Abstract: Objective To investigate the risk factors associated with hypophosphatemia and their dynamic changes in chronic Hepatitis B (CHB) patients treated with Entecavir of initial treatment. Methods 148 CHB patients treated with Entecavir of initial ireatment in the Department of infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020 to June 2023 were selected. Patients were divided into normal phosphorus group (n=131) and low phosphorus group (n=17) according to serum phosphorus. The Multivariate Cox regression analysis was performed to analyze the independent risk factors of hypophosphatemia in CHB patients. The efficacy of predicting hypophosphatemia in patients with CHB was evaluated with the receiver operating characteristic(ROC) curve. The cumulative incidence of hypophosphatemia was analyzed by Kaplan-Meier analysis and was compared by the Log-rank test. Spearman Correlation was used for correlative analysis. Serum phosphorus and estimated glomerular filtration rate (eGFR) were dynamically observed during treatment. Methods Of all 148 patients, 17 experienced hypophosphatemia, resulting in hypophosphatemia rate of 11.5%, The results of univariate analysis showed that sex and serum phosphorus at baseline were statistically significant (P<0.05) between the normal group and the low phosphorus group. The multivariate cox regression analysis showed that baseline serum phosphorus (HR=0.001, 95%CI: 0~0.021, P＜0.001) was an independent influencing factor for hypophosphatemia in CHB patients. The area under ROC curve of baseline serum phosphorus was 0.7786, indicating a good prediction efficiency. The optimal cut-off point was 1.03, and the sensitivity and specificity were 88.2% and 60.3% respectively. The cumulative incidence of hypophosphatemia in CHB patients with baseline serum phosphorus ≤ 1.03 mmol/L was significantly higher than that in patients with baseline serum phosphorus > 1.03 mmol/L(HR=81.79, 95%CI:4.127~28.550, P<0.001). There was no correlation between hypophosphatemia and eGFR (r=-0.084, P=0.749). For all patients with both hypophosphatemia and abnormal eGFR, hypophosphatemia occurs no earlier than eGFR abnormalities, occurring 0 to 1.17 years(median 0.58 years). The levels of blood phosphorus and eGFR in CHB patients showed a decreasing trend. The levels of serum phosphorus in hypophosphatemia group were always lower than those in normal group during follow-up. Conclusion For the CHB patients treated with entecavir of initial treatment, lower baseline phosphorus level are more likely to develop hypophosphatemia. Dynamic monitoring of serum phosphorus has great significance for the safe use of entecavir.

Key words: Chronic hepatitis B, Hypophosphatemia, Entecavir