Regulatory T cells are the most important determinant factor of hepatitis B infection prognosis: a systematic review and meta-analysis.
BACKGROUND
Association of increased levels of CD4(+)CD25(+) regulatory T cells (Tregs) with impaired immune response and hepatitis B infection progression has been proposed. For determination of Tregs various effects among hepatitis B infected patients we performed a meta-analysis of the available literature.


METHODS
Current content, abstract books of congresses, and electronic databases were searched. Critical appraisal has been done. According to the result of heterogeneity tests (Q, I-squared, and Tau-squared), we used fix/random model for analysis.


RESULTS
Twelve studies that fulfilled inclusion criteria entered to analysis. Pooled estimation of reported results showed that CD4(+)CD25(+) Tregs have higher expression of forkhead box P3 (FoxP3) versus CD4(+)CD25(-) Tregs, odd ratio (OR) was 31.49 (95% Confidence Intervals (CI): 5.09-194.94). Tregs level among chronic hepatitis B (CHB) patients was 77% (OR=1.77 95% CI: 1.43-2.19) higher than healthy controls. Patients with more than 10,000,000 HBV copies/ml have higher level of Tregs (OR: 1.24 95% CI: 1.08-1.41) comparing subjects with less than that. CHB patients have increased level of Tregs versus acute hepatitis B patients (OR=1.33 95% CI: 1.16-1.52). CD8 cells activity increased significantly after depletion of circulating Tregs (OR=1.93 CI: 1.37-2.73). Also, Tregs reduce response to treatment and non-responders to INF-α had higher level of Tregs (OR=1.60 95% CI: 1.09-2.36). In addition, Tregs increase risk of hepatocellular carcinoma (HCC) (OR=1.36 95%CI: 1.10-1.69).


CONCLUSIONS
Tregs influence HBV infected patients in various states. Tregs determine the disease prognosis by leading to infection progression and impairing immune response. So, Tregs are therapeutic target for immunotherapy of HBV infection.
Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease (BRCGL), Tehran, Iran.
Seyed Hossein
SH
Aalaei-Andabili
Seyed Moayed
SM
Alavian
D018450:Disease Progression; D006509:Hepatitis B / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*