Effect Of Nucleoside（Acid）Analogues On Vitamin D、β₂ Microglobulin And Other Indices In Patients With Chronic Hepatitis B

Objective:To observe the effects of nucleoside（acid）analogues（NAs）on serum vitamin D（VitD3）levels and β₂ microglobulin（β₂-MG）in patients with chronic hepatitis B（CHB）.Methods:Ninety patients with primary treatment of Han Chinese CHB who attended the Affiliated Hospital of Inner Mongolia Medical University and the Second Hospital of Hohhot from October 2020 to September 2021 were studied,and were divided into three groups according to different antiviral treatment regimens,namely,the tenofovir propofol fumarate（TAF）group,tenofovir dipivoxil fumarate（TDF）group,and entecavir（ETV）group,with 30cases in each group,and 30 healthy Han Chinese who were examined at the physical examination center of the Affiliated Hospital of Inner Mongolia Medical University during the same period were used as the control group.Baseline data of control group and CHB patients[serum VitD3,blood calcium,blood phosphorus,blood creatinine（Scr）,serum β₂-MG,serum retinol binding protein（RBP）,serum cystatin C（CysC）,estimated glomerular filtration rate（eGFR）]and follow-up data of CHB patients（serum VitD3,blood calcium,blood phosphorus,serum Scr,serum β₂-MG,serum RBP,serum CysC,eGFR,HBV DNA）were compared and analyzed;to observe（1）whether there is any difference in serum VitD3levels between CHB patients and healthy individuals;（2）whether NAs treatment affects VitD3 levels in CHB patients;（3）whether blood calcium,blood phosphorus,serum VitD3,blood Scr,serum β₂-MG,serum RBP,serum CysC,eGFR and HBV DNA levels at different follow-up time points.Results:（1）VitD3 levels were significantly lower in patients with CHB compared to those with healthy physical examination（t=2.611,P=0.010）.（2）At week24 of antiviral treatment,the VitD3 levels of CHB patients in the TAF and TDF groups were significantly higher than baseline（P<0.05）;at week 48,the VitD3 levels of CHB patients in the ETV group were significantly higher than baseline（P<0.05）;however,there was no statistical difference between the three groups at any follow-up time point（P>0.05）.As HBV DNA load decreased in CHB patients,VitD3 levels tended to gradually increase,and there was a significant negative correlation between the two（P<0.05）.（3）The levels of β₂-MG and CysC in the TDF group were significantly higher than those in the TAF and ETV groups at week 72 of treatment（F=3.851,P=0.025;F=3.495,P=0.035）.（4）There was no statistical difference in the comparison of blood calcium,blood phosphorus,blood Scr,eGFR and RBP among the three groups of CHB patients at any follow-up time point（P>0.05）.（5）HBV DNA decreased more significantly in the TAF and TDF groups than in the ETV group at weeks 12 and 24 of antiviral treatment（F=9.539,P<0.001;F=5.241,P=0.007）.Conclusions:（1）VitD3 deficiency is common in healthy subjects and CHB patients,but is more pronounced in CHB patients.（2）HBV DNA and VitD3 are negatively correlated in CHB patients;with the reduction of viral load due to NAs,VitD3 levels can be partially restored,and VitD3 should be supplemented in time if necessary.（3）TAF and TDF have stronger antiviral effects in the short term than ETV in CHB patients.（4）CHB patients taking TDF have a certain degree of renal injury,and serum β₂-MG and CysC are more sensitive than changes in blood Scr and eGFR levels,so clinical work can improve the diagnostic positivity rate of early renal injury by combined detection of serum β₂-MG and CysC.（5）The overall safety of TAF and ETV is better than TDF for antiviral therapy in CHB patients.（6）In clinical work,attention should be paid to renal injury and VitD3 supplementation in CHB patients who have been taking NAs for a long time.