Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma

Table 5 Univariate and multivariate Cox regression analysis for hepatocellular carcinoma -related death according to 2000 and 2012 European Association for the Study of the Liver guidelines

Variables	2000 EASL guidelines (HCC patients, 2008-2012)				2012 EASL guidelines (HCC patients, 2013-2016)
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age (≥ 70 yr)	1.339 (1.004-1.783)	0.046	1.300 (0.961-1.758)	0.089	1.838 (1.336-2.529)	< 0.001	1.765 (1.269-2.687)	0.001
Male sex	1.239 (0.875-1.754)	0.227			0.592 (0.401-0.874)	0.008	0.610 (0.409-0.910)	0.153
BMI (≥ 25kg/m2)	0.890 (0.695-1.140)	0.356			0.829 (0.606-1.135)	0.242
DM	1.153 (0.880-1.510)	0.301			1.027 (0.740-1.424)	0.875
Hypertension	1.072 (0.836-1.375)	0.583			1.026 (0.757-1.391)	0.867
Etiology
Hepatitis B	0.902 (0.704-1.156)	0.415			0.852 (0.624-1.165)	0.316
Hepatitis C	1.056 (0.743-1.501)	0.763			1.270 (0.822-1.962)	0.282
Alcohol	1.109 (0.866-1.420)	0.393			0.960 (0.711-1.295)	0.787
Ascites
Mild	2.499 (1.543-4.048)	< 0.001			1.552 (0.962-2.503)	0.072
Moderate to severe	1.302 (0.486-3.509)	0.597			1.736 (0.767-3.929)	0.186
Creatinine (> 1 mg/dL)	1.283 (0.975-1.689)	0.076			1.123 (0.786-1.605)	0.524
Sodium (> 135 mmol/L)	0.620 (0.411-0.937)	0.024			0.615 (0.408-0.929)	0.021
Alanine aminotransferase (> 80 IU/L)	1.166 (0.813-1.672)	0.403			0.886 (0.556-1.412)	0.610
Platelet count (> 105/μL)	0.685 (0.529-0.886)	0.004	0.672 (0.507-0.890)	0.006	0.735 (0.526-1.025)	0.07
Serum albumin (≥ 3.5 g/dL)	0.694 (0.523-0.921)	0.011			0.605 (0.428-0.855)	0.004
Total bilirubin (> 1.2 mg/dL)	1.529 (1.153-2.027)	0.003			1.510 (1.096-2.081)	0.012	1.391 (0.998-1.938)	0.051
INR (> 1.2)	1.303 (0.982-1.729)	0.067			1.333 (0.904-1.967)	0.147
Child-Pugh score (≥ 7)	1.808 (1.187-2.754)	0.006			1.586 (0.994-2.530)	0.053
MELD score (> 9)	1.463 (1.112-1.926)	0.007			1.438 (1.035-1.998)	0.030
Alpha-fetoprotein (≥ 200 ng/mL)	1.287 (0.993-1.668)	0.056			1.626 (1.196-2.211)	0.002	1.392 (1.001-1.936)	0.049
Numbers of tumor (> 3)	1.810 (1.419-2.309)	< 0.001	1.685 (1.293-2.196)	< 0.001	1.654 (1.219-2.244)	0.001	1.673 (1.178-2.275)	0.003
Maximum tumor diameter (cm)
< 2	Ref				Ref
2-5	0.642 (0.409-1.008)	0.054	0.969 (0.608-1.545)	0.894	1.489 (0.807-2.750)	0.203	1.725 (0.908-3.276)	0.096
5-10	1.061 (0.666-1.689)	0.803	1.862 (1.136-3.055)	0.0138	1.694 (0.912-3.148)	0.095	2.378 (1.228-4.603)	0.010
> 10	2.511 (1.328-4.748)	0.005	4.377 (2.268-8.448)	< 0.001	4.023 (2.051-7.892)	< 0.001	4.358 (2.120-8.956)	< 0.001
Treatment
Guideline adherence	Ref				Ref
Upward	0.372 (0.263-0.525)	< 0.001	0.448 (0.310-0.647)	< 0.001	0.631 (0.426-0.935)	0.022	0.720 (0.478-1.086)	0.117
Downward					1.974 (1.362-2.859)	< 0.001	1.838 (1.257-2.687)	0.002

95%CI: 95%confidence interval; BMI: Body mass index; DM: Diabetes mellitus; EASL: European Association for the Study of the Liver; HCC: Hepatocellular carcinoma; HR: Hazard ratio; INR: International normalized ratio; MELD: Mayo End-Stage Liver Disease.