Metformin does not improve survival in patients with hepatocellular carcinoma

Table 1 Baseline characteristics of patients in the study

Variables	Non-diabetic (n = 438)	Diabetics not on metformin (n = 207)	Diabetics on metformin (n = 56)	P value
Age, yr
Mean ± SD	61.4 ± 13.3	64.7 ± 10.3	64.4 ± 9.7	0.003
Median	61.1	65.5	62
Q1, Q3	53.9, 71.4	56.7, 72.0	57.7, 71.4
Range	19.0-91.5	19.8-89.4	43.3-88.0
Age group				0.001
< 20 yr	2 (0.5)	1 (0.5)	0 (0.0)
21-40 yr	22 (5.0)	2 (1.0)	0 (0.0)
41-60 yr	189 (43.2)	64 (30.9)	19 (33.9)
≥ 61 yr	225 (51.4)	140 (67.6)	37 (66.1)
Gender				0.060
Female	132 (30.1)	47 (22.7)	11 (19.6)
Male	306 (69.9)	160 (77.3)	45 (80.4)
Caucasian	326 (74.4)	168 (81.2)	43 (76.8)	0.170
Etiology of liver disease
Hepatitis C	161 (37.2)	61 (29.9)	12 (21.8)	0.030
Hepatitis B	49 (11.3)	6 (2.9)	5 (9.1)	0.002
Alcoholic liver disease	129 (30.0)	59 (28.9)	10 (18.5)	0.210
Nonalcoholic fatty liver disease	25 (5.8)	63 (30.9)	14 (25.9)	< 0.0001
Other	74 (16.9)	18 (8.7)	15 (26.8)	0.012
BCLC stage
Missing	125	45	17	0.080
0/A	72 (23.0)	26 (16.0)	11 (28.2)
B	43 (13.7)	15 (9.3)	4 (10.3)
C	165 (52.7)	96 (59.3)	23 (59.0)
D	33 (10.5)	25 (15.4)	1 (2.6)

All data except for age are shown in n (%). BCLC: Barcelona-Clınic Liver Cancer.

Table 2 Survival of patients newly diagnosed with hepatocellular carcinoma, categorized according to demographics, etiologies of liver disease, stage, diabetes status and metformin use

	Number of deaths/total	Median survival (mo)	1-yr Kaplan-meier estimate (95%CI)	Unadjusted HR (95%CI)	P value	Adjusted HR (95%CI)	P value
Male	314/511	25.2	61.8% (57.7-66.3)	1.1 (0.9-1.3)	0.54	1.0 (0.8-1.3)	0.73
Age, per 10 yr	-	-	-	1.2 (1.1-1.3)	< 0.001	1.2 (1.1-1.3)	< 0.001
Caucasian	329/537	24.6	64.6% (60.6-68.9)	0.9 (0.8-1.1)	0.36
Etiology of liver disease
Hepatitis C	127/234	29	65.6% (59.7-72.1)	0.8 (0.6-0.9)	0.0095
Hepatitis B	30/60	30.2	58.1% (46.3-72.8)	0.9 (0.6-1.3)	0.52
Alcoholic liver disease	126/198	19.8	60.8% (54.3-68.1)	1.0 (0.8-1.3)	0.75
NAFLD	64/102	29.4	67.6% (58.8-77.7)	1.0 (reference)	0.98
BCLC stage
0/A	39/109	> 97.3	88.4% (82.5-94.8)	1.0 (reference)	< 0.001	1.0 (reference)	< 0.001
B	32/62	41.0	70.0% (59.3-82.7)	1.9 (1.2-3.1)	0.005	2.0 (1.2-3.1)	0.005
C	205/284	15.2	50.1% (44.5-56.4)	3.8 (2.7-5.4)	< 0.001	3.7 (2.6-5.2)	< 0.001
D	32/59	30.6	58.9% (47.2-73.5)	2.4 (1.5-3.8)	< 0.001	2.5 (1.6-4.0)	< 0.001
Diabetes
metformin status
Non-diabetic	257/438	27.3	61.4% (56.9-66.3)	1.0 (0.7-1.4)	0.98	1.1 (0.7-1.7)	0.59
Continue metformin	37/56	34.2	60.6% (48.8-75.4)	0.9 (0.7-1.1)	0.30	1.0 (0.8-1.3)	0.77
No metformin or	133/207	25.5	65.5% (59.2-72.4)	1.0 (reference)	0.52	1.0 (reference)	0.86
Discontinue within 90 d
In patients with NAFLD
Non-diabetic	11/25	46.7	79.5% (64.9-97.3)	0.4 (0.2-0.7)	0.005
Continue metformin	7/14	36.5	65.7% (43.1-100.0)	0.6 (0.3-1.4)	0.24
No metformin or discontinue within 90 d	46/63	16.3	63.0% (51.8-76.7)	1.0 (reference)	0.01

BCLC: Barcelona-Clınic Liver Cancer; NAFLD: Nonalcoholic fatty liver disease.