编者按：第68届美国肝病研究学会年会期间，美国弗吉尼亚肝脏研究所Mitchell L. Shiffman教授在“Best Practices in Clinical Hepatology”专题中介绍了肝细胞癌的多学科管理。《国际肝病》前方记者有幸采访到Shiffman教授，请他分享肝细胞癌的诊疗经验。采访中，他介绍了不同分期患者的不同治疗策略、2017年的重要进展，对当下诊疗现状进行了分析并提出了个人建议。
一、根据不同分期给予相应治疗策略
Shiffman教授在采访中指出，如何管理好肝癌患者是个复杂的问题，肿瘤分期（1～4期）不同，患者的治疗策略也相应不同，应个体化对待。
1期：
对于1期患者可以采取手术切除或消融的办法，也可等到肝癌进展到2期，因为在此阶段，肿瘤的大小意味着患者有资格接受肝脏移植治疗。
2期：
对于2期的肝癌患者，最佳治疗方案就是肝移植，这可为患者提供最佳的总体长期生存时间。与未接受肝移植的患者相比，接受肝移植的肝癌患者的五年生存率为95%，甚至更高；而未接受的患者，其五年生存率仅为30%。
3期：
3期患者的肿瘤较大（直径>5 cm）或最多可达三个1～3 cm大小的病灶。Shiffman教授认为，这类患者因为肿瘤太大而不适合接受肝移植。其中的一部分患者早期可以通过栓塞治疗，如钇-90放射栓塞或经动脉化疗栓塞使肿瘤缩小，在某些情况下，可使患者从第3阶段降低到第2阶段，使其重新获得接受肝移植治疗的资格。
但不幸的是，3期患者分期降级的情况并不多见，只有约1/4的患者可在早期通过合适的治疗降级。对于那些不能降级，并持续增长或保持较大体积的肿瘤，可以继续进行栓塞治疗或者可以添加sorafenib、regorafenib或nivolumab等药物进行化疗。
4期：
4期的肝癌是多灶性的，包括血管转移或转移到骨、肺或其他器官。这类患者预后较差，生存2年是所能期待的最好结果。治疗方面主要是化疗、姑息治疗和临终护理关怀。
二、肝癌治疗需要多学科协作
Shiffman教授指出，为了实现肝癌各个阶段的治疗目标，我们需要多学科医生的协助，如外科医生帮助适于切除的肿瘤患者进行手术、为适合的患者开展肝移植，肿瘤学家为患者制定合适的化疗方案等。
但现实中医生所接触的肝癌患者，有一半以上处于晚期（第3和第4期），并且已经超出肝移植的适应证，或者由于合并症和其他问题，许多有资格接受移植手术的患者丧失机会。因此，肝癌患者实际上可以接受肝移植治疗的人数不足10%。
三、nivolumab为肝癌患者带来新的希望
“FDA批准nivolumab用于肝癌治疗，可能是今年肝癌治疗方面的最佳进展”，Shiffman教授在采访中指出。与分子靶向治疗的相关数据相比，一年的随访期内，nivolumab在降低肿瘤大小和肿瘤进展方面具有明显优势。这一新药物为晚期肝癌患者的治疗提供了强大的支持，“当然我们更希望在临床试验中看到的相应结果转化为现实，让肝癌患者在有限的生存期内可以体验更好的生活质量。”
Hepatology Digest: Can you provide an outline for the management of liver cancer?
Dr Shiffman: Management of liver cancer is a complicated issue. It depends on the stage of the cancer (1-4), and each stage is approached differently. Stage 1 cancers can be either resected or ablated, or we can wait until they grow into the next stage, T2. At this stage, the size of the cancer means the patient is eligible for transplantation. For stage 2, the optimal treatment is liver transplantation, as this provides the best overall long-term survival for the patient. Patients with liver cancer who undergo liver transplantation have a 95% or better five-year survival, compared to patients who do not receive a liver transplant. For these patients, five-year survival is only 30%.
Stage 3 liver cancers are larger (>5cm diameter) or may have up to three lesions of 1-3cm in size. These patients are not candidates for liver transplantation because the tumor is too large. Some of these tumors can be downstaged by treatment with embolic therapy, either Yttrium-90 radioembolization or transarterial chemoembolization. The effect of this is to shrink the tumor down, and in some cases, move the patient from stage 3 to stage 2 where they will be eligible for liver transplantation. Unfortunately, downstaging of stage 3 cancers does not occur often, and only about a quarter of patients can be downstaged appropriately. For those cancers that cannot be downstaged and continue to grow or remain large, they can continue to be treated with embolic therapy, or chemotherapy can be added, either Nexavar (sorafenib), Stivarga (regorafenib) or Opdivo (nivolumab).
Finally, stage 4 liver cancers are multifocal, include vascularization or may have extrahepatic spread to bone, lungs or other organs. These patients have a very limited prognosis. Two-year survival is the best that can be hoped for. Treatment is chemotherapy and then palliative care and hospice care. To accomplish these goals for the various stages of liver cancer, we need the assistance of surgeons to resect those tumors that are appropriate for surgical resection, oncologists in those patients who are appropriate for chemotherapy, and liver transplant programs to refer those patients who are eligible for transplantation. Unfortunately, when you look at all patients who present with liver cancer, more than half are at an advanced stage (stage 3 and 4) and already outside the indications for liver transplantation. Many patients who would otherwise be eligible for transplant are not candidates because of comorbidities and other issues. So the number of patients with liver cancer that can actually get a liver transplant as a curative treatment is very small, <10%.
Hepatology Digest: What clinical research presented at this meeting interests you?
Dr Shiffman: I think the best advance in the treatment of liver cancer this year has been the FDA approval of Opdivo (nivolumab) as a chemotherapeutic option. Data comparing nivolumab to Nexavar (sorafenib) are clearly superior with significant reductions in tumor size and tumor progression over a one-year follow-up period. We are very excited to have this new drug in our armamentarium for those patients with advanced liver cancer, and we certainly hope that the results seen in clinical trials will translate into the real world, allowing our liver cancer patients with limited survival experience better quality of life.