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.