Budd-Chiari syndrome in children: Challenges and outcome

Table 1 Summary of various pediatric studies (national) of thrombophilia profile in children with Budd-Chiari syndrome

Ref.	Country	No. of cases	Age group	Disease under evaluation	Proportion of cases with prothrombotic work-up	Yield of prothrombotic work-up, n (%)	Conditions detected
Nagral et al[12]	India	16	4 yr (2-11 yr)	Primary BCS	15/16	4/15 (27)	Protein C deficiency 2; APLA syndrome 1; Antithrombin III deficiency 1
Kathuria et al[13]	India	45	10 yr (2-16 yr)	Primary BCS	12/45 children	8/12 (67)	PNH 1; APLA 4; Protein C deficiency 5; Protein S deficiency 3; Hyperhomocystinemia 2 (60% multiple prothrombotic conditions)
Sharma et al[14]	India	32	9 yr (5-15.5 yr)	Primary BCS	Not available
Alam et al[11]	India	13	9 yr (5-13.5 yr)	Primary BCS	13/13	10/13 (77)	MTHFR mutation 5; Factor V mutation 1; Celiac disease 1
Malik et al[31]	India	11	10 yr (3-16 yr)	Primary BCS	11/11	4/11 (37)	APLA 2; PNH 1; JAK2 1
Shukla et al[32]	India	36	1-10 yr	Primary BCS	36/36	15/36 (41.7)	JAK 2V617F 0; Protein C deficiency 2; Protein S deficiency 2; Antithrombin III deficiency 3; APLA 4; Factor V Leiden 4; High homocysteine level 0; Multiple conditions 0
Shukla et al[32]	India	43	10-19 yr	Primary BCS	43/43	16/43 (37)	JAK 2V617F 5; Protein C deficiency 1; Protein S deficiency 1; Antithrombin III deficiency 3; APLA 4; Factor V Leiden 1; High homocysteine level 4; Multiple conditions 4
Zhou et al[33]	China	35	22 yr (10-25 yr)	Primary BCS	35/35	22/35 (63)	Hyperhomocyteinemia14; APLA 5; JAK2 V617F 1; IBD 1; Behcet disease 1
Dobre et al[34]	England	7	7 yr (4-14 yr)	Primary BCS	7/7	7/7 (100)	JAK2 V617F 2; Protein C deficiency 3; Antithrombin III deficiency 2; PNH 1; Factor V Leiden 1; APLA syndrome 2
Revil-Vilk et al[35]	Canada	171 BCS -31 cases	3.5 yr (2-13 yr)	Venous thrombosis of different sites	171/171	23/171 (13.4)	Factor V Leiden 8; Prothrombin gene mutation 4; Protein S deficiency 2; Protein S deficiency 1; High lipoprotein a 8

PNH: Paroxysmal nocturnal haemoglobinuria; APLA: Anti phospholipid antibody; IBD: Inflammatory bowel disease; JAK: Janus kinase; MTHFR: Methyl tetrahydro folate reductase.

Table 2 Clinical presentation, site of block, radiological intervention, and outcomes of major studies in children with Budd-Chiari syndrome

	Nagral et al[12], %	Kathuria et al[13], %	Sharma et al[14], %	Singh et al[15], %	Shukla et al[32], %
No. of patients	16	45	32	113	43
Age at presentation, median (range)	22 (4-132) mo	10.5 (2-16) yr	9 (4.5-214) mo	10 (1.5-17) yr	16.7 (10-19) yr
Symptom duration, median (range)	3 (0.5-48) mo	8.9 mo (5 d–8 yr)	-	-	12.7 (0.5-150) mo
Diagnosis by USG	63	95.6	60	-	-
Symptoms
Ascites	81	82	96	84	91
GI bleed	25	35	8	22	23
Jaundice	12.5	20	24	12	14
Hepatomegaly	N/A	85	96	N/A	67
Splenomegaly	N/A	70	N/A	N/A	37
Abdominal vein dilation	N/A	70	70	N/A	N/A
Type of block
Only HV	94	71	76	74	67
Only IVC	6	4	0	2	9
Both HV + IVC	0	25	24	24	24
RI, n	13	25	24	53	24
Angioplasty alone	4	2	7	7	-
Angioplasty + stenting	3	20	3	40	10
DIPS	-	-	-	5	-
TIPSS	6	3	14	1	14
Follow-up duration, median (IQR)	31 (12-54) mo	6.5 (0.5-86) mo	44 (5-132) mo	13.5 (1-155) mo	41 (12-168) mo
Successful RI
Angioplasty	25	100	43	100	-
Angioplasty + stenting	100	87	67	90	90
DIPS	-	-	-	80%	-
TIPSS	80	67	72	100	80
Procedure related complications	TIPSS encephalopathy = 1; Neck hematoma = 1	Anaesthesia related death = 1; Neck Hematoma-1; Hemoperitoneum = 1	No major	TIPSS; Encephalopathy = 1	N/A
Stent patency rate	-	Overall 75%	-	87% at 1 yr, 82% at 5 yr, 62% at 10 yr	Overall 75%
Mortality	2: GI bleeding 1, liver failure = 1	3: Intracranial bleeding = 1, anaesthesia related = 1, liver failure = 1	5: Intracranial bleeding = 2, GI bleeding = 1, HCC = 1, liver failure = 1	3: Procedure related = 2, head trauma = 1	4: Intracranial bleeding = 1, HCC = 1, liver failure = 2
HPS	N/A	N/A	4 (12, 5%)		-
HCC	N/A	N/A	1 (3%)		1 (2.3%)

N/A: Not available; HV: Hepatic vein; IVC: Inferior vena cava; USG: Ultrasonography; GI: Gastro-intestinal; HV: Hepatic vein; IVC: Inferior vena cava; RI: Radiological intervention; DIPS: Direct intrahepatic porto-systemic shunt; TIPSS: Transjugular intrahepatic porto-systemic shunt; HPS: Hepato-pulmonary syndrome; HCC: Hepatocellular carcinoma.

Table 3 Budd-Chiari syndrome-specific prognostic indices

Score	Equation	Cut-off	Predicted survival rate
CTP	Serum bilirubin, serum albumin, INR, ascites, HE	-	-
MELD	9.57 × log (creatinine) + 3.78 × log (total bilirubin) + 11.2 × log (INR) + 6.43	-	-
Zeitoun index	Ascites scorea × 0.75 + Child-Pugh score × 0.28 + age × 0.037 + creatinine × 0.0036	5.4 (range from 3.4 to 9.1)	At 5 yr; ≤ 5.4: 95%; > 5.4: 65%
New Clichy score	0.95 × ascites score + 0.35 × CTP score + 0.047 × age + 0.0045 × serum creatinine + 2.2 × type IIIbb—2.6	5.1 (range from 2.0 to 9.7)	At 5 yr; < 5.1: 100%; ≥ 5.1: 65%
Rotterdam BCS index	1.27 × encephalopathy + 1.04 × ascites + 0.72 × prothrombin time + 0.004 × bilirubin	Bilirubin; class I: 0–1.1; class II: 1.1–1.5; class III: ≥ 1.5 (range from 0.02 to 4.03)	At 5 yr; class I: 89%; class II: 74%; class III: 42%
TIPS-BCS index	Age (yr) × 0.08 + bilirubin (mg/dL) × 0.16 + INR × 0.63	7	1-yr OLT-free survival, ≤ 7: 95%; > 7: 12%
BCS-intervention-free survival prognostic score	Ascites (yes = 1, no = 0) × 1.675 + ln creatinine (μmol/L) × 0.613 + ln bilirubin (μmol/L) × 0.440	Interval 1: ≤ 5; interval 2: 5-6; interval 3: ≥ 6	Intervention-free survival interval 1: 78.3%, interval 2: 27.8%; interval 3: 6.8%
AIIMS-HVOTO score	1.2 × response to therapy + 0.8 × child class)	Score: < 3; 3-4; > 4	% yr survival score ≤ 3: 92%; score 3-4: 79%; score > 4: 39%

^aAscites score: 1, absent with free sodium intake and no diuretic agents; 2, easy to control with sodium restriction or diuretic agents; and 3, resistant to this treatment because of hyponatremia or functional renal failure.

^bType III’ is a binary variable coded as 1 for patients with clinicopathological findings of acute injury superimposed on chronic lesions, and 0 for the other patients.

CTP: Child-Turcotte-Pugh, MELD: Model for end stage liver disease; BCS: Budd-Chiari syndrome; AIIMS: All India Institute of Medical Sciences; HVOTO: Hepatic vein outflow tract obstruction; OLT: Orthotopic liver transplantation.