AIM:To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma(HCC).METHODS:A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study.Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade,location and size of the largest tumor and adverse events of sorafenib treatment,such as hand-foot syndrome(HFS),hypertension,diarrhea,and alopecia,with the efficacy of treatment,as measured by overall survival(OS)and time to progression(TTP).RESULTS:Patients included 39 men and 7 women whose ages ranged from 48 to 85 years(70.6±9.6years).HCC was classified according to etiology as follows:hepatitis C virus(n=26),hepatitis B virus(n=9),and other(n=11).Liver function in patients was categorized as Child-Pugh grade A(n=30)or B(n=16).Tumors were categorized by size[<5 cm(n=33)or>5 cm(n=13)]and the location of the largest tumor was used to categorize patients with intrahepatic(n=28)or extrahepatic(n=18)HCC.HFS,hypertension,diarrhea,and alopecia were present in22(47.8%),19(41.3%),15(32.6%)and 7 patients(15.2%),respectively.The median OS of all patients was 373 d and the median TTP was 112 d.The etiology of HCC did not correlate with the median OS and TPP.The median OS of patients with tumors<5 cm was significantly longer than those with larger tumors(496 vs 245 d;HR=0.19,95%CI:0.07-0.48;P<0.01).According to the results of a multivariate analysis,the size of the largest tumor affected OS(HR=0.22,95%CI:0.08-0.59;P<0.01).The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC(224 vs 98 d;HR=0.32;95%CI:0.14-0.67;P<0.01).The median TTP of patients with HFS was significantly longer than those without it(195 d vs 83 d;HR=0.41,95%CI:0.20-0.82;P<0.05),and the median TTP was significantly longer in patients with hypertension(195 d vs84 d;HR=0.43,95%CI:0.21-0.84;P<0.05).According to the results of the multivariate analysis,extrahepatic major HCC(HR=0.36,P<0.01)and HFS(HR=0.44,P<0.05)prolonged TTP.CONCLUSION:Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment. AIM: To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 days at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study. Multivariate and univariate analyzes were performed to evaluate the associations of hepatic function according to Child-Pugh grade, location and size of the largest tumor and adverse events of sorafenib treatment, such as hand-foot syndrome ( HFS), hypertension, diarrhea, and alopecia, with the efficacy of treatment, as measured by overall survival (OS) and time to progression (TTP) .RESULTS: Patients included 39 men and 7 women who ages ranged from 48 to 85 years ( 70.6 ± 9.6years. HCC was classified according to etiology as follows: hepatitis C virus (n = 26), hepatitis B virus (n = 9), and other (n = 11) .Liver function in patients was categorized as Child- Pugh grade A (n = 30) or B (n = 16) .Tumors were categorized by size [<5 cm (n = 33) or> 5 cm (n = 13)] and the location of the largest tumor was used to categorize patients with intrahepatic (n = 28) or extrahepatic .HFS, hypertension, diarrhea and alopecia were present in22 (47.8%), 19 (41.3%), 15 (32.6%) and 7 patients (15.2%), respectively.The median OS of all patients was 373 d and the median TTP was 112 d. The etiology of HCC did not correlate with the median OS and TPP. Median OS of patients with tumors <5 cm was significantly longer than those with larger tumors (496 vs 245 d; HR = 0.19, 95% CI : 0.07-0.48; P <0.01). According to the results of a multivariate analysis, the size of the largest tumor affected OS (HR = 0.22, 95% CI: 0.08-0.59; longer in patients with extrahepatic compared to intrahepatic major HCC (224 vs 98 d; HR = 0.32; 95% CI: 0.14-0.67; P <0.01) .The median TTP of patients with HFS was significantly longer than those without it vs 83 d; HR = 0.41, 95% CI: 0.20-0.82; P <0.05), and the median TTP was significant ntally longer in patients with hypertension (195 d vs 84 d; HR = 0.43, 95% CI: 0.21-0.84; P <0.05). According to the results of the multivariate analysis, extrahepatic major HCC and HFS (HR = 0.44, P <0.05) prolonged TTP.CONCLUSION: Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment.