Prediction of long-term HBsAg seroclearance in patients with HBeAg-negative chronic hepatitis B
Hae Lim Lee,
Soon Kyu Lee,
Ji Won Han,
Hyun Yang,
Heechul Nam,
Pil Soo Sung,
Hee Yeon Kim,
Sung Won Lee,
Do Seon Song,
Jung Hyun Kwon,
Chang Wook Kim,
Si Hyun Bae,
Jong Young Choi,
Seung Kew Yoon,
Jeong Won Jang
Affiliations
Hae Lim Lee
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Soon Kyu Lee
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Ji Won Han
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Hyun Yang
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Heechul Nam
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Pil Soo Sung
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Hee Yeon Kim
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Sung Won Lee
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Do Seon Song
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Jung Hyun Kwon
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Chang Wook Kim
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Si Hyun Bae
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Jong Young Choi
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Seung Kew Yoon
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea
Jeong Won Jang
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea; Corresponding author. Address: Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
Background & Aims: Predicting the long-term HBsAg seroclearance, an ideal endpoint, is relevant for decision-making regarding antiviral therapy for patients with chronic hepatitis B (CHB). This study aimed to identify predictors and develop a prediction model for HBsAg seroclearance in patients with HBeAg-negative CHB. Methods: A total of 2,032 untreated HBeAg-negative patients who underwent a 2-year baseline observation period were enrolled. Prediction models were developed using independent predictors of seroclearance, and their performance was evaluated through internal and external validation using an independent cohort of 753 patients, along with sensitivity analyses. Results: The estimated annual incidence of HBsAg seroclearance was 2.22% (15,508 person-years). Hepatitis B virus DNA Level (Low-to-intermittently high-level viremia), Old age, male Sex, and hepatitis B Surface antigen level <250 IU/ml independently predicted seroclearance. Subsequently, two prediction models were developed: HepBLOSS-1 and a simplified version, HepBLOSS-2. These models demonstrated excellent performance in predicting seroclearance at 5, 10, and 15 years, with C-indices and time-dependent area under the receiver operating characteristics curve (AUROC) values of 0.81–0.89. The 10-year cumulative incidence rate in patients with scores of ≥13 in HepBLOSS-1 and those with scores of 8 in HepBLOSS-2 was over 50%. Both models underwent rigorous internal and external validation, demonstrating good predictability with time-dependent AUROCs exceeding 0.80. The predicted seroclearance rate closely aligned with the observed rate in both models. Conclusions: The HepBLOSS models for HBsAg seroclearance exhibited an outstanding ability to stratify the probability of seroclearance over a 15-year period. These models hold promising potential to guide treatment decisions, aiming to achieve a functional cure in patients with CHB. Impact and implications: Achieving a functional cure for chronic hepatitis B, defined as HBsAg seroclearance, is a realistic treatment endpoint, especially given the virus’s lifelong persistence in hepatocytes and its significant association with improved prognosis. This study identified independent predictors of seroclearance, including HBV DNA levels, age, sex, and HBsAg levels, and developed a robust prediction model based on these factors. The models demonstrated strong predictive accuracy over a 15-year period, offering valuable guidance for clinicians in establishing treatment strategies and predicting patient prognosis.
