Liver failure associated with benzbromarone: A case report and review of the literature

Table 1 Laboratory data on admission

Parameter	Result (normal value)	Parameter	Result (normal value)
AST (IU/L)	170.6 (15-40)	WBC (×109/L)	8.8 (3.5-9.5)
ALT (IU/L)	208.2 (9-50)	RBC (×109/L)	4.89 (4.3-5.8)
GGT (IU/L)	76 (10-60)	Hemoglobin (g/L)	152 (130-175)
ALP (IU/L)	94.2 (45-125)	Platelets (×109/L)	216 (125-350)
ACHE(IU/L)	5050 (4300-12000)	Eosinophils (×109/L)	0.1 (0.02-0.52)
TP (g/L)	52.7 (65-85)	Basophils (×109/L)	0.01 (0-0.06)
ALB (g/L)	34.2 (40-55)
GLB (g/L)	18.5 (20-40)	Coagulation function
TBIL (μmol/L)	702.5 (6.8-30)	Prothrombin time (s)	33.5 (9.0-13.0)
DBIL (μmol/L)	362.5 (0.0-8.6)	INR	2.86 (0.80-1.20)
IBIL (μmol/L)	340 (5.1-21.4)	PTA (%)	25 (80-120)
BUN (mmol/L)	1.64 (3.1-8)
CR (μmol/L)	64 (57-97)	Virology test
UA (μmol/L)	178 (208-428)	Anti-HAV-IgM	- (-)
CHOL (mmol/L)	3.52 (2.6-6.0)	Anti-HEV-IgM	- (-)
		HBsAg	- (-)
Immunological test		HBeAg	- (-)
Anti-dsDNA	- (-)	Anti-HBsAb	- (-)
Anti-gp210	- (-)	Anti-HBeAb	- (-)
Anti-M2	- (-)	Anti-HBcAb	+ (-)
Anti-SSA-52/Ro52	- (-)	Anti-HCV	- (-)
Anti-SP100	- (-)	Anti-HIV	- (-)
Anti-Sm	- (-)
Anti-nRNP/Sm	- (-)	Tumor marker
Immunoglobulin G4	0.545 (0.03-2.01)	α-fetoprotein (ng/mL)	82.86 (< 20)
Immunoglobulin A	3.01 (0.7-4.0)	Thyroid function
Immunoglobulin G	12.6 (7.0-16)	TSH (mIU/L)	1.62 (0.372-4.94)
Immunoglobulin M	0.86 (0.4-2.3)	FT3 (pmol/L)	5.35 (3.1-6.8)
Complement (C3)	0.58 (0.9-1.8)	FT4 (pmol/L)	32.9 (12.0-22.0)

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: γ-glutamyltransferase; ALP: Alkaline phosphatase; ACHE: Acetylcholinesterase; TP: Total protein; ALB: Albumin; GLB: Globulin; TBIL: Total bilirubin; DBIL: Direct bilirubin; IBIL: Indirect bilirubin; BUN: Blood urea nitrogen; CR: Creatinine; UA: Uric acid; CHOL: Cholesterol; Anti-dsDNA: Anti-double strand DNA antibody; AMA M2: Anti-mitochondrial antibody M2; anti-Sm: Anti-smooth muscle antibody; WBC: White blood cells; RBC: Red blood cells; INR: International standard value; PTA: Prothrombin time activity; anti-HCV: Anti-hepatitis C virus antibody; anti-HIV: Anti-human immunodeficiency virus antibody; TSH: Thyroid-stimulating hormone; FT3: Free triiodothyronine; FT4: Free thyroxine; –: Negative; +: Positive.

Table 2 Characteristics of benzbromarone-induced hepatotoxicity cases

Age	Sex	Course of benzbro-marone	Dose	Combined medication	Prior liver diseases	Other diseases	Treatment	Outcome	Ref.
68	F	3.5 mo	200 mg/d (6 wk); 100 mg/d (2 mo)	Methyldopa	-	Gout, hypertension	Conservative treatment	Recovery (24 d)	[17]
62	M	6 mo	75 mg/d	-	-	Hyperurice-mia	Bilirubin absorption	Death(62 d)	[18]
58	M	2 mo	Not described	Allopurinol, tocopherol, nicotinate, alprazolam, theophylline, azelastine hydrochloride, nilvadipine alcohol: (approximately 36 g/d)	-	Hyperurice-mia, hypertension, asthmatic bronchitis	PE + HDF, prednisolone (30 mg/d orally, reduced gradually)	Recovery (94 d)	[19]
53	F	2 mo	100 mg/d	Allopurinol	-	Hyperurice-mia, proteinuria	Liver transplant	Death (124 d)	[20]
53	M	3 d	50 mg/d	-	-	Hyperurice-mia, diabetes	Conservative treatment	Recovery (3 d)	[21]
77	F	4 mo	Not described	Torsemide, nebivolol, ramipril, thyronajod	-	Hypertension, hyperthyroid disease, adiposity	Conservative treatment	Death (53 d)	[22]
59	M	More than 1 yr	50 mg/d	Benidipine, pravastatin, alcohol (60 g/ d)	Liver dysfunction	Hyperurice-mia, hypertension, dyslipidemia	HDF, liver transplant	Recovery (70 d)	[23]
47	M	15 d	Not described	Thiopronin	NAFLD	Gout, diabetes, hyperlipide-mia	Methylprednisolone (8 mg/d orally)	Recovery (70 d)	[24]
39	M	4 mo	100 mg/d	Alcohol: (approximately 28 g/d for 10 yr)	-	Gout	PE + liver transplant	Recovery

HDF: Hemodiafiltration; NAFLD: Non-alcoholic fatty liver disease; PE: Plasma exchange; M: Male; F: Female.