Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

Table 1 Baseline characteristics of patients having Budd-Chiari syndrome with and without hepatocellular carcinoma

Characteristic	Overall population, n = 904	BCS w/o HCC, n = 869	BCS-HCC, n = 35	P value
Age in yr at first presentation	26 (21-33)	26 (20-33)	32 (25-40)	0.001
Duration of symptoms in month	12 (4-36)	12 (4-36)	3 (2-24)	< 0.001
Male sex	496 (54.87)	480 (55.24)	16 (45.71)	0.270
Site of block
Inferior vena cava	57 (6.31)	50 (5.75)	7 (20.00)	0.020
Hepatic vein	398 (44.03)	388 (44.65)	10 (28.57)
Combined inferior vena cava and hepatic vein	449 (49.67)	431 (49.60)	18 (51.43)
Type of block, BCS
Short segment	448 (49.56)	440 (50.63)	8 (22.86)	0.001
Long segment	456 (50.44)	429 (49.37)	27 (77.14)
Child class
A	420 (46.46)	399 (45.91)	21 (60.00)	0.050
B	260 (28.76)	249 (28.65)	10 (28.57)
C	71 (7.85)	68 (7.83)	4 (11.40)
Cirrhosis	751 (83.08)	716 (82.39)	35 (100.00)	0.006
Pain in abdomen	335 (37.06)	321 (36.94)	14 (40.00)	0.710
Ascites	679 (75.11)	658 (75.72)	21 (60.00)	0.035
Gastrointestinal bleeding	195 (21.57)	189 (21.75)	6 (17.14)	0.510
Jaundice	200 (22.12)	190 (21.86)	10 (28.57)	0.340
Hepatic encephalopathy at presentation	35 (3.87)	34 (3.91)	1 (2.86)	0.750
Hemoglobin in g/dL	11.7 (9.9-13.4)	11.7 (9.9-13.4)	10.7 (9.2-12.8)	0.150
Total leucocyte count as /mm3	5560 (3850-7500)	5600 (3880-7550)	3800 (4600-6900)	0.310
Platelet count as × 103/mm3	151 (110-219)	152 (110-225)	130 (75-161)	0.006
Creatinine in mg/dL	0.7 (0.6-0.9)	0.7 (0.6-0.9)	0.7 (0.6-0.9)	0.330
Total bilirubin in mg/dL	1.5 (0.9-2.4)	1.5 (0.9-2.4)	1.7 (1.0-2.3)	0.310
Aspartate transaminase in IU/L	42 (32-63)	42 (31-62)	59 (35-80)	0.008
Alanine transaminase in IU/L	31 (22-47)	31 (22-47)	46 (27-65)	0.010
Albumin in g/dL	3.9 (3.3-4.5)	3.9 (3.3-4.5)	4.2 (2.9-4.6)	0.620
Alkaline phosphatase in IU/L	250.0 (159-372)	250.5 (160.0-372.0)	239.0 (148-314)	0.820
Alpha-fetoprotein	3.3 (2.1-9.6)	2.9 (1.9-4.3)	1310.0 (237.0-14308.0)	< 0.001
BCS intervention received	654 (72.34)	628 (72.26)	26 (74.28)	0.189
Inferior vena cava	317 (35.06)	302 (34.70)	15 (42.8)
Hepatic vein	106 (11.72)	102 (11.73)	4 (11.42)
TIPSS	198 (21.90)	194 (22.32)	4 (11.42)
IVC + HV	28 (3.09)	26 (2.90)	2 (5.70)
PSRS	5 (0.50)	4 (0.46)	1 (2.80)
Stent block	159/654 (24.31)	151/637 (23.70)	8/17 (47.05)	0.063
Time to restenosis in d	496.0 (181.0-1253.0)	496.0 (18.0-1198.0)	692.5 (226.5-1540.0)	0.550
Follow-up in d	1249.5 (503.5-2573.0)	1248.0 (530.0-2513.0)	1307.0 (158.0-3811.0)	0.530

Data are n (%) or median (interquartile range) or n (%). BCS: Budd-Chiari syndrome; HCC: Hepatocellular carcinoma; HV: Hepatic vein; IVC: Inferior vena cava; PSRS: Proximal splenorenal shunt; TIPSS: Transjugular intrahepatic portosystemic shunt.

Table 2 Baseline characteristics of patients having Budd-Chiari syndrome hepatocellular carcinoma at follow-up and at presentation

Characteristic	BCS-HCC on follow-up, n = 17	BCS-HCC at first presentation, n = 18	P value
Age in yr at onset of BCS	30.0 (24.0-40.0)	32.5 (26.0-38.0)	0.640
Duration of symptoms	3 (2-18)	3 (2-24)	0.880
Sex, males	9 (52.90)	7 (38.88)	0.880
Site of block
Inferior vena cava	4 (23.50)	3 (16.67)	0.450
Hepatic vein	4 (23.50)	6 (33.33)
Combined inferior vena cava and hepatic vein	9 (52.90)	9 (50.00)
Type of block, BCS
Short segment	4 (23.50)	4 (22.22)	0.370
Long segment	13 (76.40)	14 (77.78)
Child class
A	8 (47.1)	13 (72.22)	0.120
B	5 (29.40)	5 (27.78)
C	4 (23.50)	0 (0)
Pain in abdomen	7 (41.18)	7 (38.89)	0.890
Ascites	11 (64.71)	10 (55.56)	0.580
Gastrointestinal bleeding	2 (11.76)	4 (22.22)	0.660
Hepatic encephalopathy at presentation	1 (5.88)	0 (0)	0.490
Hemoglobin in g/dL	10.40 (8.50-11.50)	12.10 (9.75-13.90)	0.110
Total leucocyte count in mm3	4300 (3500-6400)	4735 (4050-6950)	0.610
Platelet count as × 103/mm3	101.0 (71.0-156.0)	150.0 (113.0-166.5)	0.210
Creatinine in mg/dL	0.7 (0.5-0.9)	0.7 (0.6-0.9)	0.550
Total bilirubin in mg/dL	1.8 (1.5-3.2)	1.5 (0.8-2.1)	0.160
Aspartate transaminase in IU/L	66.0 (46.0-120.0)	51.5 (35.0-76.0)	0.280
Alanine transaminase in IU/L	46.0 (27.0-59.0)	42.5 (28.0-66.0)	0.890
Albumin in g/dL	4.0 (2.9-4.7)	4.3 (3.3-4.5)	0.530
Alkaline phosphatase in IU/L	274.0 (178.0-394.0)	210.5 (143.0-300.0)	0.320
Alpha-fetoprotein in ng/mL	500.0 (66.6-1320.0)	13029.0 (500.0-17943.0)	0.010
Intervention received	14 (82.35)	12 (66.67)	0.170
Inferior vena cava angioplasty/stenting	9 (52.90)	6 (33.33)
Hepatic vein angioplasty/stenting	2 (11.70)	2 (11.11)
IVC + HV angioplasty/stenting	0	2 (11.11)
TIPSS	2 (11.70)	2 (11.11)
PSRS	1 (5.80)	0
Barcelona Clinic Liver Cancer staging			0.029
A	1 (5.80)	4 (22.20)
B	10 (58.80)	7 (38.80)
C	2 (11.70)	7 (38.80)
D	4 (23.50)	0

Data are n (%) or median (interquartile range). BCS: Budd-Chiari syndrome; HCC: Hepatocellular carcinoma; HV: Hepatic vein; IVC: Inferior vena cava; PSRS: Proximal splenorenal shunt; TIPSS: Transjugular intrahepatic portosystemic shunt.

Table 3 Management of patients with Budd-Chiari syndrome at first presentation

Age	Sex	Site of obstruction	Length of block	BCS management	AFP	BCLC	CTP	HCC initial management	HCC response	Survival after HCC diagnosis in d	No. of lesions/size in cm	Reinterventions for HCC
35	M	IVC + HV	Long	IVC + HV angioplasty	115	A	A	TACE	PR	680	1 (10 cm × 10 cm)	1, TACE
38	F	HV	Long	HV angioplasty	239	B	A	TACE	PR	1656	2.0 (5.5 cm × 5.5 cm)	4, TACE, followed by TKI
37	M	IVC	Short	IVC angioplasty	17943	C (lung metastasis)	A	TACE	NA	39	1 (> 10 cm)	-
30	F	IVC	Short	IVC angioplasty	11430	B	A	TACE	PR	1280	2 (5.2 cm × 5.4 cm)	-
17	F	IVC + HV	Long	TIPSS	34930	B	A	TACE	PR	500	4 (4 cm × 5 cm)	2, TACE
38	F	HV	Long	Medical management	5905	C (PVT)	B	SC	NA	93	NA	-
52	M	HV	Long	Medical management	237	A	A	SC	NA	158	1.0 (1.6 cm × 1.8 cm)	-
22	F	IVC + HV	Long	Medical management	56804	C (PVT)	A	SC	NA	14	1 (11 cm × 11 cm)	-
48	M	HV	Long	Medical management	NA	A	A	SC	NA	51	1 (2.5 cm × 3.0 cm)	-
26	M	IVC + HV	Long	IVC angioplasty	15314	A	A	TACE	PD	172	1 (2.5 cm × 3.5 cm)	TKI
30	F	IVC + HV	Long	Medical management	31068	C (PVT)	B	TKI	NA	211	Infiltrative	-
63	M	IVC	Short	IVC angioplasty	20312	C (Rt. PVT)	A	TARE	NA	4881	3 (> 5 cm)	-
32	F	IVC + HV	Long	IVC angioplasty	3153	B	A	TACE	CR	2291	Multiple (2.9 cm × 2.8 cm)	1, TACE
32	M	IVC + HV	Long	IVC angioplasty	13211	C (Lt. PVT)	A	TACE	PD	240	3.0 (12.0 cm × 5.6 cm)	-
25	F	HV	Short	HV angioplasty	16.6	B	B	TACE	NA	4021	2.0 (5.0 cm × 3.3 cm)	-
29	F	IVC + HV	Long	IVC + HV angioplasty	13029	C (PVT)	B	TKI	NA	523	1.0 (9.5 cm × 7.1 cm)	-
21	F	HV	Long	TIPSS	500	B	A	SC	NA	91	2 (6 cm × 8 cm)	-
33	F	IVC + HV	Long	Medical management	14308	B	B	SC	NA	971	2.0 (6.9 cm × 5.4 cm)	-

¹Alive at last follow up. AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; BCS: Budd-Chiari syndrome; CR: Complete response; CTP: Child Turcotte Pugh; F: Female; HCC: Hepatocellular carcinoma; HV: Hepatic vein; IVC: Inferior vena cava; Lt.: Left; M: Male; NA: Not available; PD: Progressive disease; PR: Partial response; PVT: Portal vein thrombosis; Rt.: Right; SC: Supportive care; TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; TIPSS: Transjugular intrahepatic portosystemic shunt; TKI: Tyrosine kinase inhibitor.

Table 4 Management of patients with Budd-Chiari syndrome-hepatocellular carcinoma at follow-up

Age	Sex	Site of obstruction	Length of block	BCS intervention	BCS: Restenosis	BCS: Time between intervention and stent block in d	No. of reinterventions for BCS	Time between BCS and HCC diagnosis in d	AFP	BCLC	CTP	Initial HCC management	HCC response	Survival after diagnosis of HCC until last follow-up in d	No. of lesion/size	Reintervention for HCC
20	M	IVC + HV	Long	Medical management	No			2374	1320.0	B	B	TACE	PD	456	2.0 (3.0 cm × 3.6 cm)	2 (PAI, TACE)
35	F	IVC	Short	IVC angioplasty	Yes	1411	1 (IVC angioplasty)	2396	8.8	B	A	TACE	CR	3061	3.0 (2.9 cm × 2.5 cm)	-
40	M	IVC + HV	Long	Medical management	No			186	8489.0	B	A	SC	NA	5731	3 (6 cm × 7 cm)	-
52	M	HV	Long	HV angioplasty	Yes	116	1 (RHV stenting)	2148	4.0	B	B	TACE	CR	5241	2 (9 cm × 5 cm)	-
35	F	IVC	Long	IVC angioplasty	No			4273	3888.0	B	A	TACE	PD	1471	7.0 (4.0 cm × 3.9 cm)	-
47	F	IVC + HV	Long	IVC angioplasty	Yes	169	2 (IVC angioplasty, IVC angioplasty)	788	1240.0	B	A	TACE	PR	39281	3 (7 cm × 7 cm)	5 (TACE, TACE, PAI, TACE, TACE)
24	M	IVC + HV	Short	Medical management	No			3771	177910.0	D	C	SC	NA	58	Infiltrative	-
21	M	HV	Long	TIPSS	Yes	166	1 (TIPSS revision)	424	4.4	B	A	TACE	CR	23741	Multiple (3.1 cm × 2.3 cm)	-
22	F	IVC	Long	IVC angioplasty	Yes	973	2 (TIPSS, TIPSS revision)	2062	1300.0	C	B	TACE	NA	241	1 (11.2 cm × 8.8 cm)	-
45	F	IVC + HV	Long	IVC angioplasty	Yes	412	2 (Balloon dilatation, balloon)	4603	500.0	B	A	SC	NA	61	Multiple/NA	-
26	F	IVC + HV	Long	IVC angioplasty	No			4018	315.0	C	B	TKI	NA	2164	Infiltrative	-
52	F	IVC + HV	Long	IVC angioplasty	Yes	284	1 (IVC angioplasty)	1768	14951.0	D	C	SC	NA	401	Multiple	-
30	M	HV	Short	HV angioplasty	No			306	66.6	B	A	TACE	CR	1352	4.0 (4.1 cm × 3.6 cm)	2 (TACE, TACE)
40	M	IVC + HV	Long	IVC angioplasty	No			262	131.0	D	C	SC	NA	35	Infiltrative with PVT	-
32	F	IVC	Short	IVC angioplasty	No			3762	2.2	A	A	SC	NA	491	2 (2 cm × 1 cm)	-
30	M	IVC + HV	Long	PSRS	Yes	5484	1 (TIPSS)	5599	353.0	B	B	TACE	PR	171	2.0 (4.0 cm × 4.2 cm)	TKI
28	M	HV	Long	TIPSS	No			4023	500.0	D	C	SC	NA	221	Infiltrative with PVT	-

¹Alive at last follow-up. AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; BCS: Budd-Chiari syndrome; CR: Complete response; CTP: Child Turcotte Pugh; F: Female; HCC: Hepatocellular carcinoma; HV: Hepatic vein; IVC: Inferior vena cava; M: Male; NA: Not available; PAI: Percutaneous acetic acid injection; PD: Progressive disease; PR: Partial response; PSRS: Proximal splenorenal shunts; PVT: Portal vein thrombosis; RHV: Right hepatic vein; SC: Supportive care; TACE: Transarterial chemoembolization; TIPSS: Transjugular intrahepatic portosystemic shunt; TKI: Tyrosine kinase inhibitor.

Table 5 Management of patients with Budd-Chiari syndrome-hepatocellular carcinoma (Mumbai center)

Age	Sex	Site of obstruction	Length of block	BCS intervention	BCS: Restenosis	BCS: Time between intervention and stent block	No. of Reinterventions for HVOTO	Time between BCS and HCC diagnosis in d	AFP	BCLC	CTP	Initial HCC management	HCC response	Survival after diagnosis of HCC until last follow-up in d	No. of lesion	Reintervention for HCC
30	M	IVC + HV	Long	Medical management	No			3500	58000	C	C	Conservative		1201	4	None
46	M	IVC+ HV	Long	Medical management	No			150	25.60	D	C	Conservative		3651	4	None
51	M	HV	Short	Medical management	No			350	1.16	D	C	Conservative		901	4	None
22	M	IVC + HV	Long	Medical management	No			460	600	C	B	Conservative		1501	3	None
35	M	IVC + HV	Long	TIPSS	No			3400	1200	D	C	Conservative		30	4	None
15	F	IVC + HV	Long	Medical management	No			240	NA	B	B	LT		10001	1	None
16	M	IVC + HV	Long	TIPSS	Yes	150	IVC angioplasty	3300	NA	B	B	LT		29001	2	None
NA	NA	IVC + HV	Long	TIPSS	No			1200	NA	B	B	Conservative		601	1	None
NA	NA	IVC +HV	Long	Medical management				400	1450	D	B	Conservative		1801	4	None

¹Alive at last follow-up. AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; BCS: Budd-Chiari syndrome; CTP: Child Turcotte Pugh; F: Female; HCC: Hepatocellular carcinoma; HV: Hepatic vein; HVOTO: Hepatic venous outflow tract obstruction; IVC: Inferior vena cava; LT: Liver transplant; M: Male; NA: Not available; TIPSS: Transjugular intrahepatic portosystemic shunt.

Table 6 Summary of incidence, risk factors, and management of hepatic venous outflow tract obstruction-hepatocellular carcinoma

Ref.	Country	Patients, n	Incidence of HCC, n (%)	Risk factors	Treatment offered
Nakamura et al[31], 1968	Japan	64	28 (43.7)	Not provided	Details not provided
Nakamura and Takezawa et al[32], 1982	Japan	13	6 (46.0)	Age at BCS diagnosis < 44 yr; complete obstruction of IVC	Details not provided
Simson et al[33], 1982	South Africa	101	48 (47.5)	Not provided	Details not provided
Rector et al[34], 1985	United States	10	2 (20.0)	Not provided	Details not provided
Kew et al[35], 1989	South Africa	15	6 (40.0)	Not provided	Details not provided
Okuda et al[1], 1998	Japan	148	10 (6.7)	Not provided	Details not provided
Shrestha et al[36], 1996	Nepal	150	7 (4.6)	Not provided	Details not provided
Bayraktar et al[24], 1998	Turkey	56 (prospective study duration 10 years)	3 (5.3)	Hepatic vein thrombosis	Details not provided
Dilawari et al[37], 1994	India	115	9 (7.8)	Not provided	Details not provided
Matsui et al[38], 2000	Japan	12	3 (25.0)	Chronic congestion	Resection (1); TACE (1); chemotherapy (1)
Shin et al[23], 2004	South Korea	73	15 (20.5), 6 de novo/9 follow up	Female sex not provided	TACE (11); resection (2); conservative (2)
Moucari et al[4], 2008	France	97	11 (11.3)	Male, factor V Leiden mutation, IVC obstruction	TACE (7); LT (3); conservative (1)
Amarapurkar et al[25], 2008	India	35 (prospective study); follow-up 42 mo	1 (2.8)	Not provided	Details not provided
Shrestha et al[39], 2009	Nepal	56	6 (10.7)	HV block	PAI (1); supportive (5)
Gwon et al[11], 2010	Korea	98	23 (23.4)	Female sex	TACE (20); TACE + LT (3)
Park et al[5], 2012	Korea	95	17, annual incidence 2.8	Elevated HVPG	Intraarterial chemotherapy (3); conservative (3); LT (2)
Liu et al[6], 2013	China	246	14 (5.6)	IVC block + stricture of hepatic venous outflow	TACE (14)
Paul et al[9], 2015	India	421	16 (3.8)	Cirrhosis; combined IVC and HV block; long segment IVC block	TACE (11); TKI (1); conservative (4)
Sakr et al[8], 2017	Egypt	348	15 (4.3)	Male, older age; cigarette smoking, AFP > 24.5	TACE (4); TACE + RFA (2); TACE + TKI (1); conservative (8)
Li et al[7], 2022	China	113	12 (10.6)	IVC block + stricture of hepatic venous outflow	Resection (2); RFA (1); Conservative (4); TACE (5)

AFP: Alpha-fetoprotein; BCS: Budd-Chiari syndrome; HV: Hepatic vein; HVPG: Hepatic venous pressure gradient; IVC: Inferior vena cava; LT: Liver transplant; TACE: Transarterial chemoembolization; HCC: Hepatocellular carcinoma; PAI: Percutaneous acetic acid injection; RFA: Radiofrequency ablation; TKI: Tyrosine kinase inhibitor.