Expression features of glucocorticoid receptor and its association with treatment outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

Objective To investigate the expression features of glucocorticoid receptor( GR) and its subtypes α and β in patients with early-or middle-stage hepatitis B virus-related acute/subacute-on-chronic liver failure( HBV-ACLF) treated by glucocorticoid( GC) and their association with sensitivity to glucocorticoid therapy. Methods A prospective non-randomized controlled trial was performed for 33 patients with early-or middle-stage HBV-ACLF who were hospitalized and treated in Beijing YouAn Hospital from September 2015 to June2018,and among these patients,18 received intravenous infusion of methylprednisolone for 7 days in addition to comprehensive medical treatment. Flow cytometry and RT-PCR were used to measure the mRNA expression of GR,GR-α,and GR-β,and the expression of GR,GR-α,and GR-β was observed at baseline and on day 8. According to the response to GC on day 10,the hormone group was further divided into hormone-sensitive group with 13 patients and hormone-insensitive group with 5 patients. The two-independent-samples t test was used for comparison of continuous data between two groups,and the paired t-test was used for comparison within one group before and after treatment; the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier survival curve was used to analyze 28-day survival,and the log-rank test was used for comparison between groups. Results The hormone group had a significant reduction in the mRNA expression of GR-α on day 8 after hormone administration [( 0. 99 ± 0. 48) × 10-2 vs( 1. 96 ±0. 50) × 10-2,t = 6. 586,P < 0. 001]There was a significant difference in the mRNA expression of GR-α between the hormone group and the non-hormone group on day 8 [0. 99 ± 0. 48) × 10-2 vs( 1. 70 ± 0. 66) × 10-2,t =-3. 518,P = 0. 001]On day 8,the hormone-sensitive group had significantly higher mRNA expression of GR-α than the hormone-insensitive group [1. 21 ± 0. 34) × 10-2 vs( 0. 43 ± 0.31) × 10-2,t = 4. 456,P < 0. 001]and the hormone-sensitive group had a significantly greater reduction in the mRNA expression of GR-α compared with the hormone-insensitive group( t =-2. 904,P = 0. 01). There was no significant difference in the mRNA expression of GR-β on day 8 between the hormone-sensitive group and the hormone-insensitive group [0. 14 ± 0. 08) × 10-2 vs( 0. 10 ±0. 04) × 10-2,t = 1. 092,P = 0. 291]For the hormone group,the mean ratio of reduction in GR-α mRNA expression to baseline value was46% on day 8,and according to this,the patients were divided into ≤46% group with 10 patients and > 46% group with 8 patients. There was a significant difference in the ratio of reduction in GR-α mRNA expression to baseline value between the two groups( 26. 99% ± 25.09% vs 70. 09% ± 16. 08%,t =-4. 203,P = 0. 001). On day 10,there were significant differences between the ≤46% group and the >46% group in the ratio of reduction in total bilirubin( TBil) to baseline value( P = 0. 021) and the ratio of increase in prothrombin time activity( PTA) to baseline value( P = 0. 048). Conclusion In patients with early-or middle-stage HBV-ACLF,there is a significant reduction in the mRNA expression of GR-α after GC treatment. Patients sensitive to hormone have a relatively low degree of reduction in the mRNA expression of GR-α,with better improvements in TBil and PTA on day 28 than those insensitive to hormone. Dynamic change of GR-α mRNA has a certain reference value in predicting the outcome of hormone therapy.