Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis

doi:10.3748/wjg.v25.i39.6025

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Oct 21, 2019 (publication date) through Nov 26, 2024

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World Journal of Gastroenterology

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Meta-Analysis

World J Gastroenterol. Oct 21, 2019; 25(39): 6025-6040
Published online Oct 21, 2019. doi: 10.3748/wjg.v25.i39.6025

Table 1 Summary of included studies

Ref.	N	Participants	Diagnostic methods	Allicin group	Control group	Therapy duration	Therapies after eradication	Outcomes
Zhan et al, 2013[15]	60	Hp-infected patients with peptic ulcer	i OR ii	Am: 1000 mg b.i.d. F: 100 mg b.i.d E: 40 mg q.d. Al: 40 mg t.i.d.	Am: 1000 mg b.i.d. F: 100 mg b.i.d E: 40 mg q.d.	7 d	E: 40 mg q.d. for another 3 weeks in both groups	a, b, c, d
			i Hp histology;
			ii ¹⁴C-UBT or RUT in latest 7 days before endoscopy test
Bai et al, 2008[16]	198	Hp-infected patients with peptic ulcer	i AND ii	Am: 1000 mg b.i.d. M: 400 mg b.i.d O: 20 mg b.i.d. Al: 40 mg t.i.d.	A: 1000 mg b.i.d. M: 400 mg b.i.d O: 20 mg b.i.d.	7 d	O: 20 mg b.i.d. for another 3 weeks in both groups	a, b, c
			i Histology or RUT;
			ii ¹⁴C-UBT
Wang et al, 2006[17]	61	Hp-infected patients with peptic ulcer	i AND ii	F: 100 mg b.i.d C: 250 mg b.i.d O: 20 mg b.i.d. Al: 40 mg t.i.d.	F: 100 mg b.i.d C: 250 mg b.i.d O: 20 mg b.i.d.	7 d	O: 20 mg b.i.d. for another 3 weeks in both groups	a, b, d
			i Hp histology or RUT;
			ii ¹⁴C-UBT
Li et al, 2014[18]	86	Hp-infected patients with peptic ulcer	¹⁴C-UBT	Am: 1000 mg b.i.d. F: 100 mg b.i.d E: 40 mg q.d. Al: 40 mg t.i.d.	Am: 1000 mg b.i.d. F: 100mg b.i.d E: 40 mg q.d.	7 d	E: 40 mg q.d. for another 4 weeks in both groups	a, b, c, d
Kochar et al, 2001[19]	60	Hp-infected patients with peptic ulcer	Hp histology	Am: 1000 mg b.i.d. C: 500 mg b.i.d La: 10 mg b.i.d. Al: 1.2 mg q.d.	Am: 1000 mg b.i.d. C: 500 mg b.i.d La: 10 mg b.i.d.	14 d	None	a, d
Guan et al, 2017[20]	90	Hp-infected patients with peptic ulcer	¹⁴C-UBT	Am: 1000 mg b.i.d. F: 100 mg b.i.d E: 40 mg q.d. Al: 40 mg t.i.d.	Am: 1000 mg b.i.d. F: 100 mg b.i.d E: 40 mg q.d.	7 d	E: 40 mg q.d. for another 3 weeks in both groups	a, b, c, d
Zhao et al, 2015[21]	92	Hp-infected patients with peptic ulcer	¹⁴C-UBT	T: 500 mg b.i.d. C: 500 mg b.i.d I: 5 mg b.i.d. B: 220 mg t.i.d. Al: 40 mg t.i.d.	T: 500 mg b.i.d. C: 500 mg b.i.d I: 5 mg b.i.d. B: 220 mg t.i.d.	7 d	I: 5 mg b.i.d. for another 3 weeks in both groups	a, b, d, e
Chen et al, 2016[22]	220	Hp-infected patients with peptic ulcer	¹⁴C-UBT	T: 500 mg b.i.d. C: 500 mg b.i.d I: 5 mg b.i.d. B: 220 mg t.i.d. Al: 40 mg t.i.d.	T: 500 mg b.i.d. C: 500 mg b.i.d I: 5 mg b.i.d. B: 220 mg t.i.d.	7 d	Al: 40 mg t.i.d. and I: 5 mg b.i.d. for another 3 weeks in both groups	a, b, c, e

N: Number of participants; Hp: Helicobacter pylori; Am: Amoxicillin; F: Furazolidone; E: Esomeprazole; C: Clarithromycin; T: Tinidazole; O: Omeprazole; La: Lansoprazole; Le: Levofloxacin; I: Ilaprazole; R: Rabeprazole; B: Bismuth potassium citrate tablets; Al: Allicin; RUT: Rapid urease test;

¹⁴C-UBT: ¹⁴C-urea breath test; q.d.: Once daily; b.i.d.: Twice daily; t.i.d.: Thrice daily; a: Eradication rate; b: Healing rate of peptic ulcers; c: Total remission rate of peptic ulcers; d: Side effect rates; e: Disappearance time of abdominal pain.

Table 2 Results of quality assessment

Ref.	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Zhan, 2013[15]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Bai, 2008[16]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Wang, 2006[17]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Li, 2014[18]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Kochar, 2001[19]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Guan, 2017[20]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Zhao, 2015[21]	Unclear	Unclear	High risk of bias	Unclear	Low risk of bias	Unclear	Unclear
Chen, 2016[22]	Unclear	Unclear	High risk of bias	Unclear	High risk of bias	Unclear	Unclear

Table 3 Subgroup analyses of eradication rates

Comparison	Eradication rate (%)		Heterogeneity		OR	95%CI	P value
Comparison	Allicin group	Control	I² (%)	P value	OR	95%CI	P value
Allicin + PTT vs PTT[15-20] (ITT)	92.47	82.61	0	0.975	2.87	1.65-4.99	< 0.001
Allicin + PTT vs PTT[15-20] (PP)	92.81	82.91	0	0.984	2.66	1.53-4.64	0.001
Allicin-PPI-B-T-C vs PPI-B-T-C[21,22] (ITT/PP)	94.87	85.25	0	0.764	3.19	1.38-7.38	0.007
Allicin-PPI-Am-F vs PPI-Am-F[15,18,20] (ITT/PP)	92.46	81.33	0	0.986	2.38	0.99-5.71	0.053

PPI: Proton pump inhibitor; PTT: Proton pump inhibitor triple therapy; Am: Amoxicillin; F: Furazolidone; C: Clarithromycin; T: Tinidazole; B: Bismuth potassium citrate tablets; ITT: Intent-to-treat analysis; PP: Pre-protocol analysis; OR: Odds ratio; CI: Confidence interval.

Table 4 Subgroup analyses of healing rates of peptic ulcers

Comparison	Healing rate (%)		Heterogeneity		OR	95%CI	P value
Comparison	Allicin group	Control	I² (%)	P value	OR	95%CI	P value
Allicin + PTT vs PTT[15-18,20] (ITT)	80.32	68.29	0	0.527	2.14	1.39-3.29	0.001
Allicin + PTT vs PTT[15-18,20] (PP)	80.65	68.57	0	0.513	1.93	1.25-2.96	0.003
Allicin-PPI-B-T-C vs PPI-B-T-C[21,22] (ITT/PP)	95.51	87.82	22.924	0.255	2.83	1.13-7.10	0.026
Allicin-PPI-Am-F vs PPI-Am-F[15,18,20] (ITT/PP)	83.62	65.00	0	0.660	1.90	1.18-3.06	0.002

Table 5 Subgroup analyses of total remission rates of peptic ulcers

Comparison	Total remission rate (%)		Heterogeneity		OR	95%CI	P value
Comparison	Allicin group	Control	I² (%)	P value	OR	95%CI	P value
Allicin + PTT vs PTT[15,16,18,20] (ITT/PP)	93.12	81.48	0	0.844	3.13	1.51-6.51	0.004
Allicin-PPI-Am-F vs PPI-Am-F[15,18,20] (ITT/PP)	93.97	80.83	0	0.931	4.87	1.36-17.50	0.015

PPI: Proton pump inhibitor; PTT: Proton pump inhibitor triple therapy; Am: Amoxicillin; F: Furazolidone; C: Clarithromycin; T: tinidazole; B: Bismuth potassium citrate tablets; ITT: Intent-to-treat analysis; PP: Pre-protocol analysis; OR: Odds ratio; CI: Confidence interval.

Table 6 Subgroup analyses of side effect rates

Comparison	Side effect rate (%)		Heterogeneity		OR	95%CI	P value
Comparison	Allicin group	Control	I² (%)	P value	OR	95%CI	P value
Allicin + PTT vs PTT[17-20] (ITT)	7.38	13.51	6.66	0.36	0.52	0.22-1.20	0.125
Allicin + PTT vs PTT[17-20] (PP)	5.92	9.57	0	0.59	0.61	0.32-1.16	0.132
Allicin-PPI-B-T-C vs PPI-B-T-C[21,22] (ITT/PP)	4.49	5.77	0	0.69	0.77	0.28-2.13	0.612
Allicin-PPI-Am-F vs PPI-Am-F[18,20] (ITT/PP)	2.27	7.95	0	0.85	0.27	0.054-1.34	0.110

Table 7 Results of quality assessment

Participants (stu-dies)	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence
Eradication rate
867(8 studies)	Very serious¹	No serious inconsistency	Serious²	No serious imprecision	Undetected	Very low¹²
Healing rate of ulcers
807(7 studies)	Very serious¹	No serious inconsistency	No serious indirectness	No serious imprecision	Undetected	Low¹
Total remission rate of ulcers
807(7 studies)	Very serious¹	No serious inconsistency	No serious indirectness	No serious imprecision	Undetected	Low¹
Side effect rate
549(5 studies)	Very serious¹	No serious inconsistency	Serious³	No serious imprecision	Undetected	Very low¹³

¹We downgraded by two levels because all included studies did not state random method although declared to be randomized. What's more, blinding of patients was not mentioned in all included studies and we preferred to identify these studies as non-blindness;

²The present systematic review mainly aimed to assess the efficacy with eradication rate as primary outcome in patients with H. pylori infection. However, the participants of seven included studies (7/8, 87.50%) included patients with H. pylori infection combined with peptic ulcers. Such difference might be another origin of bias;

³The present systematic review mainly aimed to assess the safety of allicin among patients with H. pylori infection. However, four included studies (4/5, 80.00%) included patients with H. pylori infection combined with peptic ulcers. Such difference might be another origin of bias.

Citation: Si XB, Zhang XM, Wang S, Lan Y, Zhang S, Huo LY. Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis. World J Gastroenterol 2019; 25(39): 6025-6040
URL: https://www.wjgnet.com/1007-9327/full/v25/i39/6025.htm
DOI: https://dx.doi.org/10.3748/wjg.v25.i39.6025