External validation of the GOLDEN model for predicting HBsAg loss in non-cirrhotic chronic hepatitis B patients with interferon-alpha based therapy

Xingmei Liao; Qing Xie; Xiaoguang Dou; Junqi Niu; Hong Ma; Yali Liu; Shumei Lin; Huiying Rao; Song Yang; Jianping Xie; Mingxiang Zhang; Qiang Li; Yanyan Yu; Qin Ning; Wu Li; Chengzhong Li; Liaoyun Zhang; Zhengang Zhang; Tao Han; Jian Sun; Jinlin Hou; Rong Fan; Chronic Hepatitis B Study Consortium

doi:10.1016/j.cgh.2025.06.005

External validation of the GOLDEN model for predicting HBsAg loss in non-cirrhotic chronic hepatitis B patients with interferon-alpha based therapy

Clin Gastroenterol Hepatol. 2025 Jun 23:S1542-3565(25)00524-5. doi: 10.1016/j.cgh.2025.06.005. Online ahead of print.

Authors

Xingmei Liao¹, Qing Xie², Xiaoguang Dou³, Junqi Niu⁴, Hong Ma⁵, Yali Liu⁶, Shumei Lin⁷, Huiying Rao⁸, Song Yang⁹, Jianping Xie¹⁰, Mingxiang Zhang¹¹, Qiang Li¹², Yanyan Yu¹³, Qin Ning¹⁴, Wu Li¹⁵, Chengzhong Li¹⁶, Liaoyun Zhang¹⁷, Zhengang Zhang¹⁸, Tao Han¹⁹, Jian Sun¹, Jinlin Hou²⁰, Rong Fan²¹; Chronic Hepatitis B Study Consortium

Affiliations

¹ Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases; Guangdong Provincial Clinical Research Center for Viral Hepatitis; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
² Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
⁴ Department of Liver, First Hospital of Jilin University, Changchun, China.
⁵ Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
⁶ Beijing Youan Hospital, Capital Medical University, Beijing, China.
⁷ Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁸ Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China.
⁹ Beijing Ditan Hospital, Capital Medical University, Beijing, China.
¹⁰ Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China.
¹¹ The Sixth People's Hospital of Shenyang, Shenyang, China.
¹² Ji'nan Infectious Diseases Hospital, Ji'nan, China.
¹³ Department of Infectious Diseases, First Hospital of Peking University, Beijing, China.
¹⁴ Department of Infectious Diseases, Wuhan Tongji Hospital affiliated to Huazhong Technology University, Tongji Medical College, Wuhan, China.
¹⁵ Department of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
¹⁶ Department of Infectious Disease, Changhai Hospital, Shanghai, China.
¹⁷ Department of Infectious Diseases, First Hospital of Shanxi Medical University, Taiyuan, China.
¹⁸ Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁹ Department of Hepatology and Gastroenterology, Tianjin Third Central Hospital, Tianjin, China.
²⁰ Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases; Guangdong Provincial Clinical Research Center for Viral Hepatitis; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: jlhousmu@163.com.
²¹ Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases; Guangdong Provincial Clinical Research Center for Viral Hepatitis; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: rongfansmu@163.com.

PMID: 40562289
DOI: 10.1016/j.cgh.2025.06.005

Abstract

Background and aims: The GOLDEN model is designed to predict hepatitis B surface antigen (HBsAg) loss based on chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogues therapy. We aimed to validate GOLDEN model's effectiveness in predicting HBsAg loss or decline in interferon-alpha (IFN-α) treated CHB patients.

Methods: IFN-α-treated patients were enrolled from EXCEL study, a randomized controlled trial included HBeAg-positive, non-cirrhotic, treatment-naïve CHB patients, as well as Search-B cohort, a prospective real-world observational cohort of CHB. Utilizing multiple quantitative HBsAg (qHBsAg) measurements, GOLDEN model was employed to calculate patient's probability of achieving HBsAg loss or decline.

Results: Among 200 patients in EXCEL study and 1041 patients from Search-B cohort, the corresponding cumulative incidence of qHBsAg<100 IU/mL or HBsAg loss was 20.0% and 6.7%, after the median follow-up of 18.0 (IQR,18.0-30.0) and 66.7 (IQR,48.8-84.7) months, respectively. The GOLDEN model achieved an area under the curve of 0.820 (95% CI:0.737-0.902) for predicting qHBsAg<100 IU/mL in EXCEL study and 0.964 (95% CI:0.953-0.974) for predicting HBsAg loss in Search-B cohort, maintaining robust performance across subgroups. The favorable group showed higher cumulative incidences of qHBsAg<100 IU/mL (42.5% vs. 4.6%, p<0.001) or HBsAg loss (37.2% vs. 0%, p<0.001) than the unfavorable group, along with significantly lower qHBsAg levels and faster qHBsAg decline rates. Moreover, the favorable group defined by GOLDEN model and qHBsAg levels at enrolment were confirmed as independent predictors for HBsAg loss or decline.

Conclusion: GOLDEN model is a robust tool for predicting HBsAg loss or decline in IFN-α-treated CHB patients, offering valuable support for clinicians in developing personalized, effective management strategies for CHB patients.

Keywords: Chronic hepatitis B; Functional cure; GOLDEN model; Interferon-alpha; Quantitative hepatitis B surface antigen.