Redefining Budd-Chiari syndrome: A systematic review

Table 1 Epidemiology of classical Budd-Chiari syndrome and hepatic vena cava-Budd Chiari syndrome

Ref.	Country	Publication	Recruitment	n	Age	Gender		Location of obstruction (%)
		date	years		(median)	M (%)	F (%)	HV	IVC	Both
Janssen et al[27]	The Netherlands	2000	1984-1997	43	40	16 (37)	27 (63)
Perelló et al[40]	Spain	2002	1990-2000	21	361	5 (24)	16 (76)	17 (81)	0 (0)	4 (19)
Colaizzo et al[30]	Italy	2008	1997-2006	32	35	9 (28)	23 (72)
Darwish Murad et al[24]	Europe	2009	2003-2005	163	38	70 (43)	93 (57)	80 (49)	4 (2)	79 (48)
Xavier et al[31]	Brazil	2010	2000-2008	31	33	11 (35)	20 (65)
Sakr et al[22]	Egypt	2011	2009-2011	94	28.81	36 (38)	58 (62)	70 (74)	3 (3)	16 (17)
Deepak et al[29]	India	2011	2006-2009	20	36.6	14 (70)	6 (30)	17 (85)	1 (5)	2 (10)
Rautou et al[37]	France	2011	1995-2005	94	381	34 (36)	60 (64)	73 (78)		13 (14)
Raszeja-Wyszomirska et al[45]	Poland	2012	2004-2011	20	38	9 (45)	11 (55)
Westbrook et al[32]	United Kingdom	2012	1985-2008	66	36	27 (41)	39 (59)
D’Amico et al[34]	Italy	2013	2005-2011	31	46	14 (45)	17 (55)
Harmanci et al[42]	Turkey	2013	1989-2011	62	42.81	26 (42)	36 (58)	35 (56)	8 (14)	19 (30)
Nozari et al[47]	Iran	2013	1989-2012	55	291	22 (40)	33 (60)
Pavri et al[38]	United States	2014	2008-2013	47	42.4	16 (34)	31 (66)
Faraoun et al[25]	Algeria	2015	2008-2012	176	331	75 (43)	101 (57)	125 (71)	0 (0)	51 (29)
De et al[23]	India	2001	1992-1998	40	35.21	26 (65)	14 (35)	N/A	23 (72)	9 (28)
Xu et al[41]	China	2004	1983-2003	1360	33.21	833 (61)	527 (39)	2 (0)	1358 (100)2
Ebrahimi et al[46]	Iran	2011	2002-2008	21	421	11 (52)	10 (48)	6 (29)	12 (57)	3 (14)
Park et al[51]	South Korea	2012	1988-2008	67	47	34 (51)	33 (49)	5 (7)	56 (84)	6 (9)
Qi et al[35]	China	2013	1999-2011	169	38.31	66 (52)	61 (48)	53 (31)	20 (12)	96 (57)
Cheng et al[13]	China	2013	2010-2011	145	46	90 (6)	55 (38)	45 (31)	8 (6)	92 (63)
Qi et al[36]	China	2014	2012-2012	25	35.71	14 (56)	11 (44)	4 (16)	0 (0)	21 (84)
Zhou et al[26]	China	2014	2006-2010	338	41.71	209 (62)	129 (38)	45 (13)	8 (2)	285 (84)
Gao et al[49]	China	2015	2008-2012
R				98	363	62 (63)	36 (37)	31 (32)	26 (27)	41 (42)
NR				373	453	193 (52)	180 (48)	82 (22)	169 (45)	122 (33)

¹Mean values;

²No differentiation between IVC alone vs both IVC and hepatic vein;

³Provided median ages for the two groups separately. R: Recurrence of disease, NR: Non-recurrence of the disease; HV: Hepatic vein; IVC: Inferior vena cava; M: Male; F: Female; N/A: Not available.

Table 2 Signs and symptoms in classical Budd-Chiari syndrome and hepatic vena cava-Budd Chiari syndrome

	Classical BCS									HVC-BCS
	Perellóet al[40]	Darwish Murad et al[24]	Sakr et al [22]	Rautou et al[46]	Raszeja-Wyszomirska et al[45]	Westbrook et al[32]	D'Amico et al[34]	Harmanci et al[42]	Nozari et al[47]	De et al[23]	Xu et al[41]	Ebrahimi et al[46]	Qi et al[35]	Cheng et al[13]	Gao et al[49]
															R vs NR
Country	Spain	Europe	Egypt	France	Poland	United Kingdom	Italy	Sweden	Iran	India	China	Iran	China	China	China
n (%)	21	163	94	94	20	66	31	62	55	40	1360	21	169	145	98	373
Abdominal pain	18 (86)	99 (61)	78 (83)			36 (55)		28 (45)	33 (60)	28 (70)	122 (9)	5 (29)		30 (21)
Ascites	18 (86)	135 (83)	80 (85)	73 (78)	20 (100)	57 (87)			42 (76)	30 (75)	914 (67)	19 (90)	95 (56)	77 (53)	76 (78)	224 (60)
Hepatomegaly	9 (43)	109 (67)	78 (83)						33 (60)	38 (95)	1124 (83)	8 (38)		40 (28)	61 (62)	165 (44)
Splenomegaly		85 (52)	48 (51)						19 (34)	26 (65)	683 (50)			113 (78)
Abdominal wall varices			39 (41)							38 (95)	821 (60)		50 (30)	73 (50)
Esophageal varices		45 (58)1		53 (56)			18 (58)
Lower extremity edema			46 (49)					28 (45)		28 (70)		14 (67)	86 (51)	76 (52)
Jaundice	10 (48)		36 (38)						10 (18)	15 (38)	116 (9)
Encephalopathy	1 (5)	15 (9)	29 (31)	7 (7)		32 (48)						12 (57)	1 (1)
Bleeding episodes	1 (5)	8 (5)	15 (16)		5 (25)		7 (23)			6 (15)	162 (12)		25 (15)	31 (21)
Duration of symptoms	1.42	< 1						1-6	6				44	96
Chronic, > 6 mo		23 (14)	75 (80)3					25 (40)	21 (38)	30 (75)				125 (86)
Acute, < 6 mo		138 (85)	18 (19)					37 (60)	34 (62)					20 (14)

¹77 patients underwent EGD;

²Mean, not median. Most studies reported median duration of symptoms in months; when the median was not available, the mean is reported;

³No definition of “chronic” was provided. BCS: Budd-Chiari syndrome; HVC: Hepatic vena cava; R: Recurrence of BCS; NR: Non-recurrence of BCS.

Table 3 Obstruction characteristics: Location, type, and associated findings

	Classical BCS						HVC-BCS
	Perellóet al[40]	Darwish Murad et al[24]	Sakr et al[22]	Deepak et al[29]	Harmanci et al[42]	Faraoun et al[25]	De et al[23]	Xu et al[41]	Ebrahimi et al[46]	Cheng et al[13]	Zhou et al[26]
Country	Spain	Europe	Egypt	India	Turkey	Algeria	India	China	Iran	China	China
n (%)	21	163	94	20	62	176	40	1360	21	145	338
Obstruction location
HV only	17 (81)	80 (49)	70 (74)	17 (85)	35 (56)	125 (71)	N/A	2 (0)	6 (29)	45 (31)	45 (13)
IVC only	0 (0)	4 (2)	3 (3)	1 (5)	8 (14)	0 (0)	23 (72)	1358 (100)	12 (57)	8 (6)	8 (2)
Both HV and IVC	4 (19)	79 (48)	16 (17)	2 (10)	19 (30)	51 (29)	9 (28)		3 (14)	92 (63)	285 (84)
HV thrombosis	20 (95)				54 (87)	170 (97)		DNS		15 (10)
IVC thrombosis	3 (14)	DNS	DNS	DNS	27 (44)	DNS		123 (9)
IVC web/membrane	1 (5)		2 (1)	DNS	DNS	DNS	12 (30)	717 (53)	11 (52)	89 (61)
Collateral circulation										92 (63)	220 (65)
Benign regenerative nodules										36 (25)1	79 (23)

¹Described as “benign nodules”, not benign regenerative nodules. DNS: Study mentions generally, but, does not provide specific counts; BCS: Budd-Chiari syndrome; HV: Hepatic vein; HVC: Hepatic vena cava; IVC: Inferior vena cava.

Table 4 Risk factors and/or etiologies of classical Budd-Chiari syndrome and hepatic vena cava-Budd Chiari syndrome

	Classical BCS														HVC-BCS
	Perellóet al[40]	Smalberg et al[39]	Colaizzo et al[30]	Xavier et al[31]	Sakr et al[22]	Deepak et al[29]	Rautou et al[37]	Raszeja-Wyszomirska et al[45]	Westbrook et al[32]	D'Amico et al[34]	Seijo et al[11]	Harmanci et al[42]	Nozari et al[47]	Pavri et al[38]	Ebrahimi et al[46]	Qi et al[35]	Cheng et al[13]	Qi et al[36]
Country	Spain	Netherlands	Italy	Brazil	Egypt	India	France	Poland	United Kingdom	Italy	Europe	Turkey	Iran	United States	Iran	China	China	China
n (%)	21	40	32	31	94	20	94	20	66	31	157	62	55	47	21	169	145	25
MPN (%)	13 (62)	13 (33)	13 (41)	5 (16)		8 (40)	51 (59)	8 (40)	37 (56)	17 (55)	52 (33)	19 (31)	9 (16)			7 (4)9	5 (5)10
JAK2V617-F	N/A	7 (41)		8 (26)	18 (29)4	8 (40)			34 (52)							4 (2)	5 (5)10	0 (0)
PV	9 (43)										28 (18)			14 (30)		3 (2)	2 (2)10
ET	3 (14)										12 (8)			3 (6)		1 (1)	2 (2)10
FVL	2 (10)	5 (15)	6 (19)	3 (10)	34 (53)5	5 (25)	15 (19)	1 (5)	1 (2)	9 (29)	19 (12)	15 (30)	10 (18)	4 (9)		0 (0)	0 (0)11	0 (0)
PT 20210A		2 (8)	1 (3)	1 (3)	3 (5)6		6 (8)		1 (2)	1 (3)	5 (3)	1 (2)				0 (0)	0 (0)11	0 (0)
Protein C deficiency		2 (7)2			4 (4)	2 (10)	6 (12)	3 (15)	2 (3)		5 (3)	16 (31)	12 (20)	2 (4)			0 (0)12
Protein S deficiency		2 (7)2			1 (1)	1 (5)	5 (9)				3 (2)	5 (10)	3 (6)	1 (2)			0 (0)12
AT deficiency					4 (4)	3 (15)	3 (4)				4 (3)	6 (15)	3 (6)				0 (0)12
PAI-1 (4G-4G)										17 (55)
MTHFRC677T					31 (52)6					8 (26)		19 (39)				96 (71)		18 (72)
HH						2 (10)					29 (18)					64 (50)	30 (21)
PNH	4 (19)	2 (9)	1 (3)		2 (2)	1 (5)	8 (12)	1 (5)	0 (0)		15 (10)	1 (2)		3 (6)		1 (1)	0 (0)13	1 (4)
OCP, pregnancy, or puerperium1		13 (52) (OC)3	1 (4) (OC)3	7 (35)	19 (33)		21 (35) (OC)3			4 (24)	35 (39)	4 (11)	3 (9)	2 (6) (OC)3			2 (4)
Systemic diseases or local factors		2 (5)			12 (13)7				3 (5)7		37 (24)	8 (13)7	5 (9) autoimmune		4 (19)8	2 (1)	1 (1)
NAD/idiopathic	1 (5)				8 (9)			6 (30)		2 (6)		6 (10)	10 (18)		6 (29)		28 (19)
Web/membrane															11 (52)		89 (61)
MOVC																	6 (4)
MOVC + HV	1 (5)																60 (41)
MOHV																	23 (16)

¹Percentage of total female patients;

²Patients on anticoagulation were not tested;

³Number of women on OC only, no specific information on number of pregnant women;

⁴Out of 62 tested;

⁵Out of 64 tested;

⁶Out of 60 tested;

⁷Mainly Behcet’s disease;

⁸Behcet’s disease (2), Hepatitis C (1), Leukemia (1);

⁹2 of these 7 patients were diagnosed with latent MPN;

¹⁰In this study, most (105 patients), but, not all were tested; percentages are out of 105;

¹¹Out of 96 patients were tested;

¹²Out of 80 patients tested;

¹³Out of 83 patients tested. BCS: Budd-Chiari syndrome; HV: Hepatic vein; HVC: Hepatic vena cava; ET: Essential thrombocythemia; PNH: Paroxysmal nocturnal hemoglobinuria; OCP: Oral contraception; MOVC: Membranous obstruction of IVC; NAD: No associated disease/etiology found; MPN: Myeloproliferative neoplasms; FVL: Factor V Leiden mutation; HH: Hyperhomocysteinemia.

Table 5 Management and outcomes in classical Budd-Chiari syndrome and hepatic vena cava-Budd Chiari syndrome

	Classical BCS									HVC-BCS
	Perellóet al[40]		Rautou et al[37]	Raszeja-Wyszomirska et al[45]	Westbrook et al[32]	Harmanci et al[42]	Seijo et al[11]	Nozari et al[47]	Pavri et al[38]	De et al[23]	Xu et al[41]	Ebrahimi et al[46]	Park et al[51]	Cheng et al[13]	Gao et al[49]
Country	Spain		France	Poland	United Kingdom	Turkey	Europe	Iran	United States	India	China	Iran	South Korea	China	China
n (%)	21		94	20	66	62	157	55	47	40	1360	21	67	145	471
Medical management	21 (100)		94 (100)	20 (100)	61 (92)	61 (98)	139 (89)	55 (100)	≥ 40 (85)			12 (57)	32 (48)
Medical management only (%)1	7 (33)						69 (54)				0 (0)			4 (3)	31 (7)
							49 (71) alive
Interventional therapy		14 (67)			34 (52)5		88 (56)	10 (18)		23 (58)	1360 (100)	9 (43)		141 (97)	440 (93)
							72 (82) alive				1318 alive
PTA	1 (5)		17 (18)			2 (3) in IVC	22 (14)			23 (58)		9 (43)	27 (40)	134 (92)
Shunt operation		2 (10)			32 (48.5)6			2 (4)			330 (24)	3 (14)	4 (5.9)
TIPS2		13 (62)	28 (30)	2 (10)		4 (6)	62 (39)3	2 (4)	21 (45)				3 (4.5)	12
Liver transplantation			15 (16)	10 (50)	36 (55)	0 (0)8	204 (13)	5 (9)	8 (17)		0 (0)			0 (0)12
														2 (1)12
Median follow-up (in months)	5813	3813	43	17	40-739	25.212	50		32	56	81.6		103	12	19
Survival	7 (100)	12 (86)	74 (79)	15 (75)			95 (73)	65 mo10	37 (79)
At 1 yr				80%	88%	96%			37 (79)			67%7		99%	401 (94)
At 5 yr			74 (79)		56%		95 (73)			75%			86%
Mortality										1011				2 (1)

¹Medical management includes anticoagulation, diuretics, and medical treatment of any underlying causes;

²After PTA failed;

³Of the 22 patients who initially were treated with PTA/thrombolytics, 12 subsequently underwent TIPS and 2 underwent OLT;

⁴Among the 62 patients who underwent TIPS, 4 subsequently underwent OLT;

⁵Patients who failed medical management (namely anticoagulation with heparin and warfarin and diuretics) as defined by persistent transaminitis, resistant ascites or worsening hepatic function) moved on to receive stenting, shunting, or TIPS;

⁶50% success rate (16/32);

⁷Per study, 7 out of 21 patients died before hospital discharge;

⁸No patients underwent liver transplantations due to a lack of donor availability;

⁹Median follow-up post liver transplantation was 40 mo and median follow-up of patients with MPN was 73 mo;

¹⁰Mean survival time was 65 mo;

¹¹10 patients died by the 5-yr follow-up period;

¹²At the end of the follow-up period, 2 patients were waiting to receive OLT from another hospital;

¹³Mean, not median values provided. Interventional therapy includes both endovascular and surgical procedures. OLT: Orthotopic liver transplant; TIPS: Transjugular intrahepatic portosystemic shunt; PTA: Percutaneous transluminal angioplasty; BCS: Budd-Chiari syndrome; HVC: Hepatic vena cava; IVC: Inferior vena cava.