Integrative therapy with Qinghao Biejia Decoction improves survival after resection of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is characterized by high postoperative recurrence and limited benefit from conventional adjuvant therapy. Qinghao Biejia Decoction (QHBJD), a classical traditional Chinese medicine formula, has demonstrated potential anticancer effects. This study investigated the molecular mechanisms of QHBJD in ICC and evaluated its impact on postoperative survival, with a focus on AKT1 expression. In this retrospective study of 60 patients with intrahepatic cholangiocarcinoma (ICC), network pharmacology and bioinformatics analyses were used to identify candidate targets of QHBJD. AKT1 expression was validated by immunohistochemistry in tissue microarrays, and associations between AKT1 expression, treatment strategies, and survival outcomes were assessed using Kaplan-Meier and Cox regression analyses. AKT1 was identified as a key target of QHBJD. In ICC tissues, AKT1 showed predominant nuclear localization, and high nuclear expression was associated with significantly shorter overall survival (OS) (18.4 vs. 25.1 months, p = 0.046). Postoperative adjuvant therapy alone did not significantly improve survival. In contrast, QHBJD-based integrative therapy significantly prolonged OS compared with no treatment (28.8 vs. 14.2 months, p = 0.041) and conventional therapy alone (28.8 vs. 11.2 months, p = 0.001). Among patients with high nuclear AKT1 expression, QHBJD significantly improved both disease-free survival (DFS) (5.95 vs. 2.0 months, p = 0.001) and OS (23.9 vs. 8.0 months, p < 0.001). Multivariate analysis confirmed QHBJD-based therapy as an independent protective factor for OS (HR 0.47, p < 0.05). QHBJD-based integrative therapy significantly improves survival in ICC, particularly in patients with high nuclear AKT1 expression, highlighting AKT1 as a potential therapeutic target and candidate prognostic biomarker that warrants further validation.