Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

doi:10.3748/wjg.v18.i41.5972

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Nov 7, 2012 (publication date) through Nov 25, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Nov 7, 2012; 18(41): 5972-5978
Published online Nov 7, 2012. doi: 10.3748/wjg.v18.i41.5972

Table 1 Characteristics of patients with alanine aminotransferase > 10 upper limit of normal range (mean ± SD)

Causes	n (%)	Age (yr)	Female n (%)	Peak ALT values (× ULN)
Hemodynamic injury	46 (25.7)	54.2 ± 17.2^a	14 (30.4)	32.5 ± 30.7^b
Drug-induced liver injury	25 (19.4)	45.4 ± 16.8	9 (36.0)	14.5 ± 5.6
Malignancy	21 (16.3)	55.8 ± 14.6^a	2 (9.5)	17.5 ± 10.3
Biliary abnormality	15 (11.6)	52.3 ± 14.4	7 (46.7)	14.3 ± 7.7
Viral hepatitis	12 (9.3)	47.8 ± 16.8	4 (33.3)	18.6 ± 10.0
Undetermined and others	10 (7.8)	42.9 ± 12.0	5 (50)	30.9 ± 33.5^a
Total	129 (100)	51.1 ± 16.4	41 (31.8)	23.0 ± 22.7
P (between different causes)	-	0.085	0.15	0.004

Post hoc tests

^aP < 0.05,

^bP < 0.01 vs drug-induced liver injury group. ALT: Alanine aminotransferase; ULN: Upper limit of normal range.

Table 2 Demographic, clinical and laboratory parameters of 25 cases of drug-induced liver injury

Variables	Outcome
	Recovery	Improvement
Age, yr	44.6 ± 18.4	45.9 ± 16.4
Female	3 (30)	6 (40)
Body mass index, kg/m²	24.3 ± 1.6	21.6 ± 2.8
Alcohol use	2 (20)	1 (6.7)
Jaundice	2 (20)	2 (13.3)
Extrahepatic manifestations
Rash	1 (10)	1 (6.7)
Fever	6 (60)	6 (40)
Cytopenia	2 (20)	4 (26.7)
Incident cases	6 (60)	11 (73.3)
Surgical wards	5 (50)	9 (60)
Laboratory parameters, peak values
Alanine aminotransferase (U/L)	623 ± 118	808 ± 348^a
Aspartate aminotransferase (U/L)	338 ± 187	636 ± 651
Alkaline phosphatase (U/L)	169 ± 172	167 ± 75
Total bilirubin (mg/dL)	1.4 ± 1.6	1.1 ± 1.0
γ-glutamyl transpeptidase (U/L)	190 ± 224	213 ± 149
Hepatocellular type	9 (90)	14 (93.3)
Causality assessment
Highly probable	0	1 (6.7)
Probable	9 (90)	10 (66.7)
Possible	1 (10)	4 (26.7)
Time to onset, d	5.3 ± 3.8	8.9 ± 10.2
Time to enzymes resolution, d	6.7 ± 2.4	6.0 ± 3.0
Number of adjunctive drugs	2.6 ± 1.6	2.5 ± 0.8
Adjunctive drugs for treatment
Anti-inflammation	7 (70)	14 (93.3)
Antioxidants	7 (70)	11 (61.1)
Phospholipids	6 (60)	7 (46.7)
Herbs	0	3 (20.0)
Time from treatment of liver injury to discharge, d	28 ± 12	8 ± 6^a

^aP < 0.05 vs recovery group. In parentheses: Standard deviation; In brackets: Percentage.

Table 3 Implicated causative chemical drugs in 25 subjects with drug-induced liver injury

Classification (n)	Specific drugs (n)
Proton pump inhibitors (2)	Omeprazole (2)
Cardiovascular system (3)	Amiodarone (1), atorvastatin (1), cinepazide (1), telmisartan (1)
Glucocorticoids (6)	Methylprednisolone (5), dexamethasone (1)
Antibacterials for systemic use (8)	Furbenicillin (2), cefminox (2), ornidazole (2), panipenem and betamipron (2), meropenem (1), piperacillin and sulbactam (1), cefoxitin (1)
Monoclonal antibodies (1)	Bevacizumab (1)
Musculo-skeletal system (4)	Diclofenac (1), celecoxib (1), parecoxib (1), baclofen (1)
Nervous system (2)	Olanzapine (2), fluoxetine (1)

Table 4 Characteristics of 6 cases of drug-induced liver injury caused by glucocorticoids

Age/sex	Principal disease	Drug	Dose (mg/d)	Treatment duration (d)	Peak values					Follow-up
Age/sex	Principal disease	Drug	Dose (mg/d)	Treatment duration (d)	ALT (U/L)	AST (U/L)	AP (U/L)	TB (mg/dL)	GGT (U/L)	Follow-up
20/F	SLE	MP	20-160	84	600	138	83	2.31	183	Recovered
36/F	Chronic glomerulonephritis	MP	32-40	17	1085	439	162	0.34	41	Improved
25/M	Brain trauma	MP	20	10	515	257	148	0.61	446	Improved
49/M	Brain trauma	MP	40	10	516	363	108	1.19	190	Improved
42/F	Drug eruption	MP	30-160	24	668	34	110	0.61	146	Improved
49/M	Brain tumor	DXM	5-15	12	602	282	231	0.52	424	Improved

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AP: Alkaline phosphatase; TB: Total bilirubin; GGT: γ-glutamyl transpeptidase; F: Female; SLE: Systemic lupus erythematosus; MP: Methylprednisolone; DXM: Dexamethasone.

Table 5 Adjunctive drugs used for treatment of drug-induced liver injury

Classification (n)	Specific drugs (n)
Anti-inflammation (21)	Diammonium glycyrrhizinate (9), magnesium isoglycyrrhizinate (8), compound monoammonium glycyrrhetate S (4), compound glycyrrhizin (3)
Antioxidants (18)	Glutathione (17), ademetionine 1,4-butanedisulfonate (6), tiopronin (1)
Phospholipids (13)	Polyene phosphatidyl choline (13)
Herbal extrats (3)	Protoporphyrin disodium (2), silymarin (1)

Citation: Xu HM, Chen Y, Xu J, Zhou Q. Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase. World J Gastroenterol 2012; 18(41): 5972-5978
URL: https://www.wjgnet.com/1007-9327/full/v18/i41/5972.htm
DOI: https://dx.doi.org/10.3748/wjg.v18.i41.5972