Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension
Currently, the combination of targeted therapy and immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, a subset of HCC patients with severe splenomegaly, splenic hyperfunction, and esophagogastric varices due to liver cirrhosis and portal hypertension may be unable to undergo or sustain the combination therapy, ultimately missing the optimal treatment window. Prior studies have indicated that splenectomy can significantly improve liver function and hepatic reserve in cirrhotic patients. It also addresses splenic hyperfunction and reduces the risk of bleeding from esophagogastric varices by combining splenectomy with devascularization around the cardia. Additionally, splenectomy contributes to the improvement of liver fibrosis and restoration of immune function in cirrhotic patients. This study aims to elucidate the impact of splenectomy on the efficacy of combination targeted and immunotherapy in unresectable HCC patients with cirrhotic portal hypertension, particularly those with poor liver function, significant splenic hyperfunction, and severe esophagogastric varices. The research also seeks to explore whether changes in the tumor immune microenvironment before and after splenectomy can influence the effectiveness of immunotherapy. Ultimately, the goal is to provide therapeutic opportunities for this specific patient population.
• Patients aged 18 to 75 years (inclusive).
• No prior systemic antitumor treatment or meeting the criteria for splenectomy during treatment.
• Clinical or pathological diagnosis of hepatocellular carcinoma (HCC) that is unresectable initially or has recurred after surgery.
• HBV-DNA less than 1\*10\^5 copies/ml and undergoing antiviral therapy.
• ECOG performance status score of 0-1, without significant organ dysfunction.
• Child-Pugh score of 5-7.
• Spleen thickness \>4.0 cm.
• History of esophagogastric varices, red signs, or variceal bleeding with or without splenomegaly.
• Splenomegaly with WBC \<2.5 × 10\^9/L and PLT \<70 × 10\^9/L, or splenomegaly with WBC \<2.0 × 10\^9/L or PLT \<50 × 10\^9/L.
⁃ Important organ functions meeting the following criteria: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3\*ULN, total bilirubin ≤ 3\*ULN; International normalized ratio (INR) ≤ 1.5\*ULN; prothrombin time ≤ 1.5\*ULN; creatinine ≤ 1.5\*ULN.
⁃ Able to undergo local treatments such as transarterial chemoembolization (TACE), hepatic artery infusion chemotherapy (HAIC), selective internal radiation therapy with yttrium-90 (SIRT), stereotactic body radiation therapy (SBRT), and ablation (including radiofrequency ablation (RFA) and microwave ablation (MWA)).
⁃ Willing to provide informed consent.
⁃ Expected survival time of more than 3 months.