Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis: A systematic review and meta-analysis

Table 1 Characteristic of included studies evaluating the use of vitamin E in children with hepatitis B e antigen-positive chronic hepatitis

First author/year	Study design/country of origin	Sample size	Treat and VE dose	Treat period/ follow-up	End-points	Main results	Quality score3	Tolerability
Dickici B, 2007	PRT (1:1) Turkey	58 enrolled children in the immune-tolerant phase	100 mg/d vs no treatment	3 mo/6 mo	HBV-DNA clearance HBeAg seroconversion	No antiviral-effects induced by vitamin E treatment	1	No side effects
		(1) 30 treated patients
		M/F: 21/9
		(2) Age (yr): (9.0 ± 3.8)
		No data concerning age
		28 untreated patients
		M/F: 23/5
		Age (yr): (8.5 ± 4.5)
		No data available for children’s seroconversion rates by age groups and by HBV genotype
Gerner P, 2008	PRT (3.1) Germany	92 enrolled children #	From 200 to 600 IU/d depending on body weight vs placebo	6 mo/12 mo	HBV-DNA clearance HBeAg loss HBeAg seroconversion	VE may induce HBeAg seroconversion, but further studies are required	5	Well-tolerated Self-limited gastroenteritis cases
		(1) 69 in treatment group
		(2) 23 in placebo group
		76 children completed the study
		(1) 56 in treatment group
		M/F: 34/22
		Age (yr): 10.4
		(2) 20 in placebo group
		M/F: 12/8
		Age (yr): 11.8
		No data available for children’s seroconversion rates by age groups and by HBV genotype
Fiorino S, 2016	PRT (1:1) Italy	46 enrolled patients	15 mg/kg per day vs no treatment	12 mo/ 12 mo	(1) safety and tolerability (2) HBeAg loss/anti-HBe seroconversion (3) efficacy of VE in inducing: (1) ≥ 2 log10 sustained decrease in serum HBV-DNA vs baseline	VE may induce HBeAg seroconversion, but further studies are required	3	Generally good safety profile Self-limited gastroenteritis (nausea, vomiting, upper abdominal pain, diarrhoea), headache, fatigue Adverse events: ALT flare
		(1) 23 in treatment group (18 in immune-tolerant phase and 5 in immune-reactive group)
		(2) 23 in placebo group (17 in immune-tolerant phase and 6 in immune-reactive group)
		40 children completed the study
		(1) 20 in treatment group
		M/F: 15/5
		Age (yr): (11.9 ± 3.8)
		(2) 20 in placebo group
		M/F: 16/4
		Age (yr): (10.2 ± 3.5)
		HBeAg seroconversion in vitamin E
		Age (yr)/number pts/genotype
		2/0
		3/0
		4/1 (D1)
		5/0
		6/2 (1A, 1D)
		7/0
		8/3 (1C, 2D)
		9/0
		10/2 (1C, 1D)
		11/0
		12/1 (1D)
		13/6 (1A, 1C, 4D2)
		14/3 (1A1, 1D, 1NA1)
		15/0
		16/2 (1D, 1F)
		17/3 (3D2)
		HBeAg seroconversion in the control group
		Age (yr)/number pts/genotype
		2/1 (B)
		3/0
		4/1 (D)
		5/1 (A)
		6/1 (D)
		7/0
		8/3 (1C, 2F1)
		9/1 (D)
		10/1 (C)
		11/5 (1A, 2C, 2D)
		12/2 (1A, 1E)
		13/2 (1B, 1D)
		14/4 (2A, 2NA)
		15/1 (D)
		16/0
		17/0

¹Identifies 1 patients undergoing HBeAb seroconversion in a subgroup of patients;

²Identifies 2 patients, who underwent HBeAg seroconversion;

³According to the Jadad scale. PRT: Prospective randomized trial; IT: Immune-tolerant; IR: immune-reactive; VE: Vitamin E; CVR: Complete virological response, defined as sustained HBeAg loss/anti-HBe seroconversion together with serum HBV-DNA reduction < 2000 IU/mL; ALT: Alanine-aminotransferase; NA: Not available; HBeAg: Hepatitis B e antigen; M: Male; F: Female.

Table 2 Jadad scale is a procedure for assessing the methodological quality or risk of bias in randomized controlled trials, adapted from Jadad et al[17]

Item	Maximum points	Description
Randomization	2	1 point if randomization is mentioned
		1 additional point if the method of randomization is appropriate
		1 point has to be deducted if the method of randomization is inappropriate (minimum 0)
Blinding	2	1 point if blinding is mentioned
		1 additional point if the method of blinding is appropriate
		1 point has to be deducted if the method of blinding is inappropriate (minimum 0)
An account of all patients	1	The fate of all patients in the trial is known, if no data are reported the reason is stated