Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis, treatment, and outcomes

Table 1 Demographic information, clinical manifestation, and laboratory tests of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome

Reference	Wang et al[37]	Zhuge et al[17]	Song et al[38]	Wang et al[26]
Number	n = 117	n = 108	n = 116	n = 84
Sex (male/female)	78/39	66/42	78/38	45/39
Age (yr)	63 (52.5-69)1	61 (55-69)1	56.92 ± 12.392	52.97 ± 15.282
Clinical manifestation
Ascites	99.1% (116/117)	98% (50/51)	100% (79/79)	100% (83/83)
Hepatomegaly	70% (82/117)	92% (47/51)	75.95% (60/79)	65.1% (54/83)
Abdominal distention	98.3% (115/117)	99.1% (107/108)	98.3% (113/115)
Jaundice		39.8% (43/108)	52.9% (54/102)	57.8% (48/83)
Right upper quadrant pain	19.7% (23/117)		36.4% (40/110)
Edema	39.3% (46/117)		39.5% (43/109)	37.3% (31/83)
Weight gain	18% (21/117)		15.5% (16/103)
Splenomegaly	34.2% (40/117)	27% (14/51)	25.35% (18/71)[39]
Gastroesophageal varices			18.31%(13/71)[39]	36.8%(7/19)
Laboratory tests
Variable	Median (25th-75th percentiles)	Median (25th-75th percentiles)	mean ± SD	mean ± SD
ALT (U/L)	49 (25.0-152.5)	52.6 (26.8-125)	134.50 ± 154.89	216.83 ± 235.78
AST (U/L)	75 (39.0-158.5)	69.6 (42.4-115)	146.31 ± 156.30	221.15 ± 221.70
ALP (U/L)	122 (86.8-191.3)	130 (105-178)	170 ± 106.89	183.48 ± 59.96
γ-GT (U/L)	100.7 (61.8-164.8)	120 (72.4-170)	160.52 ± 114.56	155.70 ± 99.45
TB (μmol/L)	33.3 (19.7-47.0)	39.7 (28.3-62.4)	65.07 ± 78.83	52.96 ± 45.95
ALB (g/L)	30.6 (27.7-33.6)	32.1 (29.8-34.7)	30.71 ± 5.50	32.02 ± 4.51
PT (sec)	14.8 (12.7-17.0)	15.1 (14.2-16.7)	17.43 ± 2.64	18.08 ± 4.12
WBC (109/L)	6.1 (5.0-8.7)	6.1 (4.8-7.3)	6.90 ± 2.81
RBC (1012/L)	4.4 (3.9-4.9)		5 ± 4.33
PLT (109/L)	113 (78-153)	95 (74-134)	114.06 ± 63.48

¹Continuous variables were expressed as medians (25^th-75^th percentiles);

²Continuous data were expressed as mean ± standard deviations. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; γ-GT: γ-Glutamyl transpeptidase; TB: Total bilirubin; ALB: Albumin; PT: Prothrombin time; WBC: White blood cell; RBC: Red blood cell; PLT: Platelet.

Table 2 Diagnostic criteria for hepatic sinusoidal obstruction syndrome

HSCT-related HSOS			PAs-induced HSOS
Classical HSOS		Late onset HSOS (> 21 d after HSCT)	Criteria proposed by Gao et al[51]		Nanjing criteria[16]
Modified Seattle criteria[49]	Baltimore criteria[50]	New EBMT criteria[6]
Presence of 2 of the following criteria within 20 d after HSCT:	Presence of bilirubin ≥ 34.2 μmol/L within 21 d after HSCT and at least 2 of the following criteria:	Baltimore criteria beyond 21 d	1 Meeting the modified Seattle criteria		A definite history of taking herbs containing PAs
		OR
		Histologically proven HSOS			Pathological evidence	Presence of the following three criteria
			2 Meeting the criteria for DILI
						1 Abdominal distention and/or pain in the hepatic region, hepatomegaly, and ascites;
		OR
			3 A history of taking PAs-containing herbs; detection of PPAs
		Presence of at least 2 of the following criteria: Bilirubin ≥ 2 mg/dL (34.2 μmol/L)
						2 Increased serum total bilirubin or other abnormal liver function;
1 Bilirubin ≥ 34.2 μmol/L;	1 Hepatomegaly;	1 Hepatomegaly
2 Hepatomegaly or right upper quadrant pain;	2 Ascites;	2 Ascites
	3 Weight gain > 5%	3 Weight gain > 5%
3 Weight gain > 2%		AND hemodynamical or/and ultrasound evidence of HSOS
						3 Typical contrast-enhanced CT or MRI findings
				Other liver diseases were excluded

HSCT: Hematopoietic stem cell transplantation; HSOS: Hepatic sinusoidal obstruction syndrome; HVOD: Hepatic veno-occlusive disease; PAs: Pyrrolizidine alkaloids; DILI: Drug-induced liver injury; PPAs: Pyrrole-protein adducts; CT: Computed tomography; MRI: Magnetic resonance imaging.