Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma

Table 1 Clinical characteristics of hepatocellular carcinoma patients

Characteristics	Data
Age (yr)	67 ± 9.4
Sex (M:F)	276:101
Stage of liver disease
Non LC	57 (15.1)
LC
Child A	213 (56.5)
Child B	86 (22.8)
Child C	21 (5.6)
T stage in the TNM system
1	101 (26.8)
2	125 (33.2)
3	56 (14.9)
4	95 (25.2)
HBs-Ag-positive	38 (10.1)
HCV-Ab-positive	256 (67.9)
Serum AST (IU/L)	88 ± 119.1
Serum ALT (IU/L)	66 ± 62.9
Serum AFP (ng/mL)	11 623 ± 48 270
Serum PIVKA-II (mAU/mL)	15 270 ± 96 781
Habitual alcohol drinkers	203 (53.8)
Obesity (BMI > 25 kg/m2)	80 (21.1)
Presence of DM	132 (35.0)

M: Male; F: Female; LC: Liver cirrhosis; Child: Child-Pugh classification; HBs-Ag: Surface antigen of the hepatitis B virus; HCV-Ab: Hepatitis C antibody; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; AFP: α-fetoprotein; PIVKA-II: Proteins induced by vitamin KAbsense of antagonist-II; BMI: Body mass index; DM: Diabetes mellitus; TNM: Tumor, node, metastasis.

Table 2 Univariate analysis of factors related to survival period after diagnosis of stage T1-T4 hepatocellular carcinoma

	HR	95% CI	P value
Age (< 69/≥ 69 yr)	0.899	0.587-1.376	0.6232
Sex (M/F)	1.218	0.760-1.952	0.4132
Stage of underlying liver disease (non-cirrhosis, Child-Pugh A/Child-Pugh B, C)	0.537	0.394-0.733	0.0001
T stage in the TNM system (T1,T2/T3, T4)	0.419	0.330-0.531	< 0.0001
Number of HCCs (solitary/multiple)	0.192	0.119-0.309	< 0.0001
Maximum size of HCCs (< 20/≥ 20 mm)	0.403	0.260-0.623	< 0.0001
Vascular invasion of HCCs (no/yes)	0.105	0.051-0.216	< 0.0001
Method of therapy (curative/non curative)1	0.432	0.272-0.687	0.0004
HBs-Ag (negative/positive)	1.078	0.538-2.163	0.8317
HCV-Ab (negative/positive)	1.362	0.858-2.162	0.1907
AST (< 63/≥ 63 IU/L)	0.554	0.357-0.861	0.0089
ALT (< 49/≥ 49 IU/L)	0.939	0.609-1.448	0.7750
AFP (< 41/≥ 41 ng/mL)	0.260	0.155-0.439	< 0.0001
PIVKA-II (< 83/≥ 83 mAU/mL)	0.200	0.103-0.386	< 0.0001
Habitual alcohol drinkers (yes/no)	1.130	0.740-1.726	0.5722
Uninterrupted alcohol consumption after initial therapy for HCC (no/yes)	0.489	0.278-0.861	0.0135
BMI (≥ 25/< 25 kg/m2)	0.885	0.530-1.476	0.6398
Presence of DM (yes/no)	1.141	0.731-1.782	0.5623
Mean postprandial plasma glucose level after initial therapy for HCC (< 200/≥ 200 mg/dL)	0.131	0.051-0.336	< 0.0001

¹Curative therapies are surgical resection, percutaneous ethanol injection therapy, and percutaneous percutaneous radiofrequency ablation. M: Male; F: Female; HCV: Hepatitis C virus; HBs-Ag: Surface antigen of the hepatitis B virus; HCV-Ab: Hepatitis C antibody; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; AFP: α-fetoprotein; PIVKA-II: Proteins induced by vitamin KAbsense of antagonist-II; BMI: Body mass index; DM: Diabetes mellitus; HR: Hazard ratio.

Table 3 Survival period according to the T stage of hepatocellular carcinoma

T stage of hepatocellular carcinoma	Survival period (mo)
T1	43.3 ± 31.3
T2	39.8 ± 30.8
T3	23.6 ± 17.2
T4	8.7 ± 11.8

Table 4 Univariate and multivariate regression analysis of factors related to survival after diagnosis of stage T1-T3 hepatocellular carcinoma

	HR	95% CI	P value
Univariate analysis
Age (< 69/≥ 69 yr)	0.846	0.527-1.356	0.4854
Sex (male/female)	1.148	0.687-1.919	0.5975
Stage of underlying liver disease (non cirrhosis, Child-Pugh A/Child-Pugh B, C)	0.363	0.200-0.658	0.0009
T stage in the TNM system (T1/T2, T3 )	0.352	0.181-0.687	0.0023
Number of HCCs (solitary/multiple)	0.397	0.232-0.677	0.0082
Maximum size of HCCs (< 20/≥ 20 mm)	0.833	0.520-1.335	0.4469
Vascular invasion of HCCs (no/yes)	0.382	0.119-1.220	0.1039
Method of therapy (curative/non-curative)1	0.770	0.472-1.255	0.2918
HBs-Ag (negative/positive)	1.596	0.696-3.664	0.2686
HCV-Ab (negative/positive)	0.972	0.568-1.664	0.9157
AST (< 63/≥ 63 IU/L)	0.683	0.418-1.115	0.1269
ALT (< 49/≥ 49 IU/L)	0.968	0.596-1.570	0.8935
AFP (< 41/≥ 41 ng/mL)	0.365	0.205-0.649	0.0007
PIVKA-II (< 83/≥ 83 mAU/mL)	0.381	0.183-0.792	0.0101
Habitual alcohol drinkers (yes/no)	1.065	0.665-1.704	0.7939
Uninterrupted alcohol consumption after initial therapy for HCC (no/yes)	0.319	0.172-0.589	0.0002
BMI (< 25/≥ 25 kg/m2)	0.826	0.473-1.441	0.4989
Presence of diabetes mellitus (yes/no)	0.681	0.416-1.115	0.1258
Mean postprandial plasma glucose level after initial therapy for HCC (< 200/≥ 200 mg/dL)	0.143	0.054-0.381	0.0001
Multivariate regression analysis
A stepwise Cox's hazard model
Stage of underlying liver disease
Non-cirrhosis, Child-Pugh A	1.0
Child-Pugh B, C	0.649	0.476-0.885	0.0068
T stage in the TNM system
T1		1.0
T2/T3	0.788	0.653-0.945	0.0108
Uninterrupted alcohol consumption after initial therapy for HCC
No		1.0
Yes	0.641	0.469-0.877	0.0055
Mean postprandial plasma glucose level after initial therapy for HCC
< 200 mg/dL	1.0
≥ 200 mg/dL	0.502	0.337-0.747	0.0005

¹Curative therapies are surgical resection, percutaneous ethanol injection therapy, and percutaneous percutaneous radiofrequency ablation. TNM: Tumor, node, metastasis; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; HBs-Ag: Surface antigen of the hepatitis B virus; HCV-Ab: Hepatitis C antibody; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; AFP: alpha-fetoprotein; PIVKA-II: Proteins induced by vitamin KAbsense of antagonist-II; BMI: Body mass index; HR: Hazard ratio.

Table 5 Profile of T1-T3 stage hepatocellular carcinoma patients who died during observation n (%)

	Group N	Group AL	Group DM	Group AD
Age (yr)	69.1 ± 8.1	68.2 ± 8.8	68.9 ± 6.5	67.4 ± 9.6
Sex (M:F)	88:52	38:1	7:10	1:17
Stage of liver disease
Non LC	13	6	2	2
LC child
A	91	23	6	8
B	31	7	9	8
C	5	3	0	0
T stage in the TNM system
1	54	10	5	4
2	60	18	5	8
3	26	11	7	6
Habitual alcohol drinkers	47 (33.6)	39 (100)	0 (0.0)	18 (100)
Presence of diabetes mellitus	41 (29.3)	8 (20.5)	17 (100)	18 (100)

TNM: Tumor, node, metastasis; M: Male; F: Female; LC: Liver cirrhosis; DM: Diabetes mellitus.