关键词: 原发性肝癌, 腹腔镜左半肝切除术, 肝血流阻断, 高迁移率族蛋白B1, 胸苷激酶1, H2A组蛋白家族成员X, 免疫功能, 生存分析

Abstract:

Objective To investigate the effects of different hepatic blood flow occlusion methods on the serum levels of high mobility group protein B1 （HMGB1）， thymidine kinase 1 （TK1）， H2A histone family member X （H2AFX）， and the immune function in patients with primary liver cancer during laparoscopic left hemihepatectomy. Methods A total of 141 patients diagnosed with primary hepatocellular carcinoma who underwent laparoscopic left hemihepatectomy at the Rehabilitation University Qingdao Central Hospital from January 2022 to May 2023 were selected. According to the actual hepatic blood-flow occlusion technique employed during the surgery， they were divided into three groups： Group A （Pringle maneuver， n = 57）， Group B （intrahepatic sheath dissection method， n = 45）， and Group C （combined venous occlusion method， n = 39）. All three groups were followed up post-operatively until May 31， 2025， or until the patient's death. Perioperative indicators were compared among the groups. Liver function ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， prealbumin （PA）， alkaline phosphatase （ALP）］， immune function （CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺ ratio）， and serum levels of HMGB1， TK1， and H2AFX were evaluated preoperatively and on the third postoperative day. Moreover， the incidence of postoperative complications during the follow-up period， overall survival （OS）， and progression-free survival （PFS） were compared among the three groups. Results Significant differences were detected among the three groups in terms of intraoperative blood loss and postoperative recovery times （including time to first flatus， ambulation， initiation of liquid diet， and hospital stay）. Group C exhibited the most favorable outcomes， followed by Group B， and then Group A （C < B < A， P < 0.05）. When compared to preoperative levels， on the third postoperative day， the levels of ALT， AST， TBIL， ALP， and CD8⁺ increased in all groups. Group A had the highest levels， followed by Group B， and Group C had the lowest （A > B > C， P < 0.05）. Conversely， the levels of PA， CD3⁺， CD4⁺， and the CD4⁺/CD8⁺ ratio decreased. Group A had the lowest values， followed by Group B， and Group C had the highest （A < B < C， P < 0.05）. Compared with preoperative levels， the serum levels of HMGB1， TK1， and H2AFX increased on the third postoperative day in all groups. The smallest increase was observed in Group C， followed by Group B， and the greatest increase was in Group A （C < B < A， P < 0.05）. During the follow-up period， the complication rate in Group C was significantly lower than those in Groups A and B （P < 0.05）， while there was no significant difference between Groups A and B （P > 0.05）. A statistically significant difference in overall OS was identified among the three groups （χ² = 7.189， P = 0.028）. Specifically， Group C had a superior OS compared to Group A （HR = 0.517， 95%CI： 0.325 - 0.824） and Group B （HR = 0.621， 95%CI： 0.387 - 0.996）. Similarly， a statistically significant difference in PFS was found （χ² = 7.493， P = 0.024）， with Group C showing better PFS than Group A （HR = 0.509， 95%CI： 0.319 - 0.814） and Group B （HR = 0.644， 95%CI： 0.400 - 1.038）. Conclusions Compared with the conventional Pringle maneuver or the intrahepatic sheath dissection method used alone， the combined venous occlusion method can more effectively suppress the postoperative elevation of serum HMGB1， TK1， and H2AFX levels induced by laparoscopic left hemihepatectomy. It can mitigate liver function impairment and immunological dysfunction， reduce postoperative complications， and achieve superior short-term efficacy and long-term survival outcomes.

Key words: primary liver cancer, laparoscopic left hemihepatectomy, hepatic blood flow occlusion, high mobility group box 1 protein, thymidine kinase 1, H2A histone family member X, immune function, survival analysis