Hepatic sinusoidal obstruction syndrome induced by tacrolimus following liver transplantation: Three case reports

Table 1 Clinical characteristics of three presented cases during the disease course

No.	Age (yr)/sex	Clinical course	POD (d)	Ascites (mL/d)	TBIL (μmol/L)	ALT (U/mL)		AST (U/mL)		GGT (U/mL)	ALP (U/mL)	Scr (μmol/L)	BUN (mmol/L)	GFR (mL/min/L)
1	43/M	Diagnosis of HSOS	13	4600	28.2	97.6	173.2		244.6		240	231	25.61	26.92
		Tac → Siro	69	3250	48.4	273.6	210.7		113.1		153	379.9	40.11	15.16
		Discharged	74	2150	23.5	12.2	25.8		72.6		123	679.1	53.97	7.76
2	56/M	Diagnosis of HSOS	50	1200	28.2	48.7	54.3		89.2		122	227.7	13.15	25.94
		Tac → CsA + Siro	59	2480	20.4	39.2	38.3		50.7		94	702	18.33	7.08
		Resolution	87	30	12.7	22.3	27.6		79.2		121	72	3.56	97.96
3	57/M	Diagnosis of HSOS	15	850	22.5	143.6	47.3		129.9		159	111.5	12.28	58.93
		Tac → Siro	23	400	26.6	37.1	17.7		59.8		102	176.1	25.11	34.77
		Resolution	37	50	13.6	37.2	27.3		26.8		81	66.9	10	106.25

ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; GFR: Glomerular filtration rate; GGT: Gamma-glutamyl transpeptidase; HSOS: Hepatic sinusoidal obstruction syndrome; POD: Postoperative day; Scr: Serum creatinine; Siro: Sirolimus; Tac: Tacrolimus; TBIL: Total bilirubin.

Table 2 Literature review of recent progresses in the diagnosis and treatment of hepatic sinusoidal obstruction syndrome after liver transplantations

Ref.	Number of patients	Etiology of HSOS	Time after OLT	Symptoms of HSOS	Screening method of HSOS	Final diagnosis method of HSOS	Treatments
Li et al[5], 2022	1	Tacrolimus	4 mo	Abdominal distention, enlarged graft, and ascites	Doppler ultrasound and Contrast-enhanced CT	Liver biopsy: sinusoidal congestion and fibrosis of centrilobular veins	Withdraw tacrolimus and switch to CsA and MMF
Zhou et al[14], 2021	1	Tacrolimus	36 d	Abdominal distension, weight gain, ascites and positive shifting dullness	Abdominal CT	Liver biopsy: sinusoidal dilation, congestion, and fibrosis of centrilobular veins	Switch from tacrolimus to CsA and MMF
Li et al[11], 2020	5	Tacrolimus, acute rejection	6 to 183 d	Hepatomegaly, jaundice and ascites	Ultrasonography and CT	Liver biopsy: sinusoidal dilation, congestion, fibroplasias in portal areas, acute rejection, fibrous obliteration and edema in portal area.	Withdraw tacrolimusand switch to CsA-based regimen
Hosseini et al[13], 2018	1	Tacrolimus	10 d	Massive ascites	Color doppler ultrasonography	Liver biopsy: no significant abnormality	Convert tacrolimus to sirolimus
Shen et al[10], 2015	1	Tacrolimus	80 d	Anorexia, abdominal pain, polypnea, hepatomegaly, ascites and positive shifting dullness	Ultrasonography and CT	Liver biopsy: sinusoidal congestion and fibrosis of centrilobular veins	Switch from tacrolimus to CsA and MMF
Sebagh et al[12], 2011	31 of 1364	Acute rejection, tacrolimus, CsA and oxaliplatin	9 to 7378 d (median, 230 d)	Hepatomegaly, ascites, pleural effusion, pruritus or jaundice	Doppler ultrasound	Liver biopsy: fibrous obliteration of centrilobular veins, centrilobular hemorrhagic necrosis, sinusoidal dilatation and congestion, peliosis, and nodular regenerative hyperplasia	Withdraw hepatic toxic drugs, change the immunosuppression regimen, anticoagulation therapy, TIPS and re-transplantation
Sebagh et al[9], 1999	19 of 1023	Azathioprine and acute rejection	8 to 3972 d (median, 15 d)	Jaundice, painful hepatomegaly, ascites	Doppler ultrasound	Liver biopsy: sinusoidaldilatation, centrilobular congestion and acute rejection	Withdraw Azathioprine, convert to tacrolimus, TIPS and re-transplantation

CT: Computed tomography; CsA: Cyclosporine A; HSOS: Hepatic sinusoidal obstruction syndrome; MMF: Mycophenolate mofetil; OLT: Orthotopic liver transplantation; TIPS: Transjugular intrahepatic portosystemic shunt.