Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients: Incidence and risk factors

Table 1 Demographics and clinical features of primary biliary cirrhosis patients at hepatocellular carcinoma diagnosis n (%)

Variable	Total	Men	Women	P value1
	(n= 52)	(n= 16)	(n= 36)
Age (yr)	65.75 ± 10.09	69.75 ± 8.09	63.97 ± 10.47	0.093
Han nationality	47 (90.38)	14 (87.50)	33 (91.67)	0.638
Body mass index ≥ 25 (kg/m2)	16 (30.77)	4 (25.00)	12 (33.33)	0.548
History of blood transfusion	6 (11.54)	3 (18.75)	3 (8.33)	0.043
Past HBV infection	29 (55.77)	10 (62.50)	19 (52.78)	0.519
Alcohol intake	8 (15.38)	5 (31.25)	3 (8.33)	0.035
Smoking	8 (15.38)	5 (31.25)	3 (8.33)	0.010
Type 2 diabetes mellitus	8 (15.38)	0	8 (22.22)	0.040
Hypertension	12 (23.08)	5 (31.25)	7 (19.44)	0.165
Family history of malignancy	6 (11.54)	4 (25.00)	2 (5.56)	0.012
Liver cirrhosis	52 (100.00)	16 (100.00)	36 (100.00)	1.000
Tumor size
≥ 3 cm	35 (67.31)	11 (68.75)	24 (66.67)	0.882
< 3 cm	17 (32.69)	5 (31.25)	12 (33.33)	0.882
Tumor number
Single	29 (55.77)	9 (56.25)	20 (55.56)	0.963
Multiple	23 (44.23)	7 (43.75)	16 (44.44)	0.963
Pruritus	4 (7.70)	3 (18.75)	1 (2.78)	0.046
Fatigue	37 (71.15)	13 (81.25)	24 (66.67)	0.284
Anorexia	20 (38.46)	5 (31.25)	15 (41.67)	0.476
Discomfort in hepatic region	11 (21.15)	4 (25.00)	7 (19.44)	0.651
Jaundice	30 (57.69)	11 (68.75)	19 (52.78)	0.282
Ascites	41 (78.85)	12 (75.00)	29 (80.56)	0.651

¹Men compared with women. HBV: Hepatitis B virus; NA: Not applicable.

Table 2 Biochemical characteristics of male and female primary biliary cirrhosis patients at hepatocellular carcinoma diagnosis

Variable	Total	Men	Women	P value1
	(n= 52)	(n= 16)	(n= 36)
Alanine transaminase (U/L)	43.04 ± 42.28	64.25 ± 55.48	33.61 ± 31.45	0.012
Aspartate aminotransferase (U/L)	77.83 ± 56.24	111.38 ± 72.47	62.92 ± 40.19	0.005
Alkaline phosphatase (U/L)	229.29 ± 190.44	308.81 ± 209.37	193.94 ± 172.87	0.015
γ-glutamyl transpeptidase (U/L)	156.90 ± 179.05	253.13 ± 220.54	114.14 ± 140.55	0.010
Albumin (g/L)	28.42 ± 5.67	28.06 ± 5.64	28.58 ± 5.75	0.720
Total bilirubin (μmol/dL)	61.19 ± 102.13	74.14 ± 64.25	55.43 ± 115.41	0.071
α-fetoprotein elevating, n (%)	34 (65.38)	9 (56.25)	25 (69.44)	0.356
Prothrombin time (s)	13.49 ± 2.20	12.79 ± 1.91	13.8 ± 2.28	0.159
International standardization ratio	1.15 ± 0.23	1.13 ± 0.14	1.17 ± 0.26	0.410
White blood cells (109/L)	4.29 ± 2.35	5.13 ± 2.32	3.92 ± 2.30	0.073
Red blood cells (1012/L)	3.31 ± 0.66	3.56 ± 0.76	3.19 ± 0.60	0.096
Platelets (109/L)	76.57 ± 40.50	85.20 ± 48.26	72.74 ± 36.64	0.506

¹Men compared with women. Data expressed as mean ± SD or n (%) of patients.

Table 3 Demographic, clinical and biochemical characteristics of primary biliary cirrhosis patients with or without hepatocellular carcinoma at primary biliary cirrhosis diagnosis n (%)

Variable	PBC with HCC (n = 20)	PBC without HCC (n = 77)	P value
Follow-up (mo)	46.45 ± 41.85	57.20 ± 36.33	0.144
Male	8 (40)	30 (38.97)	1.000
Female	12 (60)	47 (61.04)	1.000
Age (yr)	61.05 ± 11.92	60.77 ± 11.52	0.808
Han nationality	18 (90.00)	73 (94.81)	1.000
Body mass index ≥ 25 (kg/m2)	6 (30)	7 (9.10)	0.015
History of blood transfusion	0	4 (5.19)	0.300
Family history of malignancy	4 (20)	3 (3.90)	0.014
History of alcohol intake	7 (35)	10 (12.99)	0.022
History of smoking	4 (20)	6 (7.79)	0.112
History of type 2 diabetes mellitus	3 (15)	7 (9.09)	0.441
Liver cirrhosis	17 (85)	62 (79.22)	0.958
Hepatitis B core antibody	9 (45)	37 (48.05)	0.562
Child-Pugh, A/B/C (n/n/n)	8/11/1	32/42/3	0.900
Antimitochondrial autoantibodies
(+)	18 (90)	65 (84.42)	0.529
(-)	2 (10)	12 (15.58)	0.529
IgA (mg/dL)	2.78 ± 1.32	3.13 ± 2.07	0.686
IgM (mg/dL)	3.46 ± 1.99	4.07 ± 3.34	0.482
IgG (mg/dL)	15.86 ± 3.24	15.55 ± 6.27	0.657
White blood cells (× 109/L)	4.14 ± 1.38	4.85 ± 2.52	0.449
Hemoglobin level (g/dL)	109.01 ± 16.28	108.42 ± 20.69	0.438
Alanine aminotransferase (U/L)	80.15 ± 63.50	75.91 ± 67.18	0.715
Aspartate aminotransferase (U/L)	97.5 ± 64.48	92.60 ± 72.85	0.611
Alkaline phosphatase (U/L)	278.25 ± 155.42	376.10 ± 433.46	0.918
γ-glutamyl transpeptidase level (U/L)	294.65 ± 285.01	316.29 ± 331.95	0.748
Total bilirubin level (mg/dL)	46.84 ± 64.34	46.19 ± 62.37	0.858
Albumin level (g/dL)	32.75 ± 6.20	33.21 ± 5.58	0.876
Triglyceride (mmol/L)	1.03 ± 0.43	1.36 ± 0.82	0.207
Total cholesterol (mmol/L)	4.20 ± 1.38	5.75 ± 4.05	0.113
Prothrombin time (s)	12.34 ± 1.64	12.23 ± 1.37	0.813
α-fetoprotein (ng/mL)	14.75 ± 21.84	7.62 ± 4.46	0.072
Use of ursodeoxycholic acid	19 (95)	60 (77.9)	0.080
Effective	8 (42.1)	23 (38.3)	0.769
Clinical stage
Asymptomatic	0 (0)	9 (11.69)	0.110
Symptomatic	20 (100)	68 (88.31)	0.110

HCC: Hepatocellular carcinoma; PBC: Primary biliary cirrhosis.

Table 4 Univariate (unadjusted) and multivariate (adjusted) conditional logistic regression analysis of potential risk factors for hepatocellular carcinoma in primary biliary cirrhosis patients n (%)

Variable	Univariate OR		Multivariate OR
	(95%CI)	P value	(95%CI)	P value
Body mass index ≥ 25 (kg/m2)	3.819 (1.140-12.792)	0.006	1.116 (1.002-1.244)	0.045
Family history of malignancy	6.971 (1.253-38.790)	0.027	NA	0.175
History of alcohol intake	11.525 (1.338-99.280)	0.026	10.294 (1.108-95.680)	0.040
α-fetoprotein (ng/mL)	1.132 (1.016-1.260)	0.025	NA	0.058
Use of ursodeoxycholic acid (%)	78.828 (0.053-1.169 × 105)	0.241	NA	0.159

OR: Odds ratio; NA: Not applicable.