# Clinical Benefits of Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma
## 4 Clinical Benefits and Disadvantages of HAIC  
The clinical benefits of HAIC for advanced HCC are as follows: (1) even a patient with Child-Pugh B HCC (7 or 8 points) is a candidate for HAIC [43], (2) Child-Pugh scores barely decline after HAIC [42; 44], (3) HAIC is highly effective in patients with vascular invasion compared with sorafenibly [11; 35], and 4) survival in patients receiving HAIC may not be associated with skeletal muscle volume [57]. In contrast, the disadvantages of HAIC for advanced HCC are as follows: (1) a highly technical procedure is needed to implant a catheter with a reservoir port; (2) hospitalization is needed to continue HAIC treatments; (3)patients have to return for follow-up visits every 2 weeks to maintain the reservoir system; and (4) adverse events related to the reservoir system, such as port migration, catheter dislocation, arterial occlusion, reservoir system occlusion, subcutaneous hematomas, or infection [65].  
Atezolizumab combined with bevacizumab was recently approved, and this combination will be recommended as the first-line therapy for advanced HCC. However, a comparison between atezolizumab plus bevacizumab and HAIC has not been performed. Patients with macrovascular invasion, including an invasion of the main portal trunk, accounted for 38% of those in the atezolizumab plus bevacizumab group; however, the details were not shown [9]. Therefore, as there has been no information regarding this combination therapy in real-world practice, further studies are required.  
We present a draft of the treatment proposal for HAIC for advanced HCC in Figure 1. The combination of atezolizumab and bevacizumab will be shifted to the first-line therapy in patients with Child-Pugh A HCC, regardless of EHM, and currently used MTAs will be shifted to later lines of therapy [10]. HAIC may be an optional treatment in patients with Child-Pugh A HCC and vascular invasion, especially Vp3 or Vp4, without EHM [11; 35]. MTAs are generally used in patients with Child-Pugh A HCC, whereas the use of MTAs in patients with Child-Pugh B HCC remains controversial. Some Asian guidelines recommended that sorafenib is considered in selected patients with Child-Pugh B (e.g., score, 7 points) [18; 33; 34; 66; 67], although sorafenib treatment significantly worsened survival in patients with Child-Pugh B HCC compared to those with Child-Pugh A HCC [68]. In contrast, patients with Child-Pugh B HCC (score 7 or 8 points) are candidates for HAIC [43]. The medical needs of patients receiving second-line therapy for Child-Pugh B HCC without EHM and those who have EHM with Child-Pugh B HCC, are yet to be met. However, HAIC may be considered in a subpopulation of both Child-Pugh B HCC and EHM patients if the intrahepatic tumor is directly linked to prognosis. Therefore, patients in clinical trials who can tolerate deteriorated liver function would be candidates for the novel therapy [69; 70]. We have reported the efficacy of arterial infusion of an iron chelator, deferoxamine, which is not an anti-cancer drug but is used for treating iron overload disease in advanced HCC patients, including Child-Pugh B or C patients [69]. However, deferasirox, an oral iron chelator, has limited efficacy due to associated adverse effects, especially renal dysfunction [70]. In the future, systemic therapeutic agents would be expected to be developed for the unmet medical needs of patients undergoing advanced HCC treatment.  
Figure 1: A draft of the treatment proposal for advanced HCC. HCC, hepatocellular carcinoma; HAIC, hepatic arterial infusion chemotherapy; Vp3, primary branch portal vein invasion; Vp4, main portal vein invasion.