Effects of Ozone Therapy on Adverse Events and Inflammatory Markers in Patients With Hepatocellular Carcinoma Undergoing Interventional Therapy

Background: the side effects of liver cancer treatment

Interventional therapy for hepatocellular carcinoma - the most common form of primary liver cancer - frequently causes treatment-related adverse events such as pain, fever, nausea and raised inflammatory markers. Very little research has looked at whether anything can reduce that burden.

This study set out to test whether ozone therapy, given as rectal insufflation alongside standard interventional treatment, reduced adverse events or inflammation.

Study design: 342 patients, ozone cohort versus control

Three hundred and forty-two patients with hepatocellular carcinoma undergoing interventional therapy were enrolled between December 2020 and June 2023. Of these, 221 received rectal ozone insufflation and 121 did not.

This was a retrospective study - the treatment records were gathered and analysed afterwards, rather than patients being randomly assigned in advance. Treatment-related adverse events and laboratory parameters were compared between the two groups.

Findings: no significant difference between the groups

Adverse events of any grade were reported by 122 patients (55.2%) in the ozone group and 67 patients (55.4%) in the control group - effectively identical, and not statistically significant. No difference was found in the incidence of specific adverse events either.

Ozone therapy also did not mitigate the rise in inflammatory markers following treatment.

The analysis did identify two independent predictors of adverse events regardless of ozone use: higher AFP levels (odds ratio 1.82) and a higher ALT/AST ratio (odds ratio 2.02).

What the authors concluded

The authors conclude plainly that ozone therapy did not significantly reduce the incidence of adverse events or attenuate the increase in inflammatory markers in these patients, and that further research with a larger sample size is warranted.

This is a negative result. We include it because a research library that only shows favourable findings is not a research library. What the study does support is that rectal insufflation was tolerated without adding to the side-effect burden - patients receiving it fared no worse - but it showed no measurable benefit on the outcomes tested.

Limitations of this study

The study was retrospective rather than randomised, so the two groups were not assigned by chance and unmeasured differences between them cannot be excluded. Patients were drawn from a single centre. The authors themselves call for larger studies.

This study concerns the side effects of conventional liver cancer treatment. It does not examine ozone as a treatment for cancer itself. Ozone therapy is a complementary approach and should always be discussed with your oncology team.