Clinical cure in an occult hepatitis B virus infection patient on sequential therapy: a case report

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There is increasing evidence that occult HBV infection is associated with advanced chronic liver disease, especially hepatocellular carcinoma, and that people with occult HBV infection can transmit HBV infection. Despite growing concerns about its transmissibility and clinical impact, occult HBV infection has received limited attention in the hepatitis elimination agenda. While the pursuit of functional cure for hepatitis B may lead to the conversion from overt HBV infection to OBI, few cases of this have been reported to date. This case report presents a patient with chronic hepatitis B who initially converted to occult hepatitis B infection with sequential combination therapy and ultimately achieved clinical cure. Case presentation The patient is a 28-years old male from China diagnosed with hepatitis B virus infection. In 2012, he presented with abnormal liver function and was initially treated with short-acting interferon; however, this approach yielded poor results. Consequently, he was switched to Entecavir (ETV) antiviral therapy.In August 2019, laboratory tests indicated an HBsAg level of 255.35 IU/ml, while HBV DNA was below the lower limit of detection (<500 IU/ml). The patient hadno history of hypertension, cardiovascular disease, diabetes mellitus, or cerebrovascular disease, and was subsequently started on a combination therapy of ETV and pegylated interferon (PEG-IFN). By April 2020, follow-up tests revealed HBV DNA at 2.24 log10 IU/ml and HBsAg reduced to 0.42 IU/ml. At this point, the treatment regimen was adjusted to a combination therapy of tenofovir alafenamide (TAF) and PEG-IFN. Six months later, HBsAg turned negative, HBsAb rose to 52.18IU/L, and HBV DNA was measured at 1.28 log10 IU/ml. The patient was then transitioned to PEG-IFN monotherapy. In November 2021, the patient discontinued PEG-IFN therapy. One month later, laboratory tests confirmed that both HBV DNA (<10 IU/mL) and HBsAg were negative, and these results have been maitntained to date. Conclusion: This case demonstrates that sequential combination therapy can effectively treat chronic hepatitis B, even in patients with a long history of infection. This approach may lead to a shift to latent hepatitis B infection, and timely adjustments in treatment regimens based on monitoring indicators can ultimately result in a clinical cure. chronic hepatitis B occult HBV infection( OBI) sequential combined therapy clinical cure case report Introduction Hepatitis B virus infection is a significant global health problem. Approximately 296 million people worldwide are living with chronic HBV infection, of which approximately 20% require antiviral therapy based on current guideline recommendations [ 1 ]. Approved anti-HBV therapies include IFNα and nucleoside or nucleotide analogues, both shown to improve clinical outcomes in adults with chronic HBV infection [ 2 ]. However, neither agents is universally effective when used alone. IFNα has a low (20–40%) and potential adverse effects, while nucleoside or nucleoside analogues primarily suppress HBV DNA replication but often require lifelong treatment [ 3 ]. The current therapeutic goal is a functional cure, characterized by persistent disappearance of HBsAg (undetectable at levels < 0.05 IU per ml) and undetectable HBV DNA at the end of treatment. Combination therapy is frequently employed to achieve this goal, as numerous studies have demonstrated its effectiveness in restoring the host's antiviral immune response and eliminating the virus [ 4 ]. We presenta case of chronic hepatitis B virus infection that successfully achieved clinical curethrough sequential combination therapy. Case presentation The patient is a 28-years old male from China who was diagnosed with HBV infection in 2001, exhibiting positivity for HBsAg, HBeAg, and HBcAb , but with normal liver function tests. In 2012, he presented with abnormal liver function and was treated with short-acting interferon; however, this approach yield poor results, leading to switch to ETV antiviral therapy. In 2019, the patient again presented with abnormal liver function (ALT 435 IU/L, AST 410 IU/L) and was given hepatoprotective medications. In August 2019, laboratory tests showed an HBsAg level of 255.35 IU/ml and HBcAb at 10.46 S/CO, with HBsAb, HBeAg and HBeAb negative. HBV DNA was below the lower limit of detection (<500 IU/ml). The patient had no history of hypertension, cardiovascular disease, diabetes mellitus, or cerebrovascular disease, and was initiated on combination therapy with ETV and pegylated interferon (PEG-IFN). In November 2019, blood tests revealed positive HBV DNA (1.90 log10 IU/ ml), HBsAg at 0.31 IU/ml, HBcAb at 8.92 S/CO, and abnormal liver function (ALT 126 U/L, AST 129 U/L), prompting the continuation of the current treatment. By April 2020, blood tests indicated HBV DNA at 2.24 log10 IU/ml, HBsAg at 0.42 IU/ml, HBcAb at 6.99 S/ CO, with HBsAb, HBeAg and HBeAbvnegative. The treatment regimen was adjuster to a combination of TAF and PEG-IFN. In March 2021, HBsAg firstly turned negative at the first time, with HBsAb at 134.59 IU/ml and HBV DNA at 1.28 log10 IU/ml, leading to a transition to PEG-IFN monotherapy. By November 2021, HBV DNA was below the lower limit of detection (<500 IU/ml), and HBsAg was 0.02 IU/ml, with HBcAb at 49.55 S/ CO. The patient subsequently discontinued PEG-IFN therapy In November 2021. In December 2021, blood tests confirmed that both HBV DNA (<10 IU/mL) and HBsAg were negative, with HBsAb at 89.18 IU/ml and HBcAb at 7.64 S /CO, HBeAg and HBeAb remained negative, and liver function was near normal. Regular retesting thereafter continued to show negative results for both HBV DNA (<10IU/mL) and HBsAg, with liver function maintained within normal limits (Table 1). Table 1. Evolution of hepatitis B pentameter and liver function during the treatment of patients with chronic hepatitis B. 时间 治疗方案 (干扰素针数) HBV-DNA (试剂 a普通，b高敏) HBsAg (0-0.05 IU/ml) HBsAb (0-1 mIU/ml) HBeAg (0-0.18 PEIU/ml) HBeAb (1-999S/CO) HBcAb (0-1 S/CO) ALT (0-40 U/L) AST (0-40 U/L) GGT (0-58 U/L) CAP (＜238 dB/m) LSM (2.5-7kPa) AST/ALT 2019.08.12 ETV+PEG (0) 首用干扰素 低于检测下限 a （＜500 IU/mL） 255.35 5.32 0.14 1.15 10.46 29 37 35 269 6.3 1.27586 2019.09.17 ETV+PEG (4) — 445.65 0.68 0.11 1.14 8.94 71 75 53 — — 1.05634 2019.10.14 ETV+PEG (8) — 337.45 0.24 0.09 1.13 8.75 216 217 95 — — 1.00463 2019.11.13 ETV+PEG(12) 8.00E+01 b 49.48 0.31 0.11 1.16 8.92 126 129 105 — — 1.02381 2019.12.10 ETV+PEG(16) 1.40E+02 b 5.47 0.28 0.10 1.15 8.03 109 116 113 230 7.1 1.06422 2020.04.11 TAF+PEG (33) 1.73E+02 b 0.42 1.96 0.11 1.10 6.99 122 119 120 278 7.9 0.97541 2020.07.21 TAF+PEG (48) 1.77E+02 b 0.06 6.00 0.11 1.13 9.37 61 73 86 294 11.7 1.19672 2020.10.20 TAF+PEG (61) 3.70E+01 b 0.01 52.18 0.14 1.20 8.55 91 101 119 — — 1.10989 2021.01.07 TAF+PEG (72) 9.20E+01 b 0.01 142.41 0.14 1.30 9.32 98 119 117 253 9.8 1.21429 2021.03.17 PEG (82) 1.90E+01 b 0 134.59 0.14 1.55 8.44 122 157 112 — — 1.28689 2021.05.19 PEG (91) TAF+PEG PEG PEG PEG PEG 1.10E+01 b 0.01 0.02 0.02 82.28 49.55 58.37 0.13 0.15 0.18 1.30 7.12 73 90 119 — — 1.23288 2021.07.30 PEG (101) 未检测到靶标 b （＜10IU/mL） 0.02 49.55 0.15 1.32 7.51 65 80 94 — — 1.23077 2021.11.05 PEG (115) 4.10E+01 b 0.02 58.37 0.18 1.54 7.53 30 72 120 — — 2.40000 2021.12.06 停用1月 (2021.11.08 停用干扰素) 未检测到靶标 b 0 89.18 0.22 1.43 7.64 — — — — — — 2022.02.07 停用3月 未检测到靶标 b 0 91.6 0.16 1.36 6.37 26 29 34 — — 1.11538 2022.05.02 停用6月 未检测到靶标 b 0 112.26 0.14 1.32 8.73 23 25 33 — — 1.08696 2022.08.08 停用9月 — 0 123.62 0.16 1.34 7.05 18 26 28 — — 1.44444 2022.12.26 停用13月 未检测到靶标 b 0 44.04 0.15 1.42 6.49 20 26 26 176 7.0 1.30000 2023.04.05 停用17月 未检测到靶标 b 0.03 30.84 0.18 1.46 6.61 20 30 30 — — 1.60000 2023.09.20 停用23月 低于检测下限 a 0 8.11 0.17 1.02 6.31 20 29 30 239 5.9 1.45000 ETV - entecavir; PEG - pegylated interferon; HBsAg - hepatitis B s antigen; HBsAb - hepatitis B s antibodies; HBeAg - hepatitis B e antigen; HBeAb - hepatitis B e antibodies; HBcAb - hepatitis B c antibodies; ALT - Alanine aminotransferase; AST - Aspartate aminotransferase; GGT - glutamyltransferase; CAP - Controlled Attenuation Parameter; LSM - liver stiffness measurernents. Discussion Recent advancements in chronic hepatitis B treatment have led to a clearer understanding and wider use of NAs [ 5 ]. While HBsAg clearance remains challenging with PEG-IFN or direct acting antiviral agents (DAAs) alone, Nas offer a well-tolerated and effective option, used in more than 80% of antiviral therapy patients. Although NAs effectively inhibit HBV replication, they do not directly target cccDNA transcription or HBsAgHBsAg expression[ 6 ]. Interferon, with its immunomodulatory and antiviral effects, inhibits HBV transcription and reduces viral proteins, including HBsAgHBsAg[ 7 – 9 ]. Emerging evidence suggest that combination therapy is required to achieve a functional cure for chronic hepatitis B (CHB) [ 10 ]. A meta-analysis demonstrated the superiority of sequential combination therapy over initial combination therapy in achieving HBsAgHBsAg regression compared to [ 11 ]. Furthermore, the ongoing SWAP study revealed a significantly lower rate of virological relapse in patients receiving sequential combination therapy with PEG-IFN compared to switch or control groups [ 12 ]. In HBeAg-negative patients, discontinuing Nas might lead to a higher HBsAg clearance rate than continued use [ 13 ]. The Expert Consensus on Clinical Cure of Chronic Hepatitis B (Functional Cure) outlines a roadmap for achieving a clinical cure of chronic hepatitis B [ 14 ]. According to this roadmap, patients with low baseline HBsAg levels, HBeAg negativity, and sequential PEG - IFN treatment are more likely to achieve clinical cure. Additionally, patients with undetectable HBV DNA and HBsAg levels below 3000 IU/ml treated with DAAs and sequential combination immunomodulators are strongly recommended, especially in HBeAg-negative patients with HBsAg levels below 1500 IU/ml. Regular assessments at 12 and 24 weeks are crucial, and if HBsAg levels are below 200 IU/ml or decreases by more than 1log10IU/ml, continued of sequential combination DAA and immunomodulators are strongly recommended. HBsAg testing should continue at 48 weeks, and if positive, treatment may be extended to 72 or 96 weeks. Once HBsAg negativity and serologic conversion is achieved are achived, discontinuation of DAAs and Immunomodulators is recommended [ 14 ]. In 2019, a study demonstrated the benefits of sequential/combined PEG IFNα-2b treatment with NAs in reducing or eliminating HBsAg and achieving clinical cure in patients with HBsAg level below 1500 IU/ml [ 15 ]. For patients who achieve HBsAg negativity or serological conversion, follow-up is recommended every 3 months in the first year, every 6 months for the second year, and annually thereafter if there is no HBsAg reversal [ 14 ]. OBI primarily arises in patients with prior choric hepatitis B infection who have achieved HBsAg seroclearance and in those who have recovered from self-limiting acute HBV infection [ 16 , 17 ]. The potential mechanisms of OBI include: (a) HBV gene mutations: certain OBI patients carry a higher proportion of mutations in the pre-S/S region, potentially affecting HBsAg antigenicity, production or secretion [ 18 – 24 ]; (b) Methylation patterns: Differences in HBV CpG island methylation patterns between recessive and dominant chronic HBV-infected patients suggest distinct epigenetic control mechanisms [ 25 ]. OBI Patients often exhibit higher methylation density in these islands, a characteristic associated with HBsAg-positive/HBeAg-negative patients [ 26 ]; (c) Host immunity: OBI subjects have been observed to have higher levels of HBV T-cell responses [ 17 ].Additionally, antibody responses may contribute to host control of OBI[ 27 ]; (d) immune complexes formation: HBsAg and anti-HBs immune complexes in the serum can mask HBsAg, leading to undetectable levels [ 28 ]; (e) Viral interference: co-infection with HCV or HDV can suppress HBV replication, contributing to OBI development [ 29 ]. Studies have demonstrated the possibility of detecting cccDNA as low levels during NAs treatment in patients with virally suppressed chronic hepatitis B and in liver donors with OBI [ 30 ]. Animal models have shown that persistent low-level replication of the virus can induce mild, persistent necrotizing liver inflammation [ 31 ]. In presents with OBI and chronic liver disease, hepatitis induced by a mild immune responsecan accelerate liver injury ration [ 32 ]. OBI has implications for various clinical conditions, incluiding transmission through blood transfusion or liver transplantation, reactivation in immunosuppression, adverse effects on the progression of chronic liver disease, and a role inhepatocellular carcinoma development. Prophylactic antiviral therapy is generally not cost-effective for all OBI patients [ 33 ]. In HBsAg-negative and anti-HBc-positive patients with undetectable or low HBV DNA levels and a low risk of reactivation, careful monitoring of alanine aminotransferase (ALT) and HBV DNA levels is recommended [ 34 ]. If HBV reactivation is detected, early antiviral therapy is essential to prevent acute hepatitis and liver damage [ 33 , 35 ]. In the reported case of chronic hepatitis B infection, sequential combination therapy with NAs and PEG-IFN was employed. Despite continued treatment for 72 weeks, HBsAg remained positive, indicating a transition to occult hepatitis B infection. Subsequent treatment with PEG-IFN until HBV DNA negativity led to clinical cure, characterized by negative HBsAg and HBV DNA, normal ALT and AST levels, and asymptomatic status at follow-up visits. Conclusion Sequential combination therapy using NAs and PEG-IFN has been shown to be highly effective in treating chronic hepatitis B infection. However, OBI may occur during this treatment, characterized by the presence of HBVDNA in the blood of individuals who are HBsAg negative. OBI can lead to HBV reactivation, resulting in progressive liver disease and an increased risk of liver cancer. Consequently, clinicians should focus on optimizing the management of patients with OBI. Additionally, further research is needed to explore strategies for achieving a complete cure in the near future. Declarations Ethics approval and consent to participate Not applicable. Clinical trial Clinical trial number: not applicable. Consent for publication Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Data availability statement All data generated or analysed during this study are included in this article. Competing interests The authors declare that they have no competing interests. Funding No funding was received for this study. Author contributions LJ provided case information and reviewed and revised the article; WL reviewed the literature and contributed to the drafting of the manuscript; LH, WH and L-MY helped with manuscript preparation; Z-QL and Z-PF also critically revise important intellectual elements of the article. All authors contributed to the final version of the article. Conflict of interest The authors declare that they have no competing interests. Acknowledgments Not applicable. 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Gastroenterologie clinique et biologique, 2009. 33(6-7): p. 539-54. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5338658","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":372226836,"identity":"99920244-bb39-448d-8817-426fff2cb0d2","order_by":0,"name":"Lin Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Wang","suffix":""},{"id":372226838,"identity":"c02aa118-196a-4024-8b3d-8a48ef6b0721","order_by":1,"name":"Han Liang","email":"","orcid":"","institution":"Shangqiu First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Liang","suffix":""},{"id":372226839,"identity":"03da7875-5724-43fe-bdb7-79fa2ca15dbe","order_by":2,"name":"Chen Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Chen","middleName":"","lastName":"Wang","suffix":""},{"id":372226840,"identity":"da60ec72-a604-4f96-afdf-26b6b3516477","order_by":3,"name":"Mengyu Liang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Mengyu","middleName":"","lastName":"Liang","suffix":""},{"id":372226841,"identity":"d5724c87-397b-4818-8435-602f0180ef0e","order_by":4,"name":"Zeng Qinglei","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Zeng","middleName":"","lastName":"Qinglei","suffix":""},{"id":372226842,"identity":"0c9a2b47-1445-48e8-acba-c4b341374cca","order_by":5,"name":"Zhu Pengfei","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Zhu","middleName":"","lastName":"Pengfei","suffix":""},{"id":372226843,"identity":"0fef1b3c-1988-4e7c-9174-61cd74196d73","order_by":6,"name":"Lv Jun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIie3PMQrCMBSA4RcCzfLcIwq5Qju5FHuVSKFHcC4IdekBOugdurqlZK8H6NLuCh0FF2N7gKSbYP7hQeB9PALg8/1gLAeiAOP5hS4EFYAh2WICeglhute4vSeikqR/FiB2VoJZqBE7SipJo2sB0S23kIQjNBV2AeUy2KwKkKGyXZlJiwGX7O1M1IiKo7lC3Yj5iyFpyHE4rS8tj2orYXroD+U+Eee0GR/HWFivTJFymrkZ3GX/28t10efz+f6yD6GtNwgWQTNwAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Lv","middleName":"","lastName":"Jun","suffix":""}],"badges":[],"createdAt":"2024-10-26 17:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5338658/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5338658/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70743588,"identity":"71929046-9350-43a0-863c-8c405320a465","added_by":"auto","created_at":"2024-12-06 08:09:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":468530,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5338658/v1/322e51ff-2384-4ad8-85c4-632f6c58f41c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical cure in an occult hepatitis B virus infection patient on sequential therapy: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatitis B virus infection is a significant global health problem. Approximately 296\u0026nbsp;million people worldwide are living with chronic HBV infection, of which approximately 20% require antiviral therapy based on current guideline recommendations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Approved anti-HBV therapies include IFNα and nucleoside or nucleotide analogues, both shown to improve clinical outcomes in adults with chronic HBV infection [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, neither agents is universally effective when used alone. IFNα has a low (20\u0026ndash;40%) and potential adverse effects, while nucleoside or nucleoside analogues primarily suppress HBV DNA replication but often require lifelong treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The current therapeutic goal is a functional cure, characterized by persistent disappearance of HBsAg (undetectable at levels\u0026thinsp;\u0026lt;\u0026thinsp;0.05 IU per ml) and undetectable HBV DNA at the end of treatment. Combination therapy is frequently employed to achieve this goal, as numerous studies have demonstrated its effectiveness in restoring the host's antiviral immune response and eliminating the virus [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We presenta case of chronic hepatitis B virus infection that successfully achieved clinical curethrough sequential combination therapy.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe patient is a 28-years old male from China who was diagnosed with HBV infection in 2001, exhibiting positivity for HBsAg, HBeAg, and HBcAb , but with normal liver function tests. In 2012, he presented with abnormal liver function and was treated with short-acting interferon; however, this approach yield poor results, leading to switch to ETV antiviral therapy. In 2019, the patient again presented with abnormal liver function (ALT 435 IU/L, AST 410 IU/L) and was given hepatoprotective medications. In August 2019, laboratory tests showed an HBsAg level of 255.35 IU/ml and HBcAb at 10.46 S/CO, with HBsAb, HBeAg and HBeAb negative. HBV DNA was below the lower limit of detection (\u0026lt;500 IU/ml). The patient had no history of hypertension, cardiovascular disease, diabetes mellitus, or cerebrovascular disease, and was initiated on combination therapy with ETV and pegylated interferon (PEG-IFN). In November 2019, blood tests revealed positive HBV DNA (1.90 log10 IU/ ml), HBsAg at 0.31 IU/ml, HBcAb at 8.92 S/CO, and abnormal liver function (ALT 126 U/L, AST 129 U/L), prompting the continuation of the current treatment. By April 2020, blood tests indicated HBV DNA at 2.24 log10 IU/ml, HBsAg at 0.42 IU/ml, HBcAb at 6.99 S/ CO, with HBsAb, HBeAg and HBeAbvnegative. The treatment regimen was adjuster to a combination of TAF and PEG-IFN. In March 2021, HBsAg firstly turned negative at the first time, with HBsAb at 134.59 IU/ml and HBV DNA at 1.28 log10 IU/ml, leading to a transition to PEG-IFN monotherapy. By November 2021, HBV DNA was below the lower limit of detection (\u0026lt;500 IU/ml), and HBsAg was 0.02 IU/ml, with HBcAb at 49.55 S/ CO. The patient subsequently discontinued PEG-IFN therapy In November 2021. In December 2021, blood tests confirmed that both HBV DNA (\u0026lt;10 IU/mL) and HBsAg were negative, with HBsAb at 89.18 IU/ml and HBcAb at 7.64 S /CO, HBeAg and HBeAb remained negative, and liver function was near normal. Regular retesting thereafter continued to show negative results for both HBV DNA (\u0026lt;10IU/mL) and HBsAg, with liver function maintained within normal limits (Table 1).\u003c/p\u003e\n\u003cp\u003eTable 1. Evolution of hepatitis B pentameter and liver function during the treatment of patients with chronic hepatitis B.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"766\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e时间\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e治疗方案\u0026nbsp;(干扰素针数)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003eHBV-DNA (试剂\u0026nbsp;a普通，b高敏)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003eHBsAg\u003c/p\u003e\n \u003cp\u003e(0-0.05\u003c/p\u003e\n \u003cp\u003eIU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003eHBsAb\u003c/p\u003e\n \u003cp\u003e(0-1\u003c/p\u003e\n \u003cp\u003emIU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003eHBeAg\u003c/p\u003e\n \u003cp\u003e(0-0.18\u003c/p\u003e\n \u003cp\u003ePEIU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003eHBeAb\u003c/p\u003e\n \u003cp\u003e(1-999S/CO)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003eHBcAb\u003c/p\u003e\n \u003cp\u003e(0-1\u003c/p\u003e\n \u003cp\u003eS/CO)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003cp\u003e(0-40\u003c/p\u003e\n \u003cp\u003eU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003cp\u003e(0-40\u003c/p\u003e\n \u003cp\u003eU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003eGGT\u003c/p\u003e\n \u003cp\u003e(0-58\u003c/p\u003e\n \u003cp\u003eU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003eCAP\u003c/p\u003e\n \u003cp\u003e(＜238\u003c/p\u003e\n \u003cp\u003edB/m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003eLSM\u003c/p\u003e\n \u003cp\u003e(2.5-7kPa)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003eAST/ALT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2019.08.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003eETV+PEG (0)\u003c/p\u003e\n \u003cp\u003e首用干扰素\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e低于检测下限 \u003csup\u003ea\u003c/sup\u003e（＜500 IU/mL）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e255.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e5.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n 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7.30117%;\"\u003e\n \u003cp\u003e52.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e8.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.10989\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2021.01.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003eTAF+PEG (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e9.20E+01 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e142.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e9.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n 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10.0391%;\"\u003e\n \u003cp\u003ePEG (91)\u003c/p\u003e\n \u003cp\u003eTAF+PEG\u003c/p\u003e\n \u003cp\u003ePEG\u003c/p\u003e\n \u003cp\u003ePEG\u003c/p\u003e\n \u003cp\u003ePEG\u003c/p\u003e\n \u003cp\u003ePEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e1.10E+01 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e82.28\u003c/p\u003e\n \u003cp\u003e49.55\u003c/p\u003e\n \u003cp\u003e58.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.30\u003c/p\u003e\n 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\u003cp\u003e未检测到靶标 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e（＜10IU/mL）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e49.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e7.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.23077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2021.11.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003ePEG (115)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e4.10E+01 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e58.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e7.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e2.40000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2021.12.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用1月\u003c/p\u003e\n \u003cp\u003e(2021.11.08\u003c/p\u003e\n \u003cp\u003e停用干扰素)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e未检测到靶标 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e89.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e7.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2022.02.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用3月\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e未检测到靶标 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e91.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e6.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.11538\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2022.05.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用6月\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e未检测到靶标 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e112.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e8.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.08696\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2022.08.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用9月\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e123.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e7.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.44444\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2022.12.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用13月\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e未检测到靶标 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e44.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e6.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.30000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2023.04.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用17月\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e未检测到靶标 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e30.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e6.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.60000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.86571%;\"\u003e\n \u003cp\u003e2023.09.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0391%;\"\u003e\n \u003cp\u003e停用23月\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2555%;\"\u003e\n \u003cp\u003e低于检测下限 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.25815%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e8.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.30117%;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.38853%;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.12777%;\"\u003e\n \u003cp\u003e6.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.3455%;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.47588%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5189%;\"\u003e\n \u003cp\u003e239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5.60626%;\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.04042%;\"\u003e\n \u003cp\u003e1.45000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eETV - entecavir; PEG - pegylated interferon; HBsAg - hepatitis B s antigen; HBsAb - hepatitis B s antibodies; HBeAg - hepatitis B e antigen; HBeAb - hepatitis B e antibodies; HBcAb - hepatitis B c antibodies; ALT - Alanine aminotransferase; AST - Aspartate aminotransferase; GGT - glutamyltransferase; CAP - Controlled Attenuation Parameter; LSM - liver stiffness measurernents.\u003c/p\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eRecent advancements in chronic hepatitis B treatment have led to a clearer understanding and wider use of NAs [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. While HBsAg clearance remains challenging with PEG-IFN or direct acting antiviral agents (DAAs) alone, Nas offer a well-tolerated and effective option, used in more than 80% of antiviral therapy patients. Although NAs effectively inhibit HBV replication, they do not directly target cccDNA transcription or HBsAgHBsAg expression[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Interferon, with its immunomodulatory and antiviral effects, inhibits HBV transcription and reduces viral proteins, including HBsAgHBsAg[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e–\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Emerging evidence suggest that combination therapy is required to achieve a functional cure for chronic hepatitis B (CHB) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A meta-analysis demonstrated the superiority of sequential combination therapy over initial combination therapy in achieving HBsAgHBsAg regression compared to [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, the ongoing SWAP study revealed a significantly lower rate of virological relapse in patients receiving sequential combination therapy with PEG-IFN compared to switch or control groups [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In HBeAg-negative patients, discontinuing Nas might lead to a higher HBsAg clearance rate than continued use [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe Expert Consensus on Clinical Cure of Chronic Hepatitis B (Functional Cure) outlines a roadmap for achieving a clinical cure of chronic hepatitis B [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. According to this roadmap, patients with low baseline HBsAg levels, HBeAg negativity, and sequential PEG - IFN treatment are more likely to achieve clinical cure. Additionally, patients with undetectable HBV DNA and HBsAg levels below 3000 IU/ml treated with DAAs and sequential combination immunomodulators are strongly recommended, especially in HBeAg-negative patients with HBsAg levels below 1500 IU/ml. Regular assessments at 12 and 24 weeks are crucial, and if HBsAg levels are below 200 IU/ml or decreases by more than 1log10IU/ml, continued of sequential combination DAA and immunomodulators are strongly recommended. HBsAg testing should continue at 48 weeks, and if positive, treatment may be extended to 72 or 96 weeks. Once HBsAg negativity and serologic conversion is achieved are achived, discontinuation of DAAs and Immunomodulators is recommended [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In 2019, a study demonstrated the benefits of sequential/combined PEG IFNα-2b treatment with NAs in reducing or eliminating HBsAg and achieving clinical cure in patients with HBsAg level below 1500 IU/ml [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. For patients who achieve HBsAg negativity or serological conversion, follow-up is recommended every 3 months in the first year, every 6 months for the second year, and annually thereafter if there is no HBsAg reversal [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOBI primarily arises in patients with prior choric hepatitis B infection who have achieved HBsAg seroclearance and in those who have recovered from self-limiting acute HBV infection [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The potential mechanisms of OBI include: (a) HBV gene mutations: certain OBI patients carry a higher proportion of mutations in the pre-S/S region, potentially affecting HBsAg antigenicity, production or secretion [\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e–\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]; (b) Methylation patterns: Differences in HBV CpG island methylation patterns between recessive and dominant chronic HBV-infected patients suggest distinct epigenetic control mechanisms [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. OBI Patients often exhibit higher methylation density in these islands, a characteristic associated with HBsAg-positive/HBeAg-negative patients [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]; (c) Host immunity: OBI subjects have been observed to have higher levels of HBV T-cell responses [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].Additionally, antibody responses may contribute to host control of OBI[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]; (d) immune complexes formation: HBsAg and anti-HBs immune complexes in the serum can mask HBsAg, leading to undetectable levels [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]; (e) Viral interference: co-infection with HCV or HDV can suppress HBV replication, contributing to OBI development [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Studies have demonstrated the possibility of detecting cccDNA as low levels during NAs treatment in patients with virally suppressed chronic hepatitis B and in liver donors with OBI [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Animal models have shown that persistent low-level replication of the virus can induce mild, persistent necrotizing liver inflammation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In presents with OBI and chronic liver disease, hepatitis induced by a mild immune responsecan accelerate liver injury ration [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. OBI has implications for various clinical conditions, incluiding transmission through blood transfusion or liver transplantation, reactivation in immunosuppression, adverse effects on the progression of chronic liver disease, and a role inhepatocellular carcinoma development. Prophylactic antiviral therapy is generally not cost-effective for all OBI patients [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In HBsAg-negative and anti-HBc-positive patients with undetectable or low HBV DNA levels and a low risk of reactivation, careful monitoring of alanine aminotransferase (ALT) and HBV DNA levels is recommended [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. If HBV reactivation is detected, early antiviral therapy is essential to prevent acute hepatitis and liver damage [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the reported case of chronic hepatitis B infection, sequential combination therapy with NAs and PEG-IFN was employed. Despite continued treatment for 72 weeks, HBsAg remained positive, indicating a transition to occult hepatitis B infection. Subsequent treatment with PEG-IFN until HBV DNA negativity led to clinical cure, characterized by negative HBsAg and HBV DNA, normal ALT and AST levels, and asymptomatic status at follow-up visits.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSequential combination therapy using NAs and PEG-IFN has been shown to be highly effective in treating chronic hepatitis B infection. However, OBI may occur during this treatment, characterized by the presence of HBVDNA in the blood of individuals who are HBsAg negative. OBI can lead to HBV reactivation, resulting in progressive liver disease and an increased risk of liver cancer. Consequently, clinicians should focus on optimizing the management of patients with OBI. Additionally, further research is needed to explore strategies for achieving a complete cure in the near future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLJ\u0026nbsp;provided case information and reviewed and revised the article;\u0026nbsp;WL\u0026nbsp;reviewed the literature and contributed to the drafting of the manuscript; LH, WH and L-MY helped with manuscript preparation;\u0026nbsp;Z-QL and Z-PF also critically revise important intellectual elements of the article.\u0026nbsp;All authors\u0026nbsp;contributed to the final version of the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTan, M., et al., \u003cem\u003eEstimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis.\u003c/em\u003e The Lancet Gastroenterology \u0026amp; Hepatology, 2021. 6(2): p. 106-119.\u003c/li\u003e\n\u003cli\u003eLok, A.S.F., et al., \u003cem\u003eAntiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta‐analysis.\u003c/em\u003e Hepatology, 2016. 63(1): p. 284-306.\u003c/li\u003e\n\u003cli\u003eHermann, A., et al., \u003cem\u003eWW and C2 domain\u0026ndash;containing proteins regulate hepatic cell differentiation and tumorigenesis through the hippo signaling pathway.\u003c/em\u003e Hepatology, 2018. 67(4): p. 1546-1559.\u003c/li\u003e\n\u003cli\u003eGill, U.S. and P.T.F. 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Chinese Medical, \u003cem\u003eThe expert consensus on clinical cure (functional cure) of chronic hepatitis B.\u003c/em\u003e Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2019. 27(8): p. 594-603.\u003c/li\u003e\n\u003cli\u003eNing, Q., et al., \u003cem\u003eRoadmap to functional cure of chronic hepatitis B: An expert consensus.\u003c/em\u003e Journal of Viral Hepatitis, 2019. 26(10): p. 1146-1155.\u003c/li\u003e\n\u003cli\u003eSaitta, C., T. Pollicino, and G. Raimondo, \u003cem\u003eOccult Hepatitis B Virus Infection: An Update.\u003c/em\u003e Viruses-Basel, 2022. 14(7).\u003c/li\u003e\n\u003cli\u003eMichalak, T.I., et al., \u003cem\u003eOccult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis.\u003c/em\u003e Hepatology, 1999. 29(3): p. 928-938.\u003c/li\u003e\n\u003cli\u003eZhang, L., et al., \u003cem\u003eOccult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.\u003c/em\u003e Emerging Microbes \u0026amp; Infections, 2019. 8(1): p. 1337-1346.\u003c/li\u003e\n\u003cli\u003eZhang, K., et al., \u003cem\u003eAntigenicity reduction contributes mostly to poor detectability of HBsAg by hepatitis B virus (HBV) S-gene mutants isolated from individuals with occult HBV infection.\u003c/em\u003e Journal of Medical Virology, 2018. 90(2): p. 263-270.\u003c/li\u003e\n\u003cli\u003eChen, B.F., \u003cem\u003eHepatitis B virus pre-S/S variants in liver diseases.\u003c/em\u003e World Journal of Gastroenterology, 2018. 24(14): p. 1507-1520.\u003c/li\u003e\n\u003cli\u003eHuang, X.Y., et al., \u003cem\u003eImpact of \u0026quot;\u0026lt;i\u0026gt;a\u0026lt;/i\u0026gt;\u0026quot; determinant mutations on detection of hepatitis B surface antigen (HBsAg) in HBV strains from Chinese patients with occult hepatitis B.\u003c/em\u003e Journal of Medical Virology, 2017. 89(10): p. 1796-1803.\u003c/li\u003e\n\u003cli\u003eHuang, F.Y., et al., \u003cem\u003eSequence Variations of Full-Length Hepatitis B Virus Genomes in Chinese Patients with HBsAg-Negative Hepatitis B Infection.\u003c/em\u003e Plos One, 2014. 9(6).\u003c/li\u003e\n\u003cli\u003eHuang, X.Y., et al., \u003cem\u003eMolecular analysis of the hepatitis B virus presurface and surface gene in patients from eastern China with occult hepatitis B.\u003c/em\u003e Journal of Medical Virology, 2013. 85(6): p. 979-986.\u003c/li\u003e\n\u003cli\u003eBes, M., et al., \u003cem\u003eT cell responses and viral variability in blood donation candidates with occult hepatitis B infection.\u003c/em\u003e Journal of Hepatology, 2012. 56(4): p. 765-774.\u003c/li\u003e\n\u003cli\u003eVivekanandan, P., et al., \u003cem\u003eComprehensive genetic and epigenetic analysis of occult hepatitis B from liver tissue samples.\u003c/em\u003e Clinical Infectious Diseases, 2008. 46(8): p. 1227-1236.\u003c/li\u003e\n\u003cli\u003eGuo, Y.H., et al., \u003cem\u003eEvidence That Methylation of Hepatitis B Virus Covalently Closed Circular DNA in Liver Tissues of Patients With Chronic Hepatitis B Modulates HBV Replication.\u003c/em\u003e Journal of Medical Virology, 2009. 81(7): p. 1177-1183.\u003c/li\u003e\n\u003cli\u003eLoomba, R. and T.J. 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Hollinger, \u003cem\u003eOccult hepatitis B virus infection and hepatocellular carcinoma: a systematic review.\u003c/em\u003e Journal of Viral Hepatitis, 2014. 21(3): p. 153-162.\u003c/li\u003e\n\u003cli\u003eChen, S.Y., et al., \u003cem\u003eMechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein.\u003c/em\u003e Journal of Biological Chemistry, 2003. 278(1): p. 591-607.\u003c/li\u003e\n\u003cli\u003eCaviglia, G.P., et al., \u003cem\u003eQuantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: A new tool to detect occult infection.\u003c/em\u003e Journal of Hepatology, 2018. 69(2): p. 301-307.\u003c/li\u003e\n\u003cli\u003eMulrooney-Cousins, P.M. and T.I. Michalak, \u003cem\u003ePersistent occult hepatitis B virus infection: Experimental findings and clinical implications.\u003c/em\u003e World Journal of Gastroenterology, 2007. 13(43): p. 5682-5686.\u003c/li\u003e\n\u003cli\u003eSquadrito, G., R. Spinella, and G. Raimondo, \u003cem\u003eThe clinical significance of occult HBV infection.\u003c/em\u003e Annals of gastroenterology, 2014. 27(1): p. 15-19.\u003c/li\u003e\n\u003cli\u003eYeo, W. and P.J. Johnson, \u003cem\u003eDiagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy.\u003c/em\u003e Hepatology, 2006. 43(2): p. 209-220.\u003c/li\u003e\n\u003cli\u003eKwak, M.-S. and Y.J. Kim, \u003cem\u003eOccult hepatitis B virus infection.\u003c/em\u003e World journal of hepatology, 2014. 6(12): p. 860-9.\u003c/li\u003e\n\u003cli\u003eEuropean Association For The Study Of The, L., \u003cem\u003eEASL clinical practice guidelines. Management of chronic hepatitis B.\u003c/em\u003e Gastroenterologie clinique et biologique, 2009. 33(6-7): p. 539-54.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"chronic hepatitis B, occult HBV infection( OBI), sequential combined therapy, clinical cure, case report","lastPublishedDoi":"10.21203/rs.3.rs-5338658/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5338658/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOccult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus DNA (HBV DNA) in the liver and/or blood of a individual who is currently negative for hepatitis B surface antigen (HBsAg) by standard tests. There is increasing evidence that occult HBV infection is associated with advanced chronic liver disease, especially hepatocellular carcinoma, and that people with occult HBV infection can transmit HBV infection. Despite growing concerns about its transmissibility and clinical impact, occult HBV infection has received limited attention in the hepatitis elimination agenda. While the pursuit of functional cure for hepatitis B may lead to the conversion from overt HBV infection to OBI, few cases of this have been reported to date. This case report presents a patient with chronic hepatitis B who initially converted to occult hepatitis B infection with sequential combination therapy and ultimately achieved clinical cure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient is a 28-years old male from China diagnosed with hepatitis B virus infection. In 2012, he presented with abnormal liver function and was initially treated with short-acting interferon; however, this approach yielded poor results. Consequently, he was switched to Entecavir (ETV) antiviral therapy.In August 2019, laboratory tests indicated an HBsAg level of 255.35 IU/ml, while HBV DNA was below the lower limit of detection (\u0026lt;500 IU/ml). The patient hadno history of hypertension, cardiovascular disease, diabetes mellitus, or cerebrovascular disease, and was subsequently started on a combination therapy of ETV and pegylated interferon (PEG-IFN). By April 2020, follow-up tests revealed HBV DNA at 2.24 log10 IU/ml and HBsAg reduced to 0.42 IU/ml. At this point, the treatment regimen was adjusted to a combination therapy of tenofovir alafenamide (TAF) and PEG-IFN. Six months later, HBsAg turned negative, HBsAb rose to 52.18IU/L, and HBV DNA was measured at 1.28 log10 IU/ml. The patient was then transitioned to PEG-IFN monotherapy. In November 2021, the patient discontinued PEG-IFN therapy. One month later, laboratory tests confirmed that both HBV DNA (\u0026lt;10 IU/mL) and HBsAg were negative, and these results have been maitntained to date.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This case demonstrates that sequential combination therapy can effectively treat chronic hepatitis B, even in patients with a long history of infection. This approach may lead to a shift to latent hepatitis B infection, and timely adjustments in treatment regimens based on monitoring indicators can ultimately result in a clinical cure.\u003c/p\u003e","manuscriptTitle":"Clinical cure in an occult hepatitis B virus infection patient on sequential therapy: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-11 06:02:30","doi":"10.21203/rs.3.rs-5338658/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"30d5767b-4d8d-4591-9884-69279c2866de","owner":[],"postedDate":"November 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-06T08:08:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-11 06:02:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5338658","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5338658","identity":"rs-5338658","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}