OBJECTIVETo investigate the role ofCD4+CD25+ T regulatory (Treg) cells, T helper (Th)17cells and interleukin (IL)-6 in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and determine their value as prognostic markers.

METHODSThe Chinese National Knowledge Infrastructure (CNKI), WanFang, Chinese Scientific Journals (VIP), PubMed, Embase and Web of Science databases were searched for English language case-control studies on the relationship between regulatory T lymphocytes and ACLF.The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis was designed according to the PICOS approach recommended by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. RevMan software, version 5.1, was used to perform the meta-analysis.

RESULTSNine case-cohort studies were selected for inclusion in the metaanalysis.The results of the meta-analyses showed that the level of CD4+CD25+ Treg cells was not significantly different between patients with HBV-related ACLF and patients with chronic hepatitis B (CHB) (mean difference (MD)=0.59, 95% confidence interval (CI)-1.68, 2.85, P=0.61) nor between patients with HBVrelated ACLF and healthy controls (MD=1.12, 95% CI:-1.42, 3.66, P=0.39). Thus, it appears that ACLF patients do not have a higher level of CD4+CD25+ Treg cells than CHB patients or healthy controls. However, the ACLF patients did appear to have a significantly higher level of Th17 cells than both the CHB patients (MD=1.73, 95% CI:0.21, 3.26, P=0.03) and the healthy controls (MD=1.62, 95% CI:(0.52, 2.72, P=0.004). In addition, the ACLF patients also had significantly higher level than both the CHB patients (MD=11.69, 95%CI:1.98, 21.40, P=0.02) and the healthy controls (MD=13.17, 95% CI:1.38, 24.95, P=0.03).

CONCLUSIONCD4+CD25+ Treg cells may be an important protective factor in the progression and prognosis of HBV-related ACLF, while Thl7 cells and IL-6 may be risk factors for further progression and worsened prognosis.

Acute-On-Chronic Liver Failure ; diagnosis ; immunology ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Disease Progression ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Interleukin-6 ; immunology ; Prognosis ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology