Imatinib-induced fatal acute liver failure

Table 1 Laboratory values

Date	AST	ALT	ALP	TB	DB	WBC	Neu	PT (%)
29/12/5	70	55	197	0.5	0.14	247	148.2
21/2/6	9	13	330	0.3	0.08	5.78	4.769
10/5/6	38	49	204	0.47	0.1
31/5/6	1060	1493	288	0.68	0.2
14/6/6	2224	3185	648	8.43	5.45
16/6/6	2595	3028	668	12.19	7.65			30
21/6/6	1887	1941	831	25.4	19.81	9.86	7.701	13
22/6/6	1626	1757	756	26	20.28	9.47	7.59	11
23/6/6	1495	1752	793	27	20.79	10	7.36	9
24/6/6	1467	1767	800	26.8	21.44	14.4	11.16	9
25/6/6	1359	1553	789	32	23.36	17	12.75	6
26/6/6	1212	1121	774	36	26.64	22.2	17.1	6
27/6/6	1024	900	686	24.7	9.5	86.8	39.9	N-M1
28/6/6	1269	561	362	11.5	4.8	42	33.6	N-M1

TB: Total bilirubin, n < 12 mg/L; DB: direct bilirubin, n < 3 mg/L; AST: Aspartate aminotransferase, n < 40 IU/L; ALT: Alanine aminotransferase, n < 35 IU/L; ALP: Alkaline phosphatase, n < 240 IU/L; GGT: Gamma-glutamyltransferase, n < 32 IU/L; WBC: White blood cells, n = 4000-10 000 cells/mm³; Neu: Neutrophils, n = 2000-6500 cells/mm³; PT: Prothrombin time, n = 70%-100%;

¹N-M: Non-measurable due to extremely prolonged prothrombin time.

Table 2 Summary of previously reported cases of serious (fatal and non-fatal) drug-induced liver damage following treatment with imatinib mesylate

Reference	Diagnosis	Time tohepaticdysfunction	Liverhistology	Outcome ofliver enzymes
Ohyashiki et al (2002)	CML	12 d	Focal necrosis of hepatocytes	Resolution after stopping drug
Lin et al (2003)	Polycythemia vera	7 wk	Hepatic necrosis	Patient died fatal acute hepatic necrosis
James et al (2003)	CML	49 wk	Acute severe cytolytic hepatitis.	Resolution after stopping drug
			With necrosis and mild cholestasis
	CML	22 wk	Acute cytolytic hepatitis with spotty and some piecemeal necrosis	Resolution after stopping drug
Kikuchi et al (2004)	CML	36 wk	Hepatic necrosis	Resolution after stopping drug
Ayoub et al (2005)	CML	2 yr	Portal and lobular inflammation.	Resolution after stopping drug
			Bridging and multifocal lobular necrosis
Cross et al (2007)	CML	77 wk	Severe necrosis with multilobular confluent cell dropout and reticulin collapse, multinodular regeneration	Patient died 10 d after liver transplantation
Ridruejo et al (2007)	CML	22 wk	Not available	Patient died fatal acute hepatic necrosis