FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2938642465> ?p ?o ?g. }

• W2938642465 endingPage "516.e2" @default.
• W2938642465 startingPage "514" @default.
• W2938642465 abstract "Hepatitis B surface antigen (HBsAg) seroclearance has been recommended as an optimal endpoint of antiviral treatment by the latest chronic hepatitis B management guideline.1EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.J Hepatol. 2017; 67: 370-398Abstract Full Text Full Text PDF PubMed Scopus (2951) Google Scholar However, few reports investigated the durability of response after HBsAg seroclearance, because of a lower HBsAg seroclearance rate and the difficulty of obtaining a sufficient number of samples for analysis. Our center has made a long-term commitment to investigate the personalized antiviral therapy for chronic hepatitis B. More than 300 patients achieved HBsAg seroclearance by interferon (IFN)-based antiviral treatment. In this study, the durability and the effects of hepatitis B virus (HBV) surface antibody (Anti-HBs) level on relapse after HBsAg seroclearance were investigated. During the years 2005–2017, a total of 1276 patients with chronic hepatitis B in our center received IFN-based antiviral treatment, 383 of them treated with either regular IFN or pegylated IFN, and 893 combined with nucleos(t)ide analogue (NA). A total of 305 achieved HBsAg seroclearance and 67 were not enrolled (42 of them refused to participate because of long travel distance, 25 enrolled in another antiviral observational study); 238 cases were included in this study. The patient characteristics are shown in Supplementary Table 1. From the date of treatment cessation, the patients received regular examinations for every 13 ± 2 weeks in the first year and every 26 ± 2 weeks after that, including HBV markers (HBsAg, Anti-HBs, HBV e antigen), HBV DNA, and liver functions. Sequencing of the S regions of HBV was performed using polymerase chain reaction direct sequencing. The definition of recurrence is the reappearance of either HBsAg, HBV DNA, or both at least 2 times in an interval of 4–8 weeks during the follow-up after treatment cessation. The recurrence time estimation was adjusted by inverse-probability weighting to estimate the effects of Anti-HBs level using Weibull model. Logit model was used for both the Anti-HBs level assignment and the censoring time. Adjustments were made for gender, age, HBV e antigen status, and treatment strategy. The follow-up time was 21–597 weeks after the treatment cessation, with a median of 160 weeks. A total of 18 recurrence cases were observed (Table 1). The cumulative recurrence was 0.84%, 6.29%, 6.88%, 8.18%, and 9.66% for 26 weeks, 52 weeks, 78 weeks, 104 weeks, and 597 weeks, respectively (Supplementary Figure 1A). The recurrence peak was within 52 weeks (13 recurrences were observed). The Anti-HBs <100 IU/L group had higher recurrence rate (21.1%) compared with Anti-HBs ≥100 IU/L group (4.3%) (Supplementary Figure 1B). The Weibull survival model showed that the inverse-probability weighting average recurrence time for Anti-HBs ≥100 IU/L group was 107 weeks and the length of Anti-HBs <100 IU/L group was 41 weeks, which was 66 weeks shorter (P < .001). Other factors, gender, age, and treatment (IFN types and their combination with NA) did not have significant influences on recurrence. The recurrence patterns of 18 patients were different. Among them, 8 cases were HBsAg positive; 6 cases were HBsAg and HBV DNA positive; and 4 cases were HBsAg negative, Anti-HBs positive, and HBV DNA positive. Sequencing was performed for the 5 cases to detect viral variations at the time point of HBV DNA >103 IU/mL. Three samples had variations in the S region, including sI126T, sT140I, and sD144A. During the follow-up, disease progression and end-stage liver diseases were not observed.Table 1Summary of 18 Patients With Recurrence After Treatment CessationPatientGenderAge (y)HBeAg statusaAt the time of initial antiviral treatment.TherapyTherapy duration (wk)Anti-HBs (IU/L)bAnti-HBs level at the end of therapy.Follow-up time (wk)cWeeks from the date of treatment cessation to the recurrence.HBsAg (IU/mL)dViral quantities and ALT at recurrence.Anti-HBs (IU/L)dViral quantities and ALT at recurrence.HBV DNA (IU/mL)dViral quantities and ALT at recurrence.ALT (U/L)dViral quantities and ALT at recurrence.S region variant1Male39PositiveADV+PEG-IFN725.61340.089<2<2026.2—2Male27PositivePEG-IFN96697.5520.41323.2<2037.8—3Male36PositiveADV+IFN96873.0480.621836.4<2019.4—4Male28PositiveADV+IFN84259.9432.44211.87.02E+331.5sI126T,sT140I,sD144A5Male26PositiveETV+PEG-IFN9698.7730.4373.520.216.8—6Female26PositiveETV+PEG-IFN72365.839184.8<21.66E+24.8—7Male35PositiveETV+PEG-IFN96>100021168>10006.21E+2∼ 1.7E+827.7sI126T8Male50PositiveADV+ETV+PEG-IFN9638.5990.07621.871.217.5—9Male55PositiveADV+ETV+PEG-IFN969983412602785.53.02E+7243.2Negative10Male51PositiveETV+PEG-IFN96>100099<0.05530.842.820.4—11Male46PositivePEG-IFN84>100052<0.05>100021.227.4—12Male44PositiveADV+PEG-IFN72379.434<0.0588.11.71E+315.0sD144A13Male38PositiveADV+ETV+IFN96>100043<0.05489.049.4∼ 2.09E+545.8Negative14Female32NegativeETV+PEG-IFN96502.3211.54517.9<2012.3—15Female20NegativeETV+PEG-IFN8462.81471.75185.4<207.8—16Female56NegativeIFN7290.2520.05220.4<2022.1—17Female44NegativeETV+PEG-IFN84427.4482.77767.2<208.9—18Female31NegativeETV+PEG-IFN602.9470.287<2<2012.5—NOTE. Em dash represents “not tested.”ADV, adefovir; ALT, alanine aminotransferase; Anti-HBs, hepatitis B virus surface antibody; ETV, entecavir; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; IFN, interferon; PEG, pegylated.a At the time of initial antiviral treatment.b Anti-HBs level at the end of therapy.c Weeks from the date of treatment cessation to the recurrence.d Viral quantities and ALT at recurrence. Open table in a new tab NOTE. Em dash represents “not tested.” ADV, adefovir; ALT, alanine aminotransferase; Anti-HBs, hepatitis B virus surface antibody; ETV, entecavir; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; IFN, interferon; PEG, pegylated. In this study, the recurrence for 597 weeks was 9.66%. Similar to previous reports, Chi et al2Chi H. Wong D. Peng J. et al.Durability of response after hepatitis B surface antigen seroclearance during nucleos(t)ide analogue treatment in a multiethnic cohort of chronic hepatitis B patients: results after treatment cessation.Clin Infect Dis. 2017; 65: 680-683Crossref PubMed Scopus (24) Google Scholar reported 54 cases of NA-induced HBsAg seroclearance, with an average follow-up of 1.6 years. Seven cases developed detectable HBV DNA or HBsAg, but no patients developed alanine aminotransferase levels >80 U/L.2Chi H. Wong D. Peng J. et al.Durability of response after hepatitis B surface antigen seroclearance during nucleos(t)ide analogue treatment in a multiethnic cohort of chronic hepatitis B patients: results after treatment cessation.Clin Infect Dis. 2017; 65: 680-683Crossref PubMed Scopus (24) Google Scholar Kim et al3Kim G.A. Lim Y.S. An J. et al.HBsAg seroclearance after nucleoside analog therapy in patients with chronic hepatitis B: clinical outcomes and durability.Gut. 2014; 63: 1325-1332Crossref PubMed Scopus (242) Google Scholar investigated 110 patients with NA-induced HBsAg seroclearance and the cumulative recurrence of 36 months was 11.7%. Previous reports showed that during the recurrence, HBV markers were HBsAg positive or HBsAg and HBV DNA positive but HBsAg negative, Anti-HBs positive and HBV DNA positive were rare.4Chen X. Cao Z. Liu Y. et al.Potent hepatitis B surface antigen response to treatment of hepatitis-B-e-antigen-positive chronic hepatitis B with alpha-interferon plus a nucleos(t)ide analog.J Gastroenterol Hepatol. 2012; 27: 481-486Crossref PubMed Scopus (14) Google Scholar, 5Wong R.J. Nguyen M.T. Trinh H.N. et al.Hepatitis B surface antigen loss and sustained viral suppression in Asian chronic hepatitis B patients: a community-based real-world study.J Viral Hepat. 2017; 24: 1089-1097Crossref PubMed Scopus (16) Google Scholar, 6Chen Q.Y. Wang X.Y. Harrison T.J. et al.HBsAg may reappear following reactivation in individuals with spontaneous HBsAg seroclearance 8 years previously.Epidemiol Infect. 2017; 145: 728-738Crossref PubMed Scopus (7) Google Scholar In our study S-region variation was detected in 3 samples with Anti-HBs and HBV DNA positive, and this may explain the phenomenon. Similarly, Hsu and Yeh7Hsu C. Yeh C. Emergence of hepatitis B virus S gene mutants in patients experiencing hepatitis B surface antigen seroconversion after peginterferon therapy.Hepatology. 2011; 54: 101-108Crossref PubMed Scopus (36) Google Scholar reported 2 patients treated with pegylated IFN achieved HBsAg seroclearance but continued to be positive for HBV DNA. Variations of sT125A and SW74* were detected by sequencing. HBsAg seroclearance durability is generally reported in the literature as no recurrence for 6 months after treatment cessation.8Liaw Y.F. Sheen I.S. Chen T.J. et al.Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study.Hepatology. 1991; 13: 627-631Crossref PubMed Scopus (243) Google Scholar In this study, the recurrence peak was within 52 weeks. Therefore, the follow-up time for determination of the durability of HBsAg seroclearance should be extended to 52 weeks. In summary, HBsAg seroclearance achieved after IFN treatment was durable during long-term follow-up. The recurrence peak was within 52 weeks. A recurrence type, “Anti-HBs-positive, and HBV DNA-positive,” was associated with HBV S mutants. The recurrence peak. The authors thank the research nurses Qun Wang, Junli Wang, and Fangfang Wu for performing patient follow-up, and Dr. Jennifer Steel, Department of Surgery, University of Pittsburgh, for critical reading and comments. Treatment duration: 48–96 weeks (HBsAg clearance time was 22 cases at 48 weeks, 83 cases at 48–84 weeks, 133 cases at 84–96 weeks). There was no statistical difference in the course of treatment between recurrence group and nonrecurrence group. Sixteen patients (LAM, n = 11; ADV, n = 3; ETV, n = 2) who were initially treated with NA antiviral therapy experienced virologic rebound during the course of treatment, and related drug resistance sites were detected by polymerase chain reaction sequencing, including rtL180M (+), rtM204I (+), rtA181T (+), rtT184I (+), and rtS202G (+). Remedial treatment for NA drug-resistant patients: LAM was switched to ADV for LAM drug-resistant patients, ADV was switched to ETV for ADV drug-resistant patients, and ETV was added on ADV for ETV drug-resistant patients, and all combined with IFN therapy. To improve the efficacy 28 patients initially treated with regular IFN were switched to pegylated-IFN. Statistical analysis showed that the type of IFN had no effect on recurrence. During the follow-up, disease progression and end-stage liver diseases were not observed. All the patients in this study were relatively young and the follow-up is needed to observe the long-term prognosis. The outcomes of relapse patients were investigated and can be roughly divided into 3 categories:1.Recurrent patients with low levels of HBsAg (0.052–2.77 IU/mL) and/or low levels of HBV DNA (20.2–71.2 IU/mL) (12 cases). According to the patients' wishes, 5 patients were treated with antiviral therapy again, 4 of them (2, 8, 14, and 17) chose pegylated-IFN, and all of them obtained HBsAg seroclearance. Currently, drug withdrawal is under observation. One case (5) was found during NA maintenance therapy, HBV DNA inhibition (<20 IU/mL), but HBsAg was still positive. Seven patients did not receive antiretroviral therapy, and were followed up regularly. Among them, 2 (10 and 11) had recurrence with only HBV DNA positive and HBsAg negative. At present, HBV DNA all turned negative automatically. The other 5 patients (1, 3, 15, 16, and 18) had low positive level of HBsAg and HBV DNA <20 IU/mL at the time of relapse. There was no significant change in the levels of HBsAg and HBV DNA during follow-up, HBsAg remained at a low level, and HBV DNA <20 IU/mL.2.HBV S-region variation. In this study, S-region related mutation sites were detected in the serum of 3 patients ( 4, 7, and 12). For the treatment of patients with recurrence of S-region mutation, there is no targeted therapy at present, only NA maintenance therapy can be used to inhibit HBV DNA replication for a long time.3.Clinical features of HBeAg-positive CHB after recurrence. In this study, 3 patients (7, 9, and 13) with recurrence met the indications of HBeAg-positive CHB antiviral therapy. At present, the course of antiviral therapy is 13–34 weeks, and there is no serologic conversion.Supplementary Table 1Clinical Characteristics of the PatientsCharacteristicsTotal (N = 238)Status before treatment (baseline)Gender, male, n (%)152 (63.9)Age (y)aMean ± SD.36 ± 11HBeAg-positive, n (%)114 (47.9)Cirrhosis, n (%)0Therapeutic regimen, IFN only, n (%)45 (18.9)NA combined with IFN-simultaneous start, n (%)132 (55.5) Pretreatment with NA for 24 weeks and add-on IFN, n (%)61 (25.6)Therapeutic medication,bRegular IFN 19.7%, pegylated IFN 80.3%. IFN only, n (%)45 (18.9) LAM+IFN, n (%)27 (11.3) ADV+IFN, n (%)96 (40.3) ETV+IFN, n (%)70 (29.4)Antiviral treatment duration (wk), median (range)84 (48-96)Status at the end of treatmentHBsAg <0.05 IU/mL, n (%)238 (100)Anti-HBs ≥100 IU/L, n (%)185 (77.7)HBeAg <1.0 (S/CO), n (%)238 (100)Anti-HBe-positive (S/CO), n (%)cPositive Anti-HBe is defined as Anti-HBe <1.0 S/CO according to the manufacturer’s instructions.196 (82.4)HBV DNA <20 IU/mL238 (100)Follow-up time after treatment cessation (wk)dMedian (Q1-Q3).160 (69–246)ADV, adefovir; Anti-HBs, hepatitis B virus surface antibody; ETV, entecavir; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IFN, interferon; LAM, lamivudine; NA, nucleos(t)ide analogue.a Mean ± SD.b Regular IFN 19.7%, pegylated IFN 80.3%.c Positive Anti-HBe is defined as Anti-HBe <1.0 S/CO according to the manufacturer’s instructions.d Median (Q1-Q3). Open table in a new tab ADV, adefovir; Anti-HBs, hepatitis B virus surface antibody; ETV, entecavir; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IFN, interferon; LAM, lamivudine; NA, nucleos(t)ide analogue. Muddle and Mechanism of Hepatitis B Surface Antigen SeroclearanceClinical Gastroenterology and HepatologyVol. 17Issue 12PreviewWe read with interest the article by Wu et al1 wherein they showed the durability of hepatitis B surface antigen (HBsAg) seroclearance after a finite therapy with interferon (IFN), with or without combination with nucleoside analogues in chronic hepatitis B (CHB) patients. Full-Text PDF" @default.
• W2938642465 created "2019-04-25" @default.
• W2938642465 creator A5002705488 @default.
• W2938642465 creator A5007041856 @default.
• W2938642465 creator A5011606433 @default.
• W2938642465 creator A5017010239 @default.
• W2938642465 creator A5023252420 @default.
• W2938642465 creator A5035267982 @default.
• W2938642465 creator A5042604481 @default.
• W2938642465 creator A5071243431 @default.
• W2938642465 creator A5077400423 @default.
• W2938642465 creator A5084502351 @default.
• W2938642465 creator A5084768375 @default.
• W2938642465 date "2020-02-01" @default.
• W2938642465 modified "2023-10-05" @default.
• W2938642465 title "Durability of Interferon-induced Hepatitis B Surface Antigen Seroclearance" @default.
• W2938642465 cites W1951531280 @default.
• W2938642465 cites W2114785561 @default.
• W2938642465 cites W2148314869 @default.
• W2938642465 cites W2160816585 @default.
• W2938642465 cites W2559846481 @default.
• W2938642465 cites W2605785536 @default.
• W2938642465 cites W2620792739 @default.
• W2938642465 cites W2622568650 @default.
• W2938642465 doi "https://doi.org/10.1016/j.cgh.2019.04.020" @default.
• W2938642465 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30981007" @default.
• W2938642465 hasPublicationYear "2020" @default.
• W2938642465 type Work @default.
• W2938642465 sameAs 2938642465 @default.
• W2938642465 citedByCount "27" @default.
• W2938642465 countsByYear W29386424652019 @default.
• W2938642465 countsByYear W29386424652020 @default.
• W2938642465 countsByYear W29386424652021 @default.
• W2938642465 countsByYear W29386424652022 @default.
• W2938642465 countsByYear W29386424652023 @default.
• W2938642465 crossrefType "journal-article" @default.
• W2938642465 hasAuthorship W2938642465A5002705488 @default.
• W2938642465 hasAuthorship W2938642465A5007041856 @default.
• W2938642465 hasAuthorship W2938642465A5011606433 @default.
• W2938642465 hasAuthorship W2938642465A5017010239 @default.
• W2938642465 hasAuthorship W2938642465A5023252420 @default.
• W2938642465 hasAuthorship W2938642465A5035267982 @default.
• W2938642465 hasAuthorship W2938642465A5042604481 @default.
• W2938642465 hasAuthorship W2938642465A5071243431 @default.
• W2938642465 hasAuthorship W2938642465A5077400423 @default.
• W2938642465 hasAuthorship W2938642465A5084502351 @default.
• W2938642465 hasAuthorship W2938642465A5084768375 @default.
• W2938642465 hasBestOaLocation W29386424651 @default.
• W2938642465 hasConcept C159047783 @default.
• W2938642465 hasConcept C203014093 @default.
• W2938642465 hasConcept C2776178377 @default.
• W2938642465 hasConcept C2777382497 @default.
• W2938642465 hasConcept C71924100 @default.
• W2938642465 hasConceptScore W2938642465C159047783 @default.
• W2938642465 hasConceptScore W2938642465C203014093 @default.
• W2938642465 hasConceptScore W2938642465C2776178377 @default.
• W2938642465 hasConceptScore W2938642465C2777382497 @default.
• W2938642465 hasConceptScore W2938642465C71924100 @default.
• W2938642465 hasFunder F4320324095 @default.
• W2938642465 hasIssue "2" @default.
• W2938642465 hasLocation W29386424651 @default.
• W2938642465 hasOpenAccess W2938642465 @default.
• W2938642465 hasPrimaryLocation W29386424651 @default.
• W2938642465 hasRelatedWork W1517122704 @default.
• W2938642465 hasRelatedWork W1965324567 @default.
• W2938642465 hasRelatedWork W2008431894 @default.
• W2938642465 hasRelatedWork W2107252694 @default.
• W2938642465 hasRelatedWork W2130944994 @default.
• W2938642465 hasRelatedWork W2133353331 @default.
• W2938642465 hasRelatedWork W2136046700 @default.
• W2938642465 hasRelatedWork W2151702506 @default.
• W2938642465 hasRelatedWork W2743344876 @default.
• W2938642465 hasRelatedWork W4241018568 @default.
• W2938642465 hasVolume "18" @default.
• W2938642465 isParatext "false" @default.
• W2938642465 isRetracted "false" @default.
• W2938642465 magId "2938642465" @default.
• W2938642465 workType "article" @default.