## 2 ALBI Grade Related to Treatment Modalities
### Palliative Treatment
#### 2.2.2 ALBI and mALBI Grading for TKI Treatments  
As of July 2020, multiple TKI drugs (sorafenib, regorafenib, lenvatinib, ramucirumab, cabozantinib) have become available worldwide. In an analysis of advanced HCC patients treated with sorafenib as part of a phase III study, ALBI grade 1 (\(p\) = 0.001) was associated with better progression-free survival [46]. [PERSON] et al. reported that OS differed significantly between ALBI grades 1 and 2 (HR 1.44, \(p\) = 0.011) among patients with a Child-Pugh score of 5 and treated with sorafenib [47]. In another study, a Cox regression analysis of 415 advanced HCC patients classified as Child-Pugh A who underwent sorafenib treatment, baseline ALBI grade 2 (\(p\) < 0.001) and ALBI grade increased during treatment (\(p\) < 0.001) and were strongly associated with mortality [48]. The ALBI grade is thought to be an independent predictor of survival [46; 49; 50; 48]. In 2017, regorafenib became available as a second-line therapy for patients who experienced sorafenib failure [51]. Along with the introduction of regorafenib, the ALBI grade has been found to be important. Not all u-HCC patients treated with sorafenib meet the RESORCE trial criteria [51] at the time of sorafenib failure, and thus the frequency of those indicated for regorafenib has been reported to range from only 30.6% to 44.2% after confirmation by radiological findings to have PD with sorafenib therapy [52; 53; 54; 55; 56]. [PERSON] et al. showed that, at the time of the radiological progressive disease, the factors that met the RESORCE study inclusion criteria were not only the baseline ALBI score (\(-\)2.33; OR 2.5, \(p\) = 0.01) but also the degree of change in liver function after four weeks of sorafenib treatment (<0.255; OR4.9, \(p\) < 0.001) [57]. Furthermore, [PERSON] et al. demonstrated that an ALBI score of \(-\)2.53 at the time of introduction of sorafenib was useful as acutoff value for predicting the eligibility for regorafenib after sorafenib failure [56], as did a report by [PERSON] et al. [58]. In 2018, lenvatinib was introduced as a new first-line treatment [59]. Its usefulness in clinical practice not only as a first-line but also as a second-line or later treatment option has also been reported in Japan [60; 61], and this is an important clinical issue, as many patients do not meet the RESORCE criteria because of sorafenib intolerability. It has been reported that mLBI grades 2b or 3 (\(\text{score}>-2.27\)) were the only significant prognostic factors for the survival of patients undergoing lenvatinib treatment (HR 4.632, \(p=0.004\)) [62]. Another study showed that sequential treatment with TKIs including lenvatinib had an impact in prolonging OS and that the total duration of administration of all TKIs demonstrated a good correlation with overall survival (r = 0.946, \(p<0.001\)) [63]. In that report as well, OS with a TKI sequential treatment including treatment for u-HCC was good (\(n=84\)) (median survival 46.4 months), and mLBI grades 2b or 3 (\(\text{score}>-2.27\)) at the time of introduction of the first-line TKI were also the only prognostic factors (HR 2.319, \(p=0.034\)). [PERSON] et al. reported similar results in which patients with mLBI grade 1 and 2a (\(\text{score}\leq-2.27\)) showed better prognosis for lenvatinib treatment (HR 0.16, \(p=0.006\)) [64], as did [PERSON] et al. for all patients treated with TKI therapy (median survival: mLBI grade 1:2a:2b and 3 = 20.1:16.3:9.8 months; \(p=0.0003\)) [65]. Moreover, another study indicated that the predictive value for OS of mLBI was superior to that of the Child-Pugh score (AIC: 592.3 vs. 599.7) (c-index: 0.655 vs. 0.597) and non-mLBI grade 1/2a at the start of treatment and that there was a significant risk factor for a decline to Child-Pugh class B during therapy (HR 2.552, \(p<0.001\)) when using lenvatinib treatment as a first-line drug [66].