Pahari Hirak, Peer Javid A, Tripathi Shikhar, Singhvi Suresh K, Dhir Ushast
Department of Liver Transplant and Hepatobiliary Surgery, Sir Ganga Ram Hospital, New Delhi 110060, Delhi, India.
Department of Surgical Gastroenterology and Liver Transplant, Sir Ganga Ram Hospital, New Delhi 110060, Delhi, India.
World J Gastrointest Pharmacol Ther. 2024 Sep 5;15(5):97570. doi: 10.4292/wjgpt.v15.i5.97570.
Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival.
肝细胞癌（HCC）合并慢性肝病（CLD）患者的肝移植（LT）受到肿瘤大小、数量、门静脉或肝静脉侵犯以及肝外疾病等因素的限制。尽管先前制定的标准，如米兰标准或加州大学旧金山分校（UCSF）标准，已在全球范围内放宽，以接纳更多具有相似5年预后的潜在受者，但仍有一部分人群患有晚期HCC，伴有或不伴有门静脉肿瘤血栓形成，且未检测到肝外转移，他们不符合肝移植标准，或无法通过传统方法降期，因而没有资格接受肝移植。免疫检查点抑制剂（ICI），如阿特珠单抗、帕博利珠单抗或纳武利尤单抗，给这组患者带来了希望。我们使用PubMed、谷歌学术搜索（Google Scholar）、参考文献引用分析和CrossRef完成了一项全面的文献综述。搜索使用了“肝移植”、“HCC”、“肝细胞癌（hepatocellular carcinoma）”、“免疫检查点抑制剂”、“ICI”、“阿特珠单抗”和“纳武利尤单抗”等关键词。几例病例报告记录了在LT前使用阿特珠单抗/贝伐单抗联合治疗成功使HCC降期，早期预后可接受，与其他标准相当。也有围手术期ICI不良反应的报告。在这些情况下，建议在ICI治疗和LT之间间隔1.5个月。总体而言，联合免疫治疗降期的结果令人鼓舞且充满希望。早期报告表明，对于CLD和晚期HCC患者，尤其是那些患有多灶性HCC或门静脉分支肿瘤血栓形成的患者，可能带来一线希望。然而，前瞻性研究和更多经验将揭示LT前的最佳剂量、持续时间和时机，并评估排斥反应、感染、复发率和生存率方面的短期和长期结果。
