4.1 Changes of Treg activity in acute on chronic hepatitis B
CHB can progress to acute‐on‐chronic liver failure (ACLF). It is characterized by acute deterioration of liver function, coagulopathy, and subsequent multiple organ failure with 28-d mortality in the Asia-Pacific and African regions [3, 100, 101]. A recent study revealed that HBV-ACLF patients had significantly decreased Tregs compared with HC and CHB. And they thought that the model for end-stage liver disease (MELD) score was negatively correlated with CD4+CD25+Tregs[102]. This characteristic may help to predict HBV-ACLF severity and indicate a prognosis response to guide the treatment of HBV-ACLF. Another study documented that no obvious distinction was founded of viral-specific Tregs between CHB and asymptomatic HBV carriers (ASC). But Treg/Th17 ratio was decreased in CHB patients compared with ASC[103]. As opposed to Tregs, Th17 cells can produce proinflammatory cytokine IL-17, and can participate in liver damage and viral clearance after HBV infection[80]. A few studies reported that circulating Tregs and Th17 were increased in CHB and related ACLF patients compared with HC. Furthermore, the highest frequency has been observed in active CHB patients, while Th17 cells were most abundant in ACLF patients. And they also found that the Treg/Th17 ratio gradually decreased with the progression of ACLF[90, 104, 105]. Liang et al. found that Tregs frequency increased gradually during the HBV-ACLF. However, Th17 frequency gradually increases during progression from CHB to ACLF, but decreases sharply from the peak point to the recovery point. In addition, they reported that an increased Treg/Th17 ratio was associated with the survival of ACHBLF patients[106]. Others have voiced similar views[107]. However, Zhang et al. found that there was a decrease in Tregs with a concomitant increase in Th17 cells in the peripheral blood of patients in the remission stage of ACLF when compared with patients in the progression stage, CHB patients, or normal controls[108]. An imbalance of Th17 to Tregs may be used as a prognostic marker to predict disease progression. Therefore, more research and evidence are needed in the future.