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

Table 6 Univariate and multivariate Cox regression analysis for hepatocellular carcinoma-related death according to 2005 and 2010 American Association for the Study of Liver Diseases guidelines

Variables	2005 AASLD guidelines (HCC patients, 2008-2010)				2010 AASLD guidelines (HCC patients, 2011-2016)
	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)	1.229 (0.809-1.865)	0.334	1.210 (0.896-1.635)	0.214	1.775 (1.376-2.289)	< 0.001	1.587 (1.206-2.089)	0.001
Male sex	1.237 (0.776-1.972)	0.371			0.832 (0.602-1.152)	0.268
BMI (≥ 25 kg/m2)	1.164 (0.819-1.654)	0.397			0.827 (0.650-1.053)	0.123
DM	0.990 (0.681-1.438)	0.958			1.236 (0.954-1.600)	0.109
Hypertension	1.129 (0.798-1.596)	0.493			1.101 (0.868-1.398)	0.428
Etiology
Hepatitis B	0.867 (0.608-1.235)	0.429			0.828 (0.652-1.051)	0.121
Hepatitis C	1.068 (0.633-1.801)	0.807			1.225 (0.884-1.698)	0.223
Alcohol	1.155 (0.815-1.637)	0.417			0.994 (0.785-1.259)	0.961
Ascites
Mild	1.984 (0.872-4.516)	0.102			1.907 (1.303-2.791)	0.001
Creatinine (> 1 mg/dL)	1.322 (0.901-1.940)	0.153			1.206 (0.919-1.582)	0.176
Sodium (≥ 135 mmol/L)	0.876 (0.445-1.724)	0.702			0.573 (0.407-0.807)	0.002
Alanine aminotransferase (> 80 IU/L)	1.021 (0.614-1.699)	0.937			0.968 (0.670-1.400)	0.865
Platelet count (> 105/μL)	0.590 (0.414-0.839)	0.003	0.684 (0.518-0.904)	0.008	0.736 (0.568-0.952)	0.020
Serum albumin (≥ 3.5 g/dL)	0.865 (0.573-1.306)	0.491			0.533 (0.408-0.696)	< 0.001	0.596 (0.416-0.855)	0.005
Total bilirubin (> 1.2 mg/dL)	1.619 (1.102-2.378)	0.014			1.509 (1.162-1.959)	0.002
INR (> 1.2)	1.229 (0.838-1.802)	0.291			1.421 (1.054-1.915)	0.021
Child-Pugh score (≥ 7)	1.430 (0.667-3.065)	0.358			1.822 (1.288-2.577)	0.001	2.429 (1.434-4.114)	0.001
MELD score (> 9)	1.465 (1.018-2.108)	0.040			1.521 (1.163-1.988)	0.002
Alpha-fetoprotein (≥ 200 ng/mL)	1.436 (1.004-2.055)	0.048			1.319 (1.029-1.692)	0.029
Numbers of tumor (> 3)	1.458 (1.036-2.051)	0.030	1.570 (1.208-2.040)	0.001	1.830 (1.443-2.320)	< 0.001	1.870 (1.426-2.452)	< 0.001
Maximum tumor diameter
< 2	Ref				Ref
2-5	0.767 (0.408-1.442)	0.411	0.967 (0.606-1.543)	0.889	0.974 (0.623-1.522)	0.908	1.294 (0.794-2.107)	0.310
5-10	0.925 (0.475-1.800)	0.818	1.792 (1.093-2.939)	0.021	1.459 (0.929-2.291)	0.101	2.210 (1.338-3.650)	0.002
> 10	4.267 (0.918-19.839)	0.064	3.437 (1.784-6.623)	< 0.001	2.692 (1.578-4.594)	< 0.001	3.261 (1.834-5.797)	< 0.001
Treatment
Guideline adherence	Ref				Ref
Upward	0.442 (0.283-0.691)	< 0.001	0.465 (0.322-0.670)	< 0.001	0.678 (0.524-0.879)	0.003	0.478 (0.333-0.685)	< 0.001

95%CI: 95% confidence interval; AASLD: American Association for the Study of Liver Diseases; BMI: body mass index; DM: diabetes mellitus; HCC: Hepatocellular carcinoma; HR: Hazard ratio; INR: International normalized ratio; MELD: Mayo End-Stage Liver Disease.