Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management

Table 2 Incidence rates of liver cancer, stratified by sex, age, comorbidities and medications, and comparing herb nonusers with herb users in diabetes mellitus patients with insulin management

Variables	HCC			cHR	95%CI	P value	aHR1	95%CI	P value
	n	PY	IR
Herb non-users	1487	771295	1.93	1.00	(Ref.)		1.00	(Ref.)
Herb users	639	309158	2.07	1.04	(0.94, 1.14)	0.461	0.88	(0.80, 0.97)b	0.001
Sex
Female	799	573926	1.39	1.00	(Ref.)		1.00	(Ref.)
Male	1327	506527	2.62	1.93	(1.77, 2.10)c	< 0.001	1.77	(1.62, 1.94)c	< 0.001
Age, yr
20-40	24	100697	0.24	1.00	(Ref.)		1.00	(Ref.)
40-60	777	469199	1.66	7.01	(4.67, 10.52)c	< 0.001	5.59	(3.71, 8.40)c	< 0.001
> 60	1325	510557	2.60	11.80	(7.90, 17.73)c	< 0.001	11.19	(7.43, 16.86)c	< 0.001
Comorbidities
Hypertension	1653	798612	2.07	1.29	(1.16, 1.43)c	< 0.001	1.10	(0.98, 1.23)	0.046
Coronary heart disease	954	443562	2.15	1.19	(1.09, 1.29)c	< 0.001	1.07	(0.97, 1.17)	0.052
Ischemic stroke	457	217351	2.10	1.14	(1.02, 1.26)a	0.016	0.98	(0.88, 1.09)	0.948
Hemorrhagic stroke	45	20459	2.20	1.21	(0.90, 1.62)	0.210	1.09	(0.81, 1.48)	0.400
Hyperlipidemia	1502	875554	1.72	0.57	(0.52, 0.62)c	< 0.001	0.67	(0.61, 0.74)c	< 0.001
Renal insufficiency	300	146465	2.05	1.15	(1.01, 1.30)a	0.030	0.92	(0.81, 1.04)	0.326
Cirrhosis	574	29944	19.17	14.20	(12.91, 15.65)c	< 0.001	4.28	(3.80, 4.82)c	< 0.001
Alcoholic liver damage	264	67522	3.91	2.24	(1.97, 2.55)c	< 0.001	1.08	(0.94, 1.25)	0.165
Nonalcoholic fatty liver disease	244	90700	2.69	1.42	(1.25, 1.63)c	< 0.001	1.24	(1.09, 1.42)b	< 0.001
HBV infection	647	68514	9.44	6.61	(6.03, 7.25)c	< 0.001	2.59	(2.32, 2.90)c	< 0.001
HCV infection	592	39215	15.10	10.60	(9.68, 11.71)c	< 0.001	4.56	(4.09, 5.08)c	< 0.001
Medication
Lipid-lowering drug
Statin	108	63427	1.70	0.85	(0.70, 1.04)	0.112	0.88	(0.70, 1.11)	0.313
Non-statin	169	106674	1.58	0.78	(0.67, 0.92)b	0.002	0.86	(0.73, 1.01)	0.124
Aspirin	64	35231	1.82	0.93	(0.73, 1.20)	0.590	0.75	(0.56, 1.01)	0.050
HBV treatment	324	13557	23.90	14.70	(13.05, 16.54)c	< 0.001	3.69	(3.21, 4.25)c	< 0.001
HCV treatment	71	3899	18.21	9.20	(7.26, 11.66)c	< 0.001	1.47	(1.14, 1.88)b	0.012
OAD
Biguanides	168	68930	2.44	1.27	(1.08, 1.48)b	0.003	1.16	(0.84, 1.61)	0.368
Sulfonamide	166	66481	2.50	1.30	(1.11, 1.52)b	0.001	1.08	(0.78, 1.50)	0.676
AGI	379	175908	2.15	1.12	(1.00, 1.25)	0.052	0.93	(0.83, 1.06)	0.475
Thiazolidinediones	344	161421	2.13	1.09	(0.97, 1.23)	0.134	1.07	(0.95, 1.21)	0.197
DPP4 inhibitors	289	119437	2.42	1.26	(1.11, 1.42)c	< 0.001	1.15	(0.99, 1.32)	0.085
GLP-1 receptor agonist	14	27416	0.51	0.25	(0.15, 0.42)c	< 0.001	0.40	(0.24, 0.68)c	< 0.001
SGLT2 inhibitors	88	76062	1.16	0.56	(0.45, 0.69)c	< 0.001	0.79	(0.64, 0.98)a	0.010
Glinide	418	195582	2.14	1.11	(1.00, 1.24)	0.051	0.93	(0.82, 1.04)	0.222

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

¹adjusted by variables in Table 1.

AGI: -Glucosidase inhibitors; aHR: Adjusted hazard ratio; cHR: Crude hazard ratio; DPP4: Dipeptidyl peptidase 4; GLP-1: Glucagon-like peptide-1; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis B virus; IR: Incidence rate per 1000 person-years; N: Number of events; OAD: Oral antidiabetic agents; PY: Person-years; SGLT2: Sodium-glucose co-transporter 2.