| Autor: |
Jia R; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China Department of Gastroenterology, the 985th Hospital of Chinese PLA Joint Support Force, Taiyuan 030001, China., Wang WX; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China Peking University 302 Clinical Medical School, Beijing 100039, China., Zhou ZP; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China., Nie WM; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China., Cheng YQ; Department of Geriatric Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China., Zhao J; Department of Liver Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China., Lian F; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China., Luan JQ; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China., Wang FS; Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China Peking University 302 Clinical Medical School, Beijing 100039, China., Fu JL; Peking University 302 Clinical Medical School, Beijing 100039, China Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China. |
| Abstrakt: |
Objective: To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB). Methods: 144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ (2) test between groups. Results: 41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline ( OR = 0.090, 95% CI : 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level ( OR = 7.788, 95% CI : 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI : 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95% CI : 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two ( Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95% CI : 0.941-0.997) was superior to that of single baseline HBsAg quantification ( Z = 3.017, P = 0.003) and 24-week drop in HBsAg level ( Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks ( HR = 0.364, 95% CI : 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion: The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment. |
