The Changes Of Vitamin D And Vitamin D Receptor In Patients With Hepatitis B Virus-Related Acute-On-Chronic Liver Failure

Objective: Hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) is a life-threatening syndrome that is characterized by variant complications such as progressive jaundice, hepatic encephalopathy, ascites, hepatorenal syndrome and so on. The mortality of HBV-related ACLF remains very high.To date, treatment options are limited. Many scholars believed that immune injury, ischemia, hypoxia and endotoxemia contributed to the development of liver failure. When liver failure occurs, severe liver function is out of function. Synthesis, detoxification, excretion, biotransformation are also out of order. Vitamin D is synthesized predominantly in the liver and functions as an important secosteroid hormone with pleiotropic effects. Free of active vitamin D can rapidly enter cells, bind vitamin D receptor and play their biological role. While its key regulatory role in calcium and bone homeostasis is well established, recently there is increasing recognition that vitamin D also regulates cell proliferation and differentiation, and has immunomodulatory, anti-inflammatory and anti-fibrotic properties. Therefore, this study aims to detect serum vitamin D levels in chronic hepatitis patients, while VDR expression were compared between HBV-related ACLF and CHB groups.Methods: 70 patients, including 21 patients with HBV-related ACLF, 29 patients with chronic hepatitis B(CHB) and 20 healthy controls(HC) involved in our study were recruited. In addition, liver tissues were obtained from 13 HBV-related ACLF patients, 16 CHB patients and 4 liver donors. The diagnoses of HBV-related ACLF and CHB were made according to the Diagnostic and Treatment Guidelines for Liver Failure(2012) and the Guidelines on Prevention and Treatment for Chronic Hepatitis B in China(2010) issued by the Chinese Society of Hepatology and the Chinese Society of Infectious Disease. Serum biochemical parameters, coagulation function parameters and serum HBV DNA load were measured. The serum VD concentrations were detected by enzyme-linked immunosorbent assays. The VDR m RNA expression in liver tissues were detected by quantitative real-time polymerase chain reaction, and VDR protein expression in liver tissues were measured by western blot. Immunohistochemical staining was performed to illustrate the expression and the distribution of VDR. Moreover, The relationships between the serum VD levels and the HBV DNA loadings was also calculated.SPSS13.0 was applicated to analyse all data.Results:1 Demographic and clinical characteristics of the studied subjects includ- ing HBV-related ACLF patients, CHB patients and healthy control patientsThe ages and sex ratio were no significantly differences for the chosen healthy control people group compared with that of patient groups. The detected levels of alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBIL), and direct bilirubin(DBIL) in ACLF group were obviously higher than that of CHB patients and healthy controls(P<0.01 for both conditions), but the serum albumin(Alb) level and prothrombin activity(PTA) were much lower(compared with the healthy controls). And there were no significantly differences for HBV DNA loading between the HBV-related ACLF patients and CHB patients(P>0.05).2 The level of serum 25-(OH)VD3 for the ACLF patients21 of HBV-related ACLF patients, 20 of CHB patients and 29 of healthy people were detected. There was an decrease of VD levels in HBV-related ACLF patients and CHB patients.The VD levels were significantly different between three groups.(P<0.01)and the HBV-related ACLF patients had the lowest VD level.3 The expression of VDR protein in the ACLF and CHB patient livers13 of HBV-related ACLF patients, 16 of CHB patients and 4 of healthy people were detected. The IHC detection demonstrated that VDR widely expressed in liver cells and liver inflammation cells. The WB detection demonstrated that the VDR protein expressed in the HBV-related ACLF patients(1.336±0.115) were obviously higher than that in CHB patient(1.071± 0.079)and control(0.830 ± 0.112)groups. Between three groups, the differences were significant(P<0.01). The conditions for the HBV-related ACLF patients and CHB patients had significant differences. The VDR m RNA expression was significantly higher for the HBV-related ACLF patients(2.65±0.32)than that of CHB patients(1.20±0.39)and control(0.93±0.07)groups. And the differences were significant(P<0.01). The conditions for CHB patients and control groups were not significant.4 The correlation of VD levels and HBV DNA in serumThe serum VD levels in HBV-related ACLF and CHB patient groups were significantly different from that of controls,(38.09% vs. 6.8%, P<0.01). The serum VD levels were correlated with HBV DNA loadings in the CHB patient groups(r=0.62, P<0.01), while there were no correlations in the HBV-ralated ACLF groups.Conclusions:1 There was a correlation between HBV DNA loadings and VD levels in CHB patients.2 VDR widely expressed in liver cells and inflammation of the liver cells.VDR expressed in HBV-related ACLF patients were increased more than CHB patients and control group. VDR may paticipate in the pathogenesis of HBV-related ACLF.