation through mechanisms such as increased intestinal permeability and bacterial translocation. These processes may influence inflammatory markers and potentially impact treatment outcomes, underscoring the need for comprehensive portal hypertension evaluation before TACE.

The impact of previous treatments on inflammatory markers and treatment outcomes deserves special attention. Our findings demonstrate that patients with a history of surgical resection or percutaneous ablation were more likely to have poor outcomes following TACE. This could be attributed to several factors, including the selection of more aggressive tumors for prior treatments, cumulative hepatic injury from multiple interventions, or alterations in the tumor microenvironment following previous therapies. These observations align with recent recommendations that emphasize careful patient selection for TACE in previously treated individuals, as noted in clinical practice guidelines [31].

Several previous studies have proposed prognostic models for patients undergoing TACE. The TACE Predict model, published in Hepatology 2019, incorporates clinical and laboratory parameters to predict overall survival after TACE [32]. Similarly, the ASAR score (BMC Cancer 2020) combines various clinical and imaging features to stratify patients into risk groups [33]. Recent studies have also highlighted the prognostic significance of post-TACE transient hypertransaminasemia, demonstrating its correlation with radiological response and survival outcomes [34].

Our inflammatory markers, particularly PIV with its high AUC of 0.803, could potentially complement these existing prognostic models. We propose that integrating PIV, along with other significant inflammatory markers like NPR, into existing prediction tools might enhance their prognostic accuracy. A combined approach that incorporates both conventional prognostic factors (tumor characteristics, liver function) and inflammatory markers could provide a more comprehensive assessment of treatment outcomes. Furthermore, the post-TACE transient elevation in transaminases could be evaluated alongside pre-TACE inflammatory markers to develop an integrated pre- and post-treatment prognostic model.

In this context, these inflammatory markers offer insights beyond static prognostic stratification. They help dynamically gauge the interplay between tumor biology, systemic inflammation, and liver dysfunction, vital in guiding personalized management plans. These include optimizing the timing and frequency of TACE, informing immunotherapeutic strategies, and refining patient selection for adjunctive treatments based on inflammatory profiles.

While this study provides valuable insights into the prognostic utility of inflammatory markers in patients undergoing TACE for HCC with liver cirrhosis, it does have several limitations. Firstly, the retrospective design may introduce selection bias and limit the generalizability of the findings. Secondly, the study population was drawn from a single hospital, which may not be representative of diverse geographic or demographic settings. Additionally, the lack of data on potential confounding factors, such as genetic predispositions and lifestyle variables, could influence inflammatory marker levels and patient outcomes. Future prospective, multicenter studies that incorporate a broader range of clinical and biological variables were needed to confirm and expand upon these findings.

Conclusion

In conclusion, our findings stress the considerable predictive value of PIV, PLR, LMR, NLR, and NPR in assessing the prognosis of HCC patients undergoing TACE in the backdrop of liver cirrhosis, echoing their indicative significance of the inflammatory milieu intertwined with tumor-host dynamics. They accentuate the notion that a comprehensive prognostic assessment must encompass both typical tumor-related factors and systemic inflammatory indicators, ultimately aiding in tailoring clinical decisions and therapeutic interventions.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Oncology, The First Clinical Medical College, Three Gorges University/Yichang City Central People’s Hospital, Yichang, 443000, China

    Yanan Wei, Tiantian Liu, Wanyan Wu, Ziwei Yang & Xiuli Liu

  2. Department of Clinical Laboratory, The First Clinical Medical College, Three Gorges University, Yichang City Central People’s Hospital, Yichang, 443000, China

    Dongting Mao

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Contributions

YNW and DTM were involved in the conception and design, or analysis and interpretation of the data; TTL and WYW the drafting of the paper, revising it critically for intellectual content; ZWY and XLL the final approval of the version to be published; and that all authors agree to be accountable for all aspects of the work.

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Correspondence to Xiuli Liu.

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Wei, Y., Mao, D., Liu, T. et al. The predictive value of PIV, PLR, LMR, NPR, and NLR for the prognosis of transarterial chemoembolization in patients with hepatocellular carcinoma combined with liver cirrhosis. BMC Gastroenterol 25, 315 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12876-025-03815-0

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Keywords

BMC Gastroenterology

ISSN: 1471-230X

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