Simple Preoperative Inflammation-based Markers Predict Early And Late Recurrence Of Hepatocellular Carcinoma After Curative Hepatectomy

Background:Recurrence of hepatocellular carcinoma(HCC)after curative resection remains a major cause of treatment failure and tumor-related death.Patterns of HCC recurrence can be categorized into early recurrence and late recurrence which have different underlying mechanisms.Early recurrence is mainly associated with invasive tumor characteristics whereas late recurrence is largely contributed by continuous liver disease.As a hallmark of cancer,systemic inflammation and inflammatory tumor microenvironment play significant roles in the development and progression of cancer.And HCC represents a typical example of inflammation-related cancer.Multiple signaling pathways has been identified to be associated with inflammation in HCC,including NF-?B,JAK-STAT and MAPK pathways etc.Importantly,inflammation is also linked to cancer-related malnutrition.However,in clinical situation,these molecular pathways are not readily accessible and clinical significance of the molecular markers is ambiguous for clinicians.In this study,we investigated if simple inflammation-based clinical markers can distinguish patterns of recurrence after curative resection of HCC.The use of simple inflammation-based markers may help improve the prognosis of HCC by enabling risk stratification,personalized surveillance and active intervention.Methods:Follow-up was conducted regularly in outpatient clinic of our hospital.Only patients with complete follow-up information and required clinicopathologic data were included.Patients with evidence of infection or systemic inflammatory diseases were excluded.A retrospective analysis of 223 patients who underwent curative hepatectomy for HCC was performed.Diagnosis of HCC was based on imaging information,serum alpha-fetoprotein(AFP)test and was finally confirmed by at least two experienced pathologists.Inflammation-based scores were calculated using preoperative data from whole blood cell count and liver function test.Preoperative inflammation-based factors including neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR),y-glutamyl transpeptidase/alanine aminotransferase ratio(GGT/ALT),aspartate transaminase-platelet ratio index(APRI)and prognostic nutritional index(PNI)together with other clinicopathologic parameters were evaluated by univariate analysis and multivariate analysis to identify independent prognostic factors.By combining risk factors,predictive models were established to distinguish populations at high risk of early or late recurrence.Results:Age?50 years,resection margin?1 cm,TNM stage ?-?,NLR>2.75,APRI>0.23 and positive alpha-fetoprotein(AFP)were independent adverse prognostic factors for early recurrence.Patients with three or more risk factors were at significant higher risk of early recurrence.For late recurrence,only APRI>0.23 and positive hepatitis B e antigen(HBeAg)were independent risk factors.Co-existence of high APRI and positive HBeAg identified patients at significantly higher risk of late recurrence.Conclusions:Preoperative inflammation-based prognostic factors predict early and late recurrence of HCC after curative resection.Different prognostic factor combinations distinguish high-risk populations of early or late HCC recurrence.