At present, there is no consensus on the cut-off point for the time period for early recurrence following radical resection of HCC. Some clinical practice guidelines and most studies consider 2 years as the time cut-off point to distinguish early recurrence from late recurrence [3, 7, 23–29]. This study demonstrated that most patients (67.7%) showed recurrence within 2 years following surgery, and the risk of recurrence decreased and tended to lever off after 2 years. Therefore, the time of early recurrence was set within 2 years following surgery in this study. Studies have confirmed that early recurrence and late recurrence are independent entities caused by different risk factors . Early recurrence is considered to be intrahepatic or multicentric metastasis of the primary tumor, and is related to the invasiveness of the primary tumor, such as tumor number, tumor size, MVI, tumor differentiation, microsatellite nodules, and AFP [5, 6, 30], while late recurrence is mainly based on the etiology and background of liver cirrhosis [26, 28]. The results of multivariate analysis demonstrated that tumor diameter > 5 cm and MVI were independent risk factors for early recurrence of HCC following radical resection; however, there was no significant difference in the degree of tumor differentiation.
As one of the most common indicators for the diagnosis and prognosis of HCC, AFP still has a controversial predictive value for early postoperative recurrence . We found that AFP had a poor predictive effect on early recurrence of HCC, with an AUC of only 0.576. Multivariate analysis also indicated that AFP could not be used as an independent factor influencing early recurrence of HCC following curative resection (p > 0.05). This result is consistent with previous studies [5, 6, 30], whether AFP could be used as a predictor needs to be further verified.
In recent years, an increasing number of studies have demonstrated that inflammation plays an important role in the occurrence, development, and metastasis of malignant tumors [13, 25, 31]. The potential mechanisms could be that neutrophils are mainly concentrated in the peritumoral matrix of liver cancer tissues,  and can release angiogenic factors and inflammatory mediators, such as interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS). In addition, neutrophils can inhibit the cytolytic activity of immune cells, which promotes the proliferation and metastasis of cancer cells [5, 9, 10, 31, 33]. Neutrophils and tumor-associated macrophages modulate the suppression of anti-tumor immunity by inhibiting the immune function of natural killer cells and T cells, leading to malignant progression . Lymphocytes play an anticancer role in host immunity by inducing apoptosis and inhibiting the migration and invasion of cancer cells . Platelets could protect tumor cells from natural killer cell-mediated lysis, and induce rapid activation of neutrophils, thereby promoting metastasis [28, 31].
The majority of HCC cases occur in the context of hepatitis and cirrhosis; therefore, inflammation is particularly significant in the process of its occurrence and development. Preoperative scoring systems based on peripheral inflammatory indicators, such as NLR, MLR, and PLR, have also been proven to be associated with the prognosis of HCC [5, 9, 10]. In 2016, Qi proposed a new inflammatory index based on peripheral blood lymphocytes, neutrophils, and monocytes, namely SIRI , and it has been proven to predict the prognosis of various malignant tumors, such as pancreatic cancer, cervical cancer, esophageal cancer of the stomach, and breast cancer [12–14]; however, its prognostic value in HCC has not been studied. In this study, patients with HCC complicated with hematological diseases and infectious diseases were excluded to prevent them from influencing routine blood indicators and interfere with the predictive value of early recurrence. The results showed that SIRI, NLR, and MLR could all be used to predict the early recurrence of single HCC following radical surgery, except for PLR. However, only SIRI was an independent risk factor for early postoperative recurrence. ROC curve analysis showed that among these indices, SIRI was of higher value in predicting early recurrence of single HCC following radical resection.
Child-Pugh grade was proposed by Child, Turcotte, and Paugh and used to evaluate the liver function of patients with liver cirrhosis and portal hypertension [34, 35]. Since then, it has been widely applied to evaluate the liver function reserve of patients with liver disease and has been applied in various tumor staging systems, including American Joint Committee on Cancer tumor/node/metastasis (AJCC TNM) staging, BCLC staging, and China liver cancer staging (CNLC) staging. The Child-Pugh score system is composed of five indicators: bilirubin, albumin, PT, ascites, and hepatic encephalopathy, in which ascites and hepatic encephalopathy are highly subjective, and the degree of ascites is correlated with albumin concentration, decreasing the ability to evaluate liver function reserve [16, 17]. In addition, with the constant improvement of antiviral therapy and diagnosis of HCC, the number of patients with early HCC with good liver function has increased . In this study, the preoperative Child-Pugh grades of 233 patients were all grade A; therefore, it cannot be applied to predict early recurrence of HCC.
ALBI, which was put forward in 2015, is a new index evaluating liver function in patients with HCC, especially those with good liver function reserve. [16, 18]. This index is only composed of bilirubin and albumin, which are both convenient and objective markers. Many studies have proved that its prediction effect is better than that of the Child-Pugh grade. In this study, 233 patients were divided into two groups by ALBI, and the ABLI > -2.7 group indicated that the prognosis was worse, which further confirmed the previous study.
We speculate that the combination of SIRI and ALBI can improve the prediction of early recurrence following curative resection, because the combination can simultaneously evaluate the inflammation, immune status, and liver function of patients with HCC. In this study, SIRI combined with ALBI was superior to SIRI or ALBI alone in predicting early recurrence in patients with single HCC. Patients in the low SIRI-low ALBI group had a lower 2-year recurrence-free survival rate. Therefore, preoperative SIRI combined with ALBI is an important reference value for predicting early recurrence of HCC following radical resection.
At present, there is no consensus on risk stratification tools for the early postoperative recurrence of HCC. Except for the AJCC-TNM tumor staging system in the United States, most tumor staging systems are not from surgically treated patients and do not consider MVI [26, 36]. This study showed that the area under the ROC curve for TNM staging was only 0.6, which could be due to the Child-Pugh scoring system used for liver function evaluation in the TNM system, while the Child-Pugh grading of 233 patients with HCC in this study was all grade A before surgery; thus, the difference in liver function between the two groups could not be effectively distinguished. In addition, the TNM-tumor staging system lacks evaluation of tumor-related inflammatory indicators. This study combined preoperative SIRI and ALBI to construct a new PI and confirmed that it is of higher value in predicting early postoperative recurrence.
There are certain limitations to this study. First, this study is a single-center retrospective study, which is prone to selection bias. Second, the cut-off value of each index was selected by the ROC curve. Different cut-off values could affect the final statistical results and warrants further verification. Therefore, further multicenter prospective studies should be conducted.