Clinical significance of cytokine levels in HBsAg sero-clearance in patients with severe hepatitis B

To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen (HBsAg) sero-clearance in patients with severe hepatitis B.

A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020. Of them, 7 patients (aged 36.57±3.15 years) achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares (with abrupt rise of ALT level to >5 times the upper limit of normal during HBV infection) and were assigned into HBsAg clearance group, while the other 7 patients (aged 34.14±2.97 years) only obtained HBsAg decreased less than 1 g within 1 year after the onset (HBsAg non-clearance group). Then, multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients.

The serum levels IFN-γ, IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group (P<0.05), but no statistical differences were observed in other 39 cytokines between the 2 groups. And there were 5 cytokines having no mutual expression in both groups. The copy number of HBV DNA was positively correlated with serum HGF (r=0.675, P=0.008) and SDF-1α levels (r=0.587, P=0.027), while negatively with IP-10 (r=-0.600, P=0.023) and MIG level (r=-0.640, P=0.014). Meanwhile, a positive correlation was found between HBsAg titer and IL12-p70 level (r=0.593, P=0.025), and a negative correlation between HBsAg titer and TNF-α level (r=-0.609, P=0.021). In addition, the serum total bilirubin level was positively correlated with the expression of SCGF-β (r=0.543, P=0.045).

Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found, which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares. Meanwhile, it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.