T cell exhaustion markers in hepatitis C virus-related hepatocellular carcinoma: Expression patterns and prognostic significance in an Egyptian cohort

Table 12 Univariate and multivariate Cox proportional hazards regression for overall survival in hepatocellular carcinoma patients

Variable	Univariate HR (95%CI)	P value	Multivariate HR (95%CI)	P value
CD4/PD-1 (%)	2.5 (1.6-3.9)	< 0.001c	2.1 (1.3-3.4)	0.002b
CD8/PD-1 (%)	2.3 (1.5-3.5)	< 0.001c
CD4/TIGIT (%)	1.8 (1.1-2.9)	0.015a
CD8/TIGIT (%)	1.9 (1.2-3.0)	0.008b
CD4/TIM3 (%)	1.7 (1.0-2.8)	0.045a
CD8/TIM3 (%)	2.7 (1.7-4.3)	< 0.001c	2.4 (1.4-4.1)	0.001b
CD3 (%)	1.5 (0.9-2.5)	0.12
CD4 (%)	1.4 (0.8-2.4)	0.23
CD8 (%)	1.6 (0.9-2.8)	0.09
CD4/CD8 ratio	0.4 (0.2-0.7)	0.002b
AFP (ng/mL)	3.0 (1.9-4.7)	< 0.001c	2.6 (1.5-4.5)	< 0.001c
MELD score	1.1 (0.8-1.5)	0.53
Child-Pugh class (C vs A/B)	1.8 (1.0-3.2)	0.048a
BCLC stage (D vs A-C)	3.5 (2.2-5.6)	< 0.001c	3.0 (1.7-5.3)	< 0.001c

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

Multivariate model adjusted for all univariate variables (CD4/programmed death 1, CD8/ programmed death 1, CD4/T cell immunoglobulin and ITIM domain, CD8/T cell immunoglobulin and ITIM domain, CD4/T cell immunoglobulin and mucin domain-containing protein 3, CD8/T cell immunoglobulin and mucin domain-containing protein 3, CD3, CD4, CD8, CD4/CD8 ratio, alpha-fetoprotein, Model for End-Stage Liver Disease score, Child-Pugh class, Barcelona Clinic Liver Cancer stage). Child-Pugh class was not retained due to non-significant independent contribution. Etiology controlled by study design (hepatitis C virus-positive hepatocellular carcinoma patients only). PD-1: Programmed death 1; TIGIT: T-cell immunoglobulin and ITIM domain; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; AFP: Alpha-fetoprotein; MELD: Model for End-Stage Liver Disease; HR: Hazard ratio; CI: Confidence interval.