Factors associated with overall survival in patients with HCC treated with immune checkpoint inhibitors
| Univariate | Multivariate (model 1)* | Multivariate (model 2)† | ||||||||
| HR | 95% CI | P value | HR | 95% CI | P | HR | 95% CI | P value | ||
| Age, years | >60 vs ≤60 | 0.643 | 0.242 to 1.706 | 0.375 | NA | NA | ||||
| Sex | Male vs female | 1.313 | 0.299 to 5.770 | 0.718 | NA | NA | ||||
| HBsAg-positive | Yes vs no | 1.152 | 0.404 to 3.286 | 0.791 | NA | NA | ||||
| Anti-HCV-positive | Yes vs no | 0.593 | 0.168 to 2.085 | 0.415 | NA | NA | ||||
| Tumor size, cm | >7 vs ≤ 7 | 2.121 | 0.792 to 5.674 | 0.134 | NA | NA | ||||
| Tumor number | Multiple vs single | 24.183 | 0.027 to 21 310.445 | 0.357 | NA | NA | ||||
| Tumor/Liver volume | >50% vs ≤50% | 2.974 | 1.067 to 8.293 | 0.037 | 0.927 | 0.225 to 3.821 | 0.916 | 0.877 | 0.221 to 3.481 | 0.852 |
| Portal vein invasion | Yes vs no | 2.663 | 0.979 to 7.238 | 0.055 | 1.254 | 0.375 to 4.197 | 0.999 | 1.338 | 0.388 to 4.609 | 0.645 |
| Extrahepatic metastasis | Yes vs no | 1.042 | 0.394 to 2.753 | 0.934 | NA | NA | ||||
| BCLC stage | Stage C vs B | 1.274 | 0.447 to 3.630 | 0.650 | NA | NA | ||||
| AFP, ng/mL | >400 vs ≤400 | 1.667 | 0.638 to 4.357 | 0.297 | NA | NA | ||||
| NLR | >2.5 vs ≤2.5 | 2.233 | 0.719 to 6.933 | 0.165 | NA | NA | ||||
| Prothrombin time, INR | >1.2 vs ≤1.2 | 1.268 | 0.464 to 3.461 | 0.644 | NA | NA | ||||
| Platelet count | >100K vs ≤100K | 0.722 | 0.254 to 2.053 | 0.541 | NA | NA | ||||
| ALT, U/L | >40 vs ≤40 | 1.825 | 0.699 to 4.766 | 0.220 | NA | NA | ||||
| AST, U/L | >40 vs ≤40 | 10.423 | 1.377 – 78/908 | 0.023 | 5.168 | 0.528 to 50.533 | 0.158 | 6.013 | 0.631 to 57.264 | 0.119 |
| Child-Pugh class | Class B vs A | 2.950 | 1.027 to 8.473 | 0.044 | 1.238 | 0.345 to 4.443 | 0.774 | NA | ||
| ALBI grade | Grade 2, 3 vs 1 | 2.062 | 0.715 to 5.946 | 0.181 | NA | 1.490 | 0.380 to 5.841 | 0.567 | ||
| Prior sorafenib treatment | Yes vs no | 0.841 | 0.324 to 2.185 | 0.722 | NA | NA | ||||
| Combined treatment† | Yes vs no | 0.778 | 0.288 to 2.102 | 0.621 | NA | NA | ||||
| Gut microbial abundance | ||||||||||
| Low Lachnoclostridium and high Prevotella 9 | 1 | – | – | 1 | – | – | 1 | – | – | |
| Intermediate status of abundance‡ | 0.253 | 0.064 to 0.996 | 0.049 | 0.234 | 0.047 to 1.176 | 0.078 | 0.216 | 0.043 to 1.076 | 0.061 | |
| High Lachnoclostridium and low Prevotella 9 | 0.239 | 0.080 to 0.715 | 0.010 | 0.283 | 0.088 to 0.908 | 0.034 | 0.279 | 0.088 to 0.890 | 0.031 | |
| Fecal UDCA concentration | High vs low | 0.324 | 0.114 to 0.919 | 0.034 | 0.470 | 0.114 to 1.940 | 0.296 | 0.357 | 0.079 to 1.601 | 0.178 |
| Immunotherapy-related AEs | Yes vs no | 1.401 | 0.481 to 4.082 | 0.536 | NA | NA | ||||
*Model 1 enrolled parameters with p value<0.2 in univariate analysis into multivariate analysis, except ascites and ALBI grade.
†Model 2 enrolled parameters with p value<0.2 in univariate analysis into multivariate analysis, except Child-Pugh class.
‡Combined treatment: combined immune checkpoint inhibitors with tyrosine kinase inhibitors, including sorafenib, lenvatinib, and regorafenib.
§Intermediate abundance of Lachnoclostridium and Prevotella 9: either both low abundance of these two taxa or both high abundance.
AEs, adverse events; AFP, alpha fetoprotein; ALBI grade, albumin-bilirubin grade; AL(S)T, alanine(aspartate) aminotransferase; BCLC stage, Barcelona-Clinic liver cancer stage; HBsAg, hepatitis B virus surface antigen; HCV, hepatitis C; ICI, immune checkpoint inhibitor; INR, international normalized ratio; NA, not adopted; NLR, neutrophil- lymphocyte ratio; UDCA, ursodeoxycholic acid.