Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial
Qian L, Liu M, Shen J, Cen J, Zhao D. · Frontiers in Immunology. 2020;11:598359.
What kind of evidence is this?
Human
Prospective multicenter, open-label, single-arm phase 2 trial
Immune and inflammatory conditions
H₂-rich water
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Methods at a glance
People younger than 65 years with corticosteroid-refractory or corticosteroid-dependent chronic graft-versus-host disease after allogeneic stem-cell transplantation.
24 participants from four institutions; median age 27 years. Nineteen had severe cGVHD and 19 were receiving corticosteroids at entry.
Planned treatment for up to 12 months, with assessments every 3 months; survival follow-up extended to a median of 38.5 months.
Hydrogen-rich water 4 mL/kg orally three times daily as the only new intervention. Background corticosteroids and other immunosuppressants continued and could be tapered under the protocol.
H₂ dissolved in drinking water — H₂ only, not Brown's gas.
The water contained 0.8 ppm dissolved H₂.
Not applicable — drinking water, not gas inhalation.
No O₂ was co-delivered as part of the intervention.
No concurrent control group; the article discusses historical response rates only.
Outcomes and reported result
NIH organ response criteria, overall response, Karnofsky performance status, prednisone use, toxicity and survival.
At last evaluation, 18/24 participants had an objective response (8 complete and 10 partial); five progressed and one was stable. Eighteen completed 12 months, two were lost to follow-up and four died within 12 months. Among responders, median prednisone dose fell from 0.185 to 0 mg/kg/day (p=0.004). The estimated 4-year survival was 74.7%; the responder-versus-nonresponder survival comparison was post hoc and cannot establish treatment causality.
The complete publisher article, tables, protocol details, organ-level responses, deaths, toxicity, funding, product supply and conflict declaration were checked.
A reported association, difference or mechanism is not automatically a clinical benefit. Null findings, outcome type, study design and precision all matter.
Cautions and applicability
Small uncontrolled open-label study with continuing background immunosuppression, organ-specific denominators and responder-defined survival comparisons. It cannot distinguish H₂ effects from natural history, co-treatment, regression to the mean or selection. Beijing Huoliqingyuan Beverage Co. supplied the water; the study was funded by the National Natural Science Foundation of China (81800180), and authors declared no commercial or financial conflicts.
Corticosteroid-refractory/dependent cGVHD under this protocol; confirmatory controlled trials are required.
Not reported in this record.
Not reported in this record.
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No single-study GRADE certainty rating is assigned. Certainty is assessed by important outcome across a complete eligible evidence set, not by attaching a final grade to one source.
Sources and record status
PMID: 33324415 · DOI: 10.3389/fimmu.2020.598359
Open-access publisher full article and PubMed Central copy.
Frontiers publisher full article and PubMed Central copy; full-text extraction checked 8 August 2026.
2026-08-10