Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

Table 1 Developement period of reported cases of hepatocellular carcinoma associated with autoimmune hepatitis and primary biliary cirrhosis, compared to cases of general hepatocellular carcinoma in Japan

Clinical status	Compiled numbers			P-values
	HCC patients with AIH (AIH-series)	HCC patients with PBC (PBC-series)	General-HCC patients	AIH-series/General-HCC patients	PBC-series/General-HCC patients	AIH-series/PBC-series
Observation period (mean ± SD)	Total: 38 1 yr 1 mo-23 yr (10 yr 6 mo ± 6 yr 7 mo)	Total: 49 3 mo-24 yr (9 yr 4 mo ± 6 yr 4 mo)
			NA	NA	NA	P = 0.307
						(P = 0.815)
Interval between liver damage and HCC diagnosis (mean ± SD)	Total: 34	Total: 40
	0-22 yr 9 mo	0-24 yr	NA	NA	NA	P = 0.740
	(10 yr 2 mo ± 6y 5 mo)	(9 yr 9 mo ± 7 yr 0 mo)				(P = 0.688)
Period from HCC development to death (mean ± SD)	Total: 18	Total: 16
	2 mo-3 yr	0-5 yr	NA	NA	NA	P = 0.047a
	(1 yr 2 mo ± 12 mo)	(8.4 ± 14 mo)				(P = 0.401)

The P-value above was calculated from the Mann-Whitney U-test and the P-value below, indicated in parentheses, was calculated from the F-test.

^aP < 0.05, Statistically significant. HCC: Hepatocellular carcinoma; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; SD: Standard deviation; NA: Not available.

Table 2 Analysis on gender and age of reported cases of hepatocellular carcinoma associated with autoimmune hepatitis and primary biliary cirrhosis, compared to cases of general hepatocellular carcinoma in Japan

	Compiled numbers (%)			P-values
Clinical status	HCC patients with AIH (AIH-series)	HCC patients with PBC (PBC-series)	General-HCCpatients	AIH-series/General-HCC patients	PBC-series/General-HCC patients	AIH-series/PBC-series
Gender
Actual number	Total: 38	Total: 50	Total: 16743
Male	7 (18.4)	13 (26.0)	12025 (71.8)
Female	31 (81.6)	37 (74.0)	4718 (28.2)	P = 0.1491	P = 0.5121	P = 0.244
Relative number	Total: 38	Total: 50
Male	23.3 (61.3)	38.0 (76.0)
Female	14.7 (38.7)	12.0 (24.0%)
Age at HCC diagnosis	Total: 38	Total: 50	Total: 16743
(mean ± SD)	(67.61 ± 8.58)	(68.54 ± 9.30)	NA
< 40 s	0 (0)	2 (4.0)	761 (4.6)	NA	NA	P = 0.410
50 s	8 (21.0)	6 (12.0)	2818 (16.8)			(P = 0.614)
60 s	16 (42.1)	21 (42.0)	6179 (36.9)
70 s	9 (23.7)	14 (28.0)	5976 (35.7)
< 80 s	5 (13.2)	7 (14.0)	1009 (6.0)

The P-value above was calculated from the Mann-Whitney U-test and the P-value below, indicated in parentheses, was calculated from the F-test.

¹The P-value was calculated from the relative numbers. HCC: Hepatocellular carcinoma; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; SD:Standard deviation; NA: Not available.

Table 3 Clinical status of reported cases of hepatocellular carcinoma associated with autoimmune hepatitis and primary biliary cirrhosis, compared to cases of general hepatocellular carcinoma in Japan

Clinical status	Compiled numbers (%)			P-values
	HCC patients with AIH (AIH-series)	HCC patients with PBC (PBC-series)	General-HCC patients	AIH-series/General-HCC patients	PBC-series/General-HCC patients	AIH-series/PBC-series
History of blood transfusion	Total: 29	Total: 38	Total: 12602	P = 0.040a	P = 0.581	P = 0.041a
+	3 (10.3)	13 (34.2)	3633 (28.8)
-	26 (89.7)	25 (65.8)	8969 (71.2)
History of excessive alcohol intake	Total: 38	Total: 50	Total: 14694	P = 0.812	P = 0.056	P = 0.352
+	1 (2.6)	5 (10.0)	3271 (22.3)
-	37 (97.4)	45 (90.0)	11423 (77.7)
Co-infection	Total: 33	Total: 40	Total: 4121
HBV (prior) +	2 (6.1)	10 (25.0)	2138 (51.9)	P < 0.001	P <0.001	P = 0.025
HBV (prior) –	31 (93.9)	30 (75.0)	1983 (48.1)
Co-infection	Total: 38	Total: 49	Total:16492
HCV +	3 (7.9)	10 (20.4)	11488 (69.7)	P < 0.001	P < 0.001	P = 0.044
HCV -	35 (92.1)	39 (79.6)	5004 (30.3)
Pathological findings of noncancerous lesion of the liver	Total: 31	Total: 44	Total: 4941	P = 0.163	P = 0.007b	P = 0.489
NL, CH, LF	13 (41.9)	15 (34.1)	2691 (54.5)
LC	18 (58.1)	29 (65.9)	2250 (45.5)

HCC: Hepatocellular carcinoma; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; HBV: Hepatitis B virus; HCV: Hepatitis C virus; NL: Normal liver; CH: Chronic hepatitis; LF: Liver fibrosis; LC: Liver cirrhosis.

Table 4 Serum AFP levels, tumor sizes and number of HCC loci of reported cases of hepatocellular carcinoma associated with autoimmune hepatitis and primary biliary cirrhosis, compared to cases of general hepatocellular carcinoma in Japan

Clinical status	Compiled numbers (%)			P-values
	HCC patients with AIH (AIH-series)	HCC patients with PBC (PBC-series)	General-HCC patients	AIH-series/General-HCC patients	PBC-series/General-HCC patients	AIH-series/PBC-series
Serum-AFP	Total: 37	Total: 47	Total: 15831
AFP- (< 15 ng/mL)	15 (40.5)	13 (27.7)	5756 (36.4)	P = 0.597	P = 0.216	P = 0.214
AFP + (>= 15 ng/mL)	22 (59.5)	34 (72.3)	10075 (63.6)
Serum-AFP (ng/mL)	Total: 37	Total: 47	Total: 15831
(mean ± SD)	(2340.21 ± 8823.45)	(854.18 ± 2263.83)	NA
< 15	15 (40.5)	13 (27.6)	5756 (36.4)
15-199	12 (32.5)	16 (34.0)	5786 (36.5)	NA	NA	P = 0.106
200-399	1 (2.7)	6 (12.8)	902 (5.7)			(P < 0.001b)
400-999	3 (8.1)	2 (4.3)	907 (5.7)
>= 1000	6 (16.2)	10 (21.3)	2480 (15.7)
Maximum tumor size of HCC	Total: 36	Total: 48	Total: 15788	NA	NA	P = 0.744
(mean ± SD) (cm)	(3.75 ± 2.42)	(3.51 ± 1.69)	NA			(P = 0.028a)
< 2	14 (38.9)	11 (22.9)	5123 (32.4)
2.1-5.0	16 (44.4)	29 (60.4)	7434 (47.1)
>= 5.1	6 (16.7)	8 (16.7)	3231 (20.5)
Number of HCC loci	Total: 38	Total: 49	Total: 16187
(mean ± SD)	(1.58 ± 2.05)	(1.74 ± 1.97)	NA	NA	NA	P = 0.418
Single	33 (86.8)	38 (77.6)	9365 (57.9)			(P = 0.805)
Double	2 (5.3)	7 (14.3)	2850 (17.6)
Multiple	3 (7.9)	4 (8.1)	3972 (24.5)

The P-value in the first row was calculated from the χ² test and Fisher’s exact test. The P-value in the following row was calculated from the Mann-Whitney U-test and the P-value below, indicated in parentheses, was calculated from the F-test.

^aP < 0.05,

^bP < 0.01, Statistically significant. HCC: Hepatocellular carcinoma; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; AFP: &agr;-fetoprotein; SD: Standard deviation; NA: Not available.

Table 5 Therapy and outcome of reported cases of hepatocellular carcinoma associated with autoimmune hepatitis and primary biliary cirrhosis, compared to cases of general hepatocellular carcinoma in Japan

Clinical status	Compiled numbers (%)			P-values
	HCC patients with AIH (AIH-series)	HCC patients with PBC (PBC-series)	General-HCC patients	AIH-series/General-HCC patients	PBC-series/General-HCC patients	AIH-series/PBC-series
Therapy choices for HCC	Total: 38	Total: 47	Total: 17005	Operation vs CL or TAE P = 0.0481	RFA, PEIT vs CL or TAE
CL or TAE	18 (47.4)	17 (36.2)	4636 (27.2)	RFA,PEIT,MCT vs	P = 0.0271
Operation	8 (21.0)	16 (34.0)	5268 (31.0)	CL or TAE	RFA, PEIT vs
RFA, PEIT, MCT	6 (15.8)	6 (12.8)	4890 (28.8)	P = 0.0181	No therapy
Chemotherapy	0 (0)	0 (0)	765 (4.5)	RFA,PEIT,MCT vs	P = 0.0032
Others	0 (0)	0 (0)	122 (0.7)	No therapy
No therapy	6 (15.8)	8 (17.0)	1324 (7.8)	P = 0.0381
Clinical outcome	Total: 37	Total: 49	Total: 16646
Alive	20 (54.1)	31 (63.3)	13946 (83.8)	P < 0.001b	P < 0.001b	P = 0.389
Dead	17 (45.9)	18 (36.7)	2700 (16.2)
Cause of death	Total: 16	Total: 18	Total: 2700	Neoplastic death vs variceal rupture P = 0.0501 Cancer death vs GI bleeding P = 0.0131	Neoplastic death vs variceal rupture P = 0.0501
Liver failure	8 (50.0)	8 (44.4)	581 (21.5)
HCC rupture	3 (18.8)	4 (22.2)	172 (6.4)
Variceal rupture	1 (6.2)	1 (5.6)	85 (3.1)
GI bleeding	1 (6.2)	2 (11.1)	55 (2.0)
Neoplastic death	0 (0)	0 (0)	1487 (55.1)
Others	3 (18.8)	3 (16.7)	320 (11.9)

^bP < 0.01, Statistically significant.

¹The calculated P-values did not reach statistical significance with Bonferroni correction; without the correction, however, P-values were below 0.05.

²The calculated P-values reached statistical significance with Bonferroni correction. HCC: Hepatocellular carcinoma; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; CL: Chemolipiodolization; TAE: Transcatheter arterial embolization; RFA: Radiofrequency ablation therapy; PEIT: Percutaneous ethanol injection therapy; MCT: Microwave coagulation therapy; GI: Gastrointestinal.