Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments

Table 4 Published data on autoimmune hepatitis treatment different from steroids and azathioprine in children

Ref.	Country	Number and type of patients (n)	Design	Outcome	Follow-up	Dose	Side effects
Budesonide
Woynarowski et al[91], 2013	Europe	46 including naïve and second-line	Prospective	16% BR AZA+BUD 15% BR AZA+PDN at 6 mo	1 yr	6-9 mg/d	More weight gain in PDN group
Mycophenolate mofetil
Lee et al[107], 2007	Malaysia	2 second-line	Retrospective	0/2 BR at 6 mo	6-18 mo	20-40 mg/kg/d	Not reported
Aw et al[106], 2009	United Kingdom	20 AZA-NR 6 AZA-INT	Retrospective	18/26 CBR	0.75-12 mo	20-40 mg/kg/d	7 Leukopaenia
Jiménenz-Rivera et al[108], 2012	Canada	12 second-line	Retrospective	Not reported	Not reported	1000-1500 mg/d	Not reported
Dehghani et al[109], 2013	Iran	5 second-line	Retrospective	5/5 BR	None reported	Not reported	Not reported
Cyclosporine A
Jackson et al[120], 1995	South Africa	1 AZA-INT	Retrospective	1/1 BR at 2 wk	19 mo	5 mg/kg/d	None
Debray et al[111], 1999	France	8 naïve 7 second-line (all type 2 AIH)	Retrospective	8/8 naïve BR 7/7 second-line (including 3 with ALF)	1-6 yr	4.7-5.6 mg/kg/d	Minimal
Ben Halima etal[122], 2002	Tunisia	1 first-line	Retrospective	1/1 BR	Not reported	Not reported	None
Sciveres et al[184], 2004	Italy	4 naïve 4 steroid/AZA-intolerant	Retrospective	8/8 BR at 2-8 wk	1.5-15 yr	4-10 mg/kg per day	2 gingival hypertrophy, 1 creatinine elevation
Cuarterolo et al[124], 2006	Agentina	86 naïve, type 1 AIH	Prospective	BR 94%	2 yr	4 mg/kg per day	8/84 creatinine elevation 3/84 hypertension
Nastasio et al[115], 2011	Italy	19 naïve1 10 second-line1	Retrospective	19/19 naïve BR at 4-18 wk 9/10 second-line BR	6.5 yr	Not reported	11 hyperthricosis, 13 gingival hypertrophy
Dehghani et al[109], 2013	Iran	3 second-line	Retrospective	3/3 BR	Not reported	Not reported	Not reported
Lee et al[107], 2015	Malaysia	2 second-line	Retrospective	1 /2 BR	6-18 mo	5 mg/kg per day, serum level 250-350 ng/mL
Zaya et al[112], 2012	Croatia	9 naïve (1 type 2 AIH)	Retrospective	7/9 BR after 1 yr	24 mo	3-5 mg/kg per day	Minor
Jiménez-Rivera et al[108], 2012	Canada	9 naïve 15 second-line	Retrospective	Not reported	4 ± 2 yr	4 ± 0.8 mg/kg per day intially 4.9 ± 1.8 mg/kg per day in follow-up	Not reported
Tacrolimus
Zolfino et al[93], 2002	United Kingdom	1 second-line	Retrospective	NR	Not reported	2 mg/d	Not reported
Marlaka et al[138], 2012	Sweden	20 naïve	Prospective	3/20 BR in monotherapy	1 yr	Target blood levels: 2.5-5 ng/ml	1 discontinued for side-effects; 2 developed IBD
Dehghani et al[109], 2013	Iran	2 second-line	Retrospective	2/2 BR	Not reported	Not reported	Not reported
Jiménez-Rivera et al[108], 2015	Canada	6 second-line	Retrospective	Not reported	Not reported	Not reported	Not reported
Sirolimus
Kurowski et al[140], 2014	United States	4 second-line	Retrospective	2/4 BR	Not reported	Not reported	2 mo ulcers
Rituximab
D’Agostino et al[150], 2013	Canada/Argentina	2 second-line	Retrospective	2/2 CBR at 3/8 mo	26-38 mo	375 mg/m2 weekly for 4 wk	None reported
Infliximab
Rajanayagam et al[158], 2013	Australia	1 second-line	Retrospective	1/1 BR	19 mo	5 mg/kg 4 infusions at 4 wk interval	LT was not prevented
6-mercaptopurine
Pratt et al[167], 1996	United States	1 AZA-NR	Retrospective	1/1 CBR and HR	36 mo	1.5 mg/kg	None reported

¹Twelve patients had additional concomintant immunosuppressive drugs. BR: Biochemical response; AZA: Azathioprine; BUD: Budesonide; PDN: Prednisone; INT: Intolerant; NR: Non-responder; AIH: Autoimmune hepatitis; ALF: Acute liver failure; IBD: Inflammatory bowel disease; LT: Liver transplant; CRB: Complete biochemical response.