Geh Daniel, Manas Derek M, Reeves Helen L
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Hepatobiliary Surg Nutr. 2021 Jan;10(1):59-75. doi: 10.21037/hbsn.2019.08.08.
Non-alcoholic fatty liver disease (NAFLD) is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma (HCC) in many developed countries. This presents major challenges for the surveillance, diagnosis and treatment of HCC.
To discuss the clinical challenges faced by clinicians in managing the rising number of NAFLD-HCC cases.
MEDLINE, PubMed and Embase databases were searched using the keywords; NAFLD, HCC, surveillance, hepatectomy, liver transplantation, percutaneous ablation, transarterial chemoembolization (TACE), selective internal radiotherapy treatment (SIRT) and sorafenib. Relevant clinical studies were included.
Current HCC surveillance programmes are inadequate because they only screen for HCC in patients with cirrhosis, whereas in NAFLD a significant proportion of HCC develops in the absence of cirrhosis. Consequently NAFLD patients often present with a more advanced stage of HCC, with a poorer prognosis. NAFLD-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other etiologies. This limits the use of curative treatments such as liver resection and orthotopic liver transplantation (OLT). Evidence suggests that although NAFLD-HCC patients who undergo liver resection or OLT have worse perioperative and short-term outcomes, overall long-term survival is comparable to HCC of other etiologies. This highlights the importance of careful patient selection, pre-habilitation and perioperative planning for NAFLD-HCC patients being considered for surgical treatment. Careful consideration is also important for non-surgical treatments, although the evidence supporting treatment selection is frequently lacking, as these patients tend to be poorly represented in clinical trials. Locoregional therapies such as percutaneous ablation and TACE may be less well tolerated and less effective in NAFLD patients with obesity or diabetes. The tyrosine kinase inhibitor sorafenib may also be less effective.
This review highlights how international guidelines, for which NAFLD traditionally has made up a small part of the evidence base, may not be appropriate for all NAFLD-HCC patients. Future guidelines need to reflect the changing landscape of HCC, by making specific recommendations for the management of NAFLD-HCC.
非酒精性脂肪性肝病（NAFLD）是慢性肝病迅速增加的一个病因，在许多发达国家正成为肝细胞癌（HCC）的主要病因。这给HCC的监测、诊断和治疗带来了重大挑战。
探讨临床医生在管理日益增多的NAFLD-HCC病例时面临的临床挑战。
使用关键词“NAFLD”“HCC”“监测”“肝切除术”“肝移植”“经皮消融”“经动脉化疗栓塞（TACE）”“选择性内照射治疗（SIRT）”和“索拉非尼”检索MEDLINE、PubMed和Embase数据库。纳入相关临床研究。
当前的HCC监测计划并不充分，因为它们仅对肝硬化患者进行HCC筛查，而在NAFLD中，很大一部分HCC在无肝硬化的情况下发生。因此，NAFLD患者的HCC往往处于更晚期，预后较差。与其他病因的HCC相比，NAFLD-HCC患者往往年龄更大，合并症更多。这限制了肝切除术和原位肝移植（OLT）等根治性治疗方法的应用。有证据表明，尽管接受肝切除术或OLT的NAFLD-HCC患者围手术期和短期预后较差，但总体长期生存率与其他病因的HCC相当。这凸显了对考虑接受手术治疗的NAFLD-HCC患者进行仔细的患者选择、术前康复和围手术期规划的重要性。对于非手术治疗也需要仔细考虑，尽管支持治疗选择的证据常常不足，因为这些患者在临床试验中的代表性往往较差。经皮消融和TACE等局部区域治疗对肥胖或糖尿病的NAFLD患者的耐受性可能较差且效果不佳。酪氨酸激酶抑制剂索拉非尼可能也效果较差。
本综述强调了传统上NAFLD在其中仅占一小部分证据基础的国际指南可能并不适用于所有NAFLD-HCC患者。未来的指南需要通过对NAFLD-HCC的管理提出具体建议，来反映HCC不断变化的情况。
