Overview of drug induced liver injury in Brazil: What is the role of public health policy on the evidence?

Table 1 Summary of published Brazilian studies on drug-induced hepatotoxicity data

Ref.	Year	Place	State	Design	n	Class or medication	Use of algorithm	Frequency of DILI
Silva et al[22]	2019	Ho	BA	Cross-cut	306	MTX	No	2.0%
Alves et al[59]	2011	Ho	SC	Cross-cut	71	MTX/LEF	No	11.0%
Carvalho et al[74]	2014	A	RJ	Cross-cut	219	Azathioprine	No	2.7%
de-Medeiros et al[75]	1998	Ho	PR	RCT	37	Tretinoin	No	16.0%
Werner et al[61]	1989	Ho	SP	PC	389	Propylthiouracil	No	1.3%
Santos et al[63]	2013	Ho	RS	RC	185	5-Fluorouracil	No	57.8%
Uehara et al[76]	2005	Ho	SP	RC	12	Amphotericin B	No	30.0%
Magalhães[26]	2015	Ho	BA	Case series	31	Multiple	RUCAM	NA
Prado et al[27]	2019	A	BA	PC	149	Nimesulide, budesonide and valacyclovir	RUCAM	2.0%
Antonello et al[55]	2014	Ho	RS	PC	65	ARV	No	45.0%
Tovo et al[47]	2006	Ho	RS	PC	CI 385 MI 198	ARV	No	CI 57.8% MI 13.0%
Kondo et al[49]	2008	A	PR	RC	157	Nevirapine	No	4.0%
Gil et al[48]	2007	A	SP	Cross-cut	152	Tuberculostatic ARV and sulfonamides	No	19.7%
Tomich et al[77]	2015	Ho	SP	RC	149	Tuberculostatic, ARV among others1	No	22.1%
Santos et al[23]	2019	Ho	RJ	PC	45	Tuberculostatic	No	13.0%
Heinrich[24]	2014	A	MS	PC	100	Tuberculostatic	NARANJO	11.1%
Monteiro et al[25]	2012	A	RJ	PC	177	Tuberculostatic	RUCAM	33.3%
Gusmão Filho et al[43]	2001	Ho	PE	RC	52	RHZ/ RHE/	No	35.6%
Lima Mde et al[65]	2012	Ho	PE	Control case	156	RHZ and RHZE	No	26.9%
Zaverucha-do-Valle et al[41]	2014	A	RJ	RC	131	RHZ	No	26.7%
Coca et al[73]	2010	Ho	MG	Control case	162	RHZ	No	H3 56.2% and H4 10.4%
de Castro et al[44]	2010	A	RJ	PC	154	RHZ	No	19.5%
Nader et al[45]	2010	Ho	RS	RC	534	RHZ	No	8.8%
Vieira et al[78]	2008	A	SP	RC	297	RHZ	No	8.1%
de Souza et al[79]	1996	Ho	MG	PC	1096	RHZ	NI	6.0%
Fernandes et al[68]	2015	Ho	PA	PC	220	RHZ/RH	No	14.1%
Brito et al[64]	2014	A	RS	PC	245	RHZ/RH	No	6.1%
Schultz et al[46]	2014	Ho	RS	RC	69	Rifampicin	No	33.3%
Santos et al[53]	2013	A	PA	PC	270	Isoniazid	No	6.5%
Teixeira et al[52]	2011	A	RJ	Control case	167	Isoniazid	No	16.0%
Szklo et al[67]	2007	A	RJ	RC	40	SEO32/EO92	No	12.5%
Picon et al[66]	2002	A	RS	PC	78	SHE32/HE32/H32	No	1.3%

¹Sulfa drugs, statins, imidazole, anticonvulsant, nonsteroidal.

²Months.

H³ transaminases > 1.25 to 2.5 × upper limits of normality.

H⁴ transaminases > 2.6 to 5 × upper limits of normality. RUCAM: Causality algorithm; ARV: Antiretrovirals; MTX/LEF: Methotrexate/leflunomide; NA: Not applicable; CI: Human immunodeficiency virus and hepatitis C coinfected; PC: Prospective cohort; RC: Retrospective cohort; MI: Monoinfected for human immunodeficiency virus; DILI: Drug-induced liver injury; RCT: Randomized clinical trial; R: Rifampicin; H: Isoniazid; Z: Pyrazinamide; S: Streptomycin; and ethambutol. O: Ofloxacin, Ho: Hospital; A: Ambulatory.