Clinical and Molecular Hepatology

"Hepatitis B surface antigen"

Reviews

Targeting the innate immune system in treating hepatitis B: prospects for functional cure: Karen Cheuk-Ying Ho, Rex Wan-Hin Hui, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak; Clin Mol Hepatol 2026;32(1):184-199.
Published online November 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0935

Abstract
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Chronic hepatitis B (CHB) infection remains a significant global public health concern. Functional cure, defined as hepatitis B surface antigen seroclearance with unquantifiable HBV DNA at 24 weeks off treatment, is a desirable endpoint in the treatment of CHB, yet challenging to achieve. Given the limitations of current therapies including nucleos(t)ide analogues and pegylated interferon alpha, novel agents targeting functional cure are emerging. As hepatitis B virus (HBV) is a non-cytolytic virus, liver damage stems from the host immune response towards HBV-infected cells. The innate immune response during the initial phase of HBV infection is crucial in establishing an adequate level of immunity against the virus. However, HBV adopts various mechanisms to evade the host’s innate immunity, partly contributing to the chronicity of infection. This article provides a comprehensive review on how the HBV life cycle interacts with the host’s innate immune system. The latest evidence of novel agents targeting the innate immunity will also be covered. Retinoic acid inducible gene I agonists, toll-like receptor agonists, and interferons are therapies that target the HBV evasion strategies against host’s innate immunity. While small interfering RNAs and antisense oligonucleotides are originally designed for antigen knockdown and reinvigoration of the adaptive immune response, they have also shown additional impacts on the innate immunity. With ongoing research and innovation in combination strategies, advancement in the management of CHB is anticipated in the future.

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Viral hepatitis

Prospect of emerging treatments for hepatitis B virus functional cure: Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen; Clin Mol Hepatol 2025;31(Suppl):S165-181.
Published online November 14, 2024; DOI: https://doi.org/10.3350/cmh.2024.0855

Abstract
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Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha. Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides and small-interfering RNAs are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

Citations

Citations to this article as recorded by

Large-scale profile study on hepatitis B surface antigen levels in chronic hepatitis B: implications for drug development targeting functional cure
Rex Wan-Hin Hui, Trevor Kwan-Hung Wu, Karen Cheuk-Ying Ho, Ryan Hin-Man Leung, Matthew Shing-Hin Chung, Danny Ka-Ho Wong, James Fung, Wai-Kay Seto, Lung Yi Mak, Man-Fung Yuen
Gut.2026; 75(1): 119. CrossRef
Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef
Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on “Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalentl
Mehrangiz Dezhbord, Kyun-Hwan Kim
Clinical and Molecular Hepatology.2026; 32(1): 385. CrossRef
Targeting the innate immune system in treating hepatitis B: prospects for functional cure
Karen Cheuk-Ying Ho, Rex Wan-Hin Hui, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak
Clinical and Molecular Hepatology.2026; 32(1): 184. CrossRef
Large-scale screening of HBV epitopes restricted by multiple prevalent HLA-B/C allotypes and routine detection of HBV-specific T cells in CHB patients
Yandan Wu, Yu Zhao, Ruixue Ji, Pinqing Li, Huijuan Chen, Fangping Yue, Yi Wu, Jie Qiu, Chuanlai Shen
Frontiers in Immunology.2026;[Epub] CrossRef
Reply to: “ALT to qHBsAg ratio predicts HBsAg seroclearance in HBeAg-negative patients receiving Peg-IFNα based therapy”
Rex Wan-Hin Hui, Lung-Yi Mak, Man-Fung Yuen
Journal of Hepatology.2025; 82(5): e228. CrossRef
Expanding treatment indications in chronic hepatitis B: Should we treat all patients?
Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen
Hepatology International.2025; 19(2): 304. CrossRef
Combining therapeutic agents to target the immune systems of hepatitis B patients: what do we need to consider?
Shang-Chin Huang, Jia-Horng Kao
Expert Review of Gastroenterology & Hepatology.2025; 19(4): 371. CrossRef
Efficacy of Antiviral Therapy in Chronic Hepatitis B Patients With Normal Alanine Aminotransferase: A Systematic Review and Meta‐Analysis
Yuting Diao, Yueying Zeng, Zhihao Huang, Chunfang You, Kevork M. Peltekian
Canadian Journal of Gastroenterology and Hepatology.2025;[Epub] CrossRef
Hepatitis B: Neue therapeutische Ansätze für eine funktionelle Heilung
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Bioorganic & Medicinal Chemistry.2025; 128: 118259. CrossRef
Emerging therapies for HBsAg seroclearance: spotlight on novel combination strategies
Rex Wan-Hin Hui, James Fung, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak
Hepatology International.2025; 19(4): 704. CrossRef
Advancing HIV cure: insights from developing chronic hepatitis b therapies for functional cure
Ana Verma, Raymond T. Chung
Current Opinion in HIV and AIDS.2025; 20(5): 449. CrossRef
Challenges and advances in clinical cure of chronic hepatitis B
Xu-Ling Liu, Yu-Lang Jiang, Ming-Yu Sun
World Chinese Journal of Digestology.2025; 33(9): 693. CrossRef
Small molecule HBV RNA destabilizing drugs: Drugs of the future or compounds from the past?
Timothy M. Block, Dimitar Gotchev, Yanming Du
Antiviral Research.2025; 244: 106288. CrossRef
Global strategies and actions to eliminate hepatitis B virus infection
Chih-Lin Lin, Jia-Horng Kao
Clinical and Molecular Hepatology.2025; 31(4): 1197. CrossRef
Morphometric and structural dynamic parameters of hepatitis viruses: implications for therapeutic and vaccine failure
Saganuwan Alhaji Saganuwan
Discover Viruses.2025;[Epub] CrossRef
Functional cure of chronic hepatitis B virus infection: current therapeutic regimens
Yi-Wei Shi, Rui Pu, Yi-Bo Ding, Wen-Bin Liu, Zi-Shuai Li, Jia-Yi Zhao, Yi-Fan Chen, Guang-Wen Cao
Hepatoma Research.2025;[Epub] CrossRef

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Correspondence

Artificial intelligence, epidemiology, methodology, or others

Harnessing hepatitis B core-related antigen measurement to optimize posttreatment monitoring: Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu; Clin Mol Hepatol 2024;30(2):293-296.
Published online February 19, 2024; DOI: https://doi.org/10.3350/cmh.2024.0101

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Reviews

Viral hepatitis

Safety considerations for withdrawal of nucleos(t)ide analogues in patients with chronic hepatitis B: First, do no harm: Yao-Chun Hsu, Cheng-Hao Tseng, Jia-Horng Kao; Clin Mol Hepatol 2023;29(4):869-890.
Published online March 14, 2023; DOI: https://doi.org/10.3350/cmh.2022.0420

Abstract
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Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.

Citations

Citations to this article as recorded by

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Nucleos(t)ide Analog Treatment Discontinuation in Chronic Hepatitis B Virus Infection: A Systematic Literature Review
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Comparison of hepatocellular carcinoma incidence after long-term treatment with besifovir vs. tenofovir AF
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Association Between Elevation of Serum Alanine Aminotransferase and HBsAg Seroclearance After Nucleos(t)ide Analog Withdrawal
Ying‐Nan Tsai, Jia‐Ling Wu, Cheng‐Hao Tseng, Shang‐Chen Tseng, Chih‐Lung Hung, Mindie H. Nguyen, Jaw‐Town Lin, Yao‐Chun Hsu
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RNA interference as a novel treatment strategy for chronic hepatitis B infection: Rex Wan-Hin Hui, Lung-Yi Mak, Wai-Kay Seto, Man-Fung Yuen; Clin Mol Hepatol 2022;28(3):408-424.
Published online February 17, 2022; DOI: https://doi.org/10.3350/cmh.2022.0012

Abstract
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Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. Functional cure of CHB, defined as sustainable hepatitis B surface antigen (HBsAg) seroclearance, is associated with improved clinical outcomes. However, functional cure is rarely attainable by current treatment modalities. RNA interference (RNAi) by small-interfering RNA (siRNA) and anti-sense oligonucleotide (ASO) has been studied as a novel treatment strategy for CHB. RNAi targets post-transcriptional messenger RNAs and pregenomic RNAs to reduce hepatitis B virus (HBV) antigen production and viral replication. By reducing viral antigens, host immune reconstitution against HBV may also be attained. Phase I/II trials on siRNAs have demonstrated them to be safe and well-tolerated. siRNA is effective when given in monthly doses with different total number of doses according to different trial design, and can lead to sustainable dose-dependent mean HBsAg reduction by 2–2.5 log. Incidences of HBsAg seroclearance after siRNA therapy have also been reported. ASOs have also been studied in early phase trials, and a phase Ib study using frequent dosing regimen within 4 weeks could achieve similar HBsAg reduction of 2 log from baseline. Given the established efficacy and safety of nucleos(t) ide analogues (NAs), future RNAi regimens will likely include NA backbone. While the current evidence on RNAi appears promising, it remains undetermined whether the potent HBsAg reduction by RNAi can result in a high rate of HBsAg seroclearance with durability. Data on RNAi from phase IIb/III trials are keenly anticipated.

Citations

Citations to this article as recorded by

Large-scale profile study on hepatitis B surface antigen levels in chronic hepatitis B: implications for drug development targeting functional cure
Rex Wan-Hin Hui, Trevor Kwan-Hung Wu, Karen Cheuk-Ying Ho, Ryan Hin-Man Leung, Matthew Shing-Hin Chung, Danny Ka-Ho Wong, James Fung, Wai-Kay Seto, Lung Yi Mak, Man-Fung Yuen
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Lung-Yi Mak, Anna SF. Lok
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Targeting the innate immune system in treating hepatitis B: prospects for functional cure
Karen Cheuk-Ying Ho, Rex Wan-Hin Hui, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak
Clinical and Molecular Hepatology.2026; 32(1): 184. CrossRef
Direct Viral Mechanisms Underlying the Onset of HBV-Related Hepatocellular Carcinoma and Implications for Therapeutic Strategies
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Reply to: “ALT to qHBsAg ratio predicts HBsAg seroclearance in HBeAg-negative patients receiving Peg-IFNα based therapy”
Rex Wan-Hin Hui, Lung-Yi Mak, Man-Fung Yuen
Journal of Hepatology.2025; 82(5): e228. CrossRef
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Expanding treatment indications in chronic hepatitis B: Should we treat all patients?
Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen
Hepatology International.2025; 19(2): 304. CrossRef
Prospect of emerging treatments for hepatitis B virus functional cure
Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen
Clinical and Molecular Hepatology.2025; 31(Suppl): S165. CrossRef
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Emerging therapies for HBsAg seroclearance: spotlight on novel combination strategies
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Christine I. Wooddell, Lung Yi Mak, Wai-Kay Seto, Bruce D. Given, Man-Fung Yuen
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Lu Zhang, Yu Cao, Sijing Zhuang, Jingjing Sun, Qiao Tong, Jianjun Xi, Shourong Liu, Rangxiao Zhuang
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Editorials

Viral hepatitis

Another oral antiviral treatment, but still far away from hepatitis B virus cure: Tai-Chung Tseng; Clin Mol Hepatol 2021;27(2):281-282.
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Original Articles

Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance: Jeong Won Jang, Jin Seoub Kim, Hye Seon Kim, Kwon Yong Tak, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Lewis R. Roberts; Clin Mol Hepatol 2021;27(1):207-218.
Published online December 3, 2020; DOI: https://doi.org/10.3350/cmh.2020.0115

Background/Aims
The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.

Methods
Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.

Result
s: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.

Conclusions
The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

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International Journal of Molecular Sciences.2021; 22(13): 7056. CrossRef

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Viral hepatitis

Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B: Han Ah Lee, Yeon Seok Seo, Seung Woon Park, Sang Jung Park, Tae Hyung Kim, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um; Clin Mol Hepatol 2016;22(3):382-389.
Published online September 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0047

Abstract
PDF

Background/Aims
Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response.
Methods
This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10 IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal.
Result
s: After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log₁₀ IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log₁₀ IU/mL (n=11) and >3 log₁₀ IU/mL (n=28), respectively.
Conclusions
The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log₁₀ IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.

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Takehisa Watanabe, Sanae Hayashi, Yasuhito Tanaka
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Florian van Bömmel, Thomas Berg
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Clinical Infectious Diseases.2021; 73(4): e892. CrossRef
Emerging Diagnostic Tools to Decide When to Discontinue Nucleos(t)ide Analogues in Chronic Hepatitis B
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Viral hepatitis

Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B: Jeong Han Kim, Hee Won Moon, Soon Young Ko, Won Hyeok Choe, So Young Kwon; Clin Mol Hepatol 2014;20(3):274-282.
Published online September 25, 2014; DOI: https://doi.org/10.3350/cmh.2014.20.3.274

Abstract
PDF

Background/Aims

Quantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy.

Methods

LMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment.

Results

Fifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020).

Conclusions

The HBsAg level at 6 months after treatment can help predict treatment response.

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Hussam Murad, Haythum O Tayeb, Mahmoud Mosli, Misbahuddin Rafeeq, Mohammed Basheikh
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Jeong Han Kim, Sung Hyun Ahn, Soon Young Ko, Won Hyeok Choe, Kyun-Hwan Kim, So Young Kwon
Clinical and Molecular Hepatology.2016; 22(2): 241. CrossRef

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The Korean Journal of Hepatology Elsewhere

Growing attention to an old marker, hepatitis B surface antigen, in the natural history of chronic hepatitis B: Jeong Won Jang; Korean J Hepatol 2010;16(3):342-346.
Published online September 30, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.3.342

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Role of Hepatitis B Surface Antigen (HBsAg) in Identifying True Inactive HBsAg Carriers Infected With Genotype C Hepatitis B Virus
Sun Young Yim, Soon Ho Um, Jin Young Jung, Yeon Seok Seo, Hyung Joon Yim, Ho Sang Ryu, Hoon Jai Chun, Yoon Tae Jeen, Chang Duck Kim, Bora Keum, Hong Sik Lee
Journal of Clinical Gastroenterology.2014; 48(2): 166. CrossRef

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Editorial

Predictors for virologic response in management of chronic hepatitis B: Jung Min Lee, M.D.1, Sang Hoon Ahn, M.D.1-3; Korean J Hepatol 2010;16(1):1-4.
Published online March 26, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.1.1

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Original Article

Comparison of Lamivudine-induced HBsAg Loss rate according to age in children with chronic hepatitis B: Jung Mi Kim , Byung Ho Choe , Mi Ae Chu , Seung Man Cho; Korean J Hepatol 2009;15(2):168-178.
Published online June 30, 2009; DOI: https://doi.org/10.3350/kjhep.2009.15.2.168

Abstract
PDF

Background/Aims
The aim of this study was to establish the characteristics of children with hepatitis B e antigens (HBeAg) positive chronic hepatitis B who were cleared of hepatitis B surface antigens (HBsAg) as a result of lamivudine treatment. Methods: Seventy-six children with chronic hepatitis B who were seropositive for HBeAg were treated with lamivudine for at least 6 months. HBeAg seroconversion occurred during treatment in 49 of these children, who were then followed up to assess their clearance of serum HBsAg. Various clinical variables were compared between those patients who were cleared of HBsAg and those who were not, including age, pretreatment serum levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA, treatment duration, the time elapsed between initiation of treatment and ALT normalization, HBV DNA negativization, HBeAg seroconversion, and HBsAg clearance. Results: HBsAg disappeared in 13 of the 49 (26.5%) patients who experienced lamivudine-induced HBeAg seroconversion; HBsAg did not reappear during follow-up period (1-86 months). The time that elapsed between initiation of lamivudine treatment and total HBsAg clearance was 25.9±27.1 months (mean±SD; range: 5-104 months). The age at which treatment was initiated was the only factor associated with HBsAg clearance. Children who were cleared of HBsAg were significantly younger than those who were not (5.1±4.3 years vs. 7.9±4.9 years, respectively; P=0.006). All 13 of these patients eventually produced antibodies to HBsAg. Conclusions: Younger children (age <7 years old) have a higher chance of HBsAg clearance than older children after the treatment of HBeAg-positive chronic hepatitis B with lamivudine. (Korean J Hepatol 2009;15:168-178)

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