Lin Chi-Han, Kuo Yung-Chia, Kuo Hsuan-Chih, Wang Ching-Ting, Lin Shi-Ming, Lee Alan Chao-Wei, Yu Ming-Chin, Lee Wei-Chen, Chen Cherry Chiao-Erh, Hsieh Jason Chia-Hsun
College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan.
J Hepatocell Carcinoma. 2024 Oct 2;11:1875-1890. doi: 10.2147/JHC.S464105. eCollection 2024.
Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear.
In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns.
One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all < 0.001) and, similarly, after excluding progressive disease ( = 0.014, = 0.002, < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin ( 0.003) and AST ( = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses.
Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.
肝炎常发生于启动免疫检查点抑制剂（ICI）治疗后。ICI开始治疗后肝炎出现的时间和分级以及免疫相关性肝炎在晚期肝细胞癌（aHCC）患者中的预后作用仍不清楚。
在这项真实世界分析中，我们纳入了接受ICI治疗的aHCC患者，记录ICI治疗期间及之后肝酶的最高水平，并分析不同肝炎模式对生存的影响。
招募了193例接受ICI治疗的aHCC患者。在ICI治疗期间，88.6%的患者出现天冬氨酸转氨酶（AST）升高（Ⅲ/Ⅳ级：7.8%）。对于丙氨酸转氨酶（ALT），81.3%的患者水平升高（Ⅲ/Ⅳ级：3.6%），41.5%的患者胆红素水平升高（3/4级：6.7%）。ICI治疗开始后，AST、ALT和总胆红素的中位数显著升高（均P<0.001），同样，排除疾病进展后也是如此（P = 0.014、P = 0.002、P<0.001）。肝炎发生的中位时间为第4.0周至15.9周。多变量分析显示，接受ICI治疗患者的AST和总胆红素肝酶变化模式与总生存期（OS）显著相关（分别为P = 0.009和P = 0.001）。ICI停药后，胆红素升高（P = 0.003）和AST升高（P = 0.005）的患者生存预后较差，校正了病毒性肝炎和ICI反应。
肝炎在ICI启动后第4周至20周出现。ICI治疗期间肝酶变化不直接影响OS，这意味着如果临床需要及时给予皮质类固醇，ICI使用是安全的。
